Let’s Stop Moving: Management of Acute Diarrhea in the Ambulatory Setting

Pharmacist Learning Objectives:

RECOGNIZE signs and symptoms associated with acute diarrhea, including those that require referral to a PCP or hospital
IDENTIFY inappropriate oral rehydration techniques
RECOGNIZE antidiarrheal misuse
REVIEW the risks and benefits associated with the most commonly used strategies to manage diarrhea

Pharmacy Technician Learning Objectives:

LIST the basic pathology and symptoms of acute diarrhea
RECALL treatments used in patients who have acute diarrhea
IDENTIFY OTC products and dietary modifications that are useful in acute diarrhea
IDENTIFY when to refer patients to the pharmacist for recommendations or referral

Although diarrhea is one of the most commonly managed medical conditions in the outpatient setting, it can be also be one of the most serious if treated inappropriately. In addition, new therapies and concerns with older ones have led to several new practice recommendations. Patients infected with coronavirus disease (COVID)-19, especially younger ones, may experience significant gastrointestinal (GI) symptoms. Unlike adults, children may present only with GI complications, such as diarrhea, nausea, vomiting, and severe abdominal pain. In one early study of patients with COVID-19, one third reported GI symptoms prior to the onset of fever or respiratory symptoms. Another challenge is the escalating opioid crisis and loperamide utilization as a drug of abuse. Patients addicted to opioids are now abusing over-the-counter (OTC) antidiarrheal medications, including loperamide, to help manage withdrawal symptoms. The purpose of this continuing education activity is to highlight several recent changes in diarrhea management and provide a general overview of the most commonly used OTC antidiarrheal agents.

“When you’re riding in a Chevy and you feel something heavy.

When you’re sliding into home and your pants are full of foam.

When you’re sitting in the bath and you feel something splash.”¹

No one likes to talk about it, but everyone knows what it is. Some call it "Montezuma's revenge," "the runs," or worse. Although diarrhea is one of the most commonly managed medical conditions in the outpatient setting, it can also be one of the most serious if treated inappropriately. In addition, concerns with older approaches to acute diarrhea have led to several new practice recommendations. The novel coronavirus disease-2019 (COVID-19) pandemic is also associated with a significant gastrointestinal (GI) component. In one early United States (U.S.) study of patients with COVID-19, one third reported GI symptoms prior to the onset of fever or respiratory symptoms.²

Another challenge is the escalating opioid crisis. Patients addicted to opioids are now abusing over-the-counter (OTC) antidiarrheal medications, such as loperamide, to help manage withdrawal symptoms. The purpose of this activity is to highlight several recent changes in diarrhea management and provide an overview of commonly used OTC antidiarrheal agents and other treatment strategies.

The classic definition of diarrhea is passage of loose or watery stools. Some have defined it as the passage of three or more watery stools per day, but it is difficult to define absolute limits. Acute diarrhea typically lasts one to two days (starting with the first loose stool, not when treatment starts). Patients and caregivers should raise concerns whenever stool patterns deviating from the norm are accompanied by other signs of illness, not just based on the stool frequency or water content. Table 1 summarizes the most common symptoms associated with acute diarrhea.

Table 1. Symptoms Associated with Acute Diarrhea³

Abdominal pain
Cramping
Fecal incontinence
Fecal urgency
Nausea
Three or more loose, watery stools daily

In the U.S., approximately 179 million cases of acute diarrhea occur annually.⁴ The following sections describe its many causes. In immunocompetent individuals, the primary etiology of infectious diarrhea includes foodborne pathogens and norovirus outbreaks.⁵

Numerous factors predispose patients to developing acute diarrhea (see Table 2). Providers should not confuse acute diarrhea with chronic diarrhea (i.e., diarrhea lasting more than two weeks). In many instances, the etiology of acute diarrhea is unknown and it resolves without treatment. Acute diarrhea is most commonly infectious in nature or related to a medication adverse effect.

Table 2. Causes of Acute Diarrhea

Cause	Description
Excessive intake of artificial sweeteners	Mannitol, sorbitol, xylitol (found in sugar-free products)
Food intolerance	Lactose intolerance
Infections	Bacterial (e.g., E. coli, Salmonella)
	Parasitic (e.g., Giardia, Cryptosporidium, E. histolytica)
	Viral (e.g., COVID-19, norovirus, rotavirus)
Medications	See Table 3
Travel (typically to developing countries)	Consuming food or drink contaminated by bacteria or parasites

COVID-19 = coronavirus disease-19

INFECTIOUS CAUSES OF DIARRHEA

Viral Gastroenteritis

Acute infectious diarrhea is often viral, resulting in more than 1.5 million outpatient visits in the U.S. annually.⁵ Typically, patients with viral diarrhea experience low-grade fevers and watery, non-bloody diarrhea lasting one to two days. Rotavirus used to be the most common cause of diarrhea in the U.S., but as rotavirus vaccination rates have increased, norovirus has taken over this title. Infant rotavirus immunization starts as early as six weeks of age but no later than 15 weeks.⁶ Healthcare providers should administer the final dose in the immunization series by eight months of age. Infants infected with rotavirus prior to receiving the full vaccine course should still initiate or complete the recommended schedule, as initial infection confers only partial immunity.

Norovirus-induced diarrhea is less severe than rotavirus, especially in children. More commonly known as the “cruise ship virus,” norovirus is now one of the leading causes of foodborne disease and a common cause of traveler’s diarrhea.⁷ Vomiting often accompanies diarrhea. In most cases, symptoms appear 12 to 48 hours after exposure and last one to three days, although the virus can continue to be shed in stools up to two weeks after resolution. Interestingly, not everyone is susceptible to norovirus infections. Individuals with type O blood are more prone to norovirus infections, while those with type B blood are least likely to contract them.⁸

Bacterial Gastroenteritis

It is sometimes difficult to distinguish between viral and bacterial gastroenteritis. Unlike viral gastroenteritis, bacterial infections associated with diarrhea have the potential to be more severe and are often associated with high fevers (exceeding 104^oF), abdominal pain, and bloody stools.⁵ Vomiting is less common. The most common causes of bacterial gastroenteritis in the U.S. are non-typhoidal Salmonella and Campylobacter species.⁵ These usually occur after eating raw or undercooked poultry or something that came in contact with it. Reptiles, such as pet turtles, can also carry Salmonella in their stool and easily transmit the bacteria to their shells, tank water, and anywhere else they live and roam.⁹

Bacterial gastroenteritis is usually mild and self-limiting, but infants younger than three months of age may experience severe complications that can result in hospitalization.⁶ In an otherwise healthy individual, bacterial gastroenteritis can resolve without any treatment. Antibiotics are reserved for treating diarrhea in immunocompromised patients, infants younger than three months of age, and patients who appear septic or toxic.^5,6

COVID-19-Related Diarrhea

Since the onset of the COVID-19 pandemic, respiratory symptoms have been the most common presentation of this viral illness. A growing number of patients, however, experience GI symptoms (e.g., anorexia, diarrhea, nausea, vomiting), sometimes without respiratory symptoms. COVID-19-induced diarrhea can last one day to as long as two weeks.² Although the mechanisms involved in the pathogenesis of COVID-19-related diarrhea are still unknown, the virus is likely altering intestinal permeability resulting in enterocyte malabsorption.¹⁰

Foodborne Disease

Produce—especially leafy green vegetables—is the most common source of diarrhea due to foodborne pathogens.¹¹ Spinach and lettuce purchased from grocery stores often come from developing countries where water contamination is common and produce does not undergo agricultural inspection. Diarrhea-producing E. coli or Salmonella are common pathogens. Contaminated poultry is associated with the highest proportion of diarrhea fatalities (19%), mainly due to Salmonella or Listeria infection.¹¹

To reduce this risk, consumers should soak leafy greens in water and rinse them thoroughly before eating. They must also use care when handling raw poultry. To prevent cross-contamination, cooks should prepare raw poultry separately from other foods. They should also clean food preparation surfaces and utensils (e.g., counters, cutting boards, forks, knives) and their hands with hot, soapy water after handling raw poultry. Finally, they must cook all raw poultry thoroughly. Updated weekly, the Centers for Disease Control and Prevention (CDC) provides extensive information on foodborne outbreak investigations on their website: https://www.cdc.gov/foodsafety/outbreaks/index.html.

Traveler’s diarrhea—commonly caused by consuming contaminated food or drinking water in foreign countries—often appears within 10 days of travel to an area with poor public hygiene.¹² In most cases, traveler’s diarrhea is not serious. However, in some instances, this type of diarrhea may last longer than usual due to infections with parasites and requires treatment with an antiprotozoal agent.¹³ Although it can occur anywhere, the areas of greatest risk are in Africa, Asia (except Japan and South Korea), Central and South America, Mexico, and the Middle East.¹⁴ The CDC publishes notices for travelers about potential health implications (e.g., disease outbreaks, gatherings, natural disasters) for destinations around the world, sorted by disease or country.¹⁵

NON-INFECTIOUS CAUSES OF DIARRHEA

Medication-Associated Diarrhea

Many medications can cause diarrhea as a side effect, usually because they affect gut motility or microbe balance.

Antibiotic-associated diarrhea

Antibiotic-associated diarrhea (AAD) results from an imbalance of intestinal bacteria where opportunistic bacteria like C. difficile are allowed to thrive.¹⁶ AAD happens during a course of antibiotics or shortly afterward. The most commonly implicated antibiotics include clindamycin, macrolides, and other broad-spectrum antibiotics, but any antibiotic can disrupt the balance of non-pathogenic bacteria flora within the intestines.

Pharmacy staff may field questions about fecal transplants (also known as “poop pills” or “poop with a purpose”). The formal name for this is fecal microbiota transplant (FMT), which entails transferring stool from a healthy individual to a patient infected with C. difficile. The goal is to restore the balance of bacteria in the infected patient’s gut. In patients with recurrent C. difficile infections, FMT may be more effective and significantly less expensive than a course of vancomycin.¹⁷ It is not an approved therapy, but the FDA does allow clinicians to use it investigationally to treat C. diff infections. It is not without risk, and patients have developed life-threatening infections from FMT contaminated with other pathogenic organisms.¹⁸

PAUSE AND PONDER: How can Halloween candy and fruit juices predispose children to diarrhea?

Table 3 lists drugs that can cause acute diarrhea. Pharmacists should refer patients to their prescribers to discuss therapeutic alternatives without diarrheal adverse effects. For example, magnesium-containing OTC antacids may cause diarrhea, but calcium carbonate and aluminum hydroxide do not, making them suitable alternatives. Likewise, herbals, such as St. John’s wort, aloe vera juice, and lobelia, have been linked with diarrhea.

Table 3. Drugs Associated with Acute Diarrhea¹⁹

Medication Class	Examples
Antibiotics	· Cephalosporins (e.g., cefdinir, cefpodoxime) · Clindamycin · Macrolides (e.g., erythromycin, clarithromycin, azithromycin, fidaxomicin) · Penicillins (e.g., amoxicillin, ampicillin)
Cancer chemotherapeutics	· Cyclophosphamide · Daunorubicin · Epirubicin · Fluorouracil · Gemcitabine · Ixabepilone · Methotrexate · Vincristine
Copper chelators	· Dimercaprol · Penicillamine · Trientine
Corticosteroids	· Dexamethasone · Prednisone
Digitalis glycosides	· Digoxin
Magnesium salts	· Magnesium hydroxide (Phillips’ Milk of Magnesia, Ducolax Milk of Magnesia, Pedi-lax Chewable Tablets)
Mood stabilizers	· Lithium
Nonsteroidal anti-inflammatory agents	· Ibuprofen · Meclofenamate sodium
Proton Pump Inhibitors	· Lansoprazole · Omeprazole · Pantoprazole

Laxative-Associated Diarrhea

Laxative-associated diarrhea is a specific form of medication-associated diarrhea.²⁰ Excessive intake of laxatives could be accidental (e.g., not understanding the directions) or intentional (e.g., child abuse, bulimia, anorexia nervosa). For example, there are cases reports of parents hiding laxatives in children’s food and/or medication as part of an ill-advised prank or an abusive gesture, resulting in serious harm.^21,22 A person buying multiple types and/or large quantities of laxatives or asking inappropriate questions about their use may be misusing them. Obtaining a thorough history and encouraging patients and caregivers to seek medical care is just as, if not more, important than recommending an antidiarrheal agent. When possible, pharmacy team members may want to discuss their observations regarding unusual laxative use with the patient’s PCP.

Toddler Diarrhea

Toddler diarrhea—also known as functional diarrhea or non-specific diarrhea of childhood—often occurs when children drink considerable amounts of hyperosmolar fluids, such as fruit juices. According to the American Academy of Pediatrics, toddlers between one and three years of age should limit their juice intake to no more than four ounces per day.²³ Toddler diarrhea management involves reducing the volume of fruit juices or other osmotically-active carbohydrate beverages that contain sorbitol or fructose. Similarly, children may develop self-limiting “Halloween diarrhea” after ingesting sorbitol- and fructose-rich candies.²⁴

Lactase Deficiency or Food Intolerance

The brush border of the small intestine produces the enzyme lactase. It is necessary for breaking down lactose (“milk sugar”) to digest milk. Lactase deficiency can occur when an enteric (intestinal) infection causes mucosal (lining) injury. Approximately 68% of the world's population has some form of lactose malabsorption.²⁵ Lactase deficiency is more prevalent in Asia and Africa, while it occurs less frequently in northern Europe where many people carry the gene that codes for lactase.²⁶ About 36% of Americans have some form of lactose malabsorption.

When lactose malabsorption occurs with a case of acute viral gastroenteritis, it tends to be mild and self-limiting. Regardless of the cause, when patients have inadequate lactase, ingested lactose is malabsorbed and gut bacteria use it as an energy source and to produce gas. Moreover, undigested lactose has an osmotic effect and pulls excessive water into the bowel, resulting in diarrhea.²⁵ Patients experience abdominal pain, flatulence, or diarrhea within several hours of ingesting a significant lactose load, and it resolves after several days of avoiding lactose-containing foods.

Other forms of food intolerance can also cause diarrhea. Drinking overly salted beverages and ingesting excessive fiber (e.g., sunflower seeds) can cause diarrhea.²⁷ Hot peppers (e.g., jalapeño peppers, cayenne peppers, and some chili peppers) contain the chemical irritant capsaicin (responsible for the “burn") which can trigger diarrhea.²⁸ Similarly, onions and large amounts of spices, fruits, and vegetables can also predispose patients to dietary diarrhea.²⁷ Avoiding the causative food is the best approach to managing symptoms.

PAUSE AND PONDER: How does an antidiarrheal alter the symptoms associated with diarrhea?

DIARRHEA TREATMENT AND PREVENTION

Some recommendations for diarrhea are the same across the board, while others are on a case-by-case basis. In cases of infectious diarrhea, all pharmacy staff should emphasize the need for good hand hygiene, especially after using the bathroom or performing diaper changes to protect others from becoming infected. People should wash their hands with soap and water for at least 15 to 30 seconds paying special attention to the fingernails, between fingers, and wrists. Alcohol-based hand sanitizers are ineffective at preventing all types of diarrhea (i.e., norovirus, Clostridiodes).²⁹ People must also use soap and water to wash visibly soiled hands. In cases of COVID-19 infection, experts recommend using an alcohol-based rub that contains at least 60% alcohol in addition to soap and water.³⁰ Pharmacy teams should be prepared to help patients and caregivers select appropriate diarrhea treatments.

Oral Rehydration Solutions

Provided they are able to drink, most patients with mild-to-moderate dehydration should use oral rehydration solutions (ORSs) to manage diarrhea symptoms. Although ORSs do not treat diarrhea, they help prevent dehydration and electrolyte losses. ORSs are safer, inexpensive alternatives to intravenous fluids. They contain dextrose and electrolytes to replace fluid and electrolytes. The dextrose in ORSs enables the intestine to absorb fluid and salts more effectively.³¹ Table 4 describes commonly-used ORS products. Breastfed infants should continue to drink breastmilk during the bout of diarrhea.

Table 4. Comparison of Oral Rehydration Solutions^31,32

	WHO Reduced-Osmolarity ORS	Pedialyte	Cerelyte 70	Gatorade	G2 + ½ teaspoon table salt
Glucose	28 g/L	25 g/L	40 g/L*	58 g/L	28 g/L
Sodium	75 mEq/L	45 mEq/L	70 mEq/L	23 mEq/L	63 mEq/L
Potassium	20 mEq/L	20 mEq/L	20 mEq/L	< 1 mEq/L	3 mEq/L
Citrate	10 mEq/L	30 mEq/L	30 mEq/L	None	None
Chloride	65 mEq/L	35 mEq/L	60 mEq/L	17 mEq/L	32 mEq/L
Osmolarity	311 mOsm/L	250 mOsm/L	220 mOsm/L	280-360 mOsm/L	254 mOsm/L

G2 = G2 Gatorade; ORS = oral rehydration solution; WHO = World Health Organization

*as rice base

Pharmacy staff should advise patients to avoid tea, rice water, fruit juice, or gelatin as ORS substitutes, as they contain insufficient electrolytes and may be too hypertonic which could worsen diarrhea. Given the widespread availability of premixed products, people should not try to prepare their own ORS. Pharmacy staff should caution patients to avoid using sports drinks as ORS, as these products contain significant amounts of sugar and can exacerbate diarrhea. Furthermore, if the patient is experiencing significant vomiting or diarrhea, sports drinks contain inadequate amounts of electrolytes, such as sodium, and cannot effectively replace losses.

In the event a commercial ORS product is unavailable, some have recommended adding table salt to G2 Gatorade (not regular Gatorade) to increase its sodium content to match traditional ORSs.³² This option, however, is prone to error and adding too much salt is just as detrimental as not adding enough. Some errors in making homemade ORS have been fatal.³³

Dietary Measures

The practice of holding solid foods and dairy products for the first 24 hours after acute diarrhea onset has come under scrutiny.³⁴ In patients who are adequately hydrated, food is allowed. Caregivers can provide bland, easily-digestible foods and beverages for the first 24 hours after diarrhea onset in patients with nausea or vomiting. Pharmacy teams should advise patients and caregivers to withhold food if antiemetics are unable to control vomiting.

Individuals may read they should eliminate specific foods while they have diarrhea. Patients should avoid foods rich in fructose (e.g., fruit juices), as they are often difficult to digest.³⁵ Similarly, sugar-sweetened drinks can worsen diarrhea, cramping, and flatulence. Most juices also contain little fiber and, in comparison to whole fruits, offer no nutritional advantage. Because they may stimulate bowel function, patients should avoid foods containing roughage (e.g., beans, Brussels sprouts, cabbage), as these may exacerbate diarrhea. Instead, during a bout of diarrhea, patients should follow a low-fiber diet limiting dietary fiber intake to 10 grams/day.³⁶ Table 5 describes foods that are appropriate during episodes of diarrhea and foods to avoid.

Table 5. Foods that Should Be Avoided or Allowed During Bouts of Diarrhea^{35, 36}

Foods to Avoid

Foods That Are Permitted

· Alcohol

· Dairy products (if lactose intolerant)

· Foods containing artificial sweeteners (sorbitol, mannitol, and xylitol)

· Foods high in roughage (e.g., beans, broccoli, Brussels sprouts, cabbage, cauliflower)

· Fructose-containing products

· Fruits (e.g., apples, peaches, pears) and fruit juices

· High-fat, greasy foods

· Spicy foods

· Applesauce

· Baked chicken with skin removed

· Bananas

· Boiled or baked potatoes with skin peeled

· Bread or toast

· Chicken soup

· Hot cereals (e.g., cream of wheat, oatmeal)

· Plain white rice

· Unseasoned crackers

Some people use astringent herbs and teas rich in tannins (e.g., blackberry, raspberry teas) as a treatment for diarrhea. When treating diarrhea, only dried berries or juice are recommended, as fresh berries may actually exacerbate symptoms.³⁷ Moreover, patients should be aware that in large doses, blackberry tea might cause more GI upset and trigger nausea and vomiting. Pregnant women should use raspberry and raspberry leaf preparations with caution as they may stimulate contraction of uterine tissue.³⁸

BRAT Diet

This diet is intended to manage diarrhea by providing a bland diet that may improve diarrhea symptoms. However, its low nutritional content has resulted in its abandonment.³⁹ Similarly, only providing clear liquids for several days can potentially prolong the duration of diarrhea, a condition often referred to as “starvation stools.”⁴⁰ This form of diarrhea is green and watery. The green bile is excreted into the stool when there is no food to digest. It is not harmful and management simply entails increasing food intake.⁴¹ Pharmacy teams should not recommend the BRAT diet to patients with diarrhea, as it is outdated.

Probiotics and Prebiotics

To prevent or treat antibiotic-associated diarrhea, healthcare providers often recommend probiotics (see Table 6 for examples). Probiotics—microorganisms that replace colonic bacteria—suppress pathogenic microorganisms’ growth thus restoring normal intestinal function. The most commonly used probiotics to decrease the duration and severity of diarrheal episodes include Saccharomyces boulardii, Lactobacillus GG, and Lactobacillus acidophilus. Some foods contain naturally-occurring probiotics, but probiotic supplements are also available.

Table 6. Examples of Probiotics⁴⁴

Type	Examples
Probiotic-containing foods	aged soft cheeses beet kvass cottage cheese dark chocolate green olives kefir kimchi kombucha	miso natto pickles sauerkraut sourdough bread tempeh yogurt
Align Resistance Formula Capsule	10 Billion CFU of Saccharomyces boulardii CNCM1-1079
Culturelle Capsule	Lactobacillus GG 10 billion CFU Inulin (chicory root extract) 200 mg Vitamin C 3 mg
FlorastorPre Capsule	Prebiotic and probiotic blend: Saccharomyces boulardii lyo CNCM I-745 250 mg Prebiotic fiber (chicory root –inulin) 300 mg
Physician’s ChoiceProbiotics 60 billion CFU (per serving)	10 Probiotic strains (220 mg): Lactobacillus casei Lactobacillus acidophilus Lactobacillus paracasei Lactobacillus salivarius Lactobacillus plantarum Lactobacillus bulgaricus Bifidobacterium lactis Bifidobacterium bifidum Bifidobacterium longum Bifidobacterium breve	Prebiotic fiber blend: Jerusalem artichoke root 50 mg Gum Arabic (Fibergum Bio) 50 mg Chicory Root powder 50 mg

One meta-analysis showed probiotic use may prevent antibiotic-induced diarrhea in adults but was not effective in those older than 65 years of age.⁴² To be most effective, patients should start probiotics early when signs of diarrhea first appear. Patients who are also receiving antibiotics should separate probiotic administration by at least two hours from the antibiotic dose. Evidence supporting probiotic use in managing viral diarrhea is mixed.⁴³

Typically used in combination with probiotics, prebiotics are oligosaccharides that stimulate growth of commensal intestinal bacteria (i.e., naturally-occurring flora that induce protective responses to prevent pathogen invasion and colonization). Data supporting the use of prebiotics to reduce severity or duration of diarrhea is weak, and they are not universally recommended.⁴⁵ Currently, prebiotics are only available in combination products containing a probiotic.

Bismuth Subsalicylate

Patients use bismuth subsalicylate (Pepto-Bismol) to treat mild, nonspecific diarrhea. It has anti-secretory, anti-inflammatory, and antimicrobial properties.⁴⁶ Developed more than 100 years ago by a physician to treat cholera, it was originally called Mixture Cholera Infantum.⁴⁷ Despite its cheery pink color, pharmacy staff should remind patients and caregivers that bismuth subsalicylate can darken the stools and tongue with repeated use. Typical dosing for patients older than 12 years of age for acute diarrhea is 524 mg every 30 to 60 minutes or 1,050 mg every 60 minutes as needed for up to 2 days (maximum: 4,200 mg/24 hours).^46,47 Most patients will experience relief within 30 to 60 minutes of a dose. Children and adolescents who have or are recovering from influenza or chicken pox should not use bismuth subsalicylate due to the association of Reye syndrome.^46,47

Patients with histories of salicylate allergy, coagulopathy, or ulcers should not use bismuth subsalicylate. Patients receiving anticoagulants or medications for gout or arthritis (e.g., allopurinol, colchicine, ibuprofen, indomethacin, naproxen) should also avoid it. It can bind with tetracyclines and may also interfere with GI contrast studies. Use of bismuth subsalicylate during a contrast study can potentially cause misinterpretation of images and decrease the test's sensitivity.⁴⁸ Because it is hyperdense liquid, it can mimic the appearance of an acute GI bleed, which may lead to potential diagnostic errors. Patients taking bismuth subsalicylate must also stop using this product if they develop ringing or buzzing in the ears (i.e., tinnitus) because it indicates salicylate toxicity.

Loperamide

Loperamide (Imodium A-D) is an opioid-receptor agonist that inhibits peristalsis (muscle contractions in the GI tract) by acting directly on the musculature of both the small and large intestine.⁴⁹ It has been available OTC since 1988. Typical OTC dosing is 4 mg, followed by 2 mg after each loose stool.⁴⁹ At the Food and Drug Administration (FDA)-recommended OTC maximum dose of 8 mg per day, it does not predispose patients to the usual side effects associated with opioid use (e.g., euphoria, lethargy, nausea, vomiting). Patients should limit use to fewer than two days unless they are receiving medical supervision. Most patients will see improvement in symptoms within one hour after a dose.⁴⁹ Caregivers should not give loperamide to children younger than three years old, as there are case reports associating it with toxic megacolon (severe swelling of the colon) and ileus (intestinal obstruction).⁴⁹

When taken at recommended doses, loperamide does not cross the blood-brain barrier or yield the “high” seen with other opioids. However, at extremely excessive doses (i.e., more than 100 to 200 mg/day), loperamide enters the central nervous system and produces effects similar to those associated with centrally-acting opioids like heroin, hydrocodone, or morphine.⁴⁹ Some individuals withdrawing from opioids use loperamide to ameliorate their symptoms, or simply to induce euphoria.

Loperamide overdoses have been associated with serious cardiac complications, including arrhythmias, loss of consciousness or fainting, and myocardial infarction. Moreover, even standard doses of loperamide may interact with medications that can cause QT prolongation such as azole antifungal drugs and macrolide antibiotics. In response to these concerns, in September 2019, the FDA approved changes to OTC loperamide products. These changes limit each container to no more than 48 mg of loperamide and require the tablets and capsules to be individually packaged (i.e., unit-dosed).⁵⁰

Supplements

Many patients prefer to use OTC supplements to prevent or treat diarrhea. For this indication, a variety of natural products and enzyme supplements are used.

Lactase Enzymes

For individuals prone to diarrhea due to lactose intolerance, lactase enzymes are beneficial for prevention.⁵¹ Most lactose intolerant individuals do not have to give up all dairy products, as they can manage their symptoms by using lactase supplements or lactase-fortified products. There are several ways to provide lactase, and Table 7 lists commonly available products. The typical dose of lactase supplementation to prevent diarrhea in intolerant individuals is 6000 to 9000 international units at the start of a lactose-containing meal.⁵¹ Some patients prefer to add lactase supplementation to milk. In this case, patients mix 2000 international units of a lactase solution into 500 mL of milk immediately before drinking.

Table 7. Common Lactase Supplements

Tablet, Oral

Tablet Chewable, Oral

Drops

(added to liquid dairy products)

Powder

Lactaid: 3000 units

Lactaid Fast Act: 9000 units

Lactase Enzyme: 3000 units

Lactase Fast Acting: 9000 units

Surelac: 3000 units

Lactaid Fast Act: 9000 units

Milkaid:

3000 units

Elepure lactase drops:

750 units per 5 drops

Seeking Health Lactase Drops: 750 units per 7 drops

Nutricost Lactase Powder: 10,000 units per 10 grams

Zinc

Zinc supplements reduce the duration of a diarrhea episode by 25% and are associated with a 30% reduction in stool volume.⁵² Zinc is available in a variety of salt forms, including zinc-gluconate, -acetate, -ascorbate, -chloride, and -sulfate. Providers may use zinc to manage acute diarrhea in children older than six months of age, but evidence supporting its efficacy is mixed. According to the World Health Organization, patients should start zinc supplementation in conjunction with ORS at the first sign of diarrhea, as it may shorten the duration and severity of episodes and prevent subsequent episodes.⁵³ In infants younger than six months of age and children, providers sometimes use doses of 20 mg elemental zinc once daily for 10 to 14 days. The most common adverse reactions associated with oral zinc include dysgeusia (altered taste), mouth irritation, nausea, and vomiting.

Goldenseal/Berberine

Capsules of dried goldenseal appear to kill many bacteria that cause diarrhea, including E. coli. The key component in the herb is berberine. In addition to its antimicrobial effects, berberine may reduce diarrhea by enhancing sodium and water absorption by the intestinal lumen.⁵⁴ In animal models, berberine appears to slow GI motility by activating opioid pathways.⁵⁵

Doses of goldenseal used in studies vary considerably, from 250 mg to 1 g administered three times daily.⁵⁶ Studies of berberine taken alone used doses of 300 to 500 mg three times daily.⁵⁷ Typically, patients take goldenseal capsules daily until diarrhea improves. Patients should be aware that, although rare, very high doses of goldenseal may cause anxiety, depression, nausea, paralysis, or seizures.⁵⁸ Goldenseal may also affect the cytochrome P450 system and may alter patient response to medications metabolized by those enzymes.

Psyllium

Ground psyllium seeds are found in the flowering plant of the plantago genus absorb excess fluid in the intestines. Patients often use psyllium to treat constipation, so patients may be unaware that it can help with diarrhea too. Typical doses are one to three tablespoons mixed in water each day, but the product is also available as capsules and wafers.⁵⁹ When taken concurrently, psyllium may bind with some medications (e.g., carbamazepine, lithium) and may decrease blood glucose levels, so caution is advised in patients taking antidiabetic agents. Adverse effects associated with psyllium use include bloating, flatulence, indigestion, nausea, and vomiting.

PAUSE AND PONDER: Why are sports drinks not used for fluid and electrolyte replacement in patients experiencing diarrhea?

UNSAFE OR INEFFECTIVE TREATMENTS

Complementary and alternative medicine refer to those medical products that are not standard of care. Many patients will use “home remedies” to manage their symptoms, employing special diets or supplements to manage bouts of diarrhea. In many instances, insufficient evidence exists to support their safety or efficacy. Pharmacy teams should be aware of the more commonly used remedies in their geographic locations (as they vary by population) and understand their limitations.⁶⁰

Wood-Tar Creosote

Some alternative medicine circles use wood-tar creosote (found in a product called Seirogan) as an antidiarrheal treatment. Wood creosotes come from the resin of the leaves of the creosote bush and beechwood.⁶¹ In its classic form, it is a dark brown round pill, but a sugar-coated tablet is also available that masks its bitter taste and distinct medicinal odor. It is not a benign therapy, as ingesting high levels of creosote may cause burning in the mouth and throat or gastritis. Moreover, creosote may be carcinogenic with long-term use. Pharmacy teams should communicate these risks to patients seeking to use wood-tar creosote and encourage them to use a safer alternative.

Attapulgite

Attapulgite is a naturally-occurring, orally-administered clay named for the U.S. town of Attapulgus, Georgia, where it is abundant.⁶² It is a non-absorbable medication that adsorbs large numbers of bacteria and toxins and thereby reduces fluid loss.⁶³ Its binding action reduces the frequency of bowel movements and improves the consistency of stools. Attapulgite can absorb eight times its weight in water. It used to be present in Kaopectate, but in 2003, the manufacturer reformulated the product and replaced attapulgite with bismuth subsalicylate as the active ingredient. The FDA did not include attapulgite as a monograph ingredient, citing that efficacy data was inadequate.⁶⁴ Attapulgite is still used as a veterinary drug in the U.S. and is available in many countries as an OTC antidiarrheal.

“RED FLAGS” TO REFER PATIENTS FOR MEDICAL ATTENTION

Fluids and OTC antidiarrheal products cannot manage all cases of acute diarrhea. Cases accompanied by fever or excessive mucus in the stool suggest evaluation by a primary care provider (PCP) is necessary. Dehydration is another concern, especially in cases where patients report weight loss or decreased urine output (i.e., more than six hours since last urination, decreased number of wet diapers). If patients fail to improve despite oral rehydration, they should seek medical attention.

Patients with a history of recent travel to an undeveloped country, backcountry camping, or consumption of processed meat may develop infectious or parasitic diarrhea. Children in daycare or using community swimming pools may also be at risk for contracting bacterial diarrhea, such as giardiasis. These patients should see their PCPs for further evaluation, as antimicrobial therapy might be necessary.

Toxic exposures to contaminated food, plants, and other substances can cause diarrhea. Obtaining a good history and knowing when to refer patients to their PCPs or hospital is an important step in managing care. For example, profuse diarrhea that occurs with excessive salivation or tearing may be suggestive of organophosphate ingestion.⁶⁵

Although most acute diarrhea cases are self-limiting, children younger than three years of age and adults older than 60 with multiple co-morbidities should seek immediate medical care.⁶⁶ Table 8 highlights other “Red Flags” that warrant immediate medical attention.

Table 8. “Red Flag” Symptoms Indicating Patients Experiencing Diarrhea Should Seek Immediate Medical Attention³

People of All Ages	Infants/Young Children
6 or more loose stools per day Bloody, black, tarry, or pus-containing stools Dizziness or lightheadedness Fever > 102°F and chills Severe pain in abdomen or rectum Vomiting Severe dehydration, evidenced by: Dark urine Decreased skin turgor Fainting/lightheadedness Oliguria (decreased urination) Thirst/dry mouth Severe fatigue Sunken eyes/cheeks	Diarrhea persists > 24 hours < 3 months old: seek medical attention at first signs of diarrhea < 3 months old: any fever Severe dehydration, evidenced by signs in left column, plus: No tears when crying No wet diapers for more than 3 hours Sunken soft spot in an infant’s skull

CONCLUSION

There is no “one size fits all” approach to diarrhea treatment, and pharmacy teams should be prepared to assist patients in selecting the most appropriate approach to manage symptoms. Acute cases of diarrhea usually resolve on their own without treatment, but preventing dehydration is crucial. Before recommending an antidiarrheal agent, pharmacists should obtain a good medication history to avoid potential drug interactions and identify red flags. It is important to remind patients that anti-diarrheal treatments do not necessarily cure the diarrhea, but they help to lessen its severity and duration. Just as important as assisting patients in selecting the best therapy, pharmacy staff can identify when prompt medical attention is necessary. Abuse of antidiarrheal agents is possible, and pharmacists and technicians should be vigilant if they encounter unusual purchasing patterns involving these products.

Pharmacist Post-test Questions

After completing this continuing education activity, the pharmacist will be able to:

RECOGNIZE signs and symptoms associated with acute diarrhea, including those that require referral to a PCP or hospital
IDENTIFY inappropriate oral rehydration techniques
RECOGNIZE antidiarrheal misuse
REVIEW the risks and benefits associated with the most commonly used strategies to manage diarrhea

1. SK is a gardener who has been spraying his yard with weed killer. After all his hard work, he ate a gallon of ice cream and then developed diarrhea. His symptoms resolved upon avoiding dairy products. Which type of acute diarrhea did SK most likely experience?

Halloween diarrhea
Lactose intolerance
Organophosphate toxicity

2. Which is TRUE about acute diarrhea?

It is treatable with stimulant laxatives
It usually resolves within 24 to 48 hours
It is associated with chronic disease (e.g., diabetes)

3. Which anti-diarrheal agent is associated with tinnitus, potentially interacts with anticoagulants, and binds with tetracyclines?

Bismuth subsalicylate
Loperamide
Lactobacillus GG

4. Which statement is TRUE regarding the BRAT diet?

It provides adequate calories to sustain an individual for several days to weeks
Patients consume bananas, rice, applesauce, and tomatoes for two days
It is no longer used to manage diarrhea because it is nutritionally inadequate

5. JB woke up this morning experiencing diarrhea. He is afebrile and otherwise feels fine. What should JB’s first step be?

Ensure adequate hydration
Start taking a prebiotic
Take 2mg of loperamide

Several members of a patient's household are experiencing acute diarrhea. What should everyone do immediately?
Ensure proper hand hygiene using alcohol-based hand sanitizer
Stock plenty of fruit juice in the home for hydration
Ensure proper hand hygiene using soap and water

7. RK is a 50-year-old male who comes to your pharmacy looking for advice on how to manage his diarrhea that started two days ago. He has not been exposed to sick contacts or travelled. He did report that about a week ago, his PCP advised him to start taking omeprazole for acid reflux. RK is afebrile and does not complain of any additional symptoms. What is the best recommendation for RK?

Offer to contact his PCP to discuss alternatives to omeprazole
Suggest he discontinue omeprazole and use a magnesium-containing antacid
Offer to contact his PCP for a prescription for an antibiotic

8. MP is a 60-year-old male who has been experiencing diarrhea and self-treating at home. He now complains of black, tarry stools. Which antidiarrheal agent has MP likely been using to self-treat his symptoms?

Psyllium seeds
Bismuth subsalicylate
Attapulgite clay

9. SN is a 6-year-old whose classmate was diagnosed with COVID-19. SN later tests positive for COVID-19 herself, but she does not have any respiratory symptoms, only diarrhea. Her mother wants to know why COVID-19 causes diarrhea, but you explain to her that the mechanisms are still unknown. What is one proposed mechanism of COVID-19-associated diarrhea?

Zinc toxicity related to COVID-19 treatment
Viral associated osmotic diarrhea secondary to lactase deficiency
Altered intestinal permeability causing enterocyte malabsorption

10. MK was at your pharmacy yesterday and purchased three boxes of loperamide caplets, stating he must have eaten something that did not agree with him. When questioned, he said he was afebrile and felt otherwise fine. Today, he has returned to buy two more boxes of loperamide. What steps should you take?

Suggest he see his PCP, as he must have an infectious form of diarrhea
Observe his behavior, as he may be abusing the loperamide
Suggest he also make a homemade oral hydration solution to prevent dehydration

Pharmacy Technician Post-test Questions

After completing this continuing education activity, pharmacy technicians will be able to:

LIST the basic pathology and symptoms of acute diarrhea
RECALL treatments used in patients who have acute diarrhea
IDENTIFY OTC products and dietary modifications that are useful in acute diarrhea
IDENTIFY when to refer patients to the pharmacist for recommendations or referral

1. What is the major difference between sports drinks (e.g., Gatorade) and oral rehydration solutions (e.g., Pedialyte)?

Sports drinks have more sodium and less carbohydrates than ORSs
Sports drinks have more carbohydrates and less sodium than ORSs
There is no difference, patients can use both interchangeably

2. Which of the following situations should prompt an adult patient with acute diarrhea to seek medical attention?

Fever of more than 102°F
Diarrhea has lasting more than 1 day
Three loose stools in 1 day

3. What is the maximum amount of loperamide allowed in an OTC container?

Twelve 2-mg capsules
Twenty-four 2-mg tablets
Fifty 2-mg capsules

4. Which of the following patients with diarrhea should you refer to the pharmacist for counseling?

The mother of an afebrile toddler who drinks 4 ounces of apple juice daily
A febrile patient who recently returned from a mission trip to Africa
A lactose-intolerant teenager who ate ice cream and forgot to take a lactase supplement

5. Which of the following is associated with laxative abuse-associated diarrhea?

Anorexia nervosa
Opioid addiction
Ethanol intoxication

6. What components are common to all oral rehydration solutions?

Water, sodium, sugar, potassium
Water, sodium, sugar, magnesium
Water, sodium, potassium, magnesium

7. How do bulk laxatives (e.g., psyllium) work to decrease diarrhea symptoms?

They absorb excess intestinal fluid and increase stool bulk
They possess antimicrobial and anti-secretory properties
They adsorb bacteria and other toxins and reduce fluid loss

8. Which of the following characteristics is associated with acute diarrhea?

Excessive vomiting
Lasts more than 2 weeks
Often self-limiting

9. What does the “BRAT” acronym refer to with respect to acute diarrhea?

A brand of oral rehydration solution
A diet of bananas, rice, applesauce, and toast
A preferred diet for children who have diarrhea

10. Which antidiarrheal product is prone to abuse?

Attapulgite clay
Berberine
Loperamide

Selzer A. Diarrhea song and diarrhea cha cha cha: The timeless classics. December 6, 2009. Accessed June 7, 2021. http://playgroundjungle.com/2009/12/diarrhea-song-and-diarrhea-cha-cha-cha-the-timeless-classics.html
Han C, Duan C, Zhang S, et al. Digestive symptoms in COVID-19 patients with mild disease severity: clinical presentation, stool viral RNA testing, and outcomes. Am J Gastroenterol. 2020;115(6):916-923.
Mayo Clinic. Diarrhea. Posted June 16, 2020. Accessed June 8, 2021. https://www.mayoclinic.org/diseases-conditions/diarrhea/symptoms-causes/syc-20352241
DuPont HL. Acute infectious diarrhea in immunocompetent adults. N Engl J Med. 2014;370(16):1532-1540.
Fleckenstein JM, Matthew Kuhlmann F, Sheikh A. Acute bacterial gastroenteritis. Gastroenterol Clin North Am. 2021;50(2):283-304.
Cortese MM, Parashar UD; Centers for Disease Control and Prevention (CDC). Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2009;58(RR-2):1-25.
Lindsay L, DuPont HL, Moe CL, et al. Estimating the incidence of norovirus acute gastroenteritis among US and European international travelers to areas of moderate to high risk of traveler's diarrhea: a prospective cohort study protocol. BMC Infect Dis. 2018;18(1):605.
Wick JY. Norovirus: noxious in nursing facilities-almost unavoidable. Consult Pharm. 2012;27(2):98-104.
Centers for Disease Control and Prevention. Salmonella outbreak linked to small turtles. June 17, 2021. Accessed July 3, 2021. https://www.cdc.gov/salmonella/typhimurium-02-21/index.html
Perisetti A, Gajendran M, Mann R, et al. COVID-19 extrapulmonary illness - special gastrointestinal and hepatic considerations. Dis Mon. 2020;66(9):101064.
Scallan E, Hoekstra RM, Angulo FJ, et al. Foodborne illness acquired in the United States — major pathogens. Emerg Infect Dis 2011;17(1):7-15.
Leung AK, Robson WL, Davies HD. Traveler's diarrhea. Adv Ther. 2006;23(4):519-527.
Leung AKC, Leung AAM, Wong AHC, Hon KL. Travelers' Diarrhea: A clinical review. Recent Pat Inflamm Allergy Drug Discov. 2019;13(1):38-48.
Centers for Disease Control and Prevention. Travelers' Diarrhea. Updated October 8, 2019. Accessed June 11, 2021. https://wwwnc.cdc.gov/travel/page/travelers-diarrhea
Centers for Disease Control and Prevention. Travel Health Notices. Accessed June 8, 2021. https://wwwnc.cdc.gov/travel/notices
Bhattacharyya M, Debnath AK, Todi SK. Clostridium difficile and antibiotic-associated diarrhea. Indian J Crit Care Med. 2020;24(Suppl 4):S162-S167.
Shaffer SR, Witt J, Targownik LE, et al. Cost-effectiveness analysis of a fecal microbiota transplant center for treating recurrent C. difficile infection. J Infect. 2020;81(5):758-765.
Fecal microbiota for transplantation: Safety alert - Risk of serious adverse events likely due to transmission of pathogenic organisms. Updated April 7, 2020. Accessed June 7, 2021. https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota-transplantation-safety-alert-risk-serious-adverse-events-likely-due-transmission
Abraham B, Sellin JH. Drug-induced diarrhea. Curr Gastroenterol Rep. 2007;9(5):365-72.
Roerig JL, Steffen KJ, Mitchell JE, Zunker C. Laxative abuse: epidemiology, diagnosis and management. 2010;70(12):1487-1503.
Florida man is charged with child abuse after 'putting laxatives in teen's daily medication.' April 26, 2020. Accessed June 13, 2021. https://www.dailymail.co.uk/news/article-8258919/Florida-man-charged-child-abuse-putting-laxatives-teens-daily-medication.html
Harness J. Yes, pranking your child with laxatives is child abuse. Posted August 12, 2018. Accessed June 13, 2021. https://vistacriminallaw.com/yes-pranking-your-child-with-laxatives-is-child-abuse/
Heyman MB, Abrams SA; Section on Gastroenterology, Hepatology, and Nutrition; Committee on Nutrition. Fruit juice in infants, children, and adolescents: Current recommendations. 2017;139(6):e20170967.
Breitenbach RA. 'Halloween diarrhea'. An unexpected trick of sorbitol-containing candy. Postgrad Med. 1992;92(5):63-66.
Di Costanzo M, Berni Canani R. Lactose intolerance: common misunderstandings. Ann Nutr Metab. 2018;73(Suppl 4):30-37.
Storhaug CL, Fosse SK, Fadnes LT. Country, regional, and global estimates for lactose malabsorption in adults: a systematic review and meta-analysis. The Lancet. Gastroenterology & Hepatology. 2017;2(10):738-746.
Ohtsuka Y. Food intolerance and mucosal inflammation. Pediatr Int. 2015;57(1):22-29.
Snyman T, Stewart MJ, Steenkamp V. A fatal case of pepper poisoning. Forensic Sci Int. 2001;124(1):43-46.
Stadler RN, Tschudin-Sutter S. What is new with hand hygiene? Curr Opin Infect Dis. 2020;33(4):327-332.
S. Food and Drug Administration. Hand Sanitizers | COVID-19. Updated January 19, 2021. Accessed June 8, 2021. https://www.fda.gov/drugs/coronavirus-covid-19-drugs/hand-sanitizers-covid-19
Nalin D. Issues and controversies in the evolution of oral rehydration therapy (ORT). Trop Med Infect Dis. 2021;6(1):34.
Stewart C. Oral rehydration solution (ORS) recipes. Updated August 15, 2014. Accessed May 30, 2021. http://www.moljinar.com/page6/files/ORS%20Formula.pdf
Cleary TG, Cleary KR, DuPont HL, et al. The relationship of oral rehydration solution to hypernatremia in infantile diarrhea. J Pediatr. 1981;99(5):739-741.
MacGillivray S, Fahey T, McGuire W. Lactose avoidance for young children with acute diarrhoea. Cochrane Database Syst Rev. 2013;2013(10):CD005433.
Hoekstra JH, van den Aker JH, Hartemink R, Kneepkens CM. Fruit juice malabsorption: not only fructose. Acta Paediatr. 1995 Nov;84(11):1241-4.
Vanhauwaert E, Matthys C, Verdonck L, De Preter V. Low-residue and low-fiber diets in gastrointestinal disease management. Adv Nutr. 2015;6(6):820-7.
Patel AV, Rojas-Vera J, Dacke CG. Therapeutic constituents and actions of Rubus species. Curr Med Chem. 2004;11(11):1501-1512.
Holst L, Haavik S, Nordeng H. Raspberry leaf--should it be recommended to pregnant women? Complement Ther Clin Pract. 2009;15(4):204-208.
Salfi SF, Holt K. The role of probiotics in diarrheal management. Holist Nurs Pract. 2012;26(3):142-9.
Benninga MA, Faure C, Hyman PE, St James Roberts I, et al. Childhood functional gastrointestinal disorders: neonate/toddler. 2016: S0016-5085(16)00182-7.
Roediger WE. Metabolic basis of starvation diarrhoea: implications for treatment. Lancet. 1986;1(8489):1082-4.
Jafarnejad S, Shab-Bidar S, Speakman JR, et al. Probiotics reduce the risk of antibiotic-associated diarrhea in adults (18-64 Years) but not the elderly (>65 Years): A meta-Analysis. Nutr Clin Pract. 2016;31(4):502-513.
Ansari F, Pashazadeh F, Nourollahi E, et al. A systematic review and meta-analysis: The effectiveness of probiotics for viral gastroenteritis. Curr Pharm Biotechnol. 2020;21(11):1042-1051.
Marco ML, Heeney D, Binda S, et al. Health benefits of fermented foods: microbiota and beyond. Curr Opin Biotechnol. 2017;44:94-102.
Brüssow H. Probiotics and prebiotics in clinical tests: an update. 2019;8:F1000 Faculty Rev-1157.
Brum JM, Gibb RD, Ramsey DL, et al. Systematic review and meta-analyses assessment of the clinical efficacy of bismuth subsalicylate for prevention and treatment of infectious diarrhea. Dig Dis Sci. 2021;66(7):2323-2335.
The History of Pepto-Bismol. Accessed June 12, 2021. https://pepto-bismol.com/en-us/article/the-history-of-pepto
Shahnazarian V, Ramai D, Sunkara T, et al. Pepto-Bismol tablets resembling foreign bodies on abdominal imaging. Cureus. 2018;10(1):e2102.
Wu PE, Juurlink DN. Clinical Review: Loperamide toxicity. Ann Emerg Med. 2017;70(2):245-252.
S. Food and Drug Administration. FDA Drug Safety Podcast: FDA limits packaging for anti-diarrhea medicine loperamide (Imodium) to encourage safe use. Updated February 6, 2018. Accessed May 30, 2021. https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-drug-safety-podcast-fda-limits-packaging-anti-diarrhea-medicine-loperamide-imodium-encourage
Ianiro G, Pecere S, Giorgio V, et al. Digestive enzyme supplementation in gastrointestinal diseases. Curr Drug Metab. 2016;17(2):187-193.
Bajait C, Thawani V. Role of zinc in pediatric diarrhea. Indian J Pharmacol. 2011;43(3):232-235.
World Health Organization (WHO); UNICEF. Clinical management of acute diarrhoea. 2004. Accessed May 30, 2021. https://www.who.int/maternal_child_adolescent/documents/who_fch_cah_04_7/en/
Schor J. Clinical Applications for Berberine. Natural Medicine Journal. 2012;4(12). Accessed May 31, 2021. http://naturalmedicinejournal.com/journal/2012-12/clinical-applications-berberine
Feng Y, Li Y, Chen C, et al. Inhibiting roles of berberine in gut movement of rodents are related to activation of the endogenous opioid system. Phytother Res. 2013;27(10):1564-1571.
Abidi P, Chen W, Kraemer FB, et al. The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms. J Lipid Res. 2006;47(10):2134-2147.
Meng S, Wang LS, Huang ZQ, et al. Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention. Clin Exp Pharmacol Physiol. 2012;39(5):406-411.
Rhizoma Hydrastis. In: WHO Monographs On Selected Medicinal Plants. Vol 3. World Health Organization. 2001:194-203. Accessed July 3, 2021. http://digicollection.org/hss/documents/s14213e/s14213e.pdf
Ford AC, Moayyedi P, Lacy BE, et al; Task Force on the Management of Functional Bowel Disorders. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(suppl 1): S2-S26.
Clarke TC, Black LI, Stussman BJ, Barnes PM, et al. Trends in the use of complementary health approaches among adults: United States, 2002-2012. Natl Health Stat Report. 2015;79:1-16..
The Agency for Toxic Substances and Disease Registry: Creosote. March 28, 2014. Accessed June 10, 2021. https://www.atsdr.cdc.gov/toxprofiles/tp85-c2.pdf
Palygorskite Wikipedia. Last edited June 8, 2021. Accessed June 11, 2021. https://en.wikipedia.org/wiki/Palygorskite
Zaid MR, Hasan M, Khan AA. Attapulgite in the treatment of acute diarrhoea: a double-blind placebo-controlled study. J Diarrhoeal Dis Res. 1995;13(1):44-46.
Kim-Jung LY, Holquist C, Phillips J. FDA Safety Page. Kaopectate reformulation and upcoming labeling changes. Drug Topics 2014;April 19, 58-60. https://www.fda.gov/media/72651/download. Accessed July 5, 2021.
Basrai Z, Koh C, Celedon M, Warren J. Clinical effects from household insecticide: pyrethroid or organophosphate toxicity?. BMJ Case Rep. 2019;12(11):e230966.
Gale AR, Wilson M. Diarrhea: Initial evaluation and treatment in the emergency department. Emerg Med Clin North Am. 2016;34(2):293-308.

LAW: The Pharmacy Implications of the PREP Act Extension

After completing this application-based continuing education activity, pharmacists and pharmacy technicians will be able to

• DESCRIBE the history and extension of the PREP Act and what the 12th Amendment of the PREP ACT authorizes pharmacists, pharmacy interns, and pharmacy technicians to do.

• EXPLAIN why pharmacy personnel are essential for providing immunization and testing for COVID-19.

• REVIEW techniques for COVID-19 testing and inactivated immunization of those 3 years and older.

The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

Pharmacists are the most accessible healthcare providers. Vaccines are a very important public health measure to prevent disease and/or severe disease and death, depending on the vaccine. Pharmacies are becoming more and more recognized as the optimal place patients receive vaccines. Recent estimates suggest that pharmacy staff administers 64% of adult influenza vaccines and almost 90% of all COVID-19 vaccines. As illnesses and deaths from COVID-19 continue to occur as do concerns over strain of the healthcare system during COVID-19 waves, the Secretary of the Health and Human Services has extended the duration of the 12th Amendment of the Public Health and Readiness (PREP) Act to December 31, 2029. The Act provides liability immunity to covered persons (pharmacists, interns, technicians) against claims of loss related to the administration or use of designated medical countermeasures. This authorization covers pharmacists to order and administer, and pharmacy interns and qualified pharmacy technicians to administer under the supervision of a pharmacist, COVID-19 and seasonal influenza vaccines and COVID-19 tests. The authorization also covers pharmacists to prescribe nirmatrelvir/ritonavir tablets (Paxlovid).

If you’ve heard it once, you've probably heard it a dozen or more times: pharmacists are the most accessible healthcare resource. Most people live close to a pharmacy. A 2022 study reported 89% of persons in the United States (U.S.) live within five miles of a pharmacy and all but 3% are within 10 miles.¹ Despite being this accessible, pharmacies are closing in record numbers.^2,3 These closures are creating pharmacy deserts—communities in which residents must travel farther to access the nearest pharmacy to fill prescriptions—in communities in urban centers or with Black and Latine (see SIDEBAR) populations most at risk.^2,3

SIDEBAR: Latine or Latinx?

Americans have used many terms to describe individuals or groups who live in the United States and have Latin American roots. Traditionally, the word “Latino” has been used to describe males or males and females, and sometimes “Latina” has been used for females. The most widely used term, however, was “Hispanic” and included people of Spanish origin (i.e., from Spain). Several years ago, the term Latinx emerged as a gender-neutral, more inclusive term. Language, however, evolves, and some people with Latin American origins objected to the inclusion of the letter X. Older languages in Latin America did not include the letter X. Colonists forced indigenous people to add X into languages during the conquest. Its pronunciation is odd or unnatural in many dialects.

While Latinx is currently used more frequently in the academic literature, the term Latine is becoming more commonly accepted in the community. For the purposes of this continuing education activity, they are interchangeable.

Vaccines are one of the most successful interventions in public health in our generation. Worldwide, vaccines have prevented 154 million deaths since 1974.⁴ In the U.S., routine childhood vaccinations provided to children born between 1994 and 2023 have had an impressive impact. Within this population, they have saved $540 billion in direct costs and prevented more than 500 million illnesses, 32 million hospitalizations, and 1.1 million deaths.⁵

Immunizing for Influenza and COVID-19

Influenza and COVID-19 vaccines are examples of vaccines whose primary goal is to prevent severe disease and death. Influenza vaccine specifically has shown to decrease risk of intensive care admission (odds ratio [OR] = 0.74 (95% confidence interval [CI]: 0.58-0.93)) and death (OR = 0.69 (95% CI 0.52-0.92)) among adults hospitalized with influenza disease.⁶ An odds ratio less than 1.0 indicates a protective effect; therefore an OR of 0.74 indicates the influenza vaccine reduces the risk of an intensive care admission by 26%, and an OR of 0.69 indicates 31% less risk of death when hospitalized with influenza disease. The CI reflects there is 95% confidence the true risk of an intensive care admission is reduced by 7% to 42%, and the risk of death is reduced by 8% to 48%. In the first year of use, primary COVID-19 vaccination prevented 14.4 million deaths.⁷ The 2023-2024 booster vaccines provided 51% and 36% effectiveness against hospitalization for the seven to 79 days post-vaccination in healthy non-immunocompromised and immunocompromised patients. Unfortunately, vaccine efficacy wanes significantly by four to six months in all people, but especially those who are immunocompromised, explaining the recommendations for boosters.⁸

Pharmacists, pharmacy technicians and interns, and pharmacies have become the most relied-upon resources for obtaining recommended vaccines, especially the COVID-19 and influenza vaccines. Sixty-eight percent of COVID-19 vaccines from September 2022 to September 2023 were administered in a pharmacy.⁹ More recently, these numbers have risen, with data showing that pharmacists provided 90% (23.5 million doses) of the 26.1 million doses of COVID-19 vaccines from August 31 through November 30, 2024.¹⁰ Data shows similar trends for adult influenza vaccinations at pharmacies, with growth from 49% in 2019 through 2020 steadily increasing each year; initial estimates (through November 2024) indicate that for the 2024-2025 season report, pharmacies have administered 64% of influenza vaccines.¹¹

Pharmacy’s response to the COVID-19 pandemic has amplified the pharmacist’s and pharmacy technician’s value and accessibility to providers, policymakers, and the public. Expanding the pharmacist’s clinical functions will only become more critical as the physician workforce continues to shrink through the coming decades. According to the Association of American Medical Colleges (AAMC), the U.S. is projected to face a physician shortage of up to 86,000 physicians by 2036, with the most significant shortage expected in primary care specialties.¹²

More than Immunizations

Beyond immunizing, the pandemic revealed the pharmacist’s valuable contributions involving point-of-care testing and follow-up care through treatments not only for COVID-19, but also for influenza, urinary tract infections, HIV, and contraceptives. The Centers for Disease Control and Prevention (CDC) recognized pharmacy’s contributions during the COVID-19 pandemic by stating, “The COVID-19 pandemic has demonstrated needed roles for the community pharmacist in an emergency, including continuity of provision of medications, providing preventive services, and ensuring health equity. Along with medication management, pharmacists provide infectious disease mitigation, point-of-care testing, and vaccinations.”¹³

The COVID-19 pandemic resulted in an excess burden of mortality in at-risk populations, precipitated by racial and ethnic disparities in health care access and use. While, as stated, 89% of Americans live within five miles of a pharmacy, heightened awareness of newly emerging pharmacy deserts in Black and Latine communities resulting in higher risk of morbidity and mortality disparities is needed.^1,3 Health Affairs published a pharmacy closure study in December 2024. It revealed that independent pharmacies were at greater risk for closure than chain pharmacies across all neighborhood and market characteristics. The authors hypothesized that independent pharmacies in predominantly Black and Latine neighborhoods would be at greatest risk for closure because they are more likely than chain pharmacies to serve populations insured through Medicaid or Medicare. The reason is that Medicaid and Medicare incentivize patients to use preferred pharmacy networks managed by pharmacy benefit managers. Because preferred networks often exclude independent pharmacies, this policy limits patient volumes and profits of independent (nonpreferred) pharmacies, thus potentially increasing their risk for closure. This may have created previous health disparities and may potentially exacerbate future disparities by worsening access and lowering adherence rates to medications and other therapies.^2,3

PUBLIC READINESS AND EMERGENCY PREPAREDNESS (PREP) ACT

The Public Readiness and Emergency Preparedness (PREP) Act is not new. Initially approved by Congress in 2005 and signed by then-President George W. Bush in 2005. The PREP Act authorizes the Secretary of Health and Human Services (HHS) to limit legal liability for losses relating to the administration of medical countermeasures such as diagnostics, treatments, and vaccines. In a declaration effective February 4, 2020, the Secretary of HHS invoked the PREP Act and declared Coronavirus Disease 2019 (COVID-19) to be a public health emergency warranting liability protections for covered countermeasures. The PREP Act is currently on its 12th amendment.¹⁴ The PREP Act defines a “covered person” to include licensed health professionals and other individuals authorized to prescribe, administer, or dispense covered countermeasures under state law, and other categories of persons identified by the Secretary in a PREP Act declaration.^14-16

The April 2020 amendment to the Act provided pharmacists federal authority to order and administer FDA-authorized COVID-19 tests. The August 2020 Amendment to the PREP Act expanded the definitions of covered diseases and covered persons. It expanded the categories of disease representing a public health emergency to include diseases resulting from “the decrease in the rate of childhood immunizations, which will lead to an increase in the rate of infectious diseases.” This allowed pharmacists to prescribe and administer, and interns to administer vaccines in accordance with the Advisory Committee for Immunization Practices (ACIP) to children 3 through 18 years old.^14-16

In the fall of 2020, the Secretary of HHS modified the Act twice more. In August, it added COVID-19 vaccines to the vaccines pharmacists and interns were permitted to administer. In September, notably, for the first time it included pharmacy technicians in the authority provisions, allowing them to administer childhood and COVID-19 vaccines to those aged 3 years and older. A year later, in August and September of 2021, the Act extended authorization covering pharmacy interns and technicians to administer seasonal influenza vaccination for those 19 years and older as recommended by ACIP. It also authorized pharmacists to prescribe and administer specific COVID-19 therapeutics, such as monoclonal antibodies, and interns and technicians to administer these products.^14-16In July 2022, another amendment added the authority for pharmacists to prescribe nirmatrelvir/ritonavir tablets (Paxlovid).^14,16

As a public health crisis resolves, the PREP Act is amended to eliminate provisions no longer deemed necessary. HHS declared the Public Health Emergency was no longer in effect as of May 11, 2023, however COVID-19 was deemed to still present a “credible risk of a future public health emergency.” As the COVID-19 emergency was no longer at its peak, the 11th Amendment in May 2023 began to decrease the authority of pharmacists, interns, and technicians. Specifically, the 11th Amendment of the PREP Act extended authority through December 31, 2024, but the authorization would only allow pharmacists to order and administer, and pharmacy interns and technicians to administer COVID-19 and seasonal influenza vaccines to age 3 and over and COVID-19 tests. The authorization no longer covers all childhood vaccines but continues to allow pharmacists to prescribe nirmatrelvir/ritonavir tablets.¹⁵

Is the PREP Act Still Needed?

COVID-19 continues to cause significant illness and death and considered to present a credible risk of a future public health emergency. In 2024, the CDC’s COVID Data Tracker reported between 300 and 2500 deaths from COVID-19 each week.¹⁷ Congress delegated the ability to amend the PREP Act to the HHS Secretary. This motivated Xavier Becerra, the then HHS Secretary, to issue the 12th amendment to the PREP Act in December 2024.¹⁴Effective January 1, 2025, it was amended to continue PREP Act coverage through December 31, 2029, barring any change from the HHS Secretary. This extension granted by the 12th amendment to the PREP act allows pharmacists, pharmacy interns, and technicians to continue providing essential services for seasonal influenza and COVID-19.¹⁴ These services include allowing pharmacists to prescribe and administer seasonal influenza and COVID-19 vaccines for those as young as 3 years of age (see SIDEBAR) in line with the ACIP recommendations (see Table 1). They still have the authority to prescribe nirmatrelvir/ritonavir tablets. Pharmacy interns and pharmacy technicians are also authorized under the Act to provide these two immunizations to these patients under the pharmacist’s supervision.

SIDEBAR: What’s Magic about Age 3?²¹

The PREP Act authorized administration of inactivated vaccines in children as young as 3 years of age. The minimum age of 3 years old was chosen because that is the age at which the vaccine administration process is the same as that employed for adults. Before age 3, the thigh is the preferred site because of the greater muscle mass.

Specifically, as these shots are all inactivated vaccines, the preferred site of administration, beginning at age 3 years, is the deltoid muscle. When administering inactivated vaccines, immunizers should inject them at a 90-degree angle into the deltoid muscle, avoiding the top 1/3 of the muscle and staying above the armpit. It is important to landmark the deltoid and use the recommended vaccine needle size to ensure efficacy and prevent shoulder injury related to vaccine administration (SIRVA).

Table 1. PREP Act Requirements for Pharmacists, Pharmacy Interns, and Pharmacy Technicians^14,18

Provider Type	Pharmacists	Pharmacy Interns	Pharmacy Technicians
Vaccine authorization	Order and administer an FDA* authorized or approved COVID-19 or seasonal influenza vaccine to those 3 years of age and older that aligns with ACIP/CDC recommendations	Administer an FDA* authorized or approved COVID-19 or seasonal influenza vaccine to those 3 years of age and older that aligns with ACIP/CDC recommendations and under the pharmacist’s supervision	Administer an FDA* authorized or approved COVID-19 or seasonal influenza vaccine to those 3 years of age and older that aligns with ACIP/CDC recommendations, and under the supervision of a pharmacist who is immediately available
Training required	Completed an immunization training course (i.e., injection techniques, application of vaccine indications and contraindications, recognition and management of vaccine reactions) that is at least 20 hours and approved by ACPE	Complete a practical immunization training course (i.e., injection techniques, application of vaccine indications and contraindications, recognition and management of vaccine reactions)
License and CPR requirements	Must be and maintain license or registration by their state board of pharmacy. Must have current CPR certification
COVID-19 additional requirements	Comply with conditions of use in the COVID-19 provider agreements and other COVID-19 vaccine requirements
Education requirements	Two-hours of immunization related continuing education (ACPE accredited) in each state licensing period	N/R	N/R
	Follow record keeping, reporting, and documentation requirements per local/state/federal requirements	N/R	N/R
Parental / caregiver information required	Educate parents/caregivers of the children being vaccinated of importance of well-child visit with their primary healthcare provider	N/R	N/R
ABBREVIATIONS: ACIP = Advisory Committee on Immunization Practices; ACPE = Accreditation Council for Pharmacy Education; CDC = Centers for Disease Control and Prevention; CPR = cardiopulmonary resuscitation; FDA = Food & Drug Administration; N/R = None required

*FDA authorized COVID-19 vaccines: Novavax for those 12 years and older, Moderna and Pfizer BioNTech for those 6 months through 11 years. FDA approved COVID-19 vaccines: Moderna and Pfizer BioNTech for those 12 years of age and older.

The HHS Secretary decides to amend or declare the PREP Act based on a variety of factors. HHS gathers expert advice and public health data and assesses legal considerations by consulting with relevant stakeholders before issuing a declaration or amendment. The HHS Secretary must consider the many variables involved encouraging the use of countermeasures (interventions that help prevent or slow the spread of disease). These include the design, clinical testing, manufacturing, labeling, marketing, purchase, donation, dispensing, licensing, prescribing, and administering of the countermeasure. A determination of a public health emergency is different than a PREP Act declaration. If HHS determines a public health emergency exists, HHS can waive certain Medicaid, Medicare, State Children’s Health Insurance Program (CHIP), and Health Insurance Portability and Accountability Act (HIPPA) requirements. A PREP Act declaration may be made in advance of a public health emergency and may provide liability immunity for activities both before and after a declared public health emergency.

Public Health Emergencies vs PREP Act Declarations

A public health emergency determination or other emergency declaration is only required for immunity under the PREP Act if this is explicitly stated in the declaration.¹⁸ Therefore, when it is determined that there is no longer concern for significant COVID-19 related illnesses, it is likely that the Secretary of HHS will sunset this provision as well. Thus, it is very important that pharmacists, pharmacy interns, and pharmacy technicians continue to advocate for expansion of their immunization authority. This advocacy, specifically in states where full immunization authority is absent, will enhance immunization care to patients in need.

PAUSE AND PONDER: What does your state authorize pharmacists, pharmacy interns, and pharmacy technicians to provide and are there vaccine or age restrictions?

In addition to the vaccination authority, the Act continues to allow pharmacists to prescribe and administer, and for interns and technicians to administer under the pharmacist supervision, COVID-19 tests.¹⁴Multiple types of COVID-19 tests are able to be used in the pharmacy. It is important for all immunizers and support staff to review the instructions on the specific tests carried in the pharmacy. Many tests (e.g., antigen, nucleic acid amplification tests [NAATs]) require nasal or nasopharyngeal sampling, but some NAAT tests may require oropharyngeal, sputum, or saliva sampling.¹⁹Importantly, the Act continues to provide liability protection for those who provide these services (i.e. vaccines, tests) per the recommendations.¹⁴

ADULT VACCINATION UPTAKE POOR, PEDIATRIC RATES DECREASING

Although the 11th amendment of the PREP Act in May 2023 removed federal authority for pharmacists to provide routine childhood vaccines (other than seasonal influenza or COVID-19), many states have worked to expand their state laws to provide these authorities. As of January 2025, only one state, Delaware, does not authorize pharmacists to provide any vaccines to children under its state laws.^15,22-24 Currently, 42 states provide pharmacists authority to administer routine vaccines beyond influenza and COVID-19 to children younger than 12 years old. At this time, 36 states allow vaccines other than COVID-19 and influenza to be administered by a pharmacist to children 7 years of age or younger.^22-30 Many states currently have no minimum age for pharmacists to provide childhood vaccines. Further, pharmacists in most states can provide many routine vaccines to adults. It is important that pharmacists continue to educate and advocate for timely vaccination of children and adults and provide an accessible way for patients to easily obtain these vaccines, when authorized.

PAUSE AND PONDER: How do you routinely advocate and provide immunizations to patients? How could you improve?

Many adults do not know that they should receive any vaccines. Data from 2022 demonstrates that only 22.8% of adults received appropriate immunizations for age including influenza. Further concerning is that Black and Latine populations reported lower rates at 12.1% and 17%, respectively.³¹ When rates associated with individual vaccines were analyzed, tetanus vaccination in the past 10 years (59.2% of all adults) and pneumococcal vaccination in those 65 years and older (64%) were the highlights, having the best coverage. Some significant deficits included pneumococcal vaccination for high-risk adults (23%) and a single dose of recombinant zoster vaccination of individuals 50 years and older (25.6%).³¹ These data provide yet another reason to continue efforts to educate adult patients within your practice that they may need vaccines.

PAUSE AND PONDER: What can you do in your pharmacy to provide education to adult individuals about their needs for vaccinations?

Unfortunately, vaccine misinformation is rampant and has led to many children not receiving the vaccines they need. Survey data from those entering kindergarten suggests that overall immunization rates have dropped from 95% just a few years ago to overall 93%.³²Some parents are either avoiding some or all vaccinations or spacing them beyond what is recommended. This has been noted by a large increase in vaccine exemptions for children.^32-34 States and localities generally establish vaccination requirements for school attendance. They also develop conditions and procedures for exemptions from vaccine requirements, timeframes for submitting documentation, and conditional registration for students who need more time to be vaccinated. In the 2023-2024 academic year, 3.3% of children who prepared to enroll in kindergarten had at least one vaccine exemption overall. Thirty states had exemption rates higher than this with Idaho reporting 14.3% of children with at least one vaccine exemption. Of note, 93% of these exemptions were nonmedical in nature.³² Readers can find the exemption rates for their own states here in Figure 1: https://pmc.ncbi.nlm.nih.gov/articles/PMC11486350/

It is a problem when many individuals decide not to be vaccinated or to not have their children vaccinated, because when a community no longer maintains a high percent of a population protected (generally considered at least 90%), the population loses herd immunity.³⁵ Without herd immunity protecting a community population, the community will be susceptible to outbreaks of these vaccine preventable diseases.

Measles is a prime example of this phenomenon. Measles is a very contagious infection that requires about 95% of a population to be vaccinated to prevent spread in a community.³⁶ Recent data suggests that the percent of children entering kindergarten receiving two doses of MMR vaccination dropped below 95% (at 93.9%) in 2021-2022 and further decreased to 92.7% in 2023-2024.^{32, 34} We have begun seeing increases in measles cases again, with 284 cases (40% requiring hospitalization) reported in 2024.^35,37

The percentage of the population that needs to be vaccinated to achieve herd immunity depends on the disease. While herd immunity for measles requires about 95% of the population to be vaccinated, for polio the threshold is about 80%. It may take several years to determine herd immunity for a specific disease, and it will likely vary according to the community, the vaccine, the populations prioritized for vaccination, and other factors.

CONCLUSION

The December 2024 12th amendment of the PREP Act provided liability immunity for pharmacists, pharmacy interns, and pharmacy technicians to continue to provide COVID-19 and influenza vaccination and testing and treatment for COVID-19. The age at which these two immunizations have been expanded by the Act is for those 3 years and older. This age was chosen for these inactivated vaccines as the administration route is the same as it is for adults (i.e., intramuscular in the deltoid). Effective January 1, 2025, the 12th Amendment of the PREP Act Declaration was extended to continue coverage through December 31, 2029.

It is essential to have pharmacy personnel continue to advocate and provide easily accessible vaccines as pharmacists are the most accessible healthcare providers, as a pharmacy is within five miles of nearly 90% of the population. However, a potentially significant health disparity is developing as decreasing access is occurring due to pharmacy closures, especially independent pharmacies and those in Black and Latine communities. Policy makers should consider strategies to increase the participation of independent pharmacies in Medicare and Medicaid preferred networks managed by pharmacy benefit managers and to increase public insurance reimbursement rates for pharmacies that are at the highest risk for closure.

LAW: The Pharmacy Implications of the PREP Act Extension

Learning Objectives
After completing this continuing education activity, pharmacists and technicians will be able to

• DESCRIBE the history and extension of the PREP Act and what the 12th Amendment of the PREP ACT authorizes pharmacists, pharmacy interns, and pharmacy technicians to do.
• EXPLAIN why pharmacy personnel are essential for providing immunization and testing for COVID-19.
• REVIEW techniques for COVID-19 testing and inactivated immunization of those 3 years and older.

1. What was the primary focus of the 12th Amendment to the PREP Act that became effective January 1, 2025?
a. It expanded pharmacy workers' authority to administer childhood vaccines to ages 3 to18.
b. It extended PREP Act coverage through December 31, 2029.
c. It declared the Public Health Emergency was no longer in effect.

2. What does the PREP Act do?
a. It authorizes pharmacy workers’ (i.e., pharmacists, pharmacy interns, and technicians) to administer COVID-19 and seasonal flu .
b. In addition to authorizing seasonal flu and COVID-19 vaccines, it authorizes pharmacy workers’ to administer childhood for ages 3 to18.
c. It limits covered persons’ legal liability for losses relating to the administration of medical countermeasures such as diagnostics, treatments, and vaccines.

3. What countermeasures does the 12th Amendment to the PREP Act cover for a pharmacist, pharmacy intern, and technician to do?
a. Pharmacists can prescribe nirmatrelvir/ritonavir tablets and pharmacists, interns, and technicians can administer seasonal flu and COVID-19 vaccines.
b. In addition to seasonal flu and COVID-19 vaccines, pharmacists, interns and technicians can administer routine childhood vaccines in accordance with the Advisory for Immunization Practices (ACIP) for ages 3 to18.
c. It limits pharmacy workers’ authority to administer seasonal flu and COVID-19 vaccines to adults over the age of 18.

4. Why is it hypothesized that Black and Latine neighborhoods are more at risk of a pharmacy desert?
a. These communities have a lower percentage of primary care physicians and higher rates of chronic disease and lower medication adherence rates.
b. Chain pharmacies in these neighborhoods are closing at a higher rate than independent pharmacies and these pharmacies dispense a higher volume of prescriptions.
c. Independent pharmacies serve greater populations insured by Medicare and Medicaid which use preferred provider networks managed by pharmacy benefit managers.

5. How do I explain that influenza vaccine prevents severe disease and death?
a. An immunized person is far less likely to die or become seriously ill than someone whose immune system is unprepared to fight an infection.
b. Data clearly shows there is a 74% reduction in hospital admission and 69% reduction in death from influenza vaccine.
c. When patients develop the flu shortly after the receiving the flu vaccine, that is evidence the vaccine is working.

6. Why did the the PREP Act authorization of influenza and COVID-19 vaccines include children aged 3 years and older and exclude children under the age of 3?
a. Parental concerns including religious or personal beliefs, and safety concerns are greater in children under age 3.
b. Since these are inactivated vaccines, the preferred site of administration is the same as for adults (the deltoid muscle).
c. The preferred site of administering these inactivated vaccines in children is in the thigh (quadriceps) muscle.

7. Why is understanding the difference between declaring a public health emergency and a PREP Act declaration important for the practice of pharmacy?
a. A public health emergency declaration is required for a pharmacist and other covered persons providing countermeasures to be protected from liability under the PREP Act.
b. Any expansion of pharmacy service, such as vaccine administration or point-of-care testing, are automatically continued after a public health emergency and PREP Act declaration expires.
c. State law dictates pharmacy personnel’s authorities, and immunizing authority reverts to the state regulations that existed before the public health emergency unless state laws

Please use the following hypothetical case for questions 8-10. You are starting to hear of a new potential outbreak occurring that could be the “bird flu” related to the H5N1 and/or the N5N9 viruses. It’s still uncertain of how it is transmitted to humans. You don’t know if a public health emergency has been declared or if the PREP Act has been enacted. You learn many people in our community are getting sick and hospitalized with flu-like symptoms and some people have died, particularly those with pre-existing chronic diseases. Certain ethnic and cultural communities seem to be experiencing a disproportionately high rate of hospitalizations and deaths.

8. A PREP Act declaration for bird flu has been invoked and a new vaccine with high efficacy and safety data has been released under Emergency Use Authorization (EUA). The PREP Act declaration lists pharmacists, pharmacy interns, and technicians as covered persons. It also lists countermeasures that can use for bird flu, including the new vaccine and a new bird flu test. What can you legally and ethically do to help your community?
a. You cannot order or administer any vaccine until HHS declares a public health emergency, but you can communicate vaccine safety and efficacy information to patients.
b. You can widely publicize your ability to test and vaccinate and include information with every prescription dispensed.
c. Recognizing this health crisis from the early COVID-19 pandemic, you vaccinate and dispense the new antiviral drug that has EUA. Your pharmacy interns and technicians also vaccinate under your supervision.

9. A public health emergency has now been declared and the Secretary of HHS has amended the PREP Act to authorize pharmacists to prescribe any antiviral under EUA or FDA-approved for bird flu for 12 months. The amendment also authorizes pharmacists, pharmacy interns, and technicians to administer any vaccine under EUA or FDA-approved bird flu vaccines. Has your ability to provide any clinical services and administer and changed?
a. The PREP Act provides liability immunity for a pharmacist to prescribe and administer the FDA-approved bird flu vaccines and antivirals as countermeasures. It also provides liability for any bird flu vaccine or antiviral under EUA. You should actively promote these services.
b. Under my state law, I am not allowed to prescribe or administer an antiviral agent under EUA. I was only allowed to prescribe nirmatrelvir/ritonavir tablets under the PREP Act declaration for COVID-19.
c. In addition to providing countermeasures for bird flu, pharmacists can supervise interns and technicians to administer childhood vaccines as recommended by ACIP for children aged 3-18, similar to the public health emergency declared for COVID-19.

10. How can pharmacy workers ensure that their communities do not endure similar health disparities that occurred during the early stages of the COVID-19 pandemic?
a. Pharmacy workers can’t control or prevent health disparities in ethnically or culturally diverse communities without a change in the law. They must follow state law and/or any PREP Act authority to provide clinical services during a pandemic.
b. Under the provisions of the public health emergency declaration during a pandemic, pharmacies will be reimbursed for countermeasures provided to anyone regardless of the pharmacy’s status as a preferred provider by the pharmacy benefit manager.
c. Urging policymakers to increase public insurance reimbursement rates for communities with significant health disparities and targeting outreach campaigns in a culturally sensitive manner helps ensure equitable access to information and medications.

REFERENCES

Berenbrok LA, Tang S, Gabriel N, et al. Access to community pharmacies: A nationwide geographic information systems cross-sectional analysis. J Am Pharm Assoc (2003). 2022;62(6):1816–1822.e2. doi: 10.1016/j.japh.2022.07.003.
Anderer S. Nearly 1 in 3 US Pharmacies Have Closed Since 2010, Widening Access Gaps. JAMA. 2025. doi: 10.1001/jama.2024.26875.
Guadamuz JS, Alexander GC, Kanter GP, Qato DM. More US Pharmacies Closed Than Opened In 2018-21; Independent Pharmacies, Those in Black, Latinx Communities Most At Risk. Health Aff (Millwood). 2024;43(12):1703–1711. doi: 10.1377/hlthaff.2024.00192.
Shattock AJ, Johnson HC, Sim SY, et al. Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization. Lancet. 2024;403(10441):2307–2316. doi: 10.1016/S0140-6736(24)00850-X.
Zhou F, Jatlaoui TC, Leidner AJ, et al. Health and Economic Benefits of Routine Childhood Immunizations in the Era of the Vaccines for Children Program - United States, 1994-2023. MMWR Morb Mortal Wkly Rep. 2024;73(31):682–685. doi: 10.15585/mmwr.mm7331a2.
Ferdinands JM, Thompson MG, Blanton L, Spencer S, Grant L, Fry AM. Does influenza vaccination attenuate the severity of breakthrough infections? A narrative review and recommendations for further research. Vaccine. 2021;39(28):3678–3695. doi: 10.1016/j.vaccine.2021.05.011.
Lives saved by COVID‐19 vaccines. J Paediatr Child Health. 2022. doi: 10.1111/jpc.16213.
Roper LE, Godfrey M, Link-Gelles R, et al. Use of Additional Doses of 2024–2025 COVID-19 Vaccine for Adults Aged ≥65 Years and Persons Aged ≥6 Months with Moderate or Severe Immunocompromise: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024. MMWR Morb Mortal Wkly Rep. 2024;73(49):1118–1123. doi: 10.15585/mmwr.mm7349a2.
El Kalach R, Jones-Jack N, Elam MA, et al. Federal Retail Pharmacy Program Contributions to Bivalent mRNA COVID-19 Vaccinations Across Sociodemographic Characteristics - United States, September 1, 2022-September 30, 2023. MMWR Morb Mortal Wkly Rep. 2024;73(13):286–290. doi: 10.15585/mmwr.mm7313a2.
Centers for Disease Control and Prevention. COVID-19 Vaccinations Administered in Pharmacies and Medical Offices*, Adults 18 Years and Older, United States. Accessed January 3, 2025.https://www.cdc.gov/ COVIDvaxview/weekly-dashboard/vaccinations-administered-pharmacies-medical.html
Centers for Disease Control and Prevention. Influenza Vaccinations Administered in Pharmacies and Physician Medical Offices*, Adults, United States. Accessed January 3, 2025.https://www.cdc.gov/fluvaxview/dashboard/adult-vaccinations-administered.html
GlobalData Plc. The Complexities of Physician Supply and Demand:

Projections From 2021 to 2036. AAMC. 2024.

Strand MA, Bratberg J, Eukel H, Hardy M, Williams C. Community Pharmacists' Contributions to Disease Management During the COVID-19 Pandemic. Prev Chronic Dis. 2020;17:E69. doi: 10.5888/pcd17.200317.
Health and Human Services Department. 12th Amendment to Declaration Under the Public Readiness and Emergency Preparedness Act for Medical Countermeasures Against COVID-19. 2024;89(238):99875–99883. Accessed January 27, 2025. https://www.federalregister.gov/documents/2024/12/11/2024-29108/12th-amendment-to-declaration-under-the-public-readiness-and-emergency-preparedness-act-for-medical
Department of Health and Human Services. Notice Eleventh Amendment to Declaration Under the Public Readiness and Emergency Preparedness Act for Medical Countermeasures Against COVID-19. Federal Register. 2023;88(92):30769–30778.
National Alliance of State of Pharmacy Associations. COVID-19: Federal PREP Act Actions. Accessed January 3, 2025. https://naspa.us/blog/resource/federal-prep-act-actions/
Centers for Disease Control and Prevention. COVID Data Tracker. Accessed January 6, 2025.
Administration for Strategic Preparedness and Response. PREP Act Questions and Answers. Accessed January 21, 2025. https://aspr.hhs.gov/legal/PREPact/Pages/PREP-Act-Question-and-Answers.aspx
Centers for Disease Control and Prevention. Overview of Testing for SARS-CoV-2. Accessed January 6, 2025.https://www.cdc.gov/ COVID/hcp/clinical-care/overview-testing-sars-cov-2.html
Wolicki J, Miller E. Vaccine Administration. In: Hall E, Wodi AP, Hamborsky J, Morelli V, Schille S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 14th ed. Washington, D.C.: Public Health Foundation; 2021.
Bancsi A, Houle SKD, Grindrod KA. Shoulder injury related to vaccine administration and other injection site events. Can Fam Physician. 2019;65(1):40–42.
State of New Hampshire Revised Statutes. 318:16-b Pharmacist Administration of Vaccines. Accessed January 3, 2025. https://www.gencourt.state.nh.us/rsa/html/XXX/318/318-16-b.htm
State of Vermont Statutes. 2023. Clinical pharmacy; prescribing. Accessed January 3, 2025. https://legislature.vermont.gov/statutes/section/26/036/02023
Girotto JE, Klein KC, Cober MP, et al. Pharmacists as Partners in Pediatric Immunizations: A White Paper From the Pediatric Pharmacy Association. J Pediatr Pharmacol Ther. 2024;29(6):660–666. doi: 10.5863/1551-6776-29.6.660
Kentucky General Assembly. House Bill 274 An ACT relating to the practice of pharmacy. Accessed January 6, 2025. https://apps.legislature.ky.gov/record/24rs/hb274.html
Hawaii State Legislature. Pharmacists; Pharmacy Interns; Pharmacy Technicians; Minors; Vaccinations. Accessed January 6, 2025. https://www.capitol.hawaii.gov/session/archives/measure_indiv_Archives.aspx?billtype=HB&billnumber=2553&year=2024
Maryland Legislature. Health Occupations – Pharmacists – Administration of Vaccines. Accessed January 6, 2025. https://legiscan.com/MD/text/HB76/2024
Minnesota Legislature. https://www.revisor.mn.gov/statutes/cite/151.01. Accessed January 6, 2025. https://www.revisor.mn.gov/statutes/cite/151.01
Joint Pharmacist Administered Vaccines Committee. Protocol for Administration of Vaccines by Pharmacists submitted by the Joint Pharmacist Administered Vaccines Committee and reviewed, revised and approved by the South Carolina Board of Medical Examiners. Accessed January 6, 2025. https://llr.sc.gov/bop/pforms/vaccines.pdf
West Virginia Legislature. West Virginia Code: Article 5. Pharmacists, Pharmacy Technicians, Pharmacy Interns and Pharmacies. Accessed January 6, 2025. https://code.wvlegislature.gov/30-5-7/#:~:text=(e)%20The%20Board%20of%20Medicine,that%20patient%20receiving%20that%20vaccine
Hung M, Srivastav A, Lu P, Black CL, Linley MC, Singleton JA. Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2022. Accessed January 21, 2025. https://www.cdc.gov/adultvaxview/publications-resources/adult-vaccination-coverage-2022.html
Hargreaves AL, Nowak G, Frew P, et al. Adherence to Timely Vaccinations in the United States. Pediatrics. 2020;145(3):e20190783. doi: 10.1542/peds.2019–0783.
Seither R, Yusuf OB, Dramann D, et al. Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten - United States, 2023-24 School Year. MMWR Morb Mortal Wkly Rep. 2024;73(41):925–932. doi: 10.15585/mmwr.mm7341a3.
Seither R, Calhoun K, Yusuf OB, et al. Vaccination Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten - United States, 2021-22 School Year. MMWR Morb Mortal Wkly Rep. 2023;72(2):26–32. doi: 10.15585/mmwr.mm7202a2
McCarthy C. Why follow a vaccine schedule for children? Accessed January 3, 2025. https://www.health.harvard.edu/blog/why-follow-a-vaccine-schedule-2020032619271
Pandey A, Galvani AP. Exacerbation of measles mortality by vaccine hesitancy worldwide. Lancet Glob Health. 2023;11(4):e478–e479. doi: 10.1016/S2214-109X(23)00063-3.
Centers for Disease Control and Prevention. Measles Cases and Outbreaks. Accessed January 3, 2025. https://www.cdc.gov/measles/data-research/index.html

The Scoop on Pharmacy Burnout: Description and Management Strategies

Burnout is a response to prolonged work-related stress that has not been managed adequately. Although burnout is present in other professions, researchers have found it to be more prevalent in health services professions. In the pharmacy profession, increasing workload, staffing shortages, and hard-to meet company performance metrics are among the factors that contribute to burnout. The consequences of burnout in the pharmacy are substantial and range from low morale and employee turnover to serious dispensing errors. The onus for addressing burnout lies with employers and companies, although employees have a role to play as well. Several states are enacting new laws to address working conditions in pharmacies. Recently passed laws include mandating breaks for pharmacists, capping shift lengths, and disallowing excessive metrics.

INTRODUCTION

Burnout is a response to prolonged work-related stress that can impair physical health and psychological wellbeing.^1,2 Interest in burnout is growing. Employers and employees alike would like to understand burnout and determine a solution that will keep employees engaged and enthusiastic about work. For healthcare professionals and the pharmacy team to carry out their roles in improving the health of the population optimally, they must pay attention to their physical and psychological wellbeing. Consequences of burnout adversely affect both providers and patients in their care.

People who experience burnout feel emotional exhaustion, depersonalization, and reduced personal accomplishment.¹ The Maslach Burnout Inventory (MBI) is the most widely used research measure on burnout.¹ The Maslach Burnout Inventory Human Services Survey (MBI-HSS) is an assessment tool for burnout syndrome in human services occupations such as healthcare.¹ Christina Maslach, a psychology professor at the University of California, Berkeley, is one of the pioneering researchers on burnout and its definition, predictors, and measurement.³ She is the architect of the Maslach Burnout Inventory and based on her work, the World Health Organization (WHO) included burnout as an occupational phenomenon in the International Classification of Diseases (ICD).³ Maslach and her colleagues’ initial research into burnout included surveys, interviews, and field observations of workers in human services professions such as health care, social services, mental health, criminal justice, and education. Their findings indicated that burnout could reduce the quality of care or service provided by the worker.¹ Their findings also found a link between burnout and negative health outcomes for the worker such as headaches, muscle tension, hypertension, sleep disturbances, and cold and flu episodes.² Burnout also seemed to be associated with personal dysfunction such as physical exhaustion, insomnia, increased use of substances, and poor interpersonal relationships.¹

The Agency for Healthcare Research and Quality estimates that 30% to 50% of physicians, nurse practitioners, and physician assistants may be affected by burnout.⁴ Various professional organizations and studies have extensively reported on burnout in physicians. While more research is needed, researchers have conducted some studies to identify occupational burnout’s prevalence and risk factors in pharmacists and pharmacy technicians. These studies detail the existence of burnout among pharmacy staff.

Health care providers’ well-being impacts patient safety and patient care quality. It is essential that pharmacy team members understand burnout syndrome, and stakeholders in the profession must take steps to improve employee well-being.

Pause and Ponder: How would you describe the working conditions at your workplace?

Burnout Definition and Description

In the early 1970s, psychologist Herbert Freudenberger was one of the first to describe professional exhaustion and is credited with introducing the concept of burnout.^4,5Freudenberger did his burnout research observing staff working in a free medical clinic.^4,5 After he completed his normal workday, he worked at a free clinic that he had helped organize during the Free Clinic Movement—a movement that involved healthcare providers in work that required almost endless effort and empathy. During these work shifts, he recognized the syndrome. He described burnout as putting a great deal of yourself into your work, with the staff and population you serve demanding this of you, while you also demand it of yourself. He further described it as eventually finding yourself in a state of exhaustion.⁵

Similar to Freudenberger’s description, the WHO defines burnout as a syndrome conceptualized as resulting from chronic workplace stress that has been poorly managed.⁶ Burnout can develop in employees such as healthcare professionals who work with other people in some capacity.¹Note that burnout is limited to work environments, an occupational hazard, if you will, and the ICD does not classify it as medical condition.⁶

Indicators of Burnout

Burnout has three subscales (scales used to obtain a rating or measurement that contributes to a rating or measurement on a larger scale). The terms that describe burnout’s three components may be familiar to pharmacists and technicians, but they have specific meaning when used to describe burnout. If pharmacists and technicians recognize how burnout presents, they will be better prepared to intervene early if they or their colleagues exhibit any of the feelings or attitudes described in the subscales.

The following are burnout’s subscales¹:

Emotional exhaustion: Presents as feelings of energy depletion or exhaustion attributed to one’s work. As emotional resources are depleted, workers feel they are no longer able to give more of themselves on a psychological level.¹ Other descriptions of emotional exhaustion are being worn out, having a loss of energy and enthusiasm for work, or feeling drained and fatigued.⁷
Depersonalization: Increased mental distance from one’s job, or feelings of negativity or cynicism related to one’s job. Other descriptions of this state are negative and cynical attitudes and feelings about one’s clients or negative, inappropriate, and irritable attitude toward clients.¹ This perception of others may lead staff to view clients or patients as somehow deserving of their troubles.¹
Decreased sense of personal accomplishment: Reduced professional efficacy, or feelings of reduced personal accomplishment. Workers may evaluate themselves negatively regarding their work and may also feel dissatisfied with their accomplishments on the job.¹ Some words used to describe this condition include reduced productivity or capability, and low morale.

Table 1 describes studies and research on burnout in different pharmacy practice settings and their findings.

Table 1. Burnout Studies in Different Pharmacy Practice Settings^8-12

Target Population	Study Design and Description	Result
Community pharmacists	· Anonymous electronic surveys including the MBI-HSS and a work-factors-based questionnaire · To identify the prevalence and risk factors for occupational burnout in community pharmacists	74.9% of respondents reported burnout in at least one MBI-HSS subscale, most owing to emotional exhaustion (68.9%).
Health system pharmacists	· Multi-center cross-sectional cohort survey study · Used MBI-HSS · To determine levels of, and risk factors for professional burnout among health system pharmacists	53.2% of study participants reported a high level in at least one MBI-HSS subscale. 8.5% of study participants had scores that indicated burnout on all 3 MBI-HSS subscales.
Clinical pharmacists in a hospital inpatient setting	· Prospective, cross-sectional pilot study · Online survey · To characterize the level of and identify factors independently associated with burnout among clinical pharmacists practicing in an inpatient hospital setting within the United States	Low response rate. However, 61.2% of respondents reported burnout, largely driven by high emotional exhaustion.
Pharmacy residents	· Electronic anonymous survey · To quantify burnout status of pharmacy residents and to correlate burnout to professional conduct and career outlook	74.4% burnout rate was reported among respondents.
Pharmacy technicians	· Used MBI-HSS · To assess burnout among pharmacy technicians working in a hospital or health system setting	69.1% of respondents were experiencing burnout.
ABBREVIATIONS: MBI-HSS = Maslach Burnout Inventory-Human Services Survey

Risk Factors and Causes of Burnout

Across many occupations, common risk factors contribute to burnout. Table 2 describes those risk factors.

Table 2. Risk Factors for Burnout²

Risk Factor	Description
Workload	· Job demands exceeds human limits · Workload is unsustainable · No opportunity to recover from, or have a restful period after a particularly demanding event such as meeting a deadline or addressing a crisis resulting in acute fatigue · Prolonged overload becomes a chronic job condition leading to exhaustion
Control	· Employees have no personal control in the workplace · Role conflict · Lack of opportunity to contribute to or participate in organizational decision-making
Reward	· Insufficient reward be it financial, institutional, or social · Lack of recognition from managers, workers, and stakeholders devalues the work and leaves the worker with a sense of inefficacy
Community	· The overall quality of social interaction at work and the ability to work as a team is inadequate. · Lack of a supportive and positive work environment
Fairness	· Decisions at work are perceived as unfair or inequitable · Employees perceive an imbalance between their inputs (time, effort, expertise) and outputs (reward, recognition)
Values	· A conflict exists between individual and organizational values o Values are the ideals or principles that originally draw people to a particular job. · Individual values unaligned with organizational goals could lead to burnout

Although employees in other professions experience burnout, workers in the human services professions such as healthcare, social services, mental health, criminal justice, and education are more prone to burnout.⁴ Workers in human services professions spend considerable amounts of time with other people. Their relationships often involve addressing a patient’s or a client’s health needs (medical, psychological, physical).¹ Patients and clients have continuous health needs and challenges and frequently require ongoing, lengthy, or chronic support and care. In an effort to make a positive impact on the lives of others, healthcare workers can become overwhelmed.¹ The nature of healthcare work coupled with stressful working conditions can be emotionally draining and lead to burnout.

Pharmacy professionals like other healthcare professionals are prone to burnout due to common risk factors and profession specific factors.

The following risk factors contribute to burnout among the pharmacy team^4,10,13

Long professional work hours
Workload and inability to meet company specified performance metrics
Staffing shortages
Incompatibility between skills and actual daily tasks

Because the pharmacy profession is highly regulated, the pharmacy team must remain up to date with regulatory requirements.⁴ Everyone on the team must document extensively with no room for error. Attention to detail is a required skill for the pharmacy team because errors could lead to injury or potentially death.

An increasing workload, long working hours, and day-to-day tasks that may sometimes be incongruent with employees’ actual skills may lead to burnout at some point.⁴ A fear of retribution from speaking up about working conditions further exacerbates the risk of burnout.¹⁴

In a March 2021 NBC news story “Overworked, understaffed: Pharmacists say industry in crisis puts patient safety at risk” that aired, NBC news interviewed 31 retail pharmacists and technicians from 15 states.¹⁴ These pharmacists and technicians described extremely busy 12-hour shifts during which they were unable to take lunch or bathroom breaks. The interviewees further described crying in their cars after work and enduring sleepless nights from worrying about mistakes they may have made while working under such busy and rushed conditions.¹⁴ For a common daily scenario in a busy community pharmacy, see the SIDEBAR.

SIDEBAR: Does this busy community pharmacy sounds familiar?¹⁴

Long lines while short-staffed
Ringing phones
Busy drive-through
Weekly order that still needs to be put away on shelves
Patients waiting for vaccines

The story described working conditions in community pharmacies where pharmacists were being “pushed to do more with less.”¹⁴ Pharmacists described working faster to fill more orders, while juggling a wider range of tasks with fewer staff members at a rate that compromised patient safety.

A 2019 national pharmacist workforce study found two-thirds of pharmacists experienced increased workload in the past year. A high percentage of retail chain pharmacists in this survey rated their workloads as high or excessively high.¹⁵

Burnout rates among pharmacy employees may differ depending on practice setting.⁴ Community pharmacists report higher rates of burnout than employees in other practice settings like hospitals and independent pharmacies.⁹

Pause and Ponder: Do you dread your upcoming shift and live for your day off? Why or why not?

BURNOUT ASSESSMENT

Assessing burnout in the pharmacy profession is necessary for research and most importantly for interventions. With the MBI-HSS specifically, employers can design interventions to address the specific burnout subscale that their employees may report.¹ Interventions addressing emotional exhaustion will differ from those addressing a reduced sense of personal accomplishment. Organizations or employers can focus strategies to address employee burnout.¹ Finally, the assessment of burnout and the subsequent awareness that a problem exists can be the initial step in preventing or alleviating full blown job burnout.

The Maslach Burnout Inventory

The MBI is an assessment tool for the three components of burnout syndrome: emotional exhaustion, depersonalization, and a reduced sense of personal accomplishment.¹ Although other measurements for burnout exist, the MBI is largely considered the gold standard for assessing burnout in a group of workers in a profession. The MBI is not an individual diagnostic instrument.¹ This assessment tool was designed originally to measure burnout in human services professions such as healthcare, social work, and criminal justice.¹ Maslach has since developed alternate forms of the MBI: the MBI-Educators Survey (MBI-ES) for the teaching profession, and the MBI-General Survey (MBI-GS) for other occupational groups.¹ The MBI-HSS distinguishes burnout in health services occupations from burnout in other professions.¹ This questionnaire is a self-administered tool and takes approximately 15 minutes to complete.¹

The MBI is copyrighted.¹ Researchers and individuals can purchase and administer it either as an online survey or as a paper and pencil survey.¹⁶ For the online surveys, score reports are generated online.¹⁶

The MBI is divided into three components, each of which includes personal statements that the respondent must rank.¹ Examples of such personal statements are “I feel burned out from my work” and “I don’t really care what happens to some recipients.” MBI-HSS administrators score the items on the questionnaire on a seven-point scale. The scale ranges from a 0 response for “never,” to a 6 response for “every day.” Below are the three components¹:

Emotional exhaustion – nine statements on this subscale assess “feelings of being emotionally overextended and exhausted by one’s work.”
Depersonalization – five statements on this subscale assesses an unfeeling and impersonal response the employee has towards their patients or clients.
Personal accomplishments – eight statements on this subscale assess “feelings of competence and achievements in one’s work with people.”

Each subscale is scored separately as low, average, or high using directions from the scoring key. There is not a total combined score. Respondents receive three separate scores—one score for each subscale. Receiving a score for each subscale benefits the assessment-taker because interventions to reduce burnout can be designed based on the specific component of burnout that needs to be addressed.¹

For the emotional exhaustion and depersonalization subscales, a higher score corresponds to a higher degree of burnout. For the personal accomplishment subscale, however, a lower scale corresponds to a higher degree of burnout.¹

The MBI has several drawbacks. Everyone has a different view of burnout and because the questionnaire is self-administered, respondents’ answers may be influenced by talking to other people such as friends and coworkers. For this reason, respondents should complete the MBI privately without knowing how other respondents are answering. The survey has also been labeled “MBI Human Services Survey” rather than “Maslach Burnout Inventory.” This reduces the chances of respondents linking the survey specifically to burnout; rather, the questionnaire’s title suggests it measures job-related attitudes and issues.¹ Once all respondents have completed the survey, an open discussion of burnout is then appropriate. MBI administrators require no special qualifications. However, as a best practice, managers or supervisors should not administer the survey since this would affect how employees respond, i.e., employees may not be candid about their feelings.¹

Although the MBI cannot be used as an individual diagnostic tool, it can be used as a self-assessment tool.¹ Employees can compare their scores to those of others in their occupational group so they can recognize potential problems.¹

ICD-11 Codes for Burnout

The ICD is the international standard for reporting diseases and health conditions and is the diagnostic classification standard for all clinical and research purposes.¹⁷ ICD-11 is the global standard for health data, clinical documentation, and statistical aggregation. It is scientifically up to date with multiple uses including use in primary care. The ICD defines diseases, disorders, injuries, and other related health conditions.¹⁷ The WHO maintains the ICD.¹⁷

The WHO’s 11^th revision of the International Classification of Diseases (ICD-11) includes burnout, defining it as “a syndrome conceptualized as resulting from workplace stress that has not been successfully managed.”⁶ The previous revision, ICD-10, also included burnout. The definition in the 11^th revision is now more detailed. According to this classification, burnout is work-related and does not apply to experiences in other areas of life.⁶

Alternative Measures to Assess Burnout

While experts consider the MBI to be the gold standard for burnout assessment, other measures exist that are not copyrighted, require no payment to use, and are publicly available.¹⁸

The Oldenburg Burnout Inventory – developed in Germany, this 16-item survey measures burnout in any occupational group. It covers two areas: exhaustion (physical, cognitive, and affective aspects) and disengagement from work (negative attitudes toward work objects, work content or work in general). It treats each burnout dimension separately.¹⁸
Single Item Burnout Measure – developed in the U.S., it measures burnout in any occupational group. The single question on the measure asks users to rate their burnout level based on their own definition of burnout. Users pick from five response options and receive scores that suggest no burnout symptoms, or one or more burnout symptoms.¹⁸
Copenhagen Burnout Inventory – developed in Denmark, this 19-item survey measures burnout in any occupational group and covers personal-, work-, and client-related burnout. It treats each burnout dimension separately.¹⁸

Recognizing Burnout’s Effects

Burnout influences quality of life and the team’s ability to perform optimally in their personal and professional capacities. In addition to negative health outcomes for employees such as muscle tension, headaches, sleep disturbances, hypertension, and cold and flu episodes,² burnout’s consequences in the workplace include^1,13,14,19

A decline in the quality of patient care
Dispensing errors
Low morale
Employee turnover
Missed days

Pause and Ponder: Do you feel rushed daily at work? How might that contribute to dispensing errors?

Dispensing Errors

We have described how an unsustainable workload is a risk factor for burnout (see Table 2). The costly effects of burnout include dispensing errors. Staff shortages, increasing workload, and long professional work hours contribute to dispensing errors in pharmacies.^14,19Community pharmacists and technicians, for example, work to fill prescriptions, give vaccinations, counsel patients, answer phones, tend to the drive-through and the register, and call insurance companies. They do all this while trying to meet their company’s specified performance metrics. The likelihood of a dispensing error is increased when working conditions in the pharmacy are rushed and chaotic.^14,19

In 2006, in a comprehensive study of medication errors, the Institute of Medicine estimated that medication errors harmed at least 1.5 million Americans annually.²⁰ Indirect costs of such errors include loss of productivity, emotional stress and suffering, and additional healthcare costs.²⁰ A recent New York Times article tells the story of working conditions in pharmacies and metrics set by companies that pharmacists find hard to meet.¹⁹ The article reports several examples of dispensing errors. In one instance, an 85-year-old woman died after receiving the chemotherapy drug methotrexate instead of an antidepressant refill. Another patient went to the emergency room after receiving ear drops instead of eye drops, which caused eye swelling and burning. In another medication mix up, a patient received a blood pressure medication instead of her asthma medication, resulting in a pounding headache, nausea, and dizziness.¹⁹

Some states including Illinois and California are trying to change pharmacy practice. In Illinois, a new law requires pharmacists to have scheduled breaks. The state could also impose penalties on companies that do not provide a safe working environment.¹⁴ California’s new law requires that pharmacists not work alone.¹⁴ Changes from state boards of pharmacy could play an important role in improving the working conditions in pharmacies.

Employee Turnover

Employee turnover is the voluntary or involuntary loss of employees and the act of replacing them. Employees may leave their jobs voluntarily for many reasons including retirement or moving on to other opportunities. Others may leave due to lack of growth opportunities in their current roles, a hostile work environment, or a feeling of not fitting the company culture. Job-seekers and applicants view an unusually high turnover negatively, making turnover costly for employers. Companies must then put great efforts into recruiting, training, and onboarding. It also takes time for employers to train new employees adequately. Others may also view the company as having problems with their working conditions. Most importantly, high turnover diminishes productivity and the chance to build a cohesive team is lost.²¹

In 2004 in the U.S., researchers conducted a study to examine the relationship between organizational and individual factors, and pharmacists’ future work plans.¹³ The study sought to determine factors that contributed to pharmacists either leaving or staying with their current employer.¹³ Researchers in this cross-sectional study mailed surveys to licensed U.S. pharmacists. Respondents were asked to state whether they would leave or stay with their current employers during the next year. The researchers also asked respondents to rate their top five reasons for leaving or staying from a predetermined list. “Leavers” were those planning to leave their employer, and “stayers” were those planning to stay.

For leavers, 35% cited high stress levels as their exit reason, 31.1% cited excessive workload, and 25% cited poor salary or insufficient staffing.¹³

Stayers’ top reasons were good salary (50%), relationships with coworkers (46.6%), and good benefits (42%).¹³

Researchers also asked respondents to identify one main factor that influenced their decision to leave or to stay. A majority of these factors were under the employer’s control. Flexible schedules, ability to use skills, and salary/benefits influenced the stayers, while insufficient or unqualified staffing, poor scheduling and salary, and workload influenced the leavers.¹³

COVID-19 and Burnout in Healthcare Workers

In March 2020, the WHO declared the novel coronavirus disease (COVID-19) a global pandemic. COVID-19 is a highly contagious respiratory illness. As of January 4, 2022, COVID-19 had affected more than 54 million Americans and claimed the lives of more than 820,000.²² Factors such as preparedness for a pandemic, political leadership, availability of personal protective equipment (PPE), and the fear of infection and infecting others have played a role in the nation’s response to the pandemic. At the forefront of these crises were healthcare workers. The pandemic increased the levels of burnout among healthcare workers who have additionally had to witness patient suffering.

Before the pandemic, several studies across various pharmacy practice settings reported burnout among pharmacists. The 2019 national pharmacists’ workforce study reported 71% of practicing pharmacists characterizing their workload as either high or excessively high.¹⁵ During the COVID-19 pandemic however, studies showed that burnout has increased among healthcare workers, pharmacists included.^23,24 Healthcare visits to hospitals and doctors’ offices are sometimes limited during the pandemic, however, community pharmacists are available for face-to face consults. While this is beneficial for patients, pharmacists and technicians face an increased risk of exposure to the virus. Additionally, pharmacists have had to take on new roles and responsibilities during the pandemic.²⁵ The U.S. Department of Health and Human Services (DHS) authorized pharmacists to procure, dispense, and administer COVID-19 vaccines when they became available.²⁵ DHS also authorized pharmacists to order and administer COVID-19 tests to aid in testing expansion in response to the COVID-19 pandemic.²⁶

In the U.S., researchers studied the impact of COVID-19 on pharmacist workload, employment status, feelings of burnout, and overall emotional health.²³ The Wisconsin Pharmacist Workforce Study was a cross-sectional study conducted before the COVID-19 vaccine was available but after the Department of Health and Human Services made the decision to permit pharmacists to administer it.²³ Researchers focused on questions related to burnout domains and emotional health. For the reward domain, questions focused on changes in personal employment, while questions for the workload domain focused on exhaustion. Researchers used questions to measure depersonalization for the social interaction domain and developed questions about pharmacists’ social and emotional health. The study focused on the 2 largest pharmacist populations – community and hospital pharmacists – and had a 33% response rate. Study results are shown in Table 3.

Table 3. The Wisconsin Pharmacist Workforce Study Results²³

Domain Questions	Percentage of Community Pharmacists Reporting	Percentage of Hospital Pharmacists Reporting
Hours Reduced	13	36
Hours Increased	19	8
Reduction in Wages	1	6
Temporary Furloughs	2	6
Concern About Being Furloughed or Losing Job	26	14
Increase in Workload or Work-Related responsibilities	41	42
Reduced interest in talking with patients	26	22
Social/emotional health	Approximately 40% reported increased anxiety. Approximately 25% experienced increased sadness or depression.

The Wisconsin Pharmacist Workforce Study had imitations. Researchers only studied Wisconsin pharmacists, which makes generalization difficult. A non-response bias was also present; pharmacists with the highest workload would have had the least amount of time to respond to the survey. Despite these limitations, the study suggested that although pharmacists rose to the challenge during the pandemic, they experienced increased burnout as a result of COVID-19.²³

Another study conducted across pharmacy practice settings in Australia to measure burnout in pharmacists during the coronavirus pandemic showed that burnout had increased.²⁴ The study, an online survey, consisted of three parts. Researchers collected demographic information such as age, sex, primary practice area, and years of practice. They also used the MBI-HSS to measure burnout, and then asked questions pertaining to psychosocial issues. The questions focused on the pharmacists’ degree of concern for personal and family health, whether duties such as working overtime and workloads changed, and if precautionary measures in the workplace (e.g., PPE and infection control) were appropriate.²⁴

Although only 17.8% of respondents reported caring for COVID-positive patients, an overwhelming 96.3% of pharmacists reported a change in their roles during the pandemic. These changes included increased workload (35.9%) and working overtime (52.2%). The pharmacists reported challenges they faced during the pandemic ranging from medication supply (40.9%) to patient incivility (24%). Regarding precautionary measures however, 71.1% of pharmacists reported that their workplace had sufficient precautionary measures.²⁴

With regards to psychosocial factors, 36% of pharmacists were “very to extremely concerned” about their family’s health and 87.2% reported that their lives had been affected most by isolation from friends and family.²⁴

With the arrival of the COVID-19 pandemic, pharmacy teams have been stretched even further with additional duties such as COVID- 19 testing, deep cleaning, and giving COVID vaccinations. COVID-19 has compounded burnout among the pharmacy team.

The federal government in the U.S. has not yet comprehensively tracked data on healthcare worker deaths, but according to “Lost on the Frontline,” a 12-month investigation by The Guardian, a British newspaper, and Kaiser Health News, more than 3600 healthcare workers in the U.S. died from the coronavirus disease in the pandemic’s first year.²⁷

BURNOUT MANAGEMENT

The responsibility of addressing burnout among the pharmacy team does not only lie with employees but also with employers. In a study to assess burnout among pharmacy technicians working in a hospital or health-system settings in North Carolina, employees’ awareness of burnout resources at their institution was associated with lower odds of burnout, whether employees used those resources or not.¹¹

Employers

The pharmacy profession as a whole must address burnout, and employers’ goals should be to identify and address factors that contribute to burnout.

Prevention strategies for burnout include²

Ensuring a sustainable workload at the workplace, while allowing for periods of rest and recovery
Encouraging active participation in organizational decision making
Providing appropriate rewards for employee achievement
Fostering a positive and supportive environment at the workplace
Promoting fairness, impartiality, or equity in decisions at work
Aligning employees’ personal expectations with the organization’s

Federal and State Legislation

Payment Reform

Pharmacists are generally only paid for filling prescriptions and do not bill for clinical services such as counseling and giving vaccinations. A proposed federal bill if passed, would grant pharmacists “provider status.” The Pharmacy and Medically Underserved Areas Enhancement Act (H.R. 2759/S.1362) was introduced in both the U.S. House of Representatives and the U.S. Senate in April 2021. This bill proposes pharmacist recognition as health care providers and allows compensation for their services to Medicare patients in medically underserved areas.^28,29 With this status, pharmacists could bill insurers for clinical services for Medicare patients under Medicare Part B.²⁸

At the state level, several states already assign some form of provider status to pharmacists. The National Alliance of State Pharmacy Associations (NASPA) identifies state provider status-related bills as those that apply to pharmacist scope of practice, payment for pharmacist provided patient care services, and/or the designation of pharmacists as providers. NASPA’s 2021 mid-year update on state provider status reports that in 18 states, 32 such bills have been signed into law. These laws include pharmacist immunization authority, broad prescriptive authority, contraceptive prescribing authority, and payment for services among others.³⁰ In response to the NBC news story “Overworked, understaffed: Pharmacists say industry in crisis puts patient safety at risk,” the American Pharmacists Association (APhA), called for payment reform in pharmacy in a press release.³¹ The APhA went on to say that the broken model of paying for the filling of prescriptions has led to a proliferation of productivity and efficiency metrics that have created a situation that compromises patient safety. The press release further stated that the APhA continues to fight for payment reform at both the federal and state levels.³¹

Burnout can occur when an incompatibility exists between employees’ skills and actual daily tasks. Giving pharmacists the opportunity to consult, provide, and bill for clinical services while spending less time in dispensing activities could be a remedy.^13,31

Legislation

States like California, Illinois, and Virginia have passed new laws that will cap shift lengths for pharmacists. These laws also seek to ensure safe staffing levels and prohibit excessive metrics.¹⁴ According to the National Association of Boards of Pharmacy, about a third of all states now have some regulation that address working conditions in the pharmacy.¹⁴

Assessing Well-Being

Employees in other human services professions experience burnout as well, and it could be beneficial to look to other professions to see what initiatives they have in place to address burnout. The American Medical Association (AMA) for example, has a STEPS Forward program that seeks to prevent provider burnout.³² The program has interactive online educational modules with strategies to confront common challenges in a busy medical practice. The program is physician-developed and physicians can earn continuing medical education credit while learning about practice efficiency and patient care, patient health, physician health, and technology and innovation.³² Programs that improve resilience and well-being among employees might be beneficial to the pharmacy profession.

In an effort to address well-being, the APhA has launched the Well-Being Index, a validated screening tool invented by the Mayo Clinic, to help pharmacists assess their well-being.³³ Respondents to the anonymous online survey that evaluates fatigue, depression, burnout, anxiety/stress, and mental/physical quality of life, receive immediate individualized feedback. This allows pharmacists to compare their well-being with their professional peers’ and directs them to tools and resources that can help promote well-being. Participants can also track their scores over time so they can be proactive in making self-care adjustments.³³

Authors of a commentary on burnout syndrome among healthcare professionals suggest actions that pharmacy organizations can take to recognize and reduce burnout among their employees. These include⁴

Establishing a panel to evaluate burnout in the profession of pharmacy
Conducting further research into the prevalence prevention and effectiveness of treatment strategies of burnout across all practice settings of pharmacy
Incorporating strategies that promote mental health wellness and resiliency into pharmacists’ training.

Employees

“You can’t pour from an empty cup” - Unknown

Employees can adopt strategies to guard against burnout. The following strategies guard against burnout and promote wellbeing in the employee.

Continue to speak up about workplace conditions that affect patient safety and employee well-being.
Adopt self-care habits and foster hobbies outside of work. Ensure adequate sleep, nutrition, and exercise.
Be sure to take your vacation time or paid time off to recharge.
Foster a supportive and positive work environment by communicating and collaborating with teammates.
Keep up with continuing education and join a professional pharmacy organization. This enhances self-esteem and promotes a sense of purpose.

CONCLUSION

The importance of high-quality healthcare cannot be stressed enough. Healthcare professionals including pharmacists and pharmacy technicians play an important role in improving the overall population’s health. Clearly, burnout’s consequences among pharmacy workers could be detrimental for employees, patients, organizations, and society as a whole. It is important to recognize the indicators and risk factors for burnout to be able to address them and improve health care provider well-being. Employers and institutions must implement strategies to combat burnout in their employees. Some state boards of pharmacy are beginning to make changes and institute new laws that will cater to appropriate work environments and employee well-being.

1. Which of the following measures assesses burnout among pharmacy professionals?

A. The Maslach Burnout Inventory
B. DSM-V
C. ICD-11 diagnostic guidelines for anxiety

2. Turnover resulting from burnout in the pharmacy profession can be described as

A. Employees tend to retire immediately after reaching retirement age
B. Employees leave because they don’t fit in with the work culture
C. Employee with good salary/benefits leave due to relocation of spouse’s job

3. Which of the following is a risk factor for burnout among pharmacy professionals?

A. Employees receive hardly any raises or recognition after favorable end-of-year performance reviews
B. Employee is included from decision making in the workplace
C. Employees find the level of social interaction and collaboration at work adequate

4. Which of the following scenarios is a risk factor for burnout among pharmacy professionals?

A. During the COVID-19 pandemic, some pharmacies hired additional staff to help administer covid shots
B. During the COVID-19 pandemic, some pharmacy staff worked overtime, while administering COVID-tests, and consulting face-to-face with patients
C. An extremely busy pharmacy has qualified staffing and flexible scheduling for their employees

5. XY has been a pharmacy technician for 5 years and works at a busy community pharmacy. XY often feels overwhelmed, stressed, and burdened by keeping up with prescription numbers, prior authorizations and patients’ health needs and challenges. What is XY experiencing?

A. Depersonalization
B. Emotional exhaustion
C. A decreased sense of personal accomplishment

6. XY usually lies awake at night dreading the next shift. Pharmacy practice now feels like a chore and XY finds patients at drop-off and pick-up very irritating. What is XY experiencing?

A. Depersonalization
B. Emotional exhaustion
C. A decreased sense of personal accomplishment
7. XY now finds pharmacy practice unmotivating and often questions having accomplished anything worthwhile, or having had a positive impact on patients. What is XY experiencing?

A. Depersonalization
B. Emotional exhaustion
C. A decreased sense of personal accomplishment

8. Which of the following would be considered a good strategy to combat burnout among the pharmacy team?

A. States must mandate more continuing education requirements for pharmacy technicians
B. Employees must seek medications from their healthcare providers

C. States should pass laws that place caps on pharmacy shift lengths and reduce excessive performance metrics

9. Which of the following is best practice for the employee to prevent full blown burnout?

A. Limit hobbies outside of work as they are distracting and hinders job focus
B. Limit communication and collaboration with team mates to help avoid dispensing errors
C. Use vacation times or restful periods to recharge and avoid fatigue

10. Coworker relationships at XY’s workplace are somewhat cordial. XY however feels blind-sided by recent company decisions about technician break times. What is the BEST way for XY’s employer to ensure that XY avoids burnout?

A. Pharmacy technicians understand that management usually makes workplace decisions without employee input.
B. Pharmacy technicians have more continuing education hour requirements within the organization
C. Pharmacy technicians must be actively involved in making certain workplace decisions

References

Maslach C, Jackson S, Leiter M. Maslach burnout inventory manual. 3^rd Consulting Psychologists Press; 1996.
Maslach C, Leiter MP. Early predictors of job burnout and engagement. J Appl Psychol. 2008;93:498-512.
Berkeley University of California. Psychology. Christina Maslach. Accessed January 3, 2022. https://psychology.berkeley.edu/people/christina-maslach
Bridgeman PJ, Bridgeman MB, Barone, J. Burnout syndrome among healthcare professionals. Am J Health-Syst Pharm. 2018;75:147-152.
Fontes, F. Herbert J. Freudenberger and the making of burnout as a psychopathological syndrome. Accessed January 3, 2022. https://www.researchgate.net/publication/346586006_
World Health Organization. Burn-out an “occupational phenomenon”: International classification of diseases. May 28, 2019. Accessed January 3, 2022.

https://www.who.int/news/item/28-05-2019-burn-out-an-occupational-phenomenon-international-classification-of-diseases

Shrijver I. Pathology in the medical profession? Taking the pulse of physician wellness and burnout. Arch Pathol Lab Med. 2016;140:976-982.
Durham ME, Bush PW, Ball AM. Evidence of burnout in health-system pharmacists. Am J Health-Syst Pharm. 2018;75:S93-S100.
Patel SK, Kelm MJ, Lee HJ, et al. Prevalence and risk factors of burnout in community pharmacists. J Am Pharm Assoc. 2021;61:145-150.
Jones GM, Roe NA, Louden L, Tubbs C. Factors associated with burnout among US hospital clinical practitioners: Results of a nationwide pilot study. Hosp Pharm. 2017;52:742-751.
Kang K, Absher R, Granko RP. Evaluation of burnout among hospital and health-system pharmacy technicians in North Carolina. Am J Health Syst Pharm. 2020;77(24):2041-2042.
Gonzalez J, Brunetti L. Assessment of burnout among postgraduate pharmacy residents: A pilot study. Curr Pharm Teach Learn. 2021;13(1):42-48.
Gaither CA, Nadkarni A, Mott DA, et al. Should I stay or should I go? The influence of individual and organizational factors on pharmacists’ future work plans. J Am Pharm Assoc. 2007;47:165-173.
Kaplan A, Nguyen V, Godie M. Overworked, understaffed: Pharmacists say industry in crisis puts patient safety at risk. NBC News. March 16, 2021. Accessed January 3, 2022.

https://www.nbcnews.com/health/health-care/overworked-understaffed-pharmacists-say-industry-crisis-puts-patient-safety-risk-n1261151

American Association of Colleges of Pharmacy. National pharmacist workforce studies. Accessed January 3, 2022. https://www.aacp.org/article/national-pharmacist-workforce-studies

Mind Garden. MBI: Human Services Survey. Accessed January 3, 2022.

https://www.mindgarden.com/314-mbi-human-services-survey

World Health Organization. International Statistical Classification of Diseases and Related Health Problems (ICD). Accessed at https://www.who.int/standards/classifications/classification-of-diseases, January 3, 2022.
National Academy of Medicine. Valid and reliable survey instruments to measure burnout, well-being, and other work-related dimensions. Accessed January 3, 2022. https://nam.edu/valid-reliable-survey-instruments-measure-burnout-well-work-related-dimensions/
Gabler E. How chaos at chain pharmacies is putting patients at risk. New York Times. January 31, 2020. Accessed January 3, 2022.

https://www.nytimes.com/2020/01/31/health/pharmacists-medication-errors.html

Eastman, P. IOM Report. Medication errors injure millions. Emergency Medicine News. 2006;28(9):44-46.
Dik, B. Staff attrition vs staff turnover: What’s the difference? March 28, 2018. Accessed at https://jobzology.com/staff-attrition-vs-staff-turnover-whats-the-difference/, June 22, 2021.
Centers for Disease Control and Prevention. Covid data tracker. Accessed January 3, 2022. https:// COVID.cdc.gov/ COVID-data-tracker/#datatracker-home
Bakken BK, Winn AN. Clinician burnout during the COVID-19 pandemic before vaccine administration. J Am Pharm Assoc. 2021;S1544-3191(21)00164-3. doi:10.1016/j.japh.2021.04.009
Johnston K, O'Reilly CL, Scholz B, et al. Burnout and the challenges facing pharmacists during COVID-19: results of a national survey. Int J Clin Pharm. 2021;1-10.
S. Department of Health and Human Services. Trump administration takes action to expand access to COVID-19 vaccines. Accessed June 20,2021. https://www.hhs.gov/about/news/2020/09/09trump-administration-takes-action-to-expand-access-to- COVID-19-vaccines.html
S. Department of Health and Human Services. Guidance for licensed pharmacists, COVID-19 testing, and immunity under the PREP Act. April 8, 2020. Accessed January 3, 2022. https://www.hhs.gov/guidance/sites/default/files/hhs-guidance-documents/authorizing-licensed-pharmacists-to-order-and-administer-covid-19-tests.pdf
Spencer J. KHN. Lost on the frontline. 12 months of trauma: More than 3600 US health workers died in Covid’s first year. April 8, 2021. Accessed January 3, 2022. https://khn.org/news/article/us-health-workers-deaths- COVID-lost-on-the-frontline/
Press Release. Pharmacy associations applaud introduction of bill expanding Medicare patients’ access to pharmacist services. April 21, 2021. Accessed at Accessed January 3, 2022. https://www.ashp.org/News/2021/04/22/ASHP-APHA-Applaud-Introduction-of-Bill-Expanding-Medicare-Patients-Access-to-Pharmacist-Services
APhA Action Center. Provider status for pharmacists. Accessed January 3, 2022. ttps://actioncenter.pharmacist.com/campaign/provider-status-for-pharmacists/, September 10, 2021.
News. 2021 State provider status mid-year legislative update. June 7, 2021. Accessed January 3, 2022. https://naspa.us/2021/06/2021-state-provider-status-mid-year-legislative-update/
Chinthamalla K. APhA: NBC news story illustrates the need for fundamental pharmacy payment reform. APhA Press Releases. March 17, 2021. Accessed at Accessed January 3, 2022. https://www.pharmacist.com/About/Newsroom/apha-nbc-news-story-illustrates-the-need-for-fundamental-pharmacy-payment-reform
Mills, RJ. AMA launches Steps Forward to address physician burnout. AMA Press Releases. June 8, 2015. Accessed January 3, 2022. https://www.ama-assn.org/press-center/press-releases/ama-launches-steps-forward-address-physician-burnout
Well-Being Index. Pharmacist Well-Being Index. Accessed January 3, 2022. https://www.mywellbeingindex.org/versions/pharmacist-well-being-index

Are You Curious about Pharmacoeconomics?

After completing this application-based continuing education activity, pharmacists will be able to

Define common pharmacoeconomic terms used for economic evaluations.

Recall the advantages of pharmacoeconomic analysis for formulary management.

Compare and contrast different types of pharmacoeconomic analyses.

List the pharmacoeconomic tools a pharmacy benefit manager uses to lower drug costs.

After completing this application-based continuing education activity, pharmacy technicians will be able to:

Define common pharmacoeconomic terms used for economic evaluations.

Recall the advantages of pharmacoeconomic analysis for formulary management.

Compare and contrast different types of pharmacoeconomic analyses.

List the pharmacoeconomic tools a pharmacy benefit manager uses to lower drug costs.

Many pharmacy practitioners have heard of pharmacoeconomics, but don't have a clear understanding of what that term means. This field of study has a unique vocabulary associated with it and compares different aspects of drugs to determine which drug will produce the best clinical and economic outcomes. Many Pharmacy and Therapeutics Committees are now requiring pharmacoeconomic analysis when they consider formulary changes, but these analysis come in several different forms. Depending on the type and quantity of information available, people preparing reports for Pharmacy and Therapeutics Committee meetings will need to decide which model or studies to use. The foundation for several of the models is quality adjusted life years or QALYs, which have advantages and limitations. Pharmacy benefit managers use cost control tools and pharmacoeconomic analysis to control costs. Some tools that they may use are negotiated price, generic substitution, rebates, and patient copayments. Not all pharmacoeconomic studies are perfect, and this continuing education activity points out some of the ways in which they may be flawed.

INTRODUCTION

Let’s start with an old joke. An economics student once asked her professor how much his shoes cost. The professor responded with “I don’t know, I haven’t finished wearing them yet.” Drugs are just like shoes because their sticker price does not reflect their true cost or value.

PHARMACOECONOMICS BACKGROUND

The term pharmacoeconomics dates back to 1986.¹ Dr. Raymond Townsend used the term in a presentation for pharmacists in Canada.² Dr. Townsend earned his PharmD at the University of California, San Francisco and developed the pharmacoeconomic research department at the Upjohn Company.³ The Upjohn team developed pharmacoeconomics to address payment concerns as the healthcare system transitioned from a cash-based system to a third-party payer system. Its goal was to ensure drug spending was efficient and effective.⁴ Pharmacoeconomics has evolved over the ensuing 30-plus years to become a subbranch of economics.

Pharmacoeconomics compares different aspects of drugs to determine which drug will produce the best clinical and economic outcomes.¹ Pharmacists who work for pharmacy benefits managers (PBMs) or prepare for Pharmacy and Therapeutics (P&T) committee meetings are most likely to use pharmacoeconomic tools. But all healthcare personnel should understand pharmacoeconomics so they can use these tools as part of their efforts to optimize patient care or explain how health systems select medications to include on a formulary.

While these tools are useful, many pharmacists will avoid using pharmacoeconomics. In preparing to write this continuing education activity (CE), we asked faculty from two Schools of Pharmacy to identify pharmacoeconomic studies that have had significant clinical impact. One university pharmacy professor said, “Most pharmacoeconomics studies are ignored in clinical practice because practitioners don’t understand them or use other reasons to select a drug.” This CE activity should address both of those barriers—lack of understanding and the other considerations when selecting drugs.

MEET GEORGE

In this CE, George will join you. George just graduated from pharmacy school. He was hired at Man with the Yellow Hat Hospital and was put in charge of a presentation for the P&T Committee meeting. George is tasked with presenting a proposal to add a new drug, Monkeydex, to the formulary. If the Committee adds Monkeydex, he also needs to make a recommendation about the similar drug that is already on the formulary, Curiosan: should it remain on the formulary or be removed? The U.S. Food and Drug Administration (FDA) has approved both drugs for adventure-induced curiosity overload (AICO). Ted, another pharmacist, suggested George use pharmacoeconomic tools to analyze each drug’s effectiveness and cost.

PAUSE AND PONDER: Before reading further, write down as many pharmacoeconomic terms as you can!

Common Pharmacoeconomic Terms

George figured that common pharmacoeconomic terms are the best spot to begin his learning. George found these terms most helpful^5,6:

Comparators: the interventions being compared (and it’s possible to have two or more comparators)
Costs
- Direct costs: paid by the health system (salary costs, drug acquisition costs)
- Indirect costs: experienced by the patient (including decreased productivity, loss of earnings, hospital travel costs)
- Intangible costs: costs of patient/family’s feelings (worry, distress)
Economic evaluation: comparing two different interventions and assessing their costs and outcomes
Opportunity cost: the loss of benefit from the option not chosen; for example, if you decide to spend two hours on a Friday night paying bills, the opportunity cost is that you cannot spend two hours pursuing leisure activities
Outcomes: the expected results from an intervention
Perspective: the different viewpoint from which an intervention can be assessed (patient, provider, payor, or just a population in general)
Target population: the group of patients who will benefit from the intervention
Willingness to pay: the maximum amount an individual, a system, an organization, or a payor will pay for an intervention

George compared the two interventions (Curiosan vs. Monkeydex) in Table 1. George used the new terms he learned.

PAUSE AND PONDER: Why is it necessary for a health system to consider indirect and intangible costs when entertaining the possibility of adding a medication to the formulary?

Table 1. George’s Use of Pharmacoeconomic Terms to Compare Two Interventions

Term	Intervention Comparison
Economic Evaluation	George will compare Curiosan vs. Monkeydex with the terms provided below
Target Population	Curiosan: Treatment of AICO Monkeydex: Treatment of AICO
Comparators	Curiosan and Monkeydex
Opportunity Cost	The hospital won’t be able to benefit from the drug not chosen
Outcomes	Curiosan Pivotal Trial - Participants: 400 Patients aged 18-40 with AICO - Endpoints: reduction of AICO events per year - Results: patients experienced a 55% reduction in AICO events over a year - Adverse Effects: 15% of patients reported minor adverse effects from the drug such as nausea, infusion site pain, and light headedness Monkeydex Pivotal Trial - Participants: 650 Patients aged 25-45 with AICO - Endpoints: reduction of AICO events per year - Results: patients experienced a 45% reduction in AICO events over a year - Adverse Effects: 20% of patients reported minor adverse effects such as headaches, constipation, and mild weight gain
Willingness to Pay	The hospital is willing to pay up to $4500 for either medication
Perspective	Each intervention will be assessed from the hospital’s viewpoint
Direct Costs	Curiosan (TOTAL - $3900) - Administration - infusion once a month for six months ($400/month) plus each infusion costs $100 in medical service fees - Monitoring - monthly blood tests ($100) - Adverse Effect Treatment - requires OTC products ($50/month) Monkeydex (TOTAL - $4200) - Administration - oral tablet taken once daily for twelve months ($300/month) - Monitoring - monthly blood tests ($25) - Adverse Effect Treatment - requires OTC products ($25/month)
Indirect Costs	Curiosan - Patients may lose productivity time due to travel to the infusion center and medication administration times (~2-3 hour/day) - Transportation costs for gas (~$10 each visit) Monkeydex - Patients may lose productivity time due to adverse effects of drug interrupting the day (~1 hour/day) - Hospital offers free mail deliver for Monkeydex
Intangible Costs	Curiosan - Patients may feel stressed about injections and possible adverse effects - Monthly infusions can take a toll on a patient’s life and having to take off work for monthly injections can be stressful - After six months the patient will be cured Monkeydex - Patients may feel calmer when taking a tablet - Patient receives the medication monthly and does not need to make any appointments - Patient needs to be on the medication for one year and they will be cured
ABBREVIATIONS: AICO = Adventure-Induced Curiosity Overload

ADVANTAGE OF PHARMACOECONOMIC TOOLS FOR FORMULARY DECISIONS

George learned a ton of new pharmacoeconomic terms and understands how they will be useful for his presentation on Curiosan and Monkeydex. George’s curiosity about formularies and the advantages of pharmacoeconomic information prompted him to look for additional material.

What is a formulary?

A drug formulary is a continuously updated list of safe and effective medications approved by a healthcare institution or insurer. The P&T committee is responsible for adding, keeping, or removing medications from the formulary. Although the P&T committee deals heavily with issues related to medications, it has representation from many departments: administrative people, nurses, pharmacists, physicians, and others. The broad membership reflects the fact that medication use is a transdisciplinary function. The P&T committee meets regularly to discuss new FDA drug approvals, revised and updated guidelines, firsthand patient drug experiences, institution policy, and new clinical trials.⁷(See the SIDEBAR.)

SIDEBAR: P&T Committee Duties⁸

Manage the formulary including any changes and the addition of new drugs
- Evaluate any candidate for the formulary using current evidence and clinical studies to either support or refute a drug’s addition
- Conduct periodic drug use evaluation for all classes of medication
Consider patient safety in all decision processes
Ensure the electronic health record (EHR) integrates strategies to support drug selection
- Specifically, the EHR should help with dosing and monitoring of patients to prevent errors
Develop strategies during drug shortages. The P&T committee finds bioequivalent drugs and decides how to ration the available drugs
Implement medication use policies. Medication use policies guide the use of a medication through prescriber education, pharmacist communication, or team rounds/meetings
Understand the reimbursement process for health systems concerning which insurances will pay for medications

Most formularies are based on a tiered system. A medication’s tier in the formulary reflects the plan’s coverage. Generic medications usually have a preferred tier and lower out of pocket costs, while brand name medications would be placed on a higher tier unless the PBM, healthcare system, or payer has negotiated a better price for a specific product (discussed below). Two types of formularies exist⁷:

Open Formulary – the plan provides coverage for all medications, even if they are not on the formulary. Certain medication classes, such as over-the-counter medications, are not covered.
Closed Formulary – the plan covers only medications that are on the formulary. Non-formulary medications may be covered when a healthcare practitioner deems it necessary, but the prescriber may need to submit a nonformulary drug request or paperwork for prior authorization. Typically, hospitals operate with a closed formulary.

Decision Analysis in Formulary Management

Pharmacoeconomics employs decision analysis to pool data related to medication to determine if one medication is more cost effective than a comparator. It’s easy to determine if a drug costs less than another based sheerly on acquisition price. But it can be a challenge to determine if a more or less expensive drug is a better, more effective choice.⁹ It is important to note that a drug’s effectiveness refers to how it performs in the real world. A drug’s effectiveness differs from its efficacy, which reflects how well a drug performs in clinical trials. Once the trials are over, drugs rarely perform as well in the real world where people who take the drug don’t receive that same support and may have characteristics that study participants did not have.¹⁰ Pharmacoeconomic researchers take into account a multitude of factors including cost, outcomes, and adverse events when analyzing two comparators.⁹

Many people, like the professor quoted at the start of this CE, wonder if pharmacoeconomics is useful. To highlight the effectiveness of decision analysis in the pharmacy profession, the University of Cincinnati James L. Winkle School of Pharmacy added a collaborative decision analysis project to its curriculum.¹¹ Its purpose was for students to evaluate a drug based on multiple factors, not just cost. Students used a decision analysis model in Microsoft Excel to compare two antibiotics, using the model to recommend the better option. Professors released a student survey at the end of the project. The survey found that more than 90% of students felt the project was useful and said it widened their thinking skills about what a drug’s cost involves. Sticker price is not the only consideration.¹¹

While decision analysis incorporates a medication’s cost and clinical outcomes, some organizations take a different approach, eschewing pharmacoeconomics entirely. The United States Preventive Services Task Force (USPSTF) makes education-based medication recommendations.¹² It does not consider a medication’s cost at all when it makes a recommendation for its use. The USPSTF made this decision to focus solely on a medication’s clinical effectiveness because it does not want to limit a patient’s healthcare options based on cost.¹²

Overall, pharmacoeconomic analysis offers tools for formulary management including enhanced decision making, cost savings, and overcoming barriers. Using pharmacoeconomic analyses in formulary decision-making evaluates changes comprehensively and helps select the best intervention.⁹ Additionally, decision makers can select a more informed approach to keep a drug on a formulary by analyzing a drug’s effects in addition to its cost. Last, by using pharmacoeconomic tools more often, it can become more mainstream in formulary decision making.⁹

PAUSE AND PONDER: What drugs or drug classes used in your pharmacy would benefit from pharmacoeconomic analysis?

Common Types of Pharmacoeconomic Analyses

George learned a considerable amount of new information about decision analysis. He sees his error in only considering these medications’ acquisition prices in the past. George was curious about the methods pharmacoeconomic professionals use in their studies to report a medication’s overall effectiveness. He decided to look at the types of analyses.

The four types of analysis in pharmacoeconomic studies are cost benefit analysis (CBA), cost effectiveness analysis (CEA), cost minimization analysis (CMA), and cost utility analysis (CUA). Table 2 provides more information about each type of analysis.⁶

Table 2. Overview of Different Analyses⁶

	CBA	CEA	CMA	CUA
Purpose	-Calculates the cost benefit of an intervention -Both the intervention and its benefits are converted to monetary values	Measures the health benefit in natural units (ex. ulcers healed) and monetary units	-Focuses only on costs to a health service -Used when two interventions have an identical benefit	-Interventions compared based on their impact on a patient’s life -Measured in QALYs
Advantages	Helps to compare the costs of different interventions in completely different therapeutic areas	Compares two or more different drugs with similar outcomes, but different success rates	Great tool to use when comparing a generic drug with its brand name counterpart	Outcomes do not need to be measured on a monetary scale
Disadvantages	May ignore benefits that cannot be measured by money value (ex. anxiety relief)	Cannot compare drugs that treat different conditions	Both interventions need to have identical benefits, besides cost	Measurements in QALYs may differ in different disease states
ABBREVIATIONS: CBA = cost benefit analysis; CEA = cost effectiveness analysis; CMA = cost minimization analysis; CUA = cost utility analysis; QALYs = Quality Adjusted Life Years

George acquired a great basic knowledge of the analyses. He was curious to learn more about some new concepts he found in his research. Specifically, he wanted to know more about calculating outcomes costs for interventions, incremental cost-effectiveness ratio calculations, and how to determine quality-adjusted life years (QALYs). As a basis to understand the different analyses, it’s critical to look at QALY first.

Health economists calculate quantity of and quality of years, which are combined into QALYs.¹³ To calculate a QALY, begin with the utility score, which is scaled from 0 to 1. A chronic condition may have a utility score of 0.6. The Health Utilities Index Mark 3 (HUI3) is used to measure utility scores. The HUI3 asks a serious of questions about eight attributes (e.g., ambulation, cognition, dexterity, emotion, hearing, pain, speech, vision) and combines them into a score that ranges from 0 to 1. The numeral 1 means perfect health and 0 represents death.¹⁴ To calculate QALY, the utility score is multiplied by the time spent in each state, which translates into the number of years of life the typical patient gains on a treatment. For example, consider patients with a chronic condition (utility score of 0.6) receiving a treatment that will add seven years to their life. To calculate the QALY, multiply 0.6 x 7, which equals 4.2 QALYs gained.¹⁵

While QALYs can effectively determine how many life years are gained in many situations, they have some downsides.¹⁶ QALYs are blind to health conditions and personal characteristics such as age, disease severity, residence location, and sex. Additionally, the QALY does not encompass all aspects of an intervention’s benefit. For example, if a single mother takes a medication that rapidly improves her health, it can also improve the health of her kids and allow her to return to work quicker.¹⁶

Cost Benefit Analysis. The main purpose is to compare interventions with different outcomes. Typically, a CBA involves adding all the costs of an intervention and subtracting that figure from the expected benefits of the intervention. A CBA helps an organization to see an intervention’s return on investment. When doing a CBA, it’s important to identify an intervention’s direct, indirect, and intangible costs to compare against the intervention’s benefits.¹⁷ George found this explanation straightforward but had to ask Ted how he would estimate the expected benefits. To calculate the expected benefits, Ted told George to list the indirect and intangible benefits of the interventions and make educated guesses about monetary values for each, looking first to see if any studies have assigned or estimated costs. George can then subtract the intervention’s costs from these expected benefits to equal the net benefits.¹⁸

Cost Effectiveness Analysis compares the cost and outcomes for two or more interventions for the same condition. A CEA is centered around the incremental cost-effectiveness ratio (ICER). This explanation had George scratching his head, and he had to review it several times to really understand it. The ICER is the ratio of cost differences to outcomes differences between interventions.¹⁹ The ICER is useful because it shows the added cost per unit of health outcome gained from a new intervention.¹⁹The ICER is calculated using the equation ICER = costs₁ minus costs₂ divided by effect₁ minus effect₂. For example, intervention 1 costs $200 with an 8 QALY benefit and intervention 2 costs $100 with a 4 QALY benefit. Plug these numbers into the equation and the ICER = 25. This means $25 per QALY for intervention 1 over intervention 2.²⁰

Cost Minimization Analysis considers only half of an economic evaluation because it does not consider the outcomes of interventions. It simply looks at cost. For a CMA to be considered a full evaluation, health economists would need to consider the outcomes of interventions, such as how many life years are saved. If the interventions’ outcomes are equal, then the CMA can be useful.²¹

Cost utility analysis helps compare costs and benefits from different interventions. CUA takes into account benefits in terms of how many years are saved and quality of life.¹³ CUA is helpful to quantify how much an intervention can extend and improve someone’s life. QALYs are used in a CUA to display quality and quantity of years saved for a patient’s life. The best time to use a CUA is when someone wants to determine the cost-effectiveness of a product that is a high cost for the payer. A CUA study plans to show where resources should be allocated for maximum health benefit.¹³

George decided to put together his own CEA after learning more about the pharmacoeconomic analyses. He chose this approach since he was able to acquire the most information about how to properly perform a CEA. Table 3 shows George’s CEA for Curiosan compared with Monkeydex.

Table 3. CEA for Curiosan and Monkeydex

	Curiosan	Monkeydex
Total Cost (Both direct and indirect/intangible)	$3900 (direct costs) + $200 (indirect/intangible costs)	$4200 (direct costs) + $100 (indirect/intangible costs)
Effect (Reduction in Curiosity Overload Events per Year)	3 events prevented	5 events prevented
ICER	($4100 - $4300) / (3 - 5)
Outcome of ICER	$100 from each episode prevented by using Curiosan over Monkeydex
ABBREVIATIONS: ICER = Incremental Cost-Effectiveness Ratio

George analyzed both costs and outcomes from the two interventions. He concluded $100 from each adventure-induced curiosity overload episode was saved by using Curiosan over Monkeydex. The CEA shows Curiosan’s effectiveness over Monkeydex when considering costs and outcomes. Let’s re-examine the pharmacy professor’s quote in which he said, “Most pharmacoeconomic studies are ignored in clinical practice because practitioners don’t understand them or use other reasons to select a drug to use.” What factors is he referring to? One other factor might be patient volume. This hospital generally sees about five AICO patients per day and they are treated in the emergency department. The P&T Committee knows that Man with the Yellow Hat Hospital has an emergency department with 20 available beds that can usually accommodate all these patients. If the emergency room experiences overflow, hospital management has designated the adjacent hallway to hold up to five excess patients. If the hospital only had a total of five beds available, however, or it was having difficulty staffing the ED, the P&T committee’s deliberations might be different.

PHARMACOECONOMIC TOOLS IN PHARMACY BENEFIT MANAGEMENT

George checked the major dailies—the most reliable newspapers across the country that fact-check before they publish—to see if any recent articles talked about the impact of pharmacoeconomics while doing his research. George checked these publications because he wanted to identify any recent major developments in the healthcare industry. He found multiple feature articles and opinion pieces on the function of PBMs. George read that PBMs contribute to formulary decision making for payors or employers and use different pharmacoeconomic tools to support their choices. George wanted to find out more about the PBM’s role and how they contribute to the formulary, so he delved into the topic again.

PBM History

PBMs surfaced in the 1950s due to a demand for special management of drug benefits.²² Pharmacists started the first PBMs, founding Prescription Services, Inc in Canada in 1958 and PAID Prescriptions in the United States (U.S.) in 1965. Through the years, health systems and payors began to collaborate with PBMs more often and they grew in size and scope. Now, PBMs handle a wide variety of tasks including formulary maintenance, pharmacy networks, mail order pharmacy operations, and contracts with wholesalers and manufacturers. A PBM’s most important service is maintaining a drug formulary. Most PBMs will handle multiple formularies for different clients. PBMs cover certain drugs on a formulary and some drugs require patients to pay a portion of the costs.²²

George learned from his reading of current events that the Federal Trade Commission (FTC) is looking into PBMs and considering preventing them from combining.²²The FTC often refers to PBMs as the prescription drug middleman industry and has launched inquiries into their operations and practices.²³ It theorizes that if PBMs continue to combine and integrate, they could possibly have unprecedented control over drug prices, blocking competition. Their concern of market concentration is based on the oligopoly theory which states that if five firms in an industry account for more than 60% of the market, competition is stifled. The FTC alleges that the three largest PBMs processed almost 80% of prescriptions dispensed by U.S. pharmacies in 2023, and the top six processed more than 90%. Describing PBM operations as opaque, the FTC reported in July 2024 that despite their efforts to obtain records from six PBMs, several have refused to comply. A significant concern is that the current PBM structure may disadvantage small pharmacies that are not in the PBM network and the patients they serve.^23,24 The FTC’s efforts are focused on promoting fair competition and protecting consumers from high medication prices.²⁵

PAUSE AND PONDER: What are some cost control tools used lower drug costs in your pharmacy?

PBM Cost Control Tools

PBMs use an assortment of cost control tools to control costs^26,27,28:

Negotiated prices. PBMs work on securing a specific price for drugs. PBMs that purchase drugs at a high volume can negotiate discounted prices. The price paid by the PBM is often much lower than other plans’ prices, such as Medicaid. PBMs will apply this discount to the pharmacies in its network, guaranteeing access for pharmacies that contract exclusively with the PBM.
Generic substitution. Here, the goal is to increase the use of generic medication whenever possible. Generally, generic drugs cost 80% to 85% less than their brand name equivalents. Pharmacists may receive an incentive for dispensing a higher number of generics.
Rebates. A rebate is money returned by the seller to the drug purchaser under certain conditions. The seller gives rebates to incentivize higher volume purchases and to stay competitive without directly lowering costs. The PBM often negotiates a rebate and reaches an agreement with the drug manufacturers. A rebate program may stimulate the PBM to increase its use of rebated drugs; on the flip side, rebates may cause the PBM to place high-priced drugs in better tiers than drugs that are more cost-effective, which creates higher out-of-pocket costs for some patients.
Copayments. A copayment is a fixed amount that patients, insureds, or beneficiaries pay for their prescriptions. PBMs use copayments as a cost-sharing mechanism to reduce the insurer’s or employer’s overall medication costs. PBMs adjust copayments depending on the plan they are managing. Generic medications generally have lower copayments, but brand and some generic medications may require a higher copayment.

Do PBMs Create Value in Healthcare?

PBMs have had many significant impacts on the drug distribution system. At their inception, they created systems to replace the manual claims filing process that was dependent on paper with electronic systems that communicated among stakeholders quickly. Today’s systems operate in real-time, which is advantageous to all stakeholders.²⁹

Controversy surrounds PBMs (See the SIDEBAR). PBMs add value to their stakeholders (e.g., insurers, health systems, payors), but it is uncertain whether PBMs contribute significant value to the U.S. healthcare system. PBMs have proprietary contracts that prevent open discussion of the terms they negotiate and tools they use. Some experts allege that PBMs engage in “spread pricing,” meaning they charge health plans and employers more for generic drugs than what they reimburse pharmacies for these drugs, keeping the difference. Again, a lack of transparency allows this to happen: PBMs’ operations are proprietary and confidential. They often lack transparency and it’s possible to conclude they may take value from healthcare. Some evidence exists indicating that agreements with manufacturers agreements require PBMs to exclude generic drugs and biosimilars from their formularies in exchange for higher rebates.^24,27,30

SIDEBAR: Have PBMs Abused the Drug Rebate System?

The 3 major PBMs—Caremark Rx, Express Scripts (ESI), and OptumRX—are currently in the FTC’s crosshairs for allegedly artificially inflating insulin drug prices. The FTC has filed an administrative complaint citing that 3 PBMs have developed and abused a drug rebate system that prioritizes high rebates from drug manufacturers, forcing consumers to spend more on life-saving medication.²⁵

The crux of the issue centers on PBMs ability to establish discounts on the manufacturer’s initial sticker price of brand name drugs. Drug companies will agree to these discounts in exchange for preference and availability on the PBM’s formularies. As the discounts grew larger over time, pharmaceutical companies were forced to raise their initial sticker prices to maintain profits. Therefore, while PBMs have cut prices in half for their clients, patients have suffered because the price at point of service often reflects the initial sticker price.³¹Even if less expensive insulins become available, PBMs are able to design their formularies strategically to exclude those options in favor of equivalent high list price, highly rebated products.³²

The PBMs’ “chase-the-rebate” strategy has shifted the burden of high insulin prices directly to patients.²⁵Take, for example, one insulin product that was listed at $122.59 in 2012. Also in 2012, PBMs introduced exclusionary drug formularies, a tactic weaponized to demand higher rebates in exchange for a desirable spot on the formulary. By 2018, the list price of that specific insulin more than doubled to $289.36. Patients with deductibles or coinsurance do not benefit from rebates at the pharmacy counter. These out-of-pocket expenses for insulin drugs are sometimes even higher than total cost of the drug to the commercial payor.²⁵

All three PBMs have pushed back on the allegations from the FTC, claiming the lawsuit “demonstrates a profound misunderstanding of how drug pricing works.”³² The FTC has also acknowledged that PBMs likely did not act alone, and actions against drug manufacturers may be on the horizon.Over the last year, Eli Lily, Novo Nordisk, and Sanofi all promised significant cuts to the list price of their insulins due to public and political pressure. The recently passed Inflation Reduction Act also has chipped away at insulin prices by establishing a $35 per month cap for Medicare Part D patients.³²

Implications for Pharmacy Teams

Pharmacoeconomics is helpful for pharmacy teams because in a healthcare setting pharmacists need to be able to determine if a drug’s value can be justified by its cost. George learned that a good way to think about cost and value is this: “Value is the results you get divided by the cost. Value is what works, not how cheap it is.”³³ Pharmacy employees, especially those who work in procurement or with the P&T Committee, should understand how to differentiate between the four types of pharmacoeconomic analyses. The different analyses help engage in informed decision making between two or more interventions. Pharmacoeconomics can guide clinical and policy decision making. Today, pharmacists in community and hospital settings provide a wide variety of services including vaccinations and medication use counseling. A health economist might perform a pharmacoeconomic analysis to determine if a pharmacist’s services are adding value to the healthcare system. Additionally, a payment model needs to be established to ensure pharmacists are compensated for their non-dispensing work.³⁴

Red Flags in Pharmacoeconomic Studies

Pharmacy staff must recognize that pharmacoeconomic studies, like all studies, can be flawed. Certain red flags decrease a study’s validity. Below are some common questions to ask after reading a pharmacoeconomic study. These questions help identify the study’s limitations³⁵:

Does the title accurately represent the study’s goals?
Did the researchers clearly state the study’s objective?
Did the researchers use a large enough data sample? Remember that larger sample sizes lead to more reliable results.
If the researchers compared interventions, did they use appropriate comparators?
- If the researchers were reporting on a new treatment, did they compare it to the current standard of care or the most popular marketed options? Or did the authors compare the treatment to a less popular, less effective, or older (and retired) alternative?
Did the researchers provide a description of the competing alternatives’ use in clinical practice?
Did the researchers identify which perspective they employed to measure the costs?
Did the researchers indicate the study structure (retrospective, prospective, etc.)?
Were all the costs of the interventions included?
Did the researchers include all important clinical outcomes from various studies?
Were the study’s conclusions appropriate for the study? Or did the conclusions go beyond the scope of the target population?
Is it possible to extrapolate the findings to your population, or are the populations too different?
Did the researchers present the conclusions in an unbiased manner?

CONCLUSION

George was able to learn so much about pharmacoeconomics. He feels confident about the different pharmacoeconomics terms used for economic evaluations. George also recalls the advantages of pharmacoeconomic analysis and can compare the different types of analyses. Last, he better understands the PBM’s role and the tools a PBM uses to lower drug costs.

Are You Curious about Pharmacoeconomics?

Pharmacist Post-test

After completing this continuing education activity, pharmacists and pharmacy technicians will be able to
• Define common pharmacoeconomic terms used for economic evaluations.
• Recall the advantages of pharmacoeconomic analysis for formulary management.
• Compare and contrast different types of pharmacoeconomic analyses.
• List the pharmacoeconomic tools a pharmacy benefit manager uses to lower drug costs.

1. The P&T Committee at Queens Hospital is considering the addition of Fixitall, a new bi-weekly intravenous infusion drug for the treatment of rheumatoid arthritis, to the hospital formulary. Which of the following describe the direct costs of the proposed intervention?

A. Monthly administration, monitoring, and adverse effect OTC treatment costs.
B. Transportation costs to and from the hospital for each treatment.
C. Loss of wages from missing work during bi-weekly infusion center visits.

2. Which of the following best describes an opportunity cost?
A. The amount of money saved by acquiring drug A instead of drug B.
B. The loss of benefit of drug A if drug B is the preferred choice.
C. The negotiation of a rebate for either drug A or drug B.

3. Which of the following defines the pharmacoeconomic term “willingness to pay”?

A. The amount a drug manufacturer will rebate a PBM to indirectly lower drug costs.
B. The calculated ratio of cost differences to outcomes differences between interventions.
C. The maximum amount an individual, system, organization, or payer will pay for an intervention.

4. Which of the following is an advantage of using pharmacoeconomic analysis to inform formulary decisions?

A. Pharmacoeconomic analysis focuses solely on the medication’s cost in an effort to save payers the most money.
B. Pharmacoeconomic analysis considers drug efficacy rather than drug effectiveness to accurately predict real world implications.
C. Pharmacoeconomic analysis considers cost, outcomes, and adverse events when analyzing two or more comparators.

5. Which of the following describes an advantage associated with a cost benefit analysis?

A. Does not require the intervention and its benefits to be converted to monetary values.
B. Compares the cost of different interventions in completely different therapeutic areas.
C. Analyzes the difference in cost of a generic drug compared to its brand name equivalent.

6. Which of the following pharmacoeconomic analyses is measured in QALYs?

A. Cost benefit analysis
B. Cost minimization analysis
C. Cost utility analysis

7. Which of the following strategies do pharmacy benefit managers implement to lower drug costs?

A. Negotiating rebates with drug manufacturers that incentivize higher volume purchases.
B. Limiting the substitution of generic medications due to the lack of incentive provided.
C. Discouraging the use of copayments due to their tendency to increase overall medication costs.

8. Which of the following is an example of an intangible cost?

A. Transportation costs for gas to and from the infusion center.
B. Copayment costs that occur with every infusion treatment.
C. Cost of patient/family’s anxiety over recurrent injections and adverse effects.

9. You are conducting a cost effectiveness analysis of two new ulcerative colitis drugs. Drug A costs $400 with a 6 QALY benefit and Drug B costs $200 with a 4 QALY benefit. Which of the following is the correctly calculated incremental cost-effectiveness ratio (ICER)?

A. $20 per QALY for Drug A over Drug B.
B. $100 per QALY for Drug A over Drug B.
C. $60 per QALY for Drug A over Drug B.

10. Which of the following describes a disadvantage of a cost minimization analysis?

A. Compared interventions must have identical benefits other than cost.
B. Calculated measurements in QALYs may differ in different disease states.
C. Cannot compare a generic drug with its brand name counterpart.

Are You Curious about Pharmacoeconomics?

Pharmacy Technician Post-test