A Practical Approach to Perioperative Oral Anticoagulation Management 2025 Revision

UConn has developed web-based continuing pharmacy education activities to enhance the practice of pharmacists and assist pharmacists in making sound clinical decisions to affect the outcome of anticoagulation therapy for the patients they serve. There are a total of 17.25 hours of CPE credit available. Successful completion of these 17.25 hours (13 activities) or equivalent training will prepare the pharmacist for the Anticoagulation Traineeship, which described below in the Additional Information Box.

The activities below are available separately for $17/hr or as a bundle price of $199 for all 13 activities (17.25 hours). These are the pre-requisites for the anticoagulation traineeship. Any pharmacist who wishes to increase their knowledge of anticoagulation may take any of the programs below.

When you are ready to submit quiz answers, go to the Blue "Take Test/Evaluation" Button.

If desired, “bundle” pricing can be obtained by registering for the activities in groups. It consists of thirteen anticoagulation activities in our online selection.

You may register for individual topics at $17/CE Credit Hour, or for the Entire Anticoagulation Pre-requisite Series.

Pharmacist General Registration for 13 Anticoagulation Pre-requisite activities-(17.25 hours of CE) $199.00

In order to attend the 2-day Anticoagulation Traineeship, you must complete all of the Pre-requisite Series or the equivalent.

Anticoagulation Traineeship at the University of Connecticut Health Center, Farmington, CT

The University of Connecticut School of Pharmacy and The UConn Health Center Outpatient Anticoagulation Clinic have developed 2-day practice-based ACPE certificate continuing education activity for registered pharmacists and nurses who are interested in the clinical management of patients on anticoagulant therapy and/or who are looking to expand their practice to involve patient management of outpatient anticoagulation therapy. This traineeship will provide you with both the clinical and administrative aspects of a pharmacist-managed outpatient anticoagulation clinic. The activity features ample time to individualize your learning experience. A “Certificate of Completion” will be awarded upon successful completion of the traineeship.

More Information About Traineeship

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.

ABSTRACT

Many different guidelines and clinical studies address how to manage anticoagulation around the time of surgeries or procedures. This module’s goal is to help learners pull dry information together and apply it to real-world anticoagulation situations. It discusses terminology, renal function assessment, recent guideline changes, and how to stratify a patient’s periprocedural risk of thrombosis and bleeding. In addition, the module covers anticoagulation during the periprocedural period, potential interactions with over-the-counter products, and how to communicate the plan with patients and caregivers. It includes practice pearls from an experienced certified anticoagulation provider. Finally, it concludes with a sample case to show learners how to use this information in typical situations in direct patient care.

INTRODUCTION

Appropriate perioperative anticoagulation management is essential for patient safety. Guidelines can be valuable tools for identifying a potential course of action when tailoring perioperative plans for individual patients who take anticoagulants. However, significant gray areas remain. Clinicians must consider individual patient characteristics before finalizing any plan. This module familiarizes learners with the most recent guidelines and demonstrates how to optimize perioperative anticoagulation care for patients.

Many guidelines about anticoagulation are available. Good clinical practice requires occasional surveillance for changes in the current landscape. Select organizations that periodically release guidelines include the American Society of Hematology (ASH), the American College of Cardiology/American Heart Association (ACC/AHA), and the American College of Chest Physicians (CHEST). This module primarily uses the 2022 Perioperative CHEST Guideline. Please note, guidelines sometimes refer to medications that are used internationally, but this module only discusses medications available in the United States. Additionally, each institution’s protocol or clinician’s opinion may vary from the views presented here.

TERMINOLOGY

"Bridging" refers to using a shorter half-life anticoagulant to act as a "bridge" between pre-procedure and post-procedure maintenance anticoagulation. This action minimizes patients' exposure to subtherapeutic anticoagulation while their maintenance anticoagulation is held for a procedure. Most commonly, this refers to using low molecular weight heparin (LMWH) while warfarin is held.
- Practice Pearl: Patients or providers sometimes incorrectly refer to simply holding an anticoagulant as "bridging."
“DOAC” refers to the direct oral anticoagulants (the Factor Xa inhibitors rivaroxaban [Xarelto], apixaban [Eliquis], edoxaban [Savaysa], and the Factor IIa inhibitor dabigatran [Pradaxa]). The old term "NOAC" has fallen out of favor as it implies a negative connotation.
“Glycoprotein IIb-IIIa inhibitor” refers to the antiplatelet agents eptifibatide (Integrilin) and tirofiban (Aggrastat).
“Low-molecular weight heparin” refers to enoxaparin (Lovenox) and dalteparin (Fragmin).
“P2Y₁₂ inhibitor” refers to the antiplatelet drugs clopidogrel (Plavix), prasugrel (Effient), ticagrelor (Brilinta), and cangrelor (Kengreal).
The terms “surgery” and “procedure” are sometimes used interchangeably.

ESTIMATING RENAL FUNCTION

Some anticoagulants are renally cleared, so clinicians must be prepared to make dose adjustments for renal impairment. Directly measuring glomerular filtration rate (GFR) is not practical, so formulas that estimate renal function guide treatment decisions. Commonly used formulas use serum creatinine (SCr), height, age, and some form of body weight (in kg) to estimate renal function (discussed in more detail later). Calculators for these equations are available online.

Renal function formulas assume stable renal function and the results are just estimates, so the anticoagulation team must consider the whole patient when making dosing adjustments. Note that neither the CKD-EPI Creatinine Equation (2021) nor the Cockcroft-Gault formula have been validated for use in children, pregnancy, or patients with low creatinine values.

The most recent Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines recommend using the CKD-EPI Creatinine Equation (2021) to estimate renal function. This formula takes body habitus (common variations in the shape of the human body, which in turn determines the position of internal viscera) and gender into account and is now widely used.¹

CKD-EPI Creatinine Equation (2021)

eGFR_Cr= 142 x min (S_Cr/k,1)^α x max (S_Cr/k,1)^-1.200 x 0.9938^Age x 1.012 [if female]

Female: k = 0.7, α = -0.241; Male: k=0.9, α= -0.302

“min” =minimum of SCr/k or 1; “max” = the maximum of SCr/k or 1

Then convert the result to a non-indexed eGFR using BSA as follows:

BSA (m²) = 0.007184 x (weight in kg) ^0.425 x (height in cm) ^0.725

Non-indexed eGFR = indexed eGFR x BSA /1.73 (result expressed as mL/min/1.73 m²)

This formula estimates kidney function more accurately than others, is widely regarded as the current standard of care, and reference laboratories use it. However, the pharmacokinetic studies that lead to United States (U.S.) Food and Drug Administration (FDA) approval often use the historical Cockcroft-Gault (CG) formula instead. Therefore, FDA-approved prescribing information often bases renal dosing adjustments on CG creatinine clearance (CrCl).²

Cockcroft-Gault Formula (1976)

CrCl = [((140–age) x (weight in kg))/ (72 x SCr)] x 0.85 (for females)

The Cockcroft-Gault formula was developed from data collected from white adult males and often yields inaccurate results when applied to the general population. The formula’s developers suggestion for an 85% correction for female gender was not derived from clinical data. They acknowledged its limitations. Its flaws have been extensively discussed.^1,3,4 Common patient characteristics that may yield inaccurate results include:

Actual body weight (ABW) either below or more than 30% above, ideal body weight (IBW)
Edema
Frailty
Height under 60"
Hydration status
Low muscle mass

Special Populations

Unfortunately, choosing an appropriate measure of body weight to use in CG is not always as simple as having the patient step on the scale. Table 1 describes how clinicians use different representations of body weights in different circumstances.

Table 1. Choosing a Measure of Body Weight for Use in Cockcroft-Gault
Representation of Body Weight	Patient Population
Actual body weight (ABW)	Underweight, and all patients using rivaroxaban
Ideal body weight (IBW)	Between IBW and 30% overweight
Adjusted body weight (AdjBW0.4)	More than 30% overweight

Adjusting Weight for Obesity

The literature suggests adjusting body weight for obesity (body weight greater than 30% over IBW). The adjusted body weight (AdjBW) is calculated using the following formula, and the result is used in the CG formula.⁵

IBW (male) = 50 + (2.3 x (height minus 60 inches))

IBW (female) = 45.5 + (2.3 x (height minus 60 inches))

AdjBW0.4 = IBW + 0.4 (ABW - IBW)

Practice Pearl: Note that the rivaroxaban prescribing information specifically calls for using Actual Body Weight when calculating CrCl.⁶

Adjusting Weight for Amputations

Currently, no validated method is available to estimate renal function in patients who are amputees. One possible method is to estimate the IBW before the amputation, subtracting an approximation of what that limb might have weighed (see Table 2), then using the AdjBW in the formula. Alternatively, clinicians can use an online calculator such as https://clincalc.com/kinetics/ebwl.aspx.⁷

Table 2. Estimating Body Weight Lost from Amputations⁸
Body Section	Specific Location	Percent of Total Weight
Lower body	Foot	1.5%
	Calf and foot	5.9%
	Entire lower extremity	16%
Upper body	Hand	0.7%
	Forearm and hand	2.3%
	Entire upper extremity	5%

Transgender Patients

Hormonal therapy influences lean body mass and should be considered when estimating renal function in transgender patients. For transgender patients who have completed at least six months of hormone therapy, the team should calculate CrCl using their gender identity, not their sex assigned at birth.⁹

PAUSE AND PONDER: In what situations should heparin be used to protect the patient from thrombosis while oral anticoagulants are held for surgery?

CHEST GUIDELINE

CHEST released an updated Clinical Practice Guideline for the Perioperative Management of Antithrombotic Therapy in 2022.¹⁰ The new more user-friendly guideline replaces the 2012 version.¹¹ It only provides guidance for elective procedures that are not urgent. The 2022 version provides more comprehensive and detailed guidance on the perioperative use of DOACs, antiplatelet medications, and heparin bridging. It also includes more specific guidance on perioperative risk of thrombosis and bleeding.

Many CHEST Guideline recommendations are presented as being supported by either "Low" or "Very Low" Certainty of Evidence. For these, individual patient characteristics and clinical judgment become more important when determining a plan of action. The main body of the text sometimes describes specific considerations for different patient populations.

The CHEST Guideline only makes two strong recommendations, both regarding warfarin¹⁰:

Prescribers should not bridge patients using warfarin with LMWH when atrial fibrillation (AF) is the sole indication.
Warfarin should be continued, not held, for ICD or pacemaker placement if the international normalized ratio (INR) is less than 3.0.

It makes several other important recommendations¹⁰:

Warfarin patients at high risk of venous thromboembolism (VTE) should be bridged with heparin.
Avoid heparin bridging for patients who take DOACs.
Avoid heparin bridging for warfarin patients with minimal to moderate risk of VTE with the following:
1. Mechanical heart valves
2. VTE as the only risk factor (post-procedure low-dose heparin may be used)
3. A colonoscopy with polypectomy
Avoid adjusting
1. LMWH or DOAC dosing to anti-Xa levels
2. Antiplatelet medications based on antiplatelet testing
Discontinue apixaban, dabigatran, edoxaban, and rivaroxaban before procedures.
Continue aspirin (ASA) for patients having non-cardiac surgery.
Patients who take ASA and have coronary artery bypass graft (CABG) scheduled should continue ASA.
Patients who take dual antiplatelet therapy (DAPT) who had a coronary artery stent placed six to 12 weeks ago should either continue both antiplatelet agents or should hold one of them seven to 10 days pre-procedure.
DAPT patients who had a coronary artery stent placed three to 12 months ago, and patients who are having CABG surgery, should hold their P2Y₁₂ inhibitor (clopidogrel, prasugrel, ticagrelor, or cangrelor).
Do not use glycoprotein IIb-IIIa inhibitors (eptifibatide, tirofiban) or cangrelor to bridge antiplatelet patients.
When holding a DOAC, continue holding until at least 24 hours post-procedure, as restarting sooner can increase bleeding risk.
Patients with an INR above 1.5 up to two days before the procedure should not receive vitamin K as this can delay return to full therapeutic INR post-procedure.
Continue warfarin for dental procedures.
1. Exceptions: Hold warfarin if the patient has poor gingival condition or is expected to bleed profusely. Consider patient history.
2. Tranexamic acid and additional sutures can be used to limit bleeding.
Continue warfarin for minor dermatologic procedures.
1. Exceptions: Hold warfarin if the patient is having a skin graft or expected to bleed profusely.
Continue warfarin for minor ophthalmologic procedures.
1. Exceptions: Retinal surgery or any time retrobulbar anesthesia is used

Practice Pearl: It can be challenging to find information that applies to a highly specific patient population in a dry document like a CHEST Guideline. This is an optional exercise: under what heading in the CHEST Guideline does it describe specific patient characteristics that may make you inclined to hold an anticoagulant or antiplatelet drug for a dental extraction?

Assessing Perioperative Risk for Surgery/Procedure Related Bleeding
Summary of Key Recommendations
Patients Having a Minor Dental, Dermatologic, or Ophthalmologic Procedure

Table 3 summarizes CHEST Guideline recommendations for how long to hold an anticoagulant before a procedure and when to resume it after a procedure.¹⁰

Table 3. Recommended Perioperative Anticoagulant Holding Times¹⁰
Anticoagulant	Procedure Bleed Risk	How Long to Hold Before Procedure	When to Resume Post-Procedure	Post-Procedure Notes
Warfarin	-	5-6 days	Within 24 hours	-
IV UFH (therapeutic dose)	-	At least 4 hours	At least 24 hours	No bolus. Target a lower aPTT.
LMWH	Low-moderate	Half the total daily dose in AM, 24 hours prior	At least 24 hours	-
LMWH	High	24 hours	At least 48-72 hours	If needed, low-dose LMWH may be used for the first 2-3 days.
Apixaban	Low-moderate	1 day	All DOACs: At least 24 hours post procedure after low-moderate risk At least 48-72 hours after high risk
Apixaban	High	2 days
Dabigatran	Low-moderate, CrCl at least 50 mL/min	1 day
	Low-moderate, CrCl less than 50 mL/min	2 days
	High risk, CrCl at least 50 mL/min	2 days
	High risk, CrCl less than 50 mL/min	4 days
Edoxaban	Low-moderate	1 day
Edoxaban	High risk	2 days
Rivaroxaban	Low-moderate	1 day
Rivaroxaban	High risk	2 days
ASA	-	At least 7 days*	*Evaluate whether antiplatelet agents need to be held at all on a case-by-case basis.
Clopidogrel	-	At least 5 days*
Ticagrelor	-	3-5 days*
Prasugrel	-	7 days*

PAUSE AND PONDER; How do clinicians decide who is at high enough risk of thromboembolism to interrupt anticoagulation for a surgery or procedure or to warrant the additional bleeding risk of LMWH during a warfarin bridge?

PATIENT-SPECIFIC PERIOPERATIVE ANTICOAGULATION PLAN

Overview

Step 1: Begin by collecting basic information:

What procedure or surgery is happening, and when?
Which anticoagulant is the patient using?
What herbal and vitamin supplements are the patient currently taking?
What is the patient's medical history and allergies? Are there any recent updates from either inside or outside your healthcare system?
Does the patient have a history of heparin-induced thrombocytopenia (HIT), severe bleeding such as SDH, thrombosis, or other complications during a historical perioperative period?
Do you need to update the patient's weight or lab work?

Step 2: Communicate with other healthcare team members involved in this patient's care.

Step 3: Assess risks and prepare the perioperative plan.

Assess the risk of thrombosis. Is holding the anticoagulant really necessary? How long? Is bridging required?
Assess the risk of procedure-related bleeding.
Calculate renal function and Child-Pugh score if applicable.
Obtain or place orders as necessary following the institution's protocol.
Review plan for feasibility and accuracy. Examples of potential errors include
1. Bridging warfarin patients in end stage renal disease (ESRD) with therapeutic-dose LMWH
2. Bridging DOAC patients with LMWH
3. Holding warfarin for 5 days without LMWH bridging in mechanical mitral valve replacement (MVR) patient with antiphospholipid syndrome (APS), a history of VTE, with low bleeding risk
4. Holding warfarin 7 days before a single dental extraction in patients with paroxysmal AF
5. Holding warfarin 1 day before spinal surgery

Step 4: Educate the patient and/or caregiver.

A written plan can facilitate adherence and communication between team members and the patient, especially if the plan is complicated. Clinicians who review the plan verbally with patients can evaluate feedback and clarify questions instantly. If applicable, patient education should cover subcutaneous injection technique and sharps disposal. Confirm that patients and caregivers understand the plan using the teach-back technique and spot-checks. A critical element is how to recognize the signs of bleeding or thrombosis with patients, so the patient knows when to call 911.

Practice Pearl: The electronic health record (EHR) often contains errors or omissions. Reviewing medication and problem lists with patients may identify medication that was discontinued (sometimes years ago!). Sometimes, patients do too much yard work and injure a knee; they start ibuprofen without notifying their healthcare provider. Perhaps they visited London and didn’t tell their provider about the pulmonary embolism they developed on the flight, or the fact that they are now using rivaroxaban. They may have been hiking in the Grand Canyon when they had a myocardial infarction and didn’t think to mention they are now using clopidogrel and aspirin. Clinicians will not know unless they ask.

OVER-THE-COUNTER PRODUCTS

Many foods and over-the-counter (OTC) products can increase bleeding risk and should be held in the perioperative period. Table 4 shows a sample of interactions between foods/supplements and selected anticoagulants. For example, using cannabidiol (CBD) with apixaban can increase the patient's bleeding risk; if patients who have a high bleeding risk procedure restart apixaban and CBD after the procedure, bleeding risk will be high during that time.

Some supplements and foods have intrinsic anticoagulant or antiplatelet properties and can increase the bleeding risk even wihout a CYP450 or P-glycoprotein interaction. St. John’s Wort can increase risk of thrombosis when used with apixaban, dabigatran, rivaroxaban, and warfarin; it induces CYP3A4 and P-glycoprotein. When in doubt, it is generally best to err on the side of caution and hold all patient-initiated supplements in the perioperative period.

Practice Pearl: Surgeons often require tobacco cessation before scheduling surgery. This can increase warfarin sensitivity through a CYP1A2 interaction.

Cannabis is widely used. It is primarily metabolized by the liver, but about a fifth is renally eliminated. It inhibits CYP450 enzymes, including 3A4, 2D6, 2C9, and 2C19. In addition to its potential interactions with anticoagulants, it can also prolong sedation and increase the risk of myocardial ischemia. Patients with cannabis use disorder can experience increased perioperative morbidity and mortality.^12-14

Table 4. Interactions Between OTCs and Common Anticoagulants^15-19
OTC Product	Possible Intrinsic Antiplatelet Activity	Possible Intrinsic Anticoagulant Activity	Apixaban	ASA	Clopidogrel	Enoxaparin	Dabigatran	Rivaroxaban	Warfarin
Aspirin	x		x	x	x	x	x	x	x
Alpha-lipoic acid	x		x	x	x	x	x	x	x
Berberine	x		x	x	x	x	x	x	x
Black seed	x	x	x	x	x	x	x	x	x
Cannabidiol			x		x			x	x
Chamomile			x		x			x	x
Cocoa	x		x	x	x	x	x	x	x
Danshen	x	x	x	x	x	x	x	x	x
Dong quai	x		x	x	x	x	x	x	x
Echinacea			x		x			x	x
Eucalyptus			x		x			x	x
Feverfew	x		x	x	x	x	x	x	x
Garcinia cambogia	x		x	x	x	x	x	x	x
Garlic	x		x	x	x	x	x	x	x
Ginger	x		x	x	x	x	x	x	x
Gingko biloba	x		x	x	x	x	x	x	x
Ginseng (American)									x
Ginseng (Panax)			x	x	x	x	x	x	x
Grapefruit			x		x			x	x
Ibuprofen*			x	x	x	x	x	x	x
Jackfruit		x	x	x	x	x	x	x	x
Lime			x		x			x	x
Melatonin		x	x	x	x	x	x	x	x
Naproxen*			x	x	x	x	x	x	x
Turmeric	x		x	x	x	x	x	x	x
Vitamin E	x	x	x	x	x	x	x	x	x
Yerba mate	x		x	x	x	x	x	x	x

*Ibuprofen and naproxen may block antiplatelet effect of ASA.

PERIOPERATIVE RISK ASSESSMENT

The following risk stratification methods are general guides, not absolute rules. Pharmacists must consider the whole patient and use good clinical judgement. Caution and prioritizing patient safety are always prudent.

Risk of Thrombosis

Certain patient characteristics increase a patient’s risk of thrombosis during a procedure. The CHEST Guideline presents three main risk categories: AF, VTE, and mechanical heart valves. When a patient has an elevated risk score in multiple categories, the team should use the highest value for stratification purposes. For example, if a patient has a CHA₂DS₂VASc score of 2 and antiphospholipid antibodies, classify the patient as high risk of thrombosis.

Atrial Fibrillation

The CHADS₂ and CHA₂DS₂VASc scoring formulas classify patients with AF as having a high, medium, or low risk of stroke as described in Table 5. the CHEST Guideline references both:

CHADS₂: Add one point for each of the following conditions: congestive heart failure (CHF), hypertension, age at least 75 years, and diabetes; add two points for a history of stroke/TIA.
CHA₂DS₂VASc: Add one point for each of the following conditions: CHF, hypertension, diabetes, vascular disease (myocardial infarction, peripheral artery disease, aortic plaque), age 65-74 years, and sex category of female; add two points each for age at least 75 years and history of cerebrovascular accident (CVA)/TIA/thromboembolism.

CHA₂DS₂VASc identifies low-risk patients more accurately and classifies fewer patients as moderate risk.²⁰

Table 5. Risk of Thrombosis Secondary to Atrial Fibrillation¹⁰

High

Moderate

Low

CHADS₂: 5-6

CHA₂DS₂VASc: at least 7

CVA/TIA in the past 3 months

Rheumatic valvular heart disease

CHADS₂: 3-4

CHA₂DS₂VASc: 5-6

CHADS₂: 0-2 (no CVA/TIA)

CHA₂DS₂VASc: 1-4

Source: Adapted from reference 10 p.e212.

Venous Thromboembolism

Table 6. Risk of Thrombosis Secondary to Hypercoagulable States.

High Risk

Moderate Risk

Low Risk

VTE within the past 3 months

Protein C or S deficiency

Antithrombin deficiency

Homozygous Factor V Leiden

Homozygous gene G20210A mutation

Antiphospholipid antibodies

Active brain, gastric, pancreatic, or esophageal cancer

Myeloproliferative disorders

VTE 3-12 months prior

Recurrent VTE

Heterozygous Factor V Leiden

Heterozygous gene G20210A mutation

Active or recent malignancy other than those specifically listed in high risk category

VTE more than 12 months prior

Mechanical Heart Valves

Table 7. Risk of Thrombosis Secondary to Mechanical Heart Valves¹⁰

High Risk

Moderate Risk

Low Risk

MVR + major risk factor(s)*

Caged-ball, tilting-disc AVR/MVR

CVA/TIA within the past 3 months

MVR without major risk factors*

AVR (bileaflet) with major risk factors

AVR (bileaflet) without major risk factors*

*Major risk factors for CVA: History of AF, CVA/TIA during previous anticoagulation hold, rheumatic heart disease, valve thrombosis, HTN, diabetes, CHF, age 75 or greater.

Bleeding Risk

Some patients develop serious bleeding during or after a procedure, so risk assessment is critical. The literature describes several different bleeding-risk scoring systems, including HAS‐BLED, HEMORR₂HAGES, ORBIT‐AF, ATRIA, and GARFIELD‐AF. In short, while these tools can help identify potentially high-bleeding-risk patients, their accuracy varies depending on the patient population studied.^21,22 The CHEST Guideline includes empiric classification guidance.¹⁰

High

Generally, surgeries and procedures performed on highly vascularized organs, that cause extensive tissue damage, or are spinal-invasive are considered high risk. Anticoagulants should be held long enough to reverse their effects. Examples include

Cancer
Cardiac
Colonic polyp or bowel resection
Epidural injections
Gastrointestinal (GI)
Kidney
Major orthopedic
Major thoracic
Neuraxial interventions
Reconstructive plastic
TURP
Urologic

Low to Moderate

These surgeries are considered low to moderate bleeding risk surgeries and procedures, regardless of whether biopsies are performed. Anticoagulants can be held for less time during the perioperative period.

Arthroscopy
Bronchoscopy
Colonoscopy
Coronary angiography, femoral approach
Foot, hand
GI endoscopy
Hemorrhoidal surgery
Hysterectomy
Laparoscopic cholecystectomy
Lymph node biopsies

Minimal

Many patients can remain fully anticoagulated for minimal bleeding risk procedures, although it would be reasonable to consider holding a DOAC on the day of the procedure. In certain circumstances, such as a dental extraction in a patient who has poor gingival health, it may be reasonable to hold anticoagulation before a minimal bleed risk procedure.

Cataract procedures
Coronary angiography, radial approach
Minor dental procedures, including extraction(s)
Minor dermatologic procedures, including excision of skin cancers
Pacemaker or ICD placement

DIRECT ORAL ANTICOAGULANTS

Since heparin bridging is not used for patients who use DOACs, these instructions are simple. Clinicians should provide patients with instructions to hold their DOAC on specific dates. However, they need to know the audience! For some patients, verbal communication suffices. In this case, the best practice would be to ask the patient to repeat the instructions to confirm understanding. Other patients find it more helpful to have written instructions, especially those who have caregivers. For patients who live in assisted living facilities that manage their medications, pharmacists can do two things: (1) review the instructions with the patient for their own knowledge and (2) provide instructions directly to the facility.

DOACs only take a few hours to become fully effective. Ask the patient to check with the surgeon after the procedure is complete to make sure it’s safe to restart the DOAC.²³

WARFARIN

The inter-patient variability in responses to warfarin cannot be understated. Warfarin’s half-life is 20 to 60 hours and varies significantly from patient to patient. Warfarin ultimately inhibits activation of clotting factors II, VII, IX, and X, and it also affects the natural anticoagulants protein C and S. Table 8 compares these factors’ half-lives and reveals that they are not necessarily pivoting in concert while warfarin doses are being adjusted.

Table 8. Half-lives of Clotting Factors Relevant to Warfarin Use
Factor	Half-life (hours)
II	42-72
VII	4-6
IX	21-30
X	27-48
Protein C	8
Protein S	60

Source: Adapted from 24 p. 20.

Many factors affect a patient's response to a warfarin dose. These include interactions with diet, pharmacokinetic medication interactions, pharmacodynamic interactions, liver function, edema status, and many more. Surgery and hospitalization commonly cause physical stress and decrease appetite; both increase warfarin sensitivity. The patient's history can be invaluable when determining post-procedure doses but caution is warranted. Even if the patient had a similar warfarin holding situation in the past available for comparison, they may respond differently this time.

It can take three to seven days (or more) to see the effect of warfarin dosing changes on the INR. Therefore, patients usually resume warfarin in the evening after a procedure is completed. It can take weeks for INR to stabilize after major surgery. This is when shorter-acting LMWH and unfractionated heparin (UFH) become useful.

Heparin Bridging During Warfarin Interruption

Unless otherwise specified, when the CHEST Guideline mentions "heparin bridging," it specifically refers to using a therapeutic-dose LMWH. Examples include enoxaparin 1 mg/kg twice daily or 1.5 mg/kg daily, dalteparin 100 international units/kg BID or 200 international units/kg daily, or full-dose UFH to achieve target aPTT of 1.5-2x the control, or a target anti-Xa level of 0.35 to 0.70 international units/mL. Lower prophylactic or intermediate doses may be used in certain circumstances.¹⁰Clinicians need to calculate renal function before finalizing a dose. If a patient with ESRD needs to bridge for a procedure, it is best to use IV UFH for inpatient bridging rather than LMWH.

Practice Pearl: It may be difficult for patients who are underweight (with little subcutaneous fat) or who have had major surgery (scarring or local trauma) to find suitable sites for subcutaneous injections.

Practice Pearl: It can be challenging to determine an appropriate therapeutic dose of LMWH for patients with BMI exceeding 40 kg/m², especially in the outpatient setting, where monitoring anti-Xa levels would be more challenging. Whether or not to cap the dose at some amount lower than 1 mg/kg twice daily is a controversial topic.^14,25

Practice Pearl: Procedures that require LMWH bridging and are scheduled without much notice can cause logistical challenges for patients. Questions to consider include

When does the patient need to start using LMWH?
Does the pharmacy have it in stock?
If not, how long will it take them to order it?
Will the patient be able to afford the copay?

Practice Pearl: Significant drops in hemoglobin, hematocrit, or platelets after a surgery or procedure can be the first warning sign of severe post-operative bleeding.

Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening condition that is a possible reaction to heparin. The ASH Guideline suggests monitoring for drops in platelet count for patients who are considered to have moderate or high risk of HIT, including patients using UFH and patients using LMWH after major surgery or trauma. In these cases, the guideline recommends monitoring platelet count every two to three days until heparin is discontinued.²⁶

Example Warfarin Bridge Plan

Oliver is a 52-year-old male patient with a MVR, antiphospholipid antibodies, and a history of CVA. He has a colonoscopy scheduled next month. Lab work done 9 months ago was largely unremarkable, except his platelets were 30 points below the minimum EHR reference range (unknown etiology). His medication list includes warfarin 5 mg daily, lisinopril 20 mg daily, and aspirin 81 mg daily. He said he does not use supplements. His INR has been stable and therapeutic for the past two months. He has had no other procedures in the past year. Repeat bloodwork indicates his platelets are now within normal limits. He will return home the same day as the procedure.

Vitals: Weight 174 lb, BP 135/82 mmHg. CrCl 65 mL/min.

Your institution's protocol indicates he should bridge with therapeutic dose enoxaparin for this procedure, and you have whatever approvals you need to proceed. You send a prescription for 80 mg enoxaparin syringes #20 to his local pharmacy, to be used twice daily as instructed in Table 9. Since his procedure is still a month away, his pharmacy has time to order the enoxaparin if necessary.

Table 9. Example Patient Instructions for Perioperative Anticoagulation
Month	Day	Day of Week	Warfarin Dose	Injectable Anticoagulant: 80 mg Enoxaparin
Apr	17	Thursday	Last dose: 5 mg	None
Apr	18	Friday	None	None
Apr	19	Saturday	None	None
Apr	20	Sunday	None	Begin enoxaparin injections under the skin every 12 hours, starting this morning
Apr	21	Monday	None	Continue enoxaparin injections every 12 hours
Apr	22	Tuesday	None	Continue enoxaparin injections, just once today, with the last dose at least 24 hours before the procedure
Apr	23	Procedure Wednesday	If the surgeon approves, restart after procedure is complete with 7.5 mg	None
Apr	24	Thursday	7.5 mg	If the surgeon approves, restart enoxaparin injections, just once today, starting 24 hours after procedure is complete
Apr	25	Friday	5 mg	Continue enoxaparin injections every 12 hours
Apr	26	Saturday	5 mg	Continue enoxaparin injections every 12 hours
Apr	27	Sunday	5 mg	Continue enoxaparin injections every 12 hours
Apr	28	Monday	Further instructions are to be provided at today's appointment	Continue enoxaparin injections, but please wait until after this morning's visit before using enoxaparin today to allow for fingerstick INR
Please continue injections until the Anticoagulation Clinic asks you to stop. Your next appointment is 4/28/25. On days when you are scheduled for a post-procedure INR check, please hold your morning injection until after your morning appointment. If you will be doing errands after your visit, please bring a syringe with you to stay on schedule with your injections.

PAUSE AND PONDER: How would you provide instructions to the patient in a way that they both understand and are willing and able to follow?

COMMUNICATION TECHNIQUES

Practice Pearl: Use active listening, reflective statements, and motivational interviewing techniques to ensure patients know you hear their concerns and are comfortable asking questions.

In the ambulatory setting, the patient must fully understand and accept the perioperative plan to minimize the risk of harm. Patients may not follow through if they think the team doesn’t care about their concerns.

Consider Emma, who has been your patient for several years. She arrives at the clinic irritated and you do not know why. You try to make small talk with her, but she snaps, “Just get on with the visit.” She crosses her arms across her chest and looks away. You do not know this yet, but her mother was just diagnosed with metastatic colon cancer and is considering foregoing treatment and entering hospice care.

Emma is here today to review perioperative instructions for her upcoming colonoscopy. She has had precancerous polyps removed in the past and has recently developed a small amount of hematochezia (presence of fresh [bright red] blood in stools). Emma was not expecting to have to bridge for her colonoscopy because she didn’t bridge for the last one. She recently established care with a new provider who is more concerned about her risk of thrombosis than her last one was.

She is expecting to hold her warfarin five days prior to her procedure and restart it the same evening, but then you show her a detailed calendar of LMWH bridging instructions and begin reviewing them. She becomes increasingly disengaged and even a little tearful and refuses to follow the plan. She says, “Forget it. I am cancelling the colonoscopy.”

The sooner you identify a bad situation developing, the easier it is to avert it. The patient's body language is a signal to address concerns immediately. The moment Emma crossed her arms across her chest and looked away was your cue to stop and attempt to determine the problem. If she shares her concern about her mother’s recent diagnosis and her concerns about her own health, use a reflective statement (summarize and repeat the problem back to her). Don’t judge, contradict, or redirect her. Demonstrate you are really listening to her and trying to understand her concerns. She will probably uncross her arms and make eye contact with you again.

At an appropriate time, gently guide the discussion back to the reason she is here. You might say something like, "Thank you for sharing your concerns. I hear that you are feeling very stressed right now. You only want the best for your mother, and this news is devastating. You’re worried about what the doctor will find in your own colonoscopy. I went right into all these details about a complicated, unexpected bridge plan. I would feel anxious myself if I were you. I want you to know that you are always in control of your own healthcare. You get to decide for yourself if you want to proceed, if and when you are ready. If it turned out that you have another polyp, would you want to have the opportunity to have it removed?"

While you are having this discussion, it is important to remain attentive and welcome her to interrupt you with new information or questions or concerns as they come up. Emma agrees to proceed, and you review the instructions with her. After presenting the plan, ask her to explain to you what she will be doing at each step of the process to confirm understanding. This is called a “teach-back technique.”

Practice Pearl: Use teach-back techniques and spot-checking to ensure understanding.

Language Barriers and Hearing Impairment

Practice Pearl: Use only qualified interpreters when communicating complicated instructions to patients who do not share your native language. Use alternate communication methods as needed for deaf or hard-of-hearing patients.

Patients may find it more difficult to understand instructions that contain slang or medical jargon. Sometimes, patients nod to indicate they understand what you are saying, even when they do not, to be polite or to avoid social discomfort. When using interpreters, make eye contact with and speak directly to the patient, not the interpreter. Speaking louder will not improve understanding when the obstacle is a language barrier. Patients with hearing impairment may benefit from careful enunciation, especially of consonants. They may also lip-read, even if they do not realize they are doing it. This can be challenging in situations when masking is required.

Practice Pearl: In the United States, the format frequently used to describe dates is month-day-year; however, other countries use day-month-year. To minimize confusion, provide written dates with the month shown as a word instead of a number, e.g., “August 3” instead of “8-3.”

Cognitive Impairment

Practice Pearl: Be prepared to repeat your instructions as often as needed to ensure understanding.

Cognitive impairment occurs across a broad spectrum that can make it challenging for patients to understand and/or follow detailed instructions.²⁷ Some patients may need to review the material with you several times. Other patients may bring a caregiver or friend to help them think of questions to ask and to remember their instructions. Some patients cannot take their medication on their own; in this case, it is essential to provide education to a caregiver who can help them navigate the process. If caregivers accompanies a patient to an appointment, acknowledge their presence and include them in the discussion. They may have relevant questions, concerns, or valuable feedback.²⁷

The following resources provide more tips on patient communication:

https://www.cds.udel.edu/wp-content/uploads/2017/02/effective-communication.pdf
https://store.jointcommissioninternational.org/assets/3/7/jci-wp-communicating-clearly-final_(1).pdf

Vision Impairment and Tremor or Arthritis

Practice Pearl: Round a dose to the nearest commercially available dose instead of strict weight-based dosing.

The more complicated or physically challenging the perioperative instructions are, the greater the risk of dosing errors. For example, enoxaparin syringes are graduated but the small markings may be hard for patients with vision impairment to see. Additionally, tasks requiring fine motor skills, such as removing a tiny amount of liquid from a syringe, or even administering an injection, may be difficult or impossible for patients with tremors or arthritis. Dose rounding to the nearest commercially available strength can help with this.

Enoxaparin comes in the following prefilled syringe doses: 30, 40, 60, 80, 100, 120, and 150 mg.²⁸

Common Patient Misconceptions

Practice Pearl: To prevent patient misunderstandings, explain the independent roles of warfarin and LMWH in the bridge and why both are used simultaneously.

Sometimes, patients misunderstand the role of warfarin and LMWH in the bridging process, even when they have detailed written instructions. They may not resume LMWH post-procedure because they think their INR will return to their therapeutic range immediately after restarting warfarin. They may not resume warfarin post-procedure because they believe the LMWH increases their INR. You can prevent these kinds of misunderstandings by providing a basic explanation of the independent roles of warfarin and LMWH in the bridge, and why they will be using both at the same time post-procedure.

Practice Pearl: Ask patients to "hold" the anticoagulant on specific dates (and resume it on specific dates). Do not use the term "stop." If you tell patients to stop their warfarin on Tuesday, they might take that to mean you want them to take their last dose of warfarin on Tuesday, not to take the last dose of warfarin on Monday and start holding it on Tuesday. This misunderstanding can result in a patient holding warfarin for only four days before their procedure, instead of five

Revisions Due to Unexpected Developments

Clinicians involved in anticoagulation must remain flexible and prepared to adapt to an evolving situation after a patient’s surgery or procedure. Some common examples of periprocedural situations that may warrant closer monitoring post-procedure include

Bleeding may delay the resumption of anticoagulation post-procedure.
NSAIDs prescribed for pain control on discharge can increase bleeding risk.
Vitamin K reversal increases warfarin dosing requirements post-procedure.
Reduced appetite or food intake post-procedure may reduce rivaroxaban absorption or increased warfarin sensitivity.
Bariatric surgery can have unpredictable effects on warfarin dosing requirements. Although patients are eating less, they may have initiated supplements that contain more vitamin K than they consumed pre-procedure.
Dental procedures can temporarily decrease food intake; however, some dentists ask patients to use protein shakes (many of which contain vitamin K) post-procedure.
Tobacco cessation increases warfarin sensitivity
Changes in kidney or liver function may affect medication clearance.

CONCLUSION

Assembling an appropriate perioperative plan for a patient's anticoagulation can be complicated. The material and pearls provided in this activity can help clinicians devise and implement a plan that is appropriate for each patient.

1. Which of the following patients should be bridged for a hip replacement surgery?
a. A 46-year-old male who uses a DOAC for atrial fibrillation
b. A 38-year-old female who uses warfarin for heterozygous Factor V Leiden mutation
c. A 42-year-old male who uses warfarin for Protein S deficiency

2. Which of the following surgeries carries the highest risk of perioperative bleeding?
a. Colonic polyp resection
b. Hemorrhoidal surgery
c. Hysterectomy

3. Which of the following patients has the highest risk of perioperative thromboembolism, assuming all medical conditions are listed?
a. A 34-year-old female with antiphospholipid antibodies
b. A 75-year-old female with atrial fibrillation and aortic plaque
c. A 65-year-old male with atrial fibrillation, history of stroke, and hypertension

4. A 26-year-old Ukrainian patient who does not speak English comes to your clinic to review perioperative instructions for a laparoscopic cholecystectomy next week. His only other medical condition is asthma. You have arranged for a professional interpreter to attend today’s visit. While using the interpreter, which of the following will help the patient understand your instructions?
a. Increasing your voice’s volume so he can hear what you are saying
b. Making eye contact and speaking directly to the patient
c. Using medical jargon and using highly technical terms

For the next two questions, consider the following patient case:
Evelyn is a 50-year-old female patient with an MVR, diabetes, protein C deficiency, Crohn’s disease, and hypertension. She has a bowel resection scheduled. Her current medications include warfarin, metformin, losartan, aspirin 81 mg, and prednisone. She also uses a daily multivitamin and alpha lipoic acid.

5. Which of the following perioperative plans would be most appropriate?
a. Hold both warfarin and ASA for seven days before the surgery, bridge with therapeutic dose LMWH, with the last pre-surgery LMWH dose, at half the total daily dose, 48 hours before the surgery and restarting LMWH 24 hours after the procedure if hemostasis is achieved. Continue ASA and alpha lipoic acid for the surgery.
b. Hold warfarin for five days before the resection and restart warfarin the evening of the surgery with no LMWH bridging if hemostasis is achieved. Hold the aspirin and alpha lipoic acid starting the week before until at least a week after the surgery.
c. Hold warfarin for five days before the surgery, bridge with therapeutic dose LMWH, at half the total daily dose, with the last pre-surgery LMWH dose 24 hours before the surgery and restarting LMWH 48 hours after the surgery if hemostasis is achieved. Continue ASA but hold alpha lipoic acid starting the week before until at least a week after the surgery.

6. If Evelyn was having a pacemaker placement instead of a bowel resection, which of the following perioperative plans would be most appropriate?
a. Hold warfarin for five days before the surgery, bridge with therapeutic dose LMWH, with the last pre-procedure LMWH dose, at half the total daily dose, 24 hours before the procedure and restarting LMWH 48 hours after the surgery if hemostasis is achieved. Continue ASA but hold alpha lipoic acid starting the week before until at least a week after the surgery.
b. Continue warfarin and ASA for the procedure but hold alpha lipoic acid starting the week before until at least a week after the surgery.
c. Hold both warfarin and ASA for seven days before the surgery, bridge with therapeutic dose LMWH, with the last pre-surgery LMWH dose, at half the total daily dose, 48 hours before the surgery and restarting LMWH 24 hours after the procedure if hemostasis is achieved. Continue ASA and alpha lipoic acid for the surgery.

7. Lily is a 78-year-old female with atrial fibrillation, CHF, and hypertension. She has a Watchman left atrial appendage closure device and a history of hemorrhagic stroke. Her current medications include sacubitril/valsartan and ASA. If she were to have an epidural injection, which of the following supplements would you be most concerned about her using during the perioperative period?
a. Echinacea
b. Gingko biloba
c. Grapefruit

8. John is a 67-year-old male who is scheduling a TURP. His medications include apixaban 5 mg BID, tamsulosin 0.4 mg daily, and metoprolol tartrate 50 mg BID. What is the minimum number of hours John would need to hold apixaban before the surgery?
a. Hold apixaban starting 12 hours before the surgery and restart no sooner than 24 hours after the surgery
b. Apixaban does not need to be held for this surgery
c. Hold apixaban starting 48 hours before the surgery and restart no sooner than 48 hours after the surgery

The following two questions are about the following patient case: Samantha is a 72-year-old female who lives alone and is 5’ 8” and weighs 210 lb. She uses topical diclofenac gel for arthritis. She also uses a daily multivitamin. She had a lab draw last month that was within normal limits. Her serum creatinine was 1.64 mg/dL. She is having hip replacement surgery in two weeks.
9. If she uses warfarin for antithrombin deficiency, what would be the most appropriate enoxaparin dose for her to use as an outpatient?
a. 95 mg
b. 40 mg
c. 100 mg

10. If she used a DOAC, which of the following would need to be held four days before the procedure?
a. Apixaban
b. Rivaroxaban
c. Dabigatran

Heparin/Low Molecular Weight Heparin and Fondaparinux Pharmacology and Pharmacotherapy 2025 Revision

When you are ready to submit quiz answers, go to the Blue "Take Test/Evaluation" Button.

If desired, “bundle” pricing can be obtained by registering for the activities in groups. It consists of thirteen anticoagulation activities in our online selection.

You may register for individual topics at $17/CE Credit Hour, or for the Entire Anticoagulation Pre-requisite Series.

Pharmacist General Registration for 13 Anticoagulation Pre-requisite activities-(17.25 hours of CE) $199.00

In order to attend the 2-day Anticoagulation Traineeship, you must complete all of the Pre-requisite Series or the equivalent.

Anticoagulation Traineeship at the University of Connecticut Health Center, Farmington, CT

More Information About Traineeship

1. Ty is admitted to your hospital for community-acquired pneumonia. You notice that he is a candidate for VTE prophylaxis. He is a 70-year-old male, 5’5”, and 75 kg (165 lbs). Labs include INR 1.1, BUN 30, and SCr 2.5. What is the most appropriate recommendation?
a. Enoxaparin 40 mg SC daily
b. Heparin IV per thromboembolic protocol
c. Enoxaparin 30 mg SC daily

2. Which of the following is an approved indication for low molecular weight heparin?
a. Treatment of venous thromboembolism
b. Anticoagulation in patients with a history of HIT
c. Prevention in patients with renal insufficiency

3. You are at a lecture on LMWH and fondaparinux and the speaker says that these two medications have three things in common. He says, “First, with both medications, you would not dose adjust or avoid using them in patients with impaired renal function. Second, you must order anti-Xa testing on Days 2 and 4 of therapy. Third, with both, active major bleeding is a contraindication for use.” What should you do?
a. Raise your hand and challenge his statement on active major bleeding
b. Raise your hand and challenge his statement on ordering anti-Xa testing
c. Do nothing; these great clinical pearls will make it easier for you to screen patients.

4. A nurse calls, concerned about a patient on heparin for a new blood clot. The patient is going for hemodialysis today. They are unsure of how dialysis will affect the patient's heparin therapy. What would you recommend?
a. Recommend an additional bolus heparin dose immediately following dialysis
b. Ask the prescriber to change to LMWH because heparin is contraindicated in dialysis
c. Say hemodialysis will not affect heparin levels so continue therapy as prescribed
5. A patient who is on LMWH is experiencing a major bleed and needs surgery. The surgeon wants to give protamine. What should you tell her?
a. Protamine will completely reverse LMWH’s anti-factor IIa and Xa effects
b. Give 1 mg protamine per mg of LMWH and repeat every 8 hours for 4 additional doses
c. Anti-factor IIa and Xa activities may return up to three hours after you give the dose

6. Why should prescribers never use enoxaparin sodium injection from multiple dose vials in neonates, infants or pregnant women?
a. No studies have established the appropriate dose
b. It contains benzyl alcohol preservative
c. It causes gastrointestinal colic-like symptoms

7. Which of the following is a contraindication for fondaparinux?
a. Body weight greater than 150 kg (330 lbs)
b. Bacterial endocarditis
c. Sever hepatic impairment

8. A patient accidentally injects her dalteparin twice and the prescriber is frantic and wants to handle the overdose quickly. What is the appropriate dose of protamine?
a. 1 mg protamine for every 1 mg dalteparin administered
b. 1 mg protamine for every 100 anti-Xa units of dalteparin given
c. 1 mg protamine for every 1 mg dalteparin in excess of the normal dose

9. What are the most serious symptoms of protamine overdose?
a. Severe hypotensive fatal reactions, often resembling anaphylaxis
b. Excessive bleeding unresponsive to further protamine doses
c. Epidural or spinal hematomas causing long-term/permanent paralysis

10. Which of the following is a boxed warning on the LMWHs and fondaparinux?
a. Severe hypotensive fatal reactions, often resembling anaphylaxis
b. Excessive bleeding unresponsive to intervention with protamine
c. Epidural or spinal hematomas with neuraxial anesthesia or spinal puncture

Drug Interaction Cases with Anticoagulation Therapy 2025 Revision

When you are ready to submit quiz answers, go to the Blue "Take Test/Evaluation" Button.

If desired, “bundle” pricing can be obtained by registering for the activities in groups. It consists of thirteen anticoagulation activities in our online selection.

You may register for individual topics at $17/CE Credit Hour, or for the Entire Anticoagulation Pre-requisite Series.

Pharmacist General Registration for 13 Anticoagulation Pre-requisite activities-(17.25 hours of CE) $199.00

In order to attend the 2-day Anticoagulation Traineeship, you must complete all of the Pre-requisite Series or the equivalent.

Anticoagulation Traineeship at the University of Connecticut Health Center, Farmington, CT

More Information About Traineeship

Drug Interaction Cases with Anticoagulation Therapy

Post-test

After completing this continuing education activity, the learner will be able to
1) Identify anticoagulation therapy’s clinically significant drug interactions
2) Discuss drug interactions that patients may ask about, but are generally not clinically significant
3) Analyze cases to determine if a drug interaction is clinically significant
4) Diminish the effect of identified drug interactions in simulated cases
5) Describe monitoring parameters for the identified drug interactions in the simulated cases

1. A patient arrives at the clinic with a new prescription for bananamycin. This drug was approved yesterday and the patient is on warfarin. Bananamycin’s prescribing information doesn’t discuss anticoagulants as it was approved based on very small studies. What would be the BEST way to determine if bananamycin is likely to interact with warfarin?
A. Check warfarin’s prescribing information
B. Request information from warfarin’s manufacturer
C. Evaluate bananamycin’s metabolic characteristics

2. Which of the following pairs correctly links the warfarin enantiomer with the CYP enzyme of concern?
A. R enantiomer = CYP1A2
B. R enantiomer = CYP2C19
C. R enantiomer = CYP3A4

3. Which of the following pairs correctly links the warfarin enantiomer with the CYP enzyme of concern?
A. S enantiomer = CYP2C9
B. S enantiomer = CYP2C19
C. S enantiomer = CYP3A4

4. Arlene comes to the clinic to have a PT/INR drawn. You note that she is drinking green tea. You tell her that under certain circumstances, green tea can affect INR, and you ask her how much green tea she drinks. Which of the following answers would be of MOST concern?
A. “I usually drink a 16 ounce bottle every day over six hours or so.”
B. “I don’t know… a gallon a day…maybe more? It’s good for you.”
C. “This is the first time I ever had it.”

5. Bob is a 77-year-old fellow who has been on warfarin for five years. He has stable hypertension and hypercholesteremia but is pretty healthy otherwise. You say, “Tell me anything that has changed regarding your health or diet since we last talked.” He responds that he recently received a diagnosis of osteoarthritis and is now taking acetaminophen. What should your next question be?
A. Is the acetaminophen providing some relief from the pain?
B. How much acetaminophen are you taking and how often?
C. Did your prescriber call your hematologist before prescribing?

6. Patients may experience drug-drug interactions that are unpredictable. Which four factors might vary between patients?
A. Patient susceptibility, response magnitude, time of onset, duration of effect
B. Drug manufacturer, INR testing method, dietary preferences, reason for anticoag
C. Brand, lot number, manufacturer reliability, patient health literacy level

7. Olivia is an 82-year-old who has frequent urinary tract infections. She takes 5 mg of warfarin daily. The culture/sensitivity results indicate that this organism is sensitive to cotrimoxazole. Her gynecologist wants to start cotrimoxazole for 10 days to treat the active infection and then use trimethoprim 100 mg daily as prophylaxis for six months. What should you expect? (You may need a drug interaction checker to answer this question.)
A. Sulfamethoxazole will decrease warfarin levels so you may need to increase the warfarin dose by 10-20%.
B. Trimethoprim will increase warfarin levels so you may need to decrease the warfarin dose by 10-20%.
C. Sulfamethoxazole usually increases warfarin levels, but trimethoprim is not expected to interact with warfarin.

8. Which of the following medications is MOST LIKELY to affect warfarin levels because it affects both warfarin enantiomers?
A. Amiodarone
B. Cimetidine
C. Omeprazole

9. According to the Anticoagulation Forum’s Direct Oral Anticoagulant (DOAC) Drug-Drug Interaction Guidance, which medications are MOST LIKELY to cause clinically significant drugs interactions? (You may pull the Guidance to answer this question.)
A. Drugs that are STRONG modifiers of CYP3A4 and CYP2C19
B. Drugs that modify BOTH p-gp and are STRONG modifiers of CYP3A4
C. The DOACs have few if any drug interactions, which is why they are so popular.

10. Roger is a 76-year-old man who is on apixaban pursuant to a diagnosis of atrial fibrillation. He has contracted an infection that is sensitive to clarithromycin, a combined p-gp and STRONG CYP3A4 inhibitor. The infection control specialist wants to prescribe it as soon as possible. What does the Anticoagulation Forum’s Direct Oral Anticoagulant (DOAC) Drug-Drug Interaction Guidance say about concurrent use of apixaban and clarithromycin?
A. Avoid use of clarithromycin entirely
B. Reduce the apixaban dose by 50% while taking clarithromycin
C. Clarithromycin does not significantly increase apixaban exposure

11. Jerrilyn, age 57, has diagnoses including HTN, hypercholesterolemia, and osteoarthritis. She takes warfarin 7.5 mg Monday and Friday, and 5 mg x 5 days after an atrial valve replacement. She develops a vaginal infection and decides to use OTC miconazole to treat it. What monitoring should you implement?
A. Recheck INR in 3-4 days
B. Recheck INR in 2 weeks
C. Recheck INR in 1 month

12. A patient is taking griseofulvin and his prescriber indicates it’s time to discontinue it. Right now! Today! When should you call the patient in for the next INR?
A. Recheck INR in 5 days
B. Recheck INR in 2 weeks
C. Recheck INR in 1 month

Challenging Topics in Anticoagulation 2025 Revision

When you are ready to submit quiz answers, go to the Blue "Take Test/Evaluation" Button.

If desired, “bundle” pricing can be obtained by registering for the activities in groups. It consists of thirteen anticoagulation activities in our online selection.

You may register for individual topics at $17/CE Credit Hour, or for the Entire Anticoagulation Pre-requisite Series.

Pharmacist General Registration for 13 Anticoagulation Pre-requisite activities-(17.25 hours of CE) $199.00

In order to attend the 2-day Anticoagulation Traineeship, you must complete all of the Pre-requisite Series or the equivalent.

Anticoagulation Traineeship at the University of Connecticut Health Center, Farmington, CT

More Information About Traineeship

INTRODUCTION

As the previous modules have demonstrated, it's inevitable that anticoagulation pharmacists will see patients who present management conundrums. Sometimes, the patient is a heavy consumer of alcohol or has actual alcohol use disorder (AUD). Other times, the patient may be pregnant or have antiphospholipid antibody syndrome. In each of these cases, the clinical team needs to pay careful attention. This section of the Anticoagulation Certificate Program is designed to help anticoagulation pharmacists develop the skills necessary to deal successfully with patients who need anticoagulation but have conditions that complicate selection of appropriate anticoagulation. Using case studies, we will navigate some of the more prevalent challenges.

CASE #1: ALCOHOL USE DISORDER

Jean Thomas is a 67-year-old male recently diagnosed with atrial fibrillation (AFib). He currently takes several medications: lisinopril, hydrochlorothiazide, simvastatin, doxazosin, and diltiazem. He has a past medical history of hypertension, hyperlipidemia, benign prostatic hypertrophy, obesity, prediabetes, and alcohol use disorder (AUD). The anticoagulation clinic has seen Jean for six weeks with occasional international normalized ratio (INR) levels above 3 necessitating multiple changes to his warfarin dose. The SIDEBAR provides some information about assessing patients’ alcohol intake.¹

SIDEBAR: Is patient-reported alcohol intake consistent with the amount they actually drink?²

Studies have found that physicians often mentally double patients’ reported alcohol consumption to obtain a more accurate estimate. Evidence suggests that self-reports are often underestimates of alcohol intake. Patient reasoning for this includes that they

Do not keep track of how much they drink
Are worried about the doctor judging them
Don’t want their health problems attributed to alcohol

Evidence indicates that the Alcohol Use Disorders Identification Test (AUDIT-C) is a suitable screening tool for most community-dwelling individuals. Clinicians can access this tool here: https://www.mentalhealth.va.gov/coe/cih-visn2/Documents/Provider_Education_Handouts/AUDIT-C_Version_3.pdf.

Indirect non-specific biomarkers can be useful in validating patient alcohol intake. An example of a short-term biomarker is ethanol in breath or urine, which indicates recent alcohol use. Long-term biomarkers include elevated mean corpuscular volume, gamma-glutamyl transferase (downregulated with chronic alcohol use), and the hepatic markers aspartate aminotransferase and alanine transaminase.

While tests evaluating these biomarkers can portray a patient’s alcohol consumption, establishing trust in patient-provider relationships is critical in making the most accurate clinical assessments. A PRO TIP is to approach patients non-judgmentally and non-confrontationally.

PAUSE AND PONDER: Which is TRUE regarding anticoagulants and alcohol use?

Alcohol use disorder (AUD) is a labeled contraindication to warfarin
Warfarin’s interaction with alcohol has been well studied
The team should discuss alcohol use openly with patients

An important aspect of developing a treatment plan based on a patient’s alcohol consumption is providing open, non-judgmental counseling. The clinical team, including prescribers and pharmacists, should discuss alcohol use openly with all patients to form an optimal treatment plan. Clinicians should acknowledge that their patients may drink regularly or have AUD because alcohol consumption is considered a risk factor for the development of AFib.³

Although many clinicians believe warfarin’s labeling lists alcoholism specifically as a contraindication to its use, it does not.⁴ This misconception may contribute to undertreatment or improper treatment of AFib in patients who use alcohol. A study found that rates of oral anticoagulant therapy (including warfarin) initiation were lower in patients with AUD.⁵

The potential interactions between warfarin and alcohol have been poorly studied. It is known that alcohol is not significantly metabolized by cytochrome P450 enzymes, as many drugs like warfarin are. Alcohol is primarily metabolized by alcohol dehydrogenase and to a much lesser extent by CYP2E1, CYP1A2, and CYP3A4.⁶ However, many additional compounds found in alcohol, like hops, flavonoids, and flavor additives, may affect warfarin’s pharmacokinetics or pharmacodynamics.

Some of the literature sources and guidelines note the possibility of alcohol’s effects such as an increased INR.⁷ Although there are not many available sources on the subject, small-scale studies have noted that^8,9

Drinking wine daily with meals has no effect on therapeutic hypoprothrombinemia.
Heavy consumption of wine during fasting has no significant effect on one-stage prothrombin activity, levels of warfarin, or hypoprothrombinemia.

Guidelines recommend that patients with AFib should reduce or discontinue alcohol consumption to lessen AFib recurrence and burden.¹⁰ Clinicians may treat patients that are hepatically impaired, whether due to their alcohol consumption or not. In these cases, warfarin’s metabolism and synthesis of clotting factors can be impaired.⁴

Other conditions affecting patients’ liver function complicate their treatment plans. Because AFib is a common diagnosis in those with liver cirrhosis, anticoagulation therapy needs to be carefully considered. Liver cirrhosis is considered a non-modifiable bleeding risk factor in AFib patients.³ A study found that direct oral anticoagulants (DOACs) are safer than warfarin in patients with decompensated liver cirrhosis, and that DOACs are contraindicated in Child-Pugh class C patients (liver impairment associated with a 45% 1-year survival rate).³ Dosing warfarin in patients with liver cirrhosis is especially difficult because the coagulopathy associated with this disease state commonly causes elevations in INR.³

Heavy alcohol intake is a significant risk factor for GI bleeding, and warfarin may increase that risk. Warfarin’s package insert lists it as contraindicated in patients with bleeding tendencies associated with active ulceration or overt bleeding of the gastrointestinal tract.⁴

An additional concern clinicians may have is the risk of falls and bleeding in patients who are frequently inebriated. Evidence from literature dispels this concern, demonstrating that the incidence of severe bleeding is not significantly impacted by the occurrence of falls.¹¹ However, it is worth noting that patients treated intensively (INR range of 2.5 to 3.5), bleeding is more likely to occur.¹¹

In summary, for AFib patients taking warfarin, alcohol use itself is not cause for concern. However, alcohol use lends itself to other comorbid conditions that may impact the way that AFib is treated. The clinical team must counsel warfarin patients about healthy lifestyle choices and reducing alcohol intake in the interest of their overall health. If patients communicate with clinicians about their heavy alcohol use or binge drinking, the team can monitor closely and determine the patient’s individual response. The team must also encourage patients to report changes in alcohol intake openly and honestly. When changes occur, increasing monitoring frequency in patients who binge drink frequently is warranted. A PRO TIP is to track each patient’s INR levels over time, noting what has changed in the patient’s alcohol intake or diet to better make informed clinical decisions going forward.

CASE #2: PREGNANCY

It's Friday afternoon and the clinic is about to close. Jules, a 32-year-old female receiving long term warfarin after experiencing a second deep vein thrombosis two years ago, phones to say she just took a pregnancy test and—oops!—she has an unplanned positive. So, what do we do now, and what are we going to do later?

PAUSE AND PONDER: Under what conditions might a prescriber use warfarin in a patient who is pregnant?

Only during the first trimester, then patients should be switched to a DOAC
Never, warfarin is absolutely contraindicated in all trimesters of pregnancy
In women with mechanical heart valves, who are at highest risk of thromboembolism

Let’s start with this, just in case you are thinking that a DOAC is the way to go: clinicians should avoid prescribing oral direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban) in patients who are pregnant or lactating. The data concerning their effects on the woman, fetus, and breastfeeding neonate are insufficient to determine safety.¹²

Warfarin crosses the placenta, and fetal plasma concentrations are similar to maternal concentrations. Since the fetus’s liver enzyme system is immature, the fetus is severely overdosed by these levels.¹³ Patients who are at highest risk for venous thromboembolism during pregnancy are those with a mechanical heart valve. Subsequently, warfarin is only approved by the Food and Drug Administration for use in pregnant women if they have mechanical heart valves, because they are at high risk of thromboembolism.¹⁴

The team’s goals for therapy in pregnant women are

Treat and prevent thrombosis during the pregnancy, as pregnancy itself increases risk of thrombosis.
If warfarin is used, it must be stopped and changed to low molecular weight heparin (LMWH) for at least the first trimester of pregnancy. Pregnant women without mechanical heart valves, that still require anticoagulation, should remain on LMWH therapy for the duration of the pregnancy.
Discontinue anticoagulation rapidly at the time of birth to prevent bleeding events.

Warfarin therapy during the first trimester of pregnancy is associated with an increased risk of prematurity, miscarriage, and stillbirth. Warfarin is a known teratogen. Warfarin therapy also increases risk of congenital abnormalities of the fetus, including nasal hypoplasia, cleft lip/palate, and skeletal abnormalities, among others.¹⁵ Mechanical valve thrombosis is prevented more effectively with warfarin compared to unfractionated heparin (UFH) or LMWH in patients with mechanical heart valves. Table 1 summarizes the data. Consequently, after the first trimester, guidelines recommend restarting warfarin therapy in pregnant patients who meet this criteria.¹⁶ Exposure to warfarin after the first trimester has been linked to some minor developmental slowing, but babies usually catch up developmentally later in childhood.¹⁵

Table 1. Risk of Mechanical Valve Thrombosis by Treatment Regimen¹⁷

Treatment Regimen	Risk of Mechanical Valve Thrombosis
Warfarin only	2.7%
LMWH only	8.7%
Unfractionated Heparin Only	11.2%
Sequential strategy (LMWH in 1^st trimester followed by warfarin)	5.8%

Clearly, the fact that warfarin is the best agent to prevent mechanical valve thrombosis is complicated by the risk to the fetus when using warfarin in the first trimester. As soon as pregnancy is detected, patients with mechanical heart valves taking warfarin should immediately discontinue warfarin and start LMWH twice daily.¹⁸ This transition period carries a high risk of mechanical valve thrombosis. Evidence suggests that the recommended therapeutic dose of enoxaparin 1 mg/kg twice daily is not sufficient to bring patients to the desired peak anti-Xa levels. Patients started on enoxaparin 1 mg/kg had to be rapidly titrated according to peak monitoring parameters, which leads to the recommendation to start LMWH at higher than the therapeutic dose recommendation, shown in Table 2.¹⁸

Table 2. Initial Dosing of LMWH in Pregnant Patients with a Mechanical Heart Valves

Low Molecular Weight Heparin	Dose
Enoxaparin	2.5 mg/kg/day
Dalteparin	250 units/kg/day
Tinzaparin	25 units/kg/day

Ultimately, LMWH dosing in patients with mechanical heart valves should be guided by target Anti-Xa levels, as seen in Table 3. Pregnant patients initiated on twice daily LMWH therapy should be frequently monitored for peak Anti-Xa levels; a PRO TIP is to draw levels 3 to 4 hours after dose is taken.

Table 3. Target Anti-Xa Levels for Pregnant Patients with Mechanical Heart Valves¹⁸

Type of Mechanical Heart Valve	Target Anti-Xa Levels
Aortic valve prosthesis	0.8-1.2 international units/mL
Mitral and right-sided valve prosthesis	1.0-1.2 international units/mL

Due to ease of dosing and proper administration in the outpatient setting, use of LMWH is recommended over UFH.¹⁹ Risk of adverse events is lower and therapeutic response is more predictable with LMWH.²⁰UFH can be used, but is not recommended. Once patients with mechanical heart valves are outside of the crucial first trimester window (around the 13^th week of pregnancy), patients can be transitioned back onto warfarin, with close INR monitoring.¹⁸ It is important to note that a patient’s warfarin dosing may not be the same as it was pre-pregnancy due to changes in anticoagulant factors during pregnancy.²¹ Two weeks before scheduled delivery or 36 weeks of pregnancy at the latest, clinicians should transition patients back onto a heparin-based therapy.¹⁸

Some evidence suggests that low-dose aspirin therapy, in combination with warfarin therapy, reduces the risk of mechanical valve thrombosis, but carries a higher risk of bleeding. Pregnant patients with mechanical heart valves should be started on low dose aspirin therapy early in pregnancy, so long as aspirin therapy is not contraindicated.¹⁸ If aspirin therapy is used, it should be stopped three days prior to planned delivery. Figure 1 summarizes anticoagulation in pregnant patients with mechanical heart valves.

Figure 1. Summary of Anticoagulation in Pregnant Patients with Mechanical Heart Valves

The CHEST guidelines don’t mention AFib in pregnancy, but the European Society of Cardiology (ESC) suggests changing anticoagulation to adjusted dose LMWH in the first trimester (as soon as pregnancy is confirmed). Warfarin has been proven to reduce the risk of stroke in these patients, although clinicians currently use DOACs preferentially. Pregnant patients cannot take DOACs, so warfarin is recommended after the first trimester to prevent stroke in patients with AFib.²² Warfarin can be resumed or initiated after the first trimester up until the last month of pregnancy when patient should be returned to LMWH prior to birth.^23,24 This follows the recommendations for anticoagulation in patients with mechanical heart valves.

Patients receiving therapeutic doses of LMWH have an almost 2-fold increased risk of postpartum hemorrhage in instances of spontaneous labor compared to planned induction of labor.¹⁹If the patient goes into labor unexpectedly while still taking warfarin therapy (or within two weeks of last warfarin dose), a cesarean section may be required to reduce fetal bleeding complications from labor.¹⁸ The newborn may need to receive vitamin K (IM or IV instead of by mouth, as is the current standard of care) and fresh plasma upon delivery.²⁰ If the patient goes into labor spontaneously within 24 hours of last LMWH or UFH dose, providers can consider protamine after monitoring the PTT and/or anti-Xa levels if the patient is at risk for life threatening hemorrhage.¹⁸ Table 4 indicates how protamine can be dosed in the pregnant woman immediately prior to giving birth.²⁵

Table 4. Protamine Dosing after Spontaneous Labor

Anticoagulant	Protamine Dose
Heparin	1 mg per 100 unit of heparin
Enoxaparin	1 mg protamine per 1 mg enoxaparin
Dalteparin or tinzaparin	1 mg of protamine per 100 unit of LMWH administered in last 3-5 half lives

*Maximum single dose of protamine is 50 mg

ABBREVIATION: LMWH = low molecular weight heparin

A key concern prior to delivery is epidural administration of analgesics for the mother, as using injectables while a patient is anticoagulated is risky. For this reason, many obstetricians will schedule and induce labor in anticoagulated patients. The European Society of Anesthesiology currently recommends waiting at least 12 hours after cessation of prophylactic LMWH or at least 24 hours after cessation of greater-than-prophylactic dose LMWH therapy before inserting an epidural catheter.²⁶ To ensure the patient has access to an epidural prior to birth, the team should attempt to discontinue LMWH therapy 24 hours before scheduled induction. In high-risk patients, clinicians can use an UFH infusion while the patient is hospitalized and discontinue it six hours before an induced delivery. If an epidural catheter needs to be placed, there must be a four to six hour interval between the last dose of UFH and epidural placement.²⁶

After birth, anticoagulation is a little easier. If the patient is anticoagulated again after delivery and an epidural is still in place, clinicians must wait a minimum of 12 hours after the last anticoagulant dose before removing the catheter.¹⁸ Additionally, clinicians must wait an additional four hours after the epidural catheter is removed before administering LMWH or UFH therapy.²⁶ Patients can be transitioned back onto warfarin five to seven days after delivery.¹⁸

Multiple options are available for breastfeeding women who need anticoagulation. UFH molecules are too large to pass into breast milk and warfarin has not been found to pass into breast milk. A PRO TIP is that warfarin dosing may differ in the post-partum period from pre-pregnancy due to differences in anticoagulation factors, so frequent monitoring is required. While LMWH products do pass into the breastmilk, their oral bioavailability is very low and has not been shown to cause fetal harm. However, the CHEST guidelines recommend against using DOACs in breastfeeding women as they cross into the breastmilk and there is not enough data to show degree of fetal harm.¹⁹

CASE #3: ANTIPHOSPOHLIPID SYNDROME

Stella is a 42-year-old female with a history of multiple miscarriages and deep vein thrombosis (DVT) after a major motor vehicle accident six weeks ago. Stella has recently been diagnosed with antiphospholipid antibody syndrome.

PAUSE AND PONDER: A colleague reviewing Stella’s case notices that keeping her INR in range has been difficult and has required a wide variation in weekly warfarin dosing. What does your experienced colleague recommend?

Continue to adjust her warfarin based on the point-of-care (POC) testing values
Maintain the same dose for two weeks regardless of the POC testing level
Try a different monitoring approach

Antiphospholipid syndrome (APS) is an autoimmune disease that manifests as a persistent presence of antiphospholipid antibodies (aPLA) coinciding with thrombotic events or pregnancy complications. Table 5 lists a few antiphospholipid antibodies and their abbreviations.²⁷Classified APS cases must meet at least two criteria – one clinical and one laboratory. The clinical criterion is met through the presence of either pregnancy morbidity or vascular thrombosis. The laboratory criterion is met through high or medium titers of aCL, LA, or aβ2GPI antibodies. Positive titers must be measured at least 12 weeks apart to meet the criterion. In recent years, new antibodies and increased awareness have changed diagnosis and definition of APS, resulting in constantly changing classification criteria.²⁸

Table 5. Antiphospholipid Antibody Abbreviations

Antiphospholipid Antibody	Abbreviation
lupus anticoagulant antibody	LA
anti-cardiolipin antibody	aCL
anti-beta-2-glycoprotein I IgG & IgM antibody	aβ2GPI

The antibodies cause a prothrombotic state, contributing to miscarriages and thrombosis.²⁹ Thrombotic outcomes may be due to aPLA contributions to increased thrombus formation and platelet activation.³⁰ Approximately 80% of APS cases are characterized by thrombosis (venous or arterial) and the remaining 20% of cases are characterized by obstetric complications (such as miscarriages or fetal death). APS is associated with the highest risk of thrombosis in cases of triple positive aPLA or LA, aCL, and aβ2GPI positivity. Cases in which aCL is detected in isolation are associated with the lowest risk. APS generally occurs more often in women than in men, and prevalence increases in patients with systemic lupus erythematosus or venous thromboembolism (VTE).²⁷

The primary treatment for APS is use of anticoagulants.²⁷However, APS is a rare disease with varying presentations and limited information on diagnosis and classification, resulting in constantly evolving management strategies.³¹

For primary antithrombotic prophylaxis, or prevention of a first thrombosis, low-dose aspirin (75-100 mg/day) is recommended. Studies show that low-dose aspirin can reduce thrombotic event occurrence 2-fold; however, these are primarily observational studies. For high-risk situations (such as severe injuries or pregnancy), LMWH can be used.²⁷

For patients with APS and a first thrombotic event, warfarin is the preferred anticoagulant treatment. The target INR is 2.0 to 3.0. DOACs are first-line treatment for first thrombotic events in the general population, but in patients with APS they are not recommended due to decreased efficacy compared to warfarin, seen in increased recurring thromboses.³²DOACs can be considered in cases where patients are adherent to warfarin therapy and are unable to achieve INR target range or patients are contraindicated to use warfarin.³¹Warfarin is also considered first-line for secondary antithrombotic prophylaxis or prevention of recurrent thrombotic events following a first thrombosis.³³

Warfarin is considered embryotoxic, and is contraindicated in pregnancy as discussed in the previous section. Pregnant women with thrombotic APS should switch from warfarin to LMWH before the 6^th gestational week and continue therapy until delivery. However, patients with strong indications for warfarin can consider re-initiation in the second and third trimester after embryogenesis.²⁷

As stated above, warfarin is essential in APS treatment. However, APS can interfere with INR measurements, usually elevating them falsely. This may be due to antiphospholipid antibodies reacting with thromboplastin.³⁴The INR elevation is more prevalent in POC testing, possibly due to the proposed interaction between antiphospholipid antibodies and test reagents (such as commercial thromboplastins). Thus, venipuncture (VP) testing may be preferred as a more accurate measurement of INR in clinical settings to attain therapeutic warfarin dosing.³⁵

However, POC testing has numerous benefits compared to VP testing. In some situations, it is operationally valuable to consider using POC testing, such as for patients on whom it is difficult to perform VP testing,³⁴ or during situations that require global precautions, like the COVID-19 pandemic. Generally, POC testing improves patient convenience and accessibility.³⁵

POC testing, VP testing, and another test—CoaguChek XS—can be performed on the same day to correlate the different test results. CoaguChek measures chromogenic factor X level (cFX). cFX is generally unaffected by APS as it is not phospholipid-dependent, but this test may not be readily available and may require sending specimens to another laboratory. A cFX goal of 20% to 40% correlates with a goal INR of 2.0 to 3.0. Several same-day samples can be collected and correlated to adjust the goal INR matched to the patient’s elevated levels.³⁴Clinicians might consider POC testing use if the variation between POC tests and VP tests is less than or equal to 0.5 in INR readings. To assess validity of the correlation between paired tests, sampling can be repeated every three to six months.³⁵

As an example, the clinic started a 31-year-old female patient with APS on warfarin with an initial INR goal of 2.0 to 3.0. Table 6 shows repeated test results. Her POC testing INR was adjusted to account for the natural elevation due to APS. After the first correlation point, her POC INR goal was set to 2.5 to 3.0, and after the second correlation point it was increased to 2.5 to 4.0. However, her VP INR remained at 2.0 to 3.0.³⁴

Table 6. Repeated Tests Results for a 31-year-old Woman with Antiphospholipid Syndrome

Correlation Point	VP INR	POCT INR	cFX
1	2.1	2.5	34%
2	2.4	3.0	--
3	2.8	4.1	--

Anticoagulation pharmacists should note aberrant INR tests, such as values at or above 4.8 and call patients back for additional testing. Additionally, APS may affect different POC devices and different laboratory equipment differently. The clinic will need to re-correlate if it receives new devices or if the lab has to change reagent in their INR machines.³⁵The correlation process is individualized and cannot be extrapolated between patients.³⁴Few formal evaluations of the reliability of testing methods exist, highlighting an area which requires more research.

CASE #4: MONITORING FREQUENCY

Shirley is a 68-year-old female with a prosthetic mechanical atrial valve. She has been in the therapeutic INR range with the same dose (no changes) for the past five months; she is remarkably stable.

PAUSE AND PONDER: When reminded to return in four weeks for INR monitoring, she says “Ugh, why do I keep having to come back? Can I come back less often?” How would you respond?

It’s dangerous to go more than four weeks without testing
Testing every four weeks is the standard
Maybe we could have you come in less often

In the United States, common practice is to monitor a patient’s INR for warfarin dose adjustments every four weeks. To compare, in the United Kingdom, anticoagulant prescribers commonly use intervals of up to 90 days.³⁶Although many clinicians feel most comfortable continuing to monitor monthly, returning every four weeks for INR monitoring creates a large burden for anticoagulated patients. Clinicians must empathize with patients and utilize alternatives when it is clinically safe to do so. This may come in the form of extended intervals between INR monitoring or at home POC testing. The 2012 CHEST guideline revision suggested an INR testing frequency of up to 12 weeks with a level of evidence of grade 2B (weak recommendation, moderate quality of evidence) in patients who have demonstrated periods of stable INR control.³⁶

The initial evidence for extended intervals dates back to 2011.³⁷ In a groundbreaking trial, Warfarin Dose Assessment every 4 weeks versus every 12 Weeks in Patients with Stable International Normalized Ratios, researchers enrolled 126 participants in a 4-week follow-up arm and 124 participants in the 12-week follow-up arm. The trial size was fairly small. Eligible participants had to have been enrolled in a clinic and receiving the same maintenance dose for at least six months. The trial was blinded in the sense that all participants had blood drawn every four weeks, but the researchers discarded the 4- and 8-week draws in the extended interval group. The researchers used a surrogate marker, time-in-therapeutic range (TTR) to measure control and quality of therapy. Participants in the 4-week monitoring group (55%) were more likely to have dose adjustments than those in the second group (37%). Groups had similar numbers of subsequent out-of-range next INR values (27.3% in the 4-week arm, 28.4% in the 12-week arm). Major bleeding events were also similar, but rates of clinically relevant non-major bleeding (0.02 per 100 patient-years versus 0.09 per 100 patient-years) and emergency department visits (0.07 per 100 patient-years versus 0.19 per 100 patient-years) were lower for eligible patients with extended INR testing intervals than for those with shorter INR testing intervals.³⁷ The researchers concluded that extending the warfarin dosing assessment interval to every 12 weeks is probably safe for patients on stable doses if they continue to have supportive contact at least every four weeks.³⁷

The ACCP recommends monitoring every 12 weeks in patients who are stable, which is indicated by at least three months of consistent results with no required adjustment of vitamin K antagonist dosing. However, instances in which the INR becomes subtherapeutic or supratherapeutic at these every 12 week appointments, the clinical team should increase the monitoring frequency until the patient achieves a stable INR again.³⁸

One proposed model adjusts follow-up frequencies based on the appropriateness for each patient. A 2019 single-arm prospective cohort study titrated patients on a stable dose of warfarin up to the 12-week recall interval to assure that appropriate patients had their follow-up times extended. Qualifying patients had achieved their target INR of 2.0 to 3.0 for six months. The follow-up interval was first extended to 5 to 6 weeks, then 7 to 8 weeks, then 11 to 12 weeks, after which the researchers repeated the 11 to 12-week follow-up interval. If patients met an exclusion criterion (such as drug interaction, procedure, or hospitalization) or their INR was out of range, they would return to the usual care follow-up time (four weeks). Only restabilized patients would be re-titrated to the 12-week interval. This study suggests a future controlled trial design for methods of extending a stabilized patient’s INR follow-up interval.³⁹

SIDEBAR: Point-of-Care Testing^40,41

Not all providers feel comfortable switching their patients to 12-week monitoring. Since their patients might be seeking alternatives to returning to the clinic every four weeks, providers should know what other options are available. POC testing offers an alternative to patients who wish to avoid returning to the clinic for INR monitoring and dose adjustment every four weeks. Although the POC testing systems can be quite pricey, the time the patient saves by reducing clinic visits may be worth it.

Patient Self-Testing (PST): Patients test their own INR at home, data is reported to the clinic remotely, and a clinician adjusts the dose if necessary.
- Reduces patient burden by limiting trips to the anticoagulation clinic, and also limits provider burden
- Studies show that patients who monitored frequently (mostly weekly) had a greater TTR.
- Depends on the individual patient’s health literacy
- Increased convenience can be pricy–a trade off
- Overall - a safe option for patients that meet the criteria, even if it is not the most cost effective
Patient Self-Monitoring (PSM): Patients test their INR at home and are allowed to adjust their dose in response to the INR based on predetermined protocols.
- Lessens burden on providers who are no longer consistently monitoring a patient’s INR and making adjustments
- Requires extensive patient education
- Success also depends on a patient’s ability to afford and manage these POC devices and calculate dose adjustments
- Has been proven superior to PST in reducing mortality.
- Overall - this might not be the most cost-effective option but is safe

The 2018 American Society of Hematology guideline includes a conditional suggestion for recall intervals no longer than 4 weeks for patients undergoing dose adjustment due to out-of-target-range INR measurements. However, for patients experiencing periods of stable INR control, a longer recall interval is strongly recommended, generally 6 to 12 weeks. Additionally, patient self-testing (PST) - a form of home POC testing - is recommended over other INR testing approaches with the exception of patient self-management (PSM). PSM is a form of POC testing in which the patient tests their INR at home and self-adjusts vitamin K antagonist dosing.⁴¹

CONCLUSION

Pharmacists who work in anticoagulation will see patients like those described in this module. A PRO TIP is to think of each patient as an individual, ask questions, and avoid making judgments.

1. Patrick James, who goes by “PJ,” is a 33-year-old male who works in construction. He is obese and reports that he does not drink during the week but goes bar-hopping on Fridays and Saturdays, often staying out til 2 or 3 AM. He also watches sports on Sundays and drinks beer with the guys. He says, “I only have a few drinks, maybe six over the whole weekend.” It’s Wednesday afternoon. What is the BEST way to assess his chronic alcohol use?

A. Assume that his actual alcohol intake is twice what he reports

B. Sit with him and work through the AUDIT-C AUD screening tool

C. Order blood work for long-term biomarkers to determine if they are abnormal

2. After your assessment of PJ, you realize he is a heavy drinker who binges all weekend. Which counseling point is critical when you prescribe warfarin for PJ?

A. “You should carry a small notebook with you and record all of your drinks and the time that you drank them.”

B. “We need to train you to use a self-testing device so you can adjust your warfarin dose on the weekends.”

C. “I understand that you drink and we’ve talked about the risks. We will need to monitor your INR often.

3. Under what conditions might a prescriber use warfarin in a patient who is pregnant?

A. Only during the first trimester, then patients should be switched to a DOAC

B. Never, warfarin is absolutely contraindicated in all trimesters of pregnancy

C. In women with mechanical heart valves, who are at highest risk of thromboembolism

4. Emily is a 29-year-old woman who is at risk for mechanical valve thrombosis. She is scheduled to deliver on October 11. On what day should you tell her to stop her low-dose aspirin?

A. October 1

B. October 8

C. No need to stop the aspirin

5. Which of the following patients is the BEST candidate for INR testing every 12 weeks?

A. A 72-year-old woman who has been stable on warfarin for five years

B. A 33-year-old male who appears to be a binge drinker

C. A 24-year-old woman who is in her second trimester of pregnancy

6. Michael is a patient whose INR results have been stable for three months and has not necessitated any dose adjustments. What does the ACCP recommend as a monitoring interval for Michael?

A. Every 5 weeks

B. Every 7 weeks

C. Ever 12 weeks

7. In the ground-breaking 2011 trial that explored longer intervals between INR testing, what did the researchers measure?

A. aβ2GPI positivity

B. point-of-care INR

C. time-in-therapeutic range

8. When reminded to return in four weeks for INR monitoring, one of your patients says “Ugh, why do I keep having to come back? Can I come back less often?” She has been stable for 5 months. How would you respond?

A. It’s dangerous to go more than four weeks without testing

B. Testing every four weeks is the standard

C. Maybe we could have you come in less often

9. Roberta experienced a thrombosis and has been diagnosed with antiphospholipid syndrome. What is the recommended prophylaxis going forward?

A. low-dose aspirin

B. dabigatran

C. warfarin

10. Which of the following is a concern when dealing with patients who have APS?

A. APS can interfere with INR measurements, usually lowering them falsely.

B. APS can interfere with INR measurements, usually elevating them falsely.

C. DOACs are generally ineffective in patients who have APS.

11. Which of the following is a significant concern in patients who drink often or heavily and take anticoagulants?

A. Interaction between warfarin and alcohol

B. Falls

C. Comorbid liver cirrhosis

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Chan WS, Anand S, Ginsberg JS. Anticoagulation of Pregnant Women With Mechanical Heart Valves: A Systematic Review of the Literature. Arch Intern Med.2000;160(2):191-196. doi:10.1001/archinte.160.2.
Scheres LJJ, Bistervels IM, Middeldorp S. Everything the clinician needs to know about evidence-based anticoagulation in pregnancy. Blood Rev. 2019;33:82-97. doi:10.1016/j.blre.2018.08.001
Lester W, Walker N, Bhatia K, et al. British Society for Haematology guideline for anticoagulant management of pregnant individuals with mechanical heart valves. Br J Haematol. 2023;202(3):465-478. doi:10.1111/bjh.18781
Bates SM, Rajasekhar A, Middeldorp S, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv. 2018;2(22):3317-3359. doi:10.1182/bloodadvances.2018024802
ACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy: Correction. Obstet Gynecol. 2018;132(4):1068. doi:10.1097/AOG.0000000000002923
Uppuluri E, Idrees N, Shapiro N. Warfarin dosage in a postpartum woman while breastfeeding: A case report. Pharmacotherapy. 2024; 44: 343-347. doi:10.1002/phar.2917
Amin A. Oral anticoagulation to reduce risk of stroke in patients with atrial fibrillation: current and future therapies. Clin Interv Aging. 2013;8:75-84. doi:10.2147/CIA.S37818
Ghada Sayed Youssef. Management of atrial fibrillation during pregnancy. Escardioorg. 2019;17(15). https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-17/management-of-atrial-fibrillation-during-pregnancy
Regatiz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy: The Task Force for the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). European Heart Journal. 2018; 39(34):3165-3241. doi:10.1093/eurheartj/ehy340
Protamine. Lexi-Drugs. Lexicomp. Wolters Kluwer. Updated October 14, 2024. Accessed March 4, 2024. https://online.lexi.com
Gogarten W, Vandermeulen E, Van Aken H, et al. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol. 2010;27(12):999-1015. doi:10.1097/EJA.0b013e32833f6f6f
Capecchi M, Abbattista M, Ciavarella A, Uhr M, Novembrino C, Martinelli I. Anticoagulant Therapy in Patients with Antiphospholipid Syndrome. J Clin Med. 2022;11(23):6984. doi:10.3390/jcm11236984
Dabit JY, Valenzuela-Almada MO, Vallejo-Ramos S, Duarte-García A. Epidemiology of Antiphospholipid Syndrome in the General Population. Curr Rheumatol Rep. 2022;23(12):85. Published 2022 Jan 5. doi:10.1007/s11926-021-01038-2
Sammaritano LR. Antiphospholipid syndrome. Best Pract Res Clin Rheumatol. 2020;34(1):101463. doi:10.1016/j.berh.2019.101463
Pastori D, Menichelli D, Cammisotto V, Pignatelli P. Use of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Comparison of the International Guidelines. Front Cardiovasc Med. 2021;8:715878.
Tektonidou MG, Andreoli L, Limper M, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019;78(10):1296-1304. doi:10.1136/annrheumdis-2019-215213
Sayar Z, Moll R, Isenberg D, Cohen H. Thrombotic antiphospholipid syndrome: A practical guide to diagnosis and management. Thromb Res. 2021;198:213-221. doi:10.1016/j.thromres.2020.10.010
Rodziewicz M, D'Cruz DP. An update on the management of antiphospholipid syndrome. Ther Adv Musculoskelet Dis. 2020;12:1759720X20910855. doi:10.1177/1759720X20910855
Dush A, Erdeljac HP. INR Management of an Antiphospholipid Syndrome Patient With Point-of-Care INR Testing. J Pharm Pract. 2020;33(3):390-391. doi:10.1177/0897190019838192
Masucci M, Li Kam Wa A, Shingleton E, Martin J, Mahir Z, Breen K. Point of care testing to monitor INR control in patients with antiphospholipid syndrome. EJHaem. 2022;3(3):899-902. doi:10.1002/jha2.522
Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S-e184S. doi:10.1378/chest.11-2295
Schulman S, Parpia S, Stewart C, Rudd-Scott L, Julian JA, Levine M. Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. Ann Intern Med. 2011;155(10):653-W203. doi:10.7326/0003-4819-155-10-201111150-00003
Wigle P, Hein B, Bernheisel CR. Anticoagulation: Updated Guidelines for Outpatient Management. Am Fam Physician. 2019;100(7):426-434.
Porter AL, Margolis AR, Staresinic CE, et al. Feasibility and safety of a 12-week INR follow-up protocol over 2 years in an anticoagulation clinic: a single-arm prospective cohort study. J Thromb Thrombolysis. 2019;47(2):200-208. doi:10.1007/s11239-018-1760-9
Guidance on the Use of Point-of-Care Testing of International Normalized Ratio for Patients on Oral Anticoagulant Therapy. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; July 2014.
Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018;2(22):3257-3291. doi:10.1182/bloodadvances.2018024893

Resilience vs. Resistance: Winning the Battle Against Vancomycin-Resistant Infections

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

• EXPLAIN the common mechanisms of bacterial resistance and their impact on antibiotic efficacy

• RECOGNIZE the importance of early and effective management of resistant bacterial infections.

• IDENTIFY first- and second-line treatment options for VRE.

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

• DESCRIBE proper storage, reconstitution, and other considerations for antibiotics used for resistant infections

• IDENTIFY strategies to prevent dispensing errors when handling antibiotics and increase awareness of high-risk medications

• RECOGNIZE common dosing of antibiotics used for resistant bacterial infections

Pharmacist Learning Objectives:
1. Explain the common mechanisms of bacterial resistance and their impact on antibiotic efficacy
2. Recognize the importance of early and effective management of resistant bacterial infections
3. Identify first- and second-line treatment options for vancomycin resistant enterococci (VRE)

Pharmacist Questions:
1. How do enterococci develop resistance to vancomycin?
a. The terminus of the peptidoglycan cell wall changes
b. Production of enzymes inactivate vancomycin
c. Decreased outer membrane permeability

2. What prevention strategy involves early and effective therapy intervention?
a. Chlorhexidine bathing
b. Environmental cleaning
c. Antimicrobial Stewardship

3. Common enterococcal infection sites include the urinary tract, bloodstream, heart, and intra-abdominal space. What is the recommended first line agent for infective endocarditis?
a. High dose ampicillin
b. Linezolid
c. Tigecycline

4. Which prevention strategy can reduce the risk of VRE by addressing the risk factor of transmission through healthcare workers?
a. In vitro susceptibility testing
b. Hand hygiene
c. Active surveillance

5. The most common phenotype seen in VRE isolates is Van A. What mechanism of resistance is the VanA phenotype responsible for?
a. Increasing the efflux of antibiotics
b. Ribosomal protection
c. Changes in peptidoglycan cell wall

6. A provider calls the pharmacy asking for antibiotic recommendations for a bloodstream infection (bacteremia) growing gram positive cocci. The patient has a history of enterococcal bacteremia previously treated with antibiotics. What antibiotic should be recommended to the provider?
a. Ampicillin 2g every 4 hours
b. Daptomycin 8-12 mg/kg once daily
c. Nitrofurantoin 100mg twice daily

Resilience vs Resistance:
Winning the Battle Against Vancomycin-Resistant Infections
Pharmacy Technician Learning Objectives:
1. Describe proper storage, reconstitution, and other considerations for antibiotics used for resistant infections
2. Identify strategies to prevent dispensing errors when handling antibiotics and increase awareness of high-risk medications
3. Recognize common dosing of antibiotics used for resistant bacterial infections

Pharmacy Technician Questions:
1. A patient is receiving daptomycin 400 mg IV every 24 hours. As a technician, you want to compound today’s dose as well as tomorrow’s dose. Is this appropriate?
a. Yes, reconstituted solutions of daptomycin are stable at room temperature for up to 48 hours
b. No, reconstituted solutions of daptomycin are stable at room temperature for up to 12 hours
c. No, reconstituted solutions of daptomycin are stable at room temperature for up to 5 hours

2. What is a potential strategy to prevent medication dispensing errors?
a. Build a culture that encourages error reporting
b. Reducing the number of medications dispensed daily
c. Require pharmacist double checks on every medication dispensed

3. You see a label print for oritavancin. What would be an appropriate dosing you would expect to see?
a. 1200 mg IV once
b. 1200 mg IV every 12 hours
c. 1200 mg IV every 24 hours

4. Linezolid is reconstituted in the morning for patient administration. The nurse is unable to administer the medication because the patient is in the OR. How, and for how long can linezolid be stored after reconstitution?
a. Store at room temperature 20ºC to 25ºC (68ºF to 77ºF) for up to 24 hours
b. Store at room temperature 20ºC to 25ºC (68ºF to 77ºF) for up to 12 hours
c. Store at room temperature 20ºC to 25ºC (68ºF to 77ºF) for up to 21 days

5. Which of the following describes the medication dispensing error prevention strategy, encouraging error reporting?
a. Calling a patient’s pharmacy to confirm dispense history
b. Scanning the vial or patient label before administration
c. Filling out safety incident paperwork

6. What is a reasonable renally adjusted dose for tedizolid?
a. Tedizolid does not need to be renally adjusted
b. 200 mg IV or PO every 48 hours
c. 100 mg IV or PO every 24 hours

Carbidopa-Levodopa: Revving Up Relief – Choose Your Formula!

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

• DESCRIBE the role of carbidopa-levodopa in Parkinson's disease and the use of different carbidopa-levodopa formulations

• RECOGNIZE the differences between each carbidopa-levodopa formulation

• DISCUSS the appropriate patient who may benefit from transitioning to a different formulation of carbidopa-levodopa

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

• DESCRIBE the functions of the carbidopa-levodopa and how it aids in treatment for patients with Parkinson's disease

• LIST different forms of carbidopa-levodopa

• IDENTIFY when to refer patients with questions about Parkinson's disease to a pharmacist

Carbidopa-Levodopa: Revving Up Relief – Choose Your Formula! Pharmacist Test
Learning Objectives: Pharmacists
• Describe the role of carbidopa-levodopa in Parkinson’s disease and the use of different carbidopa-levodopa formulations
• Recognize the differences between each carbidopa-levodopa formulation
• Discuss the appropriate patient who may benefit from transitioning to a different formulation of carbidopa-levodopa

Knowledge Questions
1. What is the primary role of carbidopa-levodopa in the management of Parkinson's disease?
a. Carbidopa and levodopa directly increase dopamine production in the brain
b. Levodopa converts to dopamine in the brain, and carbidopa prevents its breakdown
c. Carbidopa and levodopa work by inhibiting the breakdown of dopamine in the brain

2. Which of the following factors can lead to reduced efficacy of carbidopa-levodopa in treating Parkinson’s disease?
a. Decreased dopamine receptors in advanced disease stages
b. Increased carbidopa leading to less peripheral conversion of levodopa
c. Lowering the carbidopa-to-levodopa ratio to reduce side effects

3. How does the formulation of carbidopa-levodopa controlled-release differ from the immediate-release version?
a. It increases peak dopamine levels in the brain
b. It reduces the amount of carbidopa needed to enhance levodopa absorption
c. It provides a slower, more continuous release of levodopa

4. What is a key difference between carbidopa-levodopa IR and foscarbidopa-foslevodopa?
a. Carbidopa-levodopa IR causes peaks and troughs of levodopa, foscarbidopa-foslevodopa is formulated to give more consistent levodopa
b. Carbidopa-levodopa IR is dosed once daily, while foscarbidopa-foslevodopa is dosed multiple times daily
c. Carbidopa-levodopa IR is dosed using levodopa concentration levels, foscarbidopa-foslevodopa is dosed using carbidopa concentration levels

5. Which of the following is a reason why we should consider switching a patient’s carbidopa-levodopa IR to carbidopa-levodopa ER (Crexont)?
a. Patient is not experiencing “off” time
b. Patient is experiencing “off” time ≥2.5 hours
c. Patient is experiencing “on” time ≥2.5 hours

6. AL is a 55-year-old with Parkinson’s disease. He takes carbidopa-levodopa IR 25mg/100mg two tablets four times daily. He has a hard time with his current number of pills and breakthrough symptoms between doses. Which of the following alternative dose of carbidopa-levodopa would be appropriate for AL?
a. Carbidopa-levodopa ER (Crexont) 420mg three times daily
b. Carbidopa-levodopa ER (Rytary) 195mg twice daily
c. Foscarbidopa-foslevodopa (Vyalev) 0.27mg/hr

Carbidopa-Levodopa: Revving Up Relief – Choose Your Formula! Technician Test

Learning Objectives: Technicians
• DESCRIBE the functions of the carbidopa-levodopa and how it aids in treatment for patients with Parkinson’s disease
• LIST different forms of carbidopa-levodopa
• IDENTIFY when to refer patients with questions about Parkinson’s disease to a pharmacist

3. How does the formulation of carbidopa-levodopa in Sinemet CR differ from the immediate-release version?
a. It increases peak dopamine levels in the brain
b. It reduces the amount of carbidopa needed to enhance levodopa absorption
c. It provides a slower, more continuous release of levodopa

4. Which of the following are approved dosage forms of carbidopa-levodopa?
a. Sublingual tablets and extended-release capsules
b. Intravenous infusion and immediate-release tablets
c. Extended-release capsules and subcutaneous infusion

5. Which of the following is a reason a patient may discuss with a pharmacist about switching from carbidopa-levodopa IR to carbidopa-levodopa ER (Crexont)?
a. Patient is not experiencing “off” time
b. Patient is experiencing “off” time >2.5 hours
c. Patient is experiencing “on” time >2.5 hours

6. Which of the following patients should be sent to pharmacist counsel window?
a. Patient with questions about drug interactions between CD-LD IR and antibiotics
b. Patient with questions about cost of CD-LD ER (Crexont) with their new insurance
c. Patients with questions about putting their PD medications on automatic refill

So Much STI Data: Information to help you stay current and informed – RECORDED WEBINAR

The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Pharmacists and Pharmacy Technicians are eligible to participate in this application-based activity and will receive 1.0 CE Hour for completing the activity (ACPE UAN 0009-0000-25-030-H01-P), passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the CPE Monitor online system and your participation will be recorded with CPE Monitor within 72 hours of submission.

1.) A 19-year-old female is at the clinic. She had recent unprotected sexual intercourse with her partner. She has not had any previous STI screenings. Which STIs are indicated for screening at this time?
a. HIV, gonorrhea, and chlamydia
b. Gonorrhea, chlamydia, and syphilis
c. Chlamydia, syphilis, and HPV

2.) Which of the following STIs have shown a continued increase in incidence based on 2023 data?
a. Congenital syphilis
b. Gonorrhea in the population
c. Chlamydia cases in men

3.) After completing gonorrhea treatment, when should a clinician re-screen the patient?
a. 1 month after completing treatment
b. 3 months after completing treatment
c. 1 year after completing treatment

4.) What is the guideline-based treatment recommendation for a 200 lb male patient with a confirmed gonorrhea and chlamydia co-infection?
a. Ceftriaxone 500 mg IM x 1 and azithromycin 1000 mg PO x 1
b. Ceftriaxone 250 mg IM x 1 and doxycycline 100 mg PO BID x 7 days
c. Ceftriaxone 500 mg IM x 1 and doxycycline 100 mg PO BID x 7 days

5.) Which population should receive seven days of treatment with metronidazole for trichomoniasis?
a. Young males 15 – 24 years old
b. Males 25 – 45 years old
c. Females of any age

6.) A pregnant patient is positive for primary syphilis. What is the guideline recommended treatment for her?
a. 2.4 million units benzathine penicillin G IM x 1
b. 2.4 million units benzathine penicillin G IM x 3 weekly doses
c. 100 mg PO doxycycline 2 time daily doses for 28 days
7.) Which of the following is a newly approved type of product that will increase patient access?
a. OTC bacterial Pre-Exposure Prophylaxis
b. OTC home screening tests for STIs
c. OTC HIV Post Exposure Prophylaxis

8.) What should pharmacists warn healthcare providers about regarding possible alternatives during a shortage of Bicillin LA for syphilis?
a. Impact of HIV cases
b. Adverse effects from the frequent use of the medication
c. Antimicrobial resistance

9.) You are working with emergency department physicians to manage a shortage of ceftriaxone. One concern is the treatment of gonorrhea. Which of the following would be a stewardship principle applied to this STI management choice?
a. Use the most recent antibiotic approved for the indication
b. Use alternative based on narrowest effect spectrum and incorporating local resistance data, if known
c. Choose an alternative that will also cover other STIs just in case

NKOTB: 2025 Updates on Management of Hypertension in Adults – RECORDED WEBINAR

The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Pharmacists and Pharmacy Technicians are eligible to participate in this application-based activity and will receive 1.0 CE Hour for completing the activity (ACPE UAN 0009-0000-25-064-H01-P), passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the CPE Monitor online system and your participation will be recorded with CPE Monitor within 72 hours of submission.

According to the 2025 guidelines, which of the following represents the blood pressure goal for adults with confirmed hypertension?
1. SBP < 120 mmHg & DBP < 70 mmHg
2. SBP < 130 mmHg & DBP < 80 mmHg
3. SBP < 140 mmHg & DBP < 90 mmHg
According to the 2025 Hypertension guidelines, which of the following would be an appropriate initial combination to start in a patient with stage 2 hypertension?
1. Lisinopril + amlodipine***
2. Valsartan + chlorthalidone
3. Verapamil + hydrochlorothiazide
When using the PREVENT equation to estimate 10-year cardiovascular disease risk, what is the threshold above which a patient with hypertension should be initiated on drug therapy medications to lower their blood pressure?
1. >5%
2. >7.5%
3. >10%
Which of the following represents a new recommendation in the 2025 Hypertension guideline that was not in the previous (2017) version?
1. Start initial combination therapy for anyone with stage 2 hypertension
2. ACEi/ARB, CCB, and diuretics are first-line therapies unless contraindicated
3. Individuals without BP ≥130/80 mmHg, no CVD, and a 10-year CVD risk ≥7.5% should start antihypertensive medication
Which of the following is most accurate about emerging drug treatments for hypertension?
1. Emerging drug therapies, while effective, have concerns for hyperkalemia and hypotension
2. Trials have exclusively been conducted in newly-diagnosed adult patients
3. Mechanisms of emerging drugs have targeted attenuation of the sympathetic nervous system

Information overload in Chronic Coronary Disease – RECORDED WEBINAR

The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Pharmacists and Pharmacy Technicians are eligible to participate in this application-based activity and will receive 1.0 CE Hour for completing the activity (ACPE UAN 0009-0000-25-028-H01-P), passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the CPE Monitor online system and your participation will be recorded with CPE Monitor within 72 hours of submission.

1. A female patient is interested in lifestyle modification. Which of the following would you recommend?
a. Switch from EVOO to coconut oil
b. Switch from smoking weed to “doing” crystal methamphetamine
c. Limit alcohol to a maximum of 1 drink a day

2. A patient with CCD is determined to have “high risk” of experiencing an ASCVD event. The patient cannot receive high- or even moderate-intensity statins due to a history of significant rises in liver enzymes 8-10 weeks after initiation on two occasions. Which is true of the patient’s recommended lipid regimen?
a. The patient needs high-intensity statin regardless of the liver issues and ezetimibe should be added if the LDL on the statin is over 70mg/dL
b. The patient could receive a low intensity statin + a PCSK9 inhibitor and if the LDL remains over 70mg/dL, ezetimibe can be added
c. The patient could receive a PCSK9 inhibitor and if the LDL remains over 70mg/dL, ezetimibe can be added

3. Why can’t metoprolol tartrate be used to terminate a new onset angina pectoris event?
a. Because the onset of action is 30 minutes, and the maximum effect is felt 2 hours after ingestion
b. Because I am a pharmacist and I said so, that’s why
c. Because metoprolol does not work on the coronary arteries and only coronary dilators can be used for acute angina pectoris events

4. A student is explaining the PPCP process to you. Which of the following statements would you question and ask the student to research?
a. The PPCP process helps structure an assessment to be sure that important drug related problems are all included
b. Major pharmacy organizations agreed upon this process to show regulators, clinicians, patients, payers and insurers our unique patient services
c. “PPCP” is an old term; major professional organizations have replaced it with the subjective-objective-assessment-plan process

5. When would it be useful to recommend nitroglycerin spray instead of sublingual nitroglycerin?
a. In a patient taking an anticholinergic
b. In a patient taking an SSRI
c. In a patient taking benzodiazepines

6. JP is a patient who has rheumatoid arthritis and chronic coronary disease. He has an hsCRP test taken and the level is 7.2 mg/dL. Would this patient be a candidate for colchicine therapy according to the AHA/ACC Guideline and why or why not?
a. Yes, colchicine should be used in all people with elevated hsCRP
b. Yes, colchicine should be used in all patients regardless of hsCRP
c. No, specific disease modifying antirheumatic drug are used in patients with RA

7. AT is a patient with heart failure with reduced ejection fraction, who also has chronic coronary disease. Would an SGLT2 inhibitor or a GLP-1 agonist be preferred for the treatment of this patient?
a. Neither drug should be used at all
b. The SGLT-2 inhibitor would be preferred
c. The GLP-1 agonist would be preferred

8. WC is a patient who just had a PCI procedure but also has atrial fibrillation and is treated with rivaroxaban. What is the proper regimen to prevent stent occlusion?
a. Clopidogrel + aspirin + rivaroxaban for one month, then clopidogrel + rivaroxaban for 5 months, then just rivaroxaban alone thereafter
b. Clopidogrel + aspirin + rivaroxaban for six months, then clopidogrel + rivaroxaban for 6 months, then just rivaroxaban alone thereafter
c. Clopidogrel + aspirin + rivaroxaban for 12 months, then rivaroxaban + clopidogrel then rivaroxaban for 6 months, then rivaroxaban alone

THYROID DISEASE: The Basics and the Latest

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

Discuss Thyroid Disease and the typical medications used to treat it
Explain drug-induced hypo/hyperthyroidism, drug interactions, and proper administration of thyroid medications
Explain the lab work and the frequency of monitoring needed for patients treated with levothyroxine
Differentiate hypothyroid disease from subclinical hypothyroid disease and their respective treatment approaches

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

Recall and list the common symptoms of thyroid disease
Identify typical medications used to treat thyroid disease
Recognize when to refer patients to the pharmacist for further consultation

Thyroid hormones, produced by the tiny thyroid gland, influence almost every organ in the body. They control the body’s energy production and metabolic rate; imbalances can have profound health consequences. Thyroid disease is classified as hypothyroidism or hyperthyroidism. In the United States, an estimated 20 million people have thyroid disease. Hashimoto’s thyroiditis, an autoimmune disease resulting in hypothyroidism, accounts for most thyroid disease in the U.S. Prescribers treat it with levothyroxine, which is among the most frequently dispensed medications. Many patients have subclinical hypothyroidism and the decision to treat with levothyroxine is based on a patient’s individual circumstances. Hyperthyroid disorders are less common, and most cases are Graves’ disease, an autoimmune disorder. The 2020 approval of teprotumumab marked a major advancement in the treatment of thyroid eye disease. Pharmacologic treatment of thyroid disease is largely safe and effective with proper management. A knowledgeable pharmacy team can have a positive impact on patient care.

INTRODUCTION

Did the Mona Lisa have hypothyroidism? Discussions around the Mona Lisa’s enigmatic smile have fascinated art lovers for centuries but now some endocrinologists have started a new line of debate. They describe telltale signs, like swollen hands, thinning hair, and a lump in the neck, that point to the famous Mona Lisa exhibiting hypothyroidism. They even suggest that the disease contributed to her mysterious smile. Amusing! When you view the painting do you see the same signs?

Theodor Kocher, a Swiss physician who was award the Nobel Prize in 1909 for his work on the thyroid gland, described the first case of hypothyroidism in the mid-19^th century.¹Effective treatment emerged about 100 years ago, so if the 16^th century Mona Lisa had hypothyroidism, she might have suffered without knowing the cause. Patients with undiagnosed or inadequately treated hypothyroidism are at risk for cardiovascular problems, osteoporosis, and infertility.²

The thyroid gland’s main hormones are responsible for controlling the body’s energy production and metabolic rate and they affect nearly every organ system in the body. Having too little or too much of these hormones can have profound consequences on health.

Millions of Americans are affected by thyroid disease with most cases classified as hypothyroidism or underactive thyroid. Children, whose cognitive and physical development depends on normal thyroid function, can also be affected.³ Levothyroxine is used to treat hypothyroidism and is consistently among the most frequently prescribed medications in the United States (U.S.).⁴ Although less common, hyperthyroid disease is a serious endocrine disorder with profound health consequences if not properly treated.

THYROID GLAND AND FUNCTION

The thyroid gland is a small bow tie shaped endocrine gland that sits at the base of the neck. It produces two main hormones: tetraiodothyronine called thyroxine (T4), and triiodothyronine (T3). T4 and T3 control energy production and metabolic rate and influence nearly every organ system in the body including the brain, bowels, and skin. They regulate protein, carbohydrate, and fat metabolism by stimulating protein production and increasing oxygen needs at the cellular level. They are essential for proper fetal and neonatal development. Thyroid hormones influence body temperature, heart rate, appetite, mood, and digestion.²

Iodine is a constituent of T4 and T3 and sufficient dietary intake of iodine and its adequate uptake by the thyroid gland is necessary for proper thyroid function. The thyroid gland produces mostly inactive hormone in the form of thyroxine, called T4 because it has four iodine atoms. T4 is highly protein bound for transport to the liver where it undergoes deiodination (the removal of one iodine atom) resulting in T3. T3, like T4, is highly protein bound and must be released from its binding protein to be active. Equilibrium is maintained between bound and free T3; as the body demands more biologically active hormone more T3 is released from the binding protein. Free T3 is the main biologically active form of thyroid hormone.²

Hypothalamic-Pituitary-Thyroid Axis

The hypothalamic-pituitary-thyroid axis governs thyroid hormone production by regulating the synthesis and secretion of thyroid stimulating hormone (TSH), also called thyrotropin. The hypothalamus is the part of the brain responsible for monitoring thyroid hormone levels in the body. When the hypothalamus detects low levels of thyroid hormone in the body, it releases a hormone called thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary gland, the small pea-size gland sitting at the base of the brain, to secrete TSH. TSH, in turn, instructs the thyroid gland to produce more T4 and T3. High levels of T4 in the body inhibit TSH secretion while low levels of T4 stimulate TSH secretion. Disease affecting any part of the hypothalamic-pituitary-thyroid axis can result in thyroid hormone imbalances and disease.²

THYROID DISEASE AND ETIOLOGY

Thyroid disease is an endocrine disorder. Primary thyroid disease refers to disease of the thyroid gland. Secondary thyroid disease is far less common and refers to disease affecting the hypothalamus or pituitary gland resulting in thyroid dysfunction. Thyroid disease is classified as either hypothyroidism or hyperthyroidism.

Hypothyroid Disease

Hypothyroid disease occurs when inadequate thyroid hormone is available to the body. It is often referred to as an underactive thyroid and it is the most common form of thyroid disease. Hypothyroid disorders are categorized as either primary hypothyroidism or secondary hypothyroidism. The vast majority of cases are primary hypothyroidism.²

Hashimoto’s Thyroiditis

Hashimoto’s thyroiditis (HT) is the most common cause of primary hypothyroidism in the U.S. Japanese physician Hakaru Hashimoto first described the disease in 1912. It wasn’t until decades later that it was recognized as an autoimmune disorder and it is now considered the most prevalent autoimmune disease.⁵ Many patients do not realize that their hypothyroid condition is caused by this autoimmune disorder.

HT is characterized by infiltration and destruction of thyroid cells by leukocytes (white blood cells). A chronic autoimmune inflammation ensues resulting in atrophy and fibrosis of the thyroid gland that leads to hypothyroidism. Circulating thyroid autoantibodies, anti-thyroperoxidase antibody (anti-TPO Ab), and anti-thyroglobulin antibody (anti-Tg Ab) can be detected but clinicians usually don’t measure them since all treatment of hypothyroidism is similar.⁶

Women are more likely to develop HT and often have a family history, implicating a genetic component. The presence of other autoimmune disorders is common and prevalence is higher among those with chromosomal disorders like Down syndrome.²

Patients may present with thyroiditis (inflammation of the thyroid gland) and symptoms of hypothyroidism, like weight gain and fatigue, but not always. Symptoms can develop gradually and go unnoticed. Laboratory assessment of thyroid function (discussed below) confirms the diagnosis. Individuals diagnosed with HT require lifelong treatment with the thyroid replacement hormone levothyroxine.⁶

HT’s complications can manifest particularly in untreated or undertreated individuals including²:

Lipid disorders (elevated total cholesterol, LDL, and triglycerides)
Anemia
Menstrual abnormalities
Infertility
Hyponatremia
Thyroid associated orbitopathy
Increased risk for papillary thyroid carcinoma

Lipid disorders are of particular concern because they can contribute to coronary artery disease. Anemia is observed in 30% to 40% of patients. Recent research has suggested greater risk for recurrent pregnancy loss in patients with HT and an additional autoimmune disorder, but more research is needed to fully understand the link.⁷

Most complications of HT are rare but prescribers must monitor and treat complications as they arise to optimize patient management.⁸

Researchers have also noted vitamin D deficiency in HT. A randomized, double blind, clinical trial observed that supplementation with vitamin D reduced circulating thyroid autoantibodies.⁵The researchers suggest a possible role for vitamin D in the alleviation of disease activity but acknowledge the need for further studies before introducing this intervention to clinical practice. Despite the need for additional research, treating vitamin D deficiency in patients with HT may be warranted.

Gut microbiota are considered intrinsic regulators of thyroid autoimmunity. Scientists have studied the composition of the microbiota in patients with thyroid autoimmunity and have found it to be altered in HT.⁹Clinical implications of this research are not fully understood, but further research may determine the role these findings may have in HT management.

With early diagnosis, prompt treatment, proper follow-up care, and attention to associated complications, HT’s prognosis is excellent, and patients lead a normal life.¹⁰

Iodine Deficiency Hypothyroidism

Although uncommon in America, iodine deficiency is the leading cause of hypothyroidism worldwide. Adequate iodine intake is necessary for the thyroid gland to function properly, and it is critical for normal fetal and neonatal development. The recommended daily allowance (RDA) for adults is 150 mcg and it increases to 250 mcg in pregnancy and to 290 mcg during lactation. Goiter (an abnormal enlargement of the thyroid gland) is common as the thyroid gland enlarges in an attempt to sequester iodine to make thyroid hormone.^11,63

Universal salt iodization programs have dramatically reduced iodine deficiency-related thyroid disease.¹² Historically, iodine deficient areas in the U.S. included the mountainous regions and the so called “goiter belt” around the Great Lakes. Most Americans now consume adequate amounts of iodine in their diets by using iodized salt and by eating dairy products, eggs, and seafood. However, certain populations may still be at risk, including vegans, pregnant women, and people who don’t use iodized salt.¹¹ Most alternative milk products are low in iodine and processed foods like canned soup and specialty salts–including kosher, Himalayan, and sea salt–rarely provide iodine.¹³ Healthcare practitioners must be aware of iodine deficiency’s consequences, especially during pregnancy.^11,63

Thyroid diets have gained interest among patients and circulate widely on the Internet. These diets promote avoiding particular foods to achieve optimal thyroid function. Certain foods including broccoli, Brussels sprouts, cabbage, cauliflower, and soy contain goitrogens, which are substances that interfere with iodine uptake by the thyroid. For most people in the U.S. who consume adequate amounts of iodine, eating foods containing goitrogens is not a concern. People with iodine deficiency who eat an abundance of these foods may have trouble consuming enough iodine.^13,63

Thyroidectomy and Cancer Treatment Resulting in Hypothyroidism

Thyroidectomy, the surgical removal of the thyroid gland, is sometimes indicated in cancer treatment and in some cases of hyperthyroidism. Thyroidectomy results in hypothyroidism and patients require life-long thyroid hormone replacement with levothyroxine.¹⁴

Most thyroid cancers respond well to treatment, but a small percentage can be very aggressive. Treatment of thyroid cancer often results in hypothyroidism and patients require lifelong treatment with thyroid replacement hormone.¹⁴

Medication-Induced Hypothyroidism

The pharmacy team must be aware that certain medications can affect thyroid function. Table 1 lists common medications that can cause hypothyroidism and hyperthyroidism. The medications that cause hypothyroidism decrease synthesis of T4/T3, inhibit T4/T3 secretion, and/or cause thyroiditis.¹⁵

Table 1. Medications that May Lead to Thyroid Dysfunction
Drug class/medications	Hypothyroidism	Hyperthyroidism
Antidysrhythmic:
Amiodarone	X	X
Bipolar Disorder Medication:
Lithium	X	X
Thyroid Medications:
PTU	X
Methimazole	X
Radioactive Iodine	X
Cancer Medications:
Biological response modifiers:
Interferon	X
Interleukin-2	X
Tyrosine kinase inhibitors:
Sunitinib	X
Sorafenib	X
Checkpoint inhibitors:
Nivolumab	X	X
Pembrolizumab	X	X
Ipilimumab	X	X
Multiple Sclerosis Medication:
Alemtuzumab		X

Medications that cause thyroid disorders are important treatments and, in most cases, they cannot be discontinued; any drug-induced hypothyroidism requires levothyroxine.

Amiodarone structurally resembles thyroid hormone and is often implicated in thyroid dysfunction, mostly hypothyroidism.¹⁶ It is comprised of 37% iodine, so a 200 mg dose provides 75 mg of organic iodide, which is 100 times more than required. Researchers estimate thyroid abnormalities occur in 14% to 18% of patients taking long-term amiodarone but a meta-analysis found that with low doses, the incidence is lower (3.7%).¹⁷ Lithium can inhibit thyroid hormone release resulting in hypothyroidism; it usually occurs in younger women within the first two years of therapy. Antineoplastic agents may cause thyroid dysfunction in 20% to 50% of patients.¹⁸ Pharmacists must educate patients about the need for routine thyroid function assessment when receiving these medications.

Hyperthyroid Disease

Hyperthyroidism is characterized by excessive metabolism and secretion of thyroid hormones. It is less common than hypothyroid disease. Graves’ disease, thyroiditis, multi-nodular goiter, and toxic nodular goiter (benign growths on the thyroid gland that produce thyroid hormone in excess) can also cause hyperthyroid disease. Ingestion of too much external thyroid hormone is another possible cause of hyperthyroidism.¹⁹

Graves’ Disease

Graves’ disease (GD) accounts for most cases of hyperthyroidism. GD is an autoimmune disorder caused by a stimulatory autoantibody against the thyroid receptor for TSH. Most autoantibodies are inhibitory; in GD, the autoantibody is stimulatory. Overstimulation of the thyroid gland results in the overproduction of T4 and T3 leading to hyperthyroidism.¹²

Graves’ disease, like HT, appears to have a genetic link and is often comorbid with other autoimmune disorders. Risk factors for GD include smoking and iodine deficiency. In the case of iodine deficiency, multifocal autonomous growth of the thyroid gland can occur and result in thyrotoxicosis (excess levels of thyroid hormone in the body).²⁰ Women are affected at a higher rate and children can also be affected. GD’s clinical presentation may be dramatic or subtle and goiter may or may not be present. Laboratory assessment of thyroid function is used to help diagnose GD.

Researchers have studied the composition of gut microbiota in patients with GD and similar to findings in HT, have found it to be altered. The researchers suggest the findings from this randomized controlled trial may offer an alternative noninvasive diagnostic methodology for GD.²¹ Further research is needed to elucidate the role microbiota may play in thyroid autoimmunity.

Thyroid Eye Disease

Thyroid eye disease is a progressive, potentially sight threatening ocular disease that is reported in almost half of patients who have GD. It arises from a separate autoimmune process involving autoantibodies that activate an insulin-like growth factor-1 receptor (IGF-1R) mediated signaling complex on cells within the eye orbit. The most common clinical feature is proptosis (bulging eyes) with edema and erythema of the surrounding eye tissue, but patients may also experience a skin manifestation called thyroid dermopathy (a nodular diffuse thickening of the skin on the legs). Patients with thyroid eye disease often complain of dry and gritty ocular sensation, photophobia, excessive tearing, double vision, and pressure sensation behind the eyes. Severe disease occurs in 3% to 5% of patients causing intense eye pain and inflammation, and threatening sight.²²

Recently, the Food and Drug Administration (FDA) approved the monoclonal antibody teprotumumab for treatment of adults with thyroid eye disease, marking a significant advancement in treatment. Prior to this approval, treatment options only included steroids or surgery.²³

Medication Induced Hyperthyroidism

Like medication that can cause hypothyroidism, some medication can cause hyperthyroidism. The pharmacy team must be knowledgeable of the medications that can cause hyperthyroidism that warrant close monitoring of thyroid function (See Table 1). Patients should understand the importance of routine thyroid function assessment when taking medications that can affect thyroid function.

Amiodarone-associated hyperthyroidism is less common than amiodarone-associated hypothyroidism; still, it is estimated to occur in 3% of patients. Onset of amiodarone-induced thyrotoxicosis (elevated levels of free thyroid hormone) can be sudden and require rapid assessment and treatment.¹⁶ Pharmacists must educate their patients about the symptoms of hyperthyroidism and instruct them to report them immediately if encountered.

PAUSE AND PONDER: How many of your patients take medications that might cause thyroid dysfunction? Why is it important to tell these patients that some of their medications might influence the thyroid gland?

PREVALENCE

As many as 20 million Americans are affected by thyroid disease. Clinicians diagnose hypothyroidism in nearly five of 100 Americans aged 12 years and older.²⁴ Thyroid disease affects men, women, and children. Women are disproportionately affected at a 10 to 15 times higher rate, and it’s estimated one in eight women will develop some form of thyroid disease in their lifetime.²⁴

HT is most often diagnosed between the ages of 40 to 60 years. Prevalence increases with age.⁸ Twenty percent of adults older than 75, most of them women, have insufficient levels of thyroid hormone.²⁴ The Colorado Thyroid Disease Prevalence Study,a cross-sectional study conducted more than 20 years ago, reported the prevalence of hypothyroid disease in symptomatic and asymptomatic adults at 9.5%.²⁵ In people not taking thyroid hormone, prevalence was 8.5% and 0.4% for subclinical and overt disease, respectively.¹⁰

Hyperthyroidism is much less common than hypothyroidism. Prevalence of hyperthyroidism in the U.S. is estimated at 1.3%. GD is the most common cause of hyperthyroidism followed by toxic nodular goiter. GD is estimated to affect 1% of the population, mainly women of childbearing age. Incidence increases with age, and it is observed more frequently in Caucasians compared to other races. Mild hyperthyroidism occurs at a higher rate in iodine deficient geographic areas.¹²

SYMPTOMS

Because thyroid hormones affect nearly every organ system in the body thyroid disease’s symptoms are wide ranging and numerous. Symptoms vary depending on the type of thyroid disease and patients may experience few or many symptoms.²⁶ Clinicians should routinely monitor patients for symptoms of thyroid disease, especially those at risk for thyroid disease including elderly women (See Table 2).²⁷

Table 2. Thyroid Disease’s Common Symptoms
	Hypothyroidism	Hyperthyroidism
Whole body	Fatigue, lethargy, cold sensitivity	Hunger, fatigue, weakness, sweating, increased appetite, heat intolerance, insomnia
Mood/behavioral	Depression, irritability, sluggish, brain fog	Nervousness, restlessness, hyperactivity, panic attacks
Cardiac	Bradycardia, elevated cholesterol	Tachycardia, palpitations
Weight	Weight gain	Weight loss
Hair, skin, nails	Hair loss, dry skin/hair, brittle nails	Hair loss, warm skin
Eyes/face	Periorbital edema, puffy face	Proptosis (abnormal protrusion of eyes)
Gastrointestinal	Constipation	Frequent bowel movements
Menstruation/fertility	Heavy or irregular menstrual periods, fertility problems	Amenorrhea, lighter or irregular menstrual periods, fertility problems
Musculoskeletal	Joint/muscle pain	Osteoporosis
Thyroid presentation	May be enlarged	May be enlarged

Weight gain is a common and often first symptom of hypothyroidism. Up to 82% of women with HT have excess body weight and a third suffer from obesity.²⁸ Despite achieving euthyroidism (normal thyroid function) with levothyroxine treatment, many women continue to struggle to lose weight. Caloric reducing diets are often unsuccessful and excess body weight increases risk for comorbidities.²⁹

Food sensitivity and the effects of elimination diets on autoimmune disease have gained interest. An interventional/observational study evaluated the effect of an elimination diet in obese women diagnosed with HT. The researchers observed that women eliminating sensitive foods (foods that may cause an IgG antibody reaction) in addition to caloric reduction had a greater decrease in body mass index (BMI) when compared to women only reducing caloric intake.³⁰Improvement in thyroid function laboratory parameters was also observed in the group eliminating sensitive foods.³¹

LABS TO ASSESS THYROID FUNCTION

Thyroid function is assessed mainly through readily available laboratory blood tests. Results of basic thyroid function laboratory tests largely differentiate and diagnose thyroid disease (See Table 3).

Table 3. Thyroid Function Tests in Hypothyroidism and Hyperthyroidism³²

	TSH (Thyrotropin)	FT4 (Thyroxine)	T3
Lab reference range*	0.5-4.8 mIU/L	0.7-1.8 ng/dL	80-220 ng/dL
Hypothyroidism
Primary, untreated	High	Low	Low or normal
Secondary to pituitary disease	Low or Normal	Low	Low or normal
Hyperthyroidism
Untreated	Low	High	High
T3 toxicosis	Low	Normal	High

*Reference ranges may vary among laboratories.

TSH is the best measurement to assess thyroid function. A normal TSH essentially rules out thyroid disease, except in the less common cases of disease affecting the hypothalamus or pituitary gland. The American Thyroid Association (ATA) recommends routine screening of TSH in adults beginning at age 35 and repeating the test every five years.²⁷

T4 is the primary thyroid hormone circulating in the blood. T4 is found in the body in two forms: free T4 and bound T4. More than 99% of T4 is bound. Because T4 is converted into T3, free T4 (FT4) is the more important hormone to measure. Any changes show up in T4 first; therefore, FT4 reflects thyroid gland function more accurately.³³ Assessment of T3 is primarily used to diagnose and manage hyperthyroidism. It is rarely assessed in hypothyroidism since it’s the last test to become abnormal.³⁴

Patients with thyroid autoimmunity disease develop thyroid autoantibodies. Measurement of autoantibodies may help diagnosis, but clinicians need not monitor them routinely for disease management. Physicians typically order TSH with reflex to FT4 to assess thyroid function in disease management. Reflex testing allows the laboratory to automatically add the FT4 test to the blood sample based on an abnormal TSH result.³⁵

Clinicians sometime use radioactive iodine uptake (a non-blood test) to assess thyroid function. Because iodine is a necessary component of thyroid hormone, administering radioactive iodine and calculating its uptake by the thyroid can determine if the gland is functioning properly. Very high uptake is associated with hyperthyroidism while low iodine uptake indicates hypothyroidism.³⁴

TREATMENT APPROACHES

Levothyroxine

Levothyroxine sodium tablets (Synthroid and many generics) are synthetic T4 and indicated as replacement therapy in all hypothyroidism, regardless of the cause. Thyroid replacement hormone has a narrow therapeutic index and prescribers must individualize each patient’s levothyroxine dose. It is available in 12 different strengths, making it possible for prescribers to titrate doses carefully and avoid under- or over-treatment. Tablets are color-coded and are available from many manufacturers. (See Table 4.)

Table 4. Various Strengths and Colors of Levothyroxine Tablets

Strength	Color
25 mcg	Orange
50 mcg	White
75 mcg	Violet
88 mcg	Mint green
100 mcg	Yellow
112 mcg	Rose
125 mcg	Brown
137 mcg	Deep blue
150 mcg	Light blue
175 mcg	Lilac
200 mcg	Pink
300 mcg	Green

Variability in levothyroxine absorption may exist across manufacturers. A cohort study in the Netherlands evaluated a forced switch of levothyroxine brand. The researchers concluded that a dose-equivalent levothyroxine brand switch might necessitate a dose adjustment.³⁶ The ATA recommends using a consistent manufacturer. If a brand switch is made, the pharmacy team must inform prescribers; it may necessitate a dose adjustment.³⁷

Sidebar: Tech Tasks for Thyroid Medications

Inform patients about the importance of using a consistent brand of levothyroxine.
Note brand of levothyroxine on each patient’s profile.
Review levothyroxine shipments when restocking to assure consistent brand use.
Tag all bags and inform the patient if a brand switch is made.

Peak therapeutic effect of levothyroxine is seen in four to six weeks. Prescribers often start levothyroxine at low doses and titrate in small increments of 12.5 to 25 mcg every four to six weeks based on TSH testing until achieving euthyroidism.³⁸ Average full replacement dose is 1.6 mcg/kg/day. Current ATA guidelines recommend adjusting the levothyroxine dose to resolve symptoms of hypothyroidism and to keep the TSH level within the range of 0.4 to 4 mIU/L.²⁹ Clinicians should assess thyroid function in patients on stable doses of levothyroxine every six to 12 months and within six to eight weeks of any dose change. Ongoing assessment helps avoid under- or over-replacement.³⁸

Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism and include the following³⁷:

Anxiety
Diarrhea
Fatigue
Hair loss
Heat intolerance, excessive sweating
Increased appetite
Increased heart rate
Muscle weakness
Nervousness
Palpitations
Weight loss

Over-replacement with levothyroxine can lead to serious consequences and can put elderly patients at risk for cardiac arrhythmias, especially atrial fibrillation.¹⁰Complications of over-replacement include

Accelerated bone loss
Increased cardiac contractility
Increased cardiac wall thickness
Increased heart rate
Osteoporosis
Reduction in bone mineral density

Medications, supplements, food, coffee, and even orange juice can decrease levothyroxine’s absorption.¹⁰Levothyroxine is taken with water one hour before breakfast and any other prescription medications. Calcium, iron, antacids, cholestyramine, and sucralfate can inhibit its absorption and must be separated by at least four hours.³⁷Individuals with celiac disease or gastric bypass surgery may absorb medication inadequately.^40,41

Bedtime dosing of levothyroxine offers an alternative to morning dosing. Randomized controlled trials have found patients taking the medication in the evening had improved thyroid hormone status control.^38,42Patients struggling with morning dosing may find evening dosing easier. The ATA recommends that if levothyroxine is taken at bedtime that it be separated by three hours from the evening meal.⁴³

Because levothyroxine is usually administered for life, dose adjustment is often necessary to optimize therapy throughout a patient’s lifetime.⁴⁴ Situations that necessitate possible dose adjustment of levothyroxine include

Aging (age older than 65)
Diagnosis of new medical conditions
Pregnancy
Start of new medications
Weight changes

The Colorado Thyroid Disease Prevalence study assessed thyroid function, symptoms, and corresponding lipid levels in more than 25,000 participants. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest TSH elevations corresponded to changes in lipid levels that may affect cardiovascular health.²⁵ Optimization of levothyroxine therapy requires that the healthcare team recognize the need for dose adjustments throughout a patient’s life.

PAUSE AND PONDER: Among your patients being treated for hypothyroidism, how many also take calcium supplements? How many of these patients know to separate them from levothyroxine by four hours?

Liothyronine

Liothyronine (Cytomel) is synthetic T3. It is not recommended, either alone or in combination with levothyroxine, as first line treatment for hypothyroidism. Combination therapy hopes to mimic thyroid hormone physiology more closely; however, current guidelines do not suggest routine use of this approach.¹⁰ A 2016 randomized, double blind, crossover study evaluated combination therapy in 32 patients and found no clear clinical benefit and observed increased heart rate in patients receiving it.⁴⁵A trial, however, may be indicated in a small group of patients who remain symptomatic despite adequate levothyroxine monotherapy.⁴⁶

Iodine

Patients with iodine deficient hypothyroidism are treated with iodine supplements to correct the deficiency while levothyroxine is used to achieve euthyroidism. When the iodine level has been restored and goiter size has decreased, levothyroxine may be interrupted. Prescribers should reassess thyroid function in four to six weeks.¹¹

Consumption of too much iodine can have a negative impact on thyroid health. The safe upper limit of iodine for adults is 1.1 mg/day.⁶³ Iodine toxicity may lead to thyroiditis, hypothyroidism, hyperthyroidism, and thyroid papillary cancer.⁴⁷ Pharmacists should be aware that drug interactions with potassium iodine exist. It can interact with antithyroid drugs and when potassium iodide is taken with ACE inhibitors or potassium sparing diuretics, serum potassium can increase.¹³

Selenium

Selenium is an important micronutrient in the diet and increases active thyroid hormone production. The RDA for selenium is 55 mcg/day. Selenium supplements are used to treat or prevent selenium deficiency. Doses exceeding 400 mcg/day can be toxic. Signs of toxicity include brittle hair and nails, diarrhea, irritability, and nausea. Extremely high intakes of selenium can cause severe problems, including difficulty breathing, tremors, kidney failure, heart attacks, and heart failure. Most people consume adequate selenium through the diet, which is preferred. Consuming two Brazil nuts daily can provide adequate selenium intake; each nut contains 68 to 91 mcg of selenium, so people should not consume too many. Selenium is also found in oysters, tuna, whole-wheat bread, sunflower seeds, meat, mushrooms, and rye.⁴⁸

Subclinical Hypothyroid Disease

Subclinical hypothyroidism is a common condition occurring in about 15% of older women and 10% of older men.²It is a persistent condition in which TSH levels are elevated but free T4 levels remain normal. Treating subclinical hypothyroidism with levothyroxine results in an improved quality of life for many while others show no benefit and continue to complain of symptoms despite treatment.

The decision to treat subclinical hypothyroidism is being reevaluated after a large European study found no clear benefit with treatment.³ Published in the New England Journal of Medicine in 2017, this double-blind, randomized, placebo-controlled, parallel-group trial concluded levothyroxine provided no apparent benefits in older people with subclinical hypothyroidism.⁴⁹ Investigators are conducting more research to evaluate the effect of discontinuing levothyroxine in subclinical hypothyroidism.⁵⁰ They hope to determine if discontinuing levothyroxine in patients with subclinical hypothyroidism is safe or will reduce quality of life.

For now, prescribers should follow current clinical practice guidelines, which state that they should tailor the decision to treat subclinical hypothyroidism to the individual patient when the serum TSH is less than 10 mIU/L. Prescribers should consider the presence of symptoms and how likely the patient will progress to overt hypothyroidism when making the decision to treat.²⁴

Antithyroid Drugs

The treatment goal for hyperthyroid disease is to lower excessive thyroid hormone levels and achieve euthyroidism. The two antithyroid drugs (ATD) available in the U.S. for the treatment of hyperthyroidism are methimazole (Tapazole) and propylthiouracil (PTU). Hepatotoxicity has been reported with both medications but methimazole has been associated with far fewer cases. Therefore, methimazole is used as first line therapy, except in pregnancy.⁵¹

ATDs inhibit T4 and T3 synthesis by blocking oxidation of iodine in the thyroid gland. PTU also partially blocks peripheral conversion of T4 to T3. Beta-blockers can provide symptomatic relief in patients with hyperthyroidism.

Methimazole is available in 5 mg and 10 mg tablets. The starting dose is 5 mg to 20 mg orally every eight hours. Prescribers must titrate the dose over time to the lowest dose needed to maintain euthyroidism. Maintenance doses range from 5 mg to 30 mg/day administered once daily. Once euthyroidism is achieved, patients usually continue the ATD for another 12 to 18 months. The prescriber should check thyroid function four to six weeks after therapy initiation and then every two to three months once the patient is euthyroid.¹²

PTU’s labeling carries a boxed warning for acute liver failure, and it is reserved for use in those who cannot tolerate other treatments such as methimazole, radioactive iodine, or surgery.⁵² It is also recommended for use in the first trimester of pregnancy because birth defects have been associated with methimazole. PTU is available as a 50 mg tablet. The initial starting dose is 50 mg to 150 mg orally every eight hours and the maintenance dose is usually 50 mg every 8 to 12 hours.⁵³

Minor side effects occur in about 5% of patients receiving an ATD. Side effects include⁵³

Agranulocytosis (severe drop in white blood cells)
Arthralgia
Gastrointestinal distress
Hepatotoxicity
Pruritus
Vasculitis (dangerous inflammation of blood vessels)

Serious side effects are less common at lower doses; patients should be maintained at the lowest possible dose needed to achieve euthyroidism. Although rare, hepatotoxicity and agranulocytosis can be life threatening. Pharmacists should educate patients to report signs of agranulocytosis, such as sudden fever, sore throat, or chills, to their prescribers immediately. Prescribers should obtain a baseline serum liver profile and white blood cell count before starting an ATD. Most side effects occur within the first 90 days of therapy. Vasculitis is more common with longer duration of therapy.

A drawback of ATD therapy is the high relapse rate. A longitudinal cohort study concluded that patients initially treated with an ATD had about a 50% relapse rate and 25% felt they had not fully recovered in six to 10 years.⁵⁴

Recent studies have shown that longer treatment time with an ATD can achieve higher remission rates. A randomized, parallel-group study compared relapse rates in patients receiving longer-term versus conventional-length methimazole therapy in GD. The authors concluded that low-dose methimazole treatment for 60 to 120 months was safe and effective and had a higher remission rate compared to conventional treatment for 18 to 24 months.⁵⁵

Long-term methimazole therapy was also evaluated in juvenile GD in a randomized parallel trial. Patients receiving short-term methimazole therapy were almost three times more likely to relapse than those on long-term therapy. The researchers found long-term methimazole treatment of 96 to 120 months to be safe and effective with a significantly higher four-year cure rate.⁵⁶

Teprotumumab

The FDA’s approval of teprotumumab (TEPEZZA) in January 2020 was the most significant advance in treating thyroid eye disease in decades. Teprotumumab binds to IGF-1R and blocks its activation and signaling. It was shown to improve the course of thyroid eye disease in patients in two separate clinical trials, leading to this monoclonal antibody’s approval.^23,57 Proptosis and diplopia improved, as did eye pain, redness and swelling, and quality of life. Serious adverse events were uncommon. The most common adverse reactions observed were

alopecia
altered sense of taste
diarrhea
dry skin
fatigue
headache
hearing loss
hyperglycemia
muscle spasm
nausea

The FDA approved teprotumumab to be given as an infusion every three weeks for a total of eight doses. Patients completing the course of therapy showed significant improvement in symptoms associated with thyroid eye disease. Infusion reactions are reported in about 4% of patients. Dose is based on weight. The first dose is 10 mg/kg, and then the dose is increased to 20 mg/kg for the remaining seven infusions. Teprotumumab is contraindicated in pregnancy. Women of childbearing age must be counseled on pregnancy prevention during treatment and for six months following the last dose.⁵⁸

PAUSE AND PONDER: Which patients with thyroid disease in your practice might benefit from teprotumumab? What is important to tell them about this new biologic?

Surgery

Thyroidectomy is not used as a first line approach for treating hyperthyroidism. It is reserved for patients who refuse radioactive iodine after relapsing on an ATD, patients who cannot tolerate an ATD, or patients with very large goiter, multinodular goiter, or toxic adenoma. Thyroidectomy destroys the thyroid gland and if indicated, patients require lifelong levothyroxine therapy.

Radioactive Iodine

In the U.S., radioactive iodine is the most common treatment for hyperthyroidism. Radioiodine therapy, like surgery, destroys the thyroid gland requiring patients to be on lifelong levothyroxine therapy.

In the last 20 years, radioiodine has been used less frequently.¹⁹ Many patients report a lower quality of life after receiving radioactive iodine than patients receiving ATD or surgical treatment.⁵⁹ A randomized parallel group trial found that long-term methimazole, when compared to radioiodine, was safe, effective, and not inferior to radioiodine further supporting the use of ATD over radioiodine.⁶⁰

Pregnancy

Undiagnosed or inadequately treated hypothyroidism during pregnancy can lead to miscarriage, preterm delivery, or developmental disorders in children. Levothyroxine is safe in pregnancy, but pregnant patients may require a 30% increase in levothyroxine dose to maintain euthyroidism.During pregnancy, attending healthcare providers should titrate levothyroxine doses against TSH, which has trimester-specific ranges. Postpartum TSH levels are similar to preconception levels, so the dose of levothyroxine should return to the preconception dose following delivery.⁶¹

Iodine is a critical mineral for proper fetal development and iodine needs increase by at least 50% in pregnancy and lactation. Pregnant women should receive a prenatal vitamin containing 150 mcg of iodine during pregnancy and lactation. Unfortunately, prenatal vitamins contain variable and inconsistent amounts of iodine. Close to 40% of marketed prenatal vitamins in the U.S. contain no iodine and when measured, the actual iodine content varied between 33 and 610 mcg.¹¹ Healthcare practitioners must be vigilant in assuring that iodine requirements are met during pregnancy and lactation when iodine requirements increase. The ATA recommends that women receive 150 mcg of supplemental iodine daily during pregnancy and lactation and that all prenatal vitamin/mineral preparations contain 150 mcg of iodine.¹¹

Hyperthyroidism in pregnancy requires special consideration. Care givers must stabilize women undergoing treatment for GD who intend to become pregnant prior to conception. Prescribers should advise women to delay attempts at conception until they achieve a stable euthyroid state, whenever possible.⁶² Additionally they should treat hyperthyroidism during pregnancy with the lowest possible dose of PTU because methimazole has been associated with cases of congenital malformation.

The majority of patients with thyroid eye disease are women of childbearing age. Physicians must explain treatment limitations to patients who are contemplating pregnancy. Teprotumumab is contraindicated in pregnancy. Caregivers must provide contraceptive counseling to women of childbearing age with thyroid eye disease treated with teprotumumab during treatment and for the six months following therapy.²³

Pharmacy Team’s Role

The pharmacy team can have a positive impact on the successful management of patients with thyroid disease by educating and screening patients regarding

Adverse effects associated with their thyroid medications
Importance of medication adherence
Laboratory assessment of thyroid function
Screening for drug interactions
Signs and symptoms of hyperthyroidism and hypothyroidism

CONCLUSION

Thyroid disease affects millions in the U.S. and most cases are well controlled with pharmacological management. Adherence to thyroid disease medications is important. A knowledgeable pharmacy team can promote good practices and provide patient education, having a positive impact on patient care. Proper management allows most patients to have an excellent prognosis and quality of life.

With your newly gained knowledge, take another look at the Mona Lisa. Did Leonardo da Vinci, a man before his time, notice a thyroid disorder that he captured in his famous painting and did it intentionally contribute to her enigmatic smile?

This test is for viewing purposes only. If you would like to submit the test, go to the blue button at the top of the page or Test/Evaluation Site.

Pharmacist Post-test
1. Which of the following statement accurately describes hypothyroid disorders?
A) They are all of autoimmune etiology
B) They require treatment with levothyroxine, regardless of cause
C) They are caused only from disease directly affecting the thyroid gland

2. A woman of childbearing age who follows a strict vegan diet and only uses sea salt is contemplating pregnancy. Which of the following is a risk?
A) Selenium deficiency
B) Vitamin D deficiency
C) Iodine deficiency

3. What is the best laboratory assessment of thyroid function?
A) TSH
B) T3
C) Total T4

4. How often should patients on stable doses of levothyroxine have lab assessment of thyroid function?
A) every 6-12 months
B) every 3-6 months
C) every 24 months

5) A patient newly diagnosed with Hashimoto’s Thyroiditis (HT) is very concerned with her new diagnosis. What statement MOST ACCURATELY describes HT?
A) It is an autoimmune disease that has an excellent prognosis and is treated with lifelong levothyroxine therapy.
B) It is an autoimmune disease that has an excellent prognosis and is treated with liothyronine and levothyroxine.
C) It is subclinical hypothyroidism and she may not need treatment with levothyroxine.

6) A patient stable on methimazole for Graves’ disease remarks that she is considering having a child. Why would you encourage her to speak to her primary care provider?
A) Pregnancy is contraindicated
B) Methimazole is contraindicated and she should be switched to PTU
C) Methimazole is contraindicated and she should be switched to teprotumumab

7) Which medication carries a boxed warning in its labeling for acute liver failure, requiring baseline liver function assessment prior to its start?
A) Methimazole
B) Propylthiouracil
C) Teprotumumab

8) A patient starting methimazole for Graves’ disease asks about symptoms that are common to the condition. Which statement MOST ACCURATELY describes possible symptoms of GD?
A) Symptoms of hyperthyroidism may include rapid heart rate, weight loss, nervousness, hunger, fatigue, and hair loss.
B) Symptoms of hyperthyroidism may include hair loss, fatigue, swelling, puffiness, and depression.
C) Symptoms of hyperthyroidism may include proptosis, anxiety, difficulty breathing, and weight gain.

9) Which statement MOST ACCURATELY reflects symptoms of hypothyroidism?
A) Patients may exhibit many or few symptoms, including fatigue, weight loss, depression, constipation, and hair loss
B) Patients may exhibit many or few symptoms, including fatigue, weight gain, depression, constipation, and hair loss
C) Patients may exhibit many or few symptoms, including insomnia, weight gain, depression, constipation, and hair loss

10) What statement MOST ACCURATELY describes subclinical hypothyroidism?
A) It is a common persistent condition in which TSH levels are elevated and free T4 is high.
B) It is a common persistent condition in which TSH levels are elevated and free T4 is low.
C) It is a common, persistent condition in which TSH levels are elevated and free T4 is normal.

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Pharmacy Technician Post-test

1. What are common symptoms of hypothyroid disease?
A) Hair loss, proptosis, hunger, fatigue
B) Hair loss, depression, weight gain, fatigue
C) Hair loss, heat intolerance, weight loss, fatigue

2. A patient who started on levothyroxine a year ago is picking up her refill; she remarks that she continues to feel sluggish, fatigue and is still overweight. The patient asks why she is still feeling unwell. What do you tell her?
A) Refer this patient to the pharmacist
B) Assure the patient nothing is wrong
C) Suggest she take a dietary supplement

3. Which medication is used to treat hyperthyroidism?
A) Liothyronine
B) Levothyroxine
C) Methimazole

4. Which medication is used to treat hypothyroidism?
A) Propylthiouracil (PTU)
B) Levothyroxine
C) Methimazole

5. What are common symptoms of hyperthyroid disease?
A) Hunger, weight loss, nervousness, palpitations, frequent bowel movements
B) Weight gain, heat intolerance, excessive sweating, increased heart rate
C) Fatigue, depression, decreased heart rate, cold sensitivity, constipation

6. What are the available dosage strengths for levothyroxine?
A) 12 different tablet strengths ranging in dose from 25-300 mcg in 12.5-25 mcg increments.
B) 8 different tablet strengths ranging in dose from 50-300 mcg in 25-50 mcg increments
C)16 different tablet strengths ranging in dose from 100-300 mcg in 25-50 mcg increments

7. A patient who recently started methimazole calls the pharmacy complaining that suddenly she is feeling feverish with sore throat and chills. What next steps should a pharmacy technician take?
A) Indicate that she probably has a cold
B) Refer her to the pharmacist
C) Tell her to call back if she isn’t better in two days

8. Which mineral is important for thyroid health?
A) Calcium
B) Iron
C) Selenium

9. What medication was recently approved for thyroid eye disease marking a significant advancement in treatment?
A) Propylthiouracil
B) Methimazole
C) Teprotumumab

10. A patient is picking up her levothyroxine refill and was told by her physician that she is anemic. She is purchasing iron supplements too. What is important to communicate to the patient?
A) Iron supplements must be separated by four hours from levothyroxine
B) Iron supplements should not be used with levothyroxine
C) Iron supplements may cause upset stomach and dark stools

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