Apixaban with Erythromycin Interaction Details

Brand Names Associated with Apixaban

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased apixaban exposure and increased risk of bleeding

Interaction Summary

Concurrent use of apixaban, a substrate of both P-gp and CYP3A4[1], with a dual P-gp and moderate CYP3A4 inhibitor may lead to increased apixaban serum concentrations [2] and an increased risk of bleeding [3]. In a pharmacokinetic study, apixaban Cmax and AUC increased by 31% and 39% when coadministered with diltiazem, a dual P-gp and moderate CYP3A4 inhibitor [2]. If concomitant use is required, use with caution [4].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concurrent use of apixaban with a dual P-gp and moderate CYP3A4 inhibitor may lead to increased apixaban serum concentrations[2] and an increased risk of bleeding [3]. If concomitant use is required, use with caution [4].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated apixaban metabolism; inhibition of P-gp-mediated efflux transport of apixaban

Literature Reports

A) Treatment with a combined P-gp and moderate CYP3A4 inhibitor significantly increased risk of bleeding in patients taking apixaban or rivaroxaban for atrial fibrillation in a retrospective observational analysis (N=426). Bleeding, defined as the composite of major, clinically relevant non-major, and minor bleeding, occurred in 26.4% of the interacting agent group vs 18.4% in the propensity-matched control group (HR, 1.8; 95% CI, 1.19 to 2.73). Interacting agents consisted of diltiazem (68.1%), amiodarone (26.8%), verapamil (5.7%), dronedarone (2.3%), and multiple agents (2.8%); no patients received concomitant erythromycin. No significant differences in bleeding rates were identified when individual drug interactions were evaluated, and the impact of renal dysfunction, specific inhibitor, or specific anticoagulant were not evaluated [3].

B) Concurrent administration of diltiazem, a dual P-gp and moderate CYP3A4 inhibitor, and apixaban increased apixaban Cmax by 31% and AUC by 39% when compared with apixaban alone. Oral apixaban 10 mg was administered 8 days after beginning diltiazem 360 mg once daily in 18 subjects [2].

References

1 ) Product Information: ELIQUIS(R) oral tablets, apixaban oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2019.

2 ) Frost CE, Byon W, Song Y, et al: Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Br J Clin Pharmacol 2015; 79(5):838-846.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

3 ) Hanigan S, Das J, Pogue K, et al: The real world use of combined P-glycoprotein and moderate CYP3A4 inhibitors with rivaroxaban or apixaban increases bleeding. J Thromb Thrombolysis 2020; 49(4):636-643.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

4 ) Burnett AE, Mahan CE, Vazquez SR, et al: Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis 2016; 41(1):206-232.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

Apixaban Overview

• Apixaban is used help prevent strokes or blood clots in people who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body and possibly causing strokes) that is not caused by heart valve disease. Apixaban is also used to prevent deep vein thrombosis (DVT; a blood clot, usually in the leg) and pulmonary embolism (PE; a blood clot in the lung) in people who are having hip replacement or knee replacement surgery. Apixaban is also used to treat DVT and PE and may be continued to prevent DVT and PE from happening again after the initial treatment is completed. Apixaban is in a class of medications called factor Xa inhibitors. It works by blocking the action of a certain natural substance that helps blood clots to form.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.