Clarithromycin with Felodipine Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Felodipine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

Increased felodipine exposure

Interaction Summary

Coadministration of clarithromycin (strong CYP3A inhibitor) and drugs primarily metabolized by CYP3A (or CYP3A substrates), such as felodipine, may result in increased substrate exposure and prolonged therapeutic and adverse effects. A small but significant 30-day increased risk of hospitalization with acute kidney injury was observed in patients who received continuous calcium channel blocker therapy and were prescribed clarithromycin in a retrospective cohort of older adults . Additionally, coadministration of clarithromycin with a calcium channel blocker (including felodipine) was associated with significantly increased short-term risk of hospital admission within 7 days for hypotension or shock in a cohort study of geriatric patients . If coadministration is clinically warranted, consider dosage adjustments and if possible, closely monitor drug levels . If clinically appropriate, consider the use of azithromycin (which does not inhibit CYP3A4) if treatment with a macrolide is required .

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Coadministration of clarithromycin and drugs primarily metabolized by CYP3A (or CYP3A substrates), such as felodipine, may result in increased substrate exposure and prolonged therapeutic and adverse effects. If coadministration is clinically warranted, consider dosage adjustments and if possible, closely monitor drug levels of the substrate. If clinically appropriate, consider the use of azithromycin (which does not inhibit CYP3A4) if treatment with a macrolide is required .

Mechanism Of Interaction

Inhibition of CYP3A-mediated metabolism of felodipine by clarithromycin

Literature Reports

A) Relative to azithromycin, clarithromycin was associated with a small but significant 30-day increased risk of hospitalization with acute kidney injury (HAKI) in patients who received continuous calcium channel blocker (CCB) therapy in a retrospective cohort of older adults (mean age, 76 years). Of the patients receiving clarithromycin, CCB usage included: amlodipine (52.7%), diltiazem (22.2%), nifedipine (17.3%), verapamil (4%), or felodipine (3.8%). The median dose of clarithromycin was 1000 mg/day for 10 days (n=96,226) and the median dose of azithromycin was 300 mg/day for 5 days (n=94,083). Pooled data was analyzed, 30 days after the antibiotic was prescribed, for diagnostic code of HAKI (median absolute acute increase in serum creatinine of 1.11 mg/dL). HAKI occurred in 0.44% of patients prescribed clarithromycin compared with 0.22% of patients prescribed azithromycin (odds ratio [OR], 1.98; 95% CI, 1.68 to 2.34; number needed to harm (NNH), 464). Relative to amlodipine (reference), the risk of HAKI was highest with nifedipine, followed by felodipine, diltiazem, and verapamil. Similarly, concomitant use of clarithromycin in CCB recipients was associated with a small but significant 30-day increased risk of hospitalization with hypotension (absolute risk increase, 0.04%) and all-cause mortality (absolute risk increase, 0.43%). Risk of HAKI appeared unaffected by presence of chronic kidney disease (CKD) or statin use; however, NNH decreased to 95 in those with CKD. Additional multiple analyses showed similar results, suggesting robustness of findings .

B) Coadministration of macrolide antibiotics erythromycin or clarithromycin with a calcium channel blocker was associated with significantly increased short-term risk of hospital admission within 7 days for hypotension or shock ([OR, 5.8; 95% CI, 2.25 to 14.98] or [OR, 3.7; 95% CI, 2.26 to 6.06]) in a case-crossover cohort study of geriatric patients (N=7100); there was no significant risk associated with azithromycin. In a stratified analysis of dihydropyridine calcium channel blockers (amlodipine, felodipine, NIFEdipine), the results remained significant for coadministration of erythromycin or clarithromycin. Calcium channel blocker treatment included diltiazem (40%), amlodipine (29.6%), NIFEdipine (19.4%), verapamil (8%), or felodipine (3%). The findings suggest that erythromycin and clarithromycin potentiate calcium channel blockers (CYP3A4 substrates) by inhibiting CYP3A4; azithromycin does not inhibit CYP3A4 .

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin 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.

Felodipine Overview

• Felodipine is used to treat high blood pressure. Felodipine is in a class of medications called calcium channel blockers. It works by relaxing the blood vessels so your heart does not have to pump as hard.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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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.