Clarithromycin with Repaglinide Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Repaglinide

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

Interaction Effect

Increased repaglinide exposure and plasma concentration

Interaction Summary

Repaglinide is metabolized by the CYP2C8 and CYP3A4 enzyme systems. Coadministration with clarithromycin, a CYP3A4 inhibitor, significantly increased repaglinide exposure and plasma concentration in healthy volunteers. In a case report, an 80-year-old man developed severe hypoglycemia while on concurrent repaglinide and clarithromycin therapy . Use caution if these agents are coadministered and dosage adjustments to repaglinide may be necessary . Blood glucose concentrations should be carefully monitored, especially in elderly patients .

Severity

Moderate

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Caution is advised if clarithromycin and repaglinide are coadministered as this has resulted in increased repaglinide exposure and plasma concentration which may lead to hypoglycemia. Dosage adjustments to repaglinide may be necessary. Blood glucose concentrations should be carefully monitored, especially in elderly patients .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated repaglinide metabolism

Literature Reports

A) In a case report, an 80-year-old man developed severe hypoglycemia while on concurrent repaglinide and clarithromycin therapy. The patient had end-stage renal disease and well-controlled type 2 diabetes (hemoglobin A1C 6.5%). The patient was receiving repaglinide 0.5 mg three times daily (for 2 years previously) when clarithromycin 500 mg twice daily and amoxicillin 250 mg twice daily were started for Helicobacter pylori infection; omeprazole 20 mg twice daily was also continued. Within 48 hours after starting clarithromycin, the patient developed severe hypoglycemia (blood glucose 25 mg/dL), which resolved with intravenous glucose administration. Repaglinide and clarithromycin (as well as amoxicillin and omeprazole) therapy was continued, and 48 hours later, the patient had another episode of severe hypoglycemia (blood glucose less than 30 mg/dL) and became unresponsive. The patient was hospitalized and intravenous glucose was given with resolution of the hypoglycemia. Repaglinide was discontinued, with no further hypoglycemic episodes reported .

B) In healthy volunteers, coadministration of clarithromycin and repaglinide resulted in significant increases in repaglinide AUC and Cmax. Following 4 days of twice-daily clarithromycin 250 mg dosing, a single 0.25 mg repaglinide dose was administered concomitantly on the 5th day. This resulted in a 40% increase in repaglinide AUC, from 5.3 ng x h/mL x h to 7.5 ng x h/mL and a 67% increase in repaglinide Cmax, from 4.4 ng/mL to 7.3 ng/mL .

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.

Repaglinide Overview

• Repaglinide is used to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Repaglinide helps your body regulate the amount of glucose (sugar) in your blood. It decreases the amount of glucose by stimulating the pancreas to release insulin.

• Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems.Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.

• This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

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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.