Clarithromycin with Tipranavir Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Tipranavir

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

Interaction Effect

Increased exposure to both tipranavir and clarithromycin

Interaction Summary

Coadministration of tipranavir/ritonavir and clarithromycin may increase exposure to both agents. A study (n=24) showed tipranavir/ritonavir AUC, Cmax, and Cmin increased by 40%, 66%, and 100%, respectively, with concomitant clarithromycin. In another study (n=15), clarithromycin AUC and Cmin increased by 19% and 68%, respectively, with concomitant tipranavir/ritonavir, but Cmax and pharmacokinetic parameters of clarithromycin's active metabolite were not significantly affected. Consider using an alternative macrolide (eg, azithromycin) . However, if concomitant use of clarithromycin and tipranavir/ritonavir is required in patients with renal impairment, reduce clarithromycin dose by 50% if CrCl is 30 to 60 mL/min and by 75% if CrCl is less than 30 mL/min. No dose adjustment is necessary in patients with normal renal function . Monitor for clarithromycin-related toxicities . Clarithromycin doses greater than 1000 mg/day with protease inhibitors are not recommended .

Severity

Moderate

Onset

Delayed

Evidence

Established

How To Manage Interaction

As concurrent use of clarithromycin and tipranavir/ritonavir may increase exposure to one or both agents, consider using an alternative macrolide (eg, azithromycin) in patients receiving tipranavir/ritonavir . However, if concomitant use of clarithromycin and tipranavir/ritonavir is required in patients with renal impairment, reduce clarithromycin dose by 50% if CrCl is 30 to 60 mL/min and by 75% if CrCl is less than 30 mL/min. No dose adjustment is necessary in patients with normal renal function . Monitor for clarithromycin-related toxicities . Clarithromycin doses greater than 1000 mg/day with protease inhibitors are not recommended .

Mechanism Of Interaction

Mutual inhibition of CYP3A4-mediated metabolism of tipranavir and clarithromycin

Literature Reports

A) Studies have demonstrated that the coadministration of tipranavir/ritonavir (TPV/RTV) with clarithromycin increased the plasma concentrations of both tipranavir and clarithromycin. In one study, healthy subjects (n=24) received TPV/RTV 500 mg/200 mg twice daily to steady state plus 25 doses of clarithromycin 500 mg twice daily. Pharmacokinetic parameters were compared to historical data (n=68) and presented as the ratio of TPV/RTV plus clarithromycin to TPV/RTV alone (90% CI). The ratios of Cmax, AUC, and Cmin of tipranavir all showed an increase with results of 1.4 (range 1.24 to 1.47), 1.66 (range 1.43 to 1.73), and 2 (range 1.58 to 2.47), respectively. In a second study 21 subjects received 15 doses of TPV/RTV 500 mg/200 mg twice daily with 25 doses of 500 mg clarithromycin twice daily. Results were expressed as the ratio of clarithromycin plus TPV/RTV to clarithromycin alone (90% CI). Ratios of the pharmacokinetic parameters of the parent drug clarithromycin demonstrated a general plasma concentration increase with Cmax 0.95 (range 0.83 to 1.09), AUC 1.19 (range 1.04 to 1.37) and Cmin 1.68 (range 1.42 to 1.98). Pharmacokinetic parameters of the active metabolite 14-OH-clarithromycin all showed a significant decrease with ratios for Cmax, AUC, and Cmin of 0.03 (range 0.02 to 0.04), 0.03 (range 0.02 to 0.04), and 0.05 (range 0.04 to 0.07), respectively .

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.

Tipranavir Overview

• Tipranavir is used with ritonavir (Norvir) and other medications to treat human immunodeficiency virus infection (HIV). Tipranavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although tipranavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.