Clarithromycin with Saquinavir Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Saquinavir

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

Interaction Effect

Increased clarithromycin and saquinavir serum concentrations; increased risk of QT-interval prolongation

Interaction Summary

Clarithromycin and saquinavir are strong inhibitors and substrates of CYP3A that prolong QT interval. Concurrent use of saquinavir/ritonavir with drugs that both increase saquinavir plasma concentrations and prolong QT interval, such as clarithromycin, is contraindicated . If concurrent use is required, initiate only if baseline QT interval is less than 450 msec and repeat ECG 3 to 4 days after initiation. If a subsequent QT interval exceeds 480 msec or has increased by more than 20 msec from baseline, consider discontinuation of 1 or both agents. With comorbid renal impairment, reduce clarithromycin dose by 50% for CrCl 30 to 60 mL/min and by 75% for CrCl less than 30 mL/min . If used with ritonavir, do not exceed clarithromycin 1000 mg/day (except if treating Mycobacterium avium complex) . Monitor for toxicities or consider using an alternative macrolide (eg, azithromycin) or antibiotic agent .

Severity

Contraindicated

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant use of saquinavir/ritonavir with drugs that both increase saquinavir plasma concentrations and prolong the QT interval, such as clarithromycin, is contraindicated. If concurrent use is required, initiate only if baseline QT interval is less than 450 msec and repeat ECG 3 to 4 days after initiation. If a subsequent QT interval exceeds 480 msec or has increased by more than 20 msec from baseline, consider discontinuation of 1 or both agents. With comorbid renal impairment, reduce clarithromycin dose by 50% for CrCl 30 to 60 mL/min and by 75% for CrCl less than 30 mL/min. If used with ritonavir, do not coadminister clarithromycin in doses greater than 1000 mg/day (except for the indication of Mycobacterium avium complex) . Monitor for toxicities or consider using an alternative macrolide (eg, azithromycin) or antibacterial agent .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated saquinavir and clarithromycin metabolism; additive effects on QT interval

Literature Reports

A) In a pharmacokinetic study in 12 healthy volunteers, coadministration of clarithromycin 500 mg twice daily and saquinavir 1200 mg 3 times daily with or without ritonavir for 7 days resulted in increased clarithromycin AUC and Cmax values by 45% and 39%, respectively, and increased saquinavir (unboosted) AUC and Cmax values by 177% and 187%, respectively. Additionally, the AUC of the active metabolite of clarithromycin, 14-OH clarithromycin, was decreased by 24% and the Cmax was decreased by 34% .

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.

Saquinavir Overview

• Saquinavir is used in combination with ritonavir (Norvir) and other medications to treat human immunodeficiency virus (HIV) infection. Saquinavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although saquinavir 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.

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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.