Clarithromycin with Ritonavir Interaction Details
Brand Names Associated with Clarithromycin
- Biaxin® Filmtab®
- Biaxin® Granules
- Biaxin® XL Filmtab
- Biaxin® XL Pac
- Clarithromycin
Brand Names Associated with Ritonavir
- Norvir®
- Ritonavir
- RTV
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 08, 2023
Interaction Effect
Increased clarithromycin exposure, decreased 14-OH-clarithromycin exposure, and increased risk of QT interval prolongation
Interaction Summary
Concomitant use of clarithromycin and ritonavir may result in increased clarithromycin exposure and decreased 14-OH-clarithromycin exposure (active metabolite). Thus, efficacy of clarithromycin therapy may be impaired based on the type of bacterial infection being treated. Consider alternative antimicrobial therapy for Mycobacterium avium complex infection. If concomitant use of clarithromycin and ritonavir is required: reduce clarithromycin dose by 50% in patients with moderate renal impairment (CrCl, 30 to 60 mL/min), and by 75% in patients with severe renal impairment (CrCl, less than 30 mL/min). Dose adjustment is not necessary in patients with normal renal function. Coadministration of clarithromycin at doses greater than 1000 mg/day with protease inhibitors should be avoided. Additionally, both clarithromycin. and ritonavir prolong the QT interval . Coadministration may cause additive prolongation effects on the QT interval. Consider dosage adjustments and monitoring of serum concentrations, if possible .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant use of clarithromycin and ritonavir may result in increased clarithromycin exposure and decreased 14-OH-clarithromycin exposure (active metabolite). Thus, efficacy of clarithromycin therapy may be impaired based on the type of bacterial infection being treated. Consider alternative antimicrobial therapy for Mycobacterium avium complex infection. If concomitant use of clarithromycin and ritonavir is required: reduce clarithromycin dose by 50% in patients with moderate renal impairment (CrCl, 30 to 60 mL/min), and by 75% in patients with severe renal impairment (CrCl, less than 30 mL/min). Dose adjustment is not necessary in patients with normal renal function. Coadministration of clarithromycin at doses greater than 1000 mg/day with protease inhibitors should be avoided. Additionally, both clarithromycin. and ritonavir prolong the QT interval . Coadministration may cause additive prolongation effects on the QT interval. Consider dosage adjustments and monitoring of serum concentrations, if possible .
Mechanism Of Interaction
Inhibition of CYP3A-mediated clarithromycin metabolism by ritonavir; additive prolongation effects on QT interval
Literature Reports
A) Coadministration of clarithromycin and ritonavir led to significant increases in clarithromycin AUC and Cmax and significant decreases in the active 14-OH-clarithromycin metabolite AUC and Cmax in a drug interaction study. Subjects received clarithromycin 500 mg twice daily and ritonavir 200 mg every eight hours for 4 days. The AUC of clarithromycin was increased by 77%, the Cmax was increased by 31%, and the minimum concentration (Cmin) was increased 2.8-fold. Additionally, the active 14-OH clarithromycin metabolite AUC and Cmax were decreased by 100% and 99%, respectively. Ritonavir pharmacokinetic parameters increased, but to a lesser extent; 12%, 15%, and 14% for AUC, Cmax, and Cmin, respectively .
Clarithromycin Overview
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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.
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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.
Ritonavir Overview
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Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir 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:
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.