Ketoconazole with Fosamprenavir Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Fosamprenavir
- Fosamprenavir
- Lexiva®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased ketoconazole plasma concentrations and increased amprenavir exposure (active metabolite of fosamprenavir)
Interaction Summary
Fosamprenavir is a prodrug of amprenavir. Coadministration of fosamprenavir and ketoconazole has been shown to increase plasma concentrations of ketoconazole and may also increase exposure of amprenavir. The mechanism of action is thought to be inhibition of the CYP3A4 isozyme and inhibition of p-glycoprotein transport in the gut. Dose adjustments may be warranted for ketoconazole, particularly if a patient is receiving more that 400 mg of ketoconazole per day. A high dose of ketoconazole (greater than 200 mg per day) is not recommended in patients receiving both fosamprenavir and ritonavir. No dose adjustment for fosamprenavir is suggested .
Severity
Moderate
Onset
Delayed
Evidence
Established
How To Manage Interaction
Concomitant use of fosamprenavir and ketoconazole may increase ketoconazole concentrations. Monitor patients for signs of ketoconazole toxicity including abdominal pain, nausea, vomiting, pruritus and hepatotoxicity. Dose reduction of ketoconazole may be needed, particularly for patients receiving more than 400 mg ketoconazole per day. High doses of ketoconazole (greater than 200 mg per day) are not recommended for patients receiving both fosamprenavir and ritonavir. Patients should also be monitored for signs and symptoms of amprenavir toxicity, including paresthesia, persistent gastrointestinal effects, and rash.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism and p-glycoprotein transport of ketoconazole and/or amprenavir (active metabolite of fosamprenavir)
Literature Reports
A) Pharmacokinetic parameters (AUC and Cmax) of ketoconazole increased significantly in healthy adult patients treated with concomitant fosamprenavir/ritonavir and ketoconazole compared to those treated with ketoconazole only in an open-label, single-sequence, three-period study (n=15) There were 3 periods including: 1) treatment with ketoconazole 200 mg/day for 4 days; 2) fosamprenavir/ritonavir 700/100 mg twice daily for 10 days; 3) fosamprenavir/ritonavir 700/100 mg twice daily plus ketoconazole 200 mg/day for 4 days. Compared to ketoconazole alone, fosamprenavir/ritonavir plus ketoconazole resulted in an increase in ketoconazole AUC of 169% (geometric least-squares (GLS) mean ratio, 2.69; 90% confidence interval (CI), 2.08 to 3.48) and an increase in ketoconazole Cmax of 25% (GLS mean ratio, 1.25; 90% CI, 1 to 1.56). However, the AUC, Cmax, and Cmin of amprenavir did not change with concomitant use of fosamprenavir/ritonavir and ketoconazole compared to fosamprenavir/ritonavir alone .
B) In a three-period, crossover study, twelve HIV-seronegative, healthy men received a single dose each of 1200 mg amprenavir, 400 mg ketoconazole, and 1200 mg amprenavir plus 400 mg ketoconazole. Each period was separated by 14 days. Ketoconazole Cmax and AUC increased 19% and 44%, respectively, and half-life increased 23%. Amprenavir Cmax decreased 16% while the AUC increased 31%, and half-life decreased 16% .
Ketoconazole Overview
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Ketoconazole is used to treat fungal infections when other medications are not available or cannot be tolerated. Ketoconazole should not be used to treat fungal meningitis (infection of the membranes surrounding the brain and spinal cord caused by a fungus) or fungal nail infections. Ketoconazole is in a class of antifungals called imidazoles. It works by slowing the growth of fungi that cause infection.
Fosamprenavir Overview
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Fosamprenavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Fosamprenavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although fosamprenavir 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 life-style 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.