Amprenavir and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amprenavir
No brand names on recordKetoconazole Topical
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased ketoconazole exposure and increased amprenavir exposure (active metabolite of fosamprenavir)
Interaction Deep Dive
Exert caution when strong CYP3A4 inhibitors (e.g. antivirals such as ritonavir-boosted fosamprenavir) coadministered with oral ketoconazole1, as it may increase ketoconazole exposure 23. Additionally, concomitant use may result in an increase in fosamprenavir exposure and the potential for serious adverse reactions. If coadministered, monitored closely for signs or symptoms of increased or prolonged pharmacologic effects of ketoconazole, and reduce the oral ketoconazole dose as deemed necessary. When appropriate, measure ketoconazole exposure 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism and P-gp transport of ketoconazole and/or amprenavir (active metabolite of fosamprenavir)
Literature reports
2 reports — tap to read
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 2.
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% 3.
Common questions
Can I take Amprenavir and Ketoconazole Topical together?
Increased ketoconazole exposure and increased amprenavir exposure (active metabolite of fosamprenavir) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amprenavir and Ketoconazole Topical interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Amprenavir or Ketoconazole Topical need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (3)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Wire MB, Ballow CH, Borland J, et al: Fosamprenavir plus ritonavir increases plasma ketoconazole and ritonavir exposure, while amprenavir exposure remains unchanged. Antimicrob Agents Chemother 2007; 51(8):2982-2984. PubMed
- Polk RE, Crouch MA, Pastor A, et al: Pharmacokinetic interaction between ketoconazole and amprenavir after single doses in healthy men. Pharmacotherapy 1999; 19(12):1378-1384. DOI
Keep reading about Amprenavir
Keep reading about Ketoconazole Topical
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist