Nelfinavir and Azithromycin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Nelfinavir
Azithromycin
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 azithromycin exposure, an increased risk of adverse effects (diarrhea, ototoxicity, hepatotoxicity) and an increased risk of QT interval prolongation
Interaction Deep Dive
Coadministered nelfinavir has significantly increased serum concentrations of azithromycin and increasing the risk for azithromycin adverse effects12. In a cohort of healthy subjects (n=12) was given nelfinavir 750 milligrams (mg) 3 times daily for 11 days, the concomitant administration of a single dose of azithromycin 1200 mg resulted in a 112% increase in azithromycin area under the concentration-time curve (AUC) and a 136% increase in azithromycin maximum serum concentration (Cmax) 3. Although no dosage adjustment is recommended, monitor patients who are given this combination for excessive adverse effects related to azithromycin toxicity (such as liver enzyme abnormalities and hearing impairment). Also, consider the risk of QT prolongation which can be fatal when initiating azithromycin in patients taking drugs that may prolong the QT interval, due to the potential for additive effects on QT interval prolongation and an increased risk of serious cardiovascular effects including torsades de pointes 1.
Why it happens (mechanism)
Reduced azithromycin clearance; additive QT interval prolongation
Literature reports
2 reports — tap to read
a) In a study (n=14), coadministration of a 1200 mg oral dose of azithromycin extended-release oral suspension on Day 9 with 750 mg nelfinavir 3 times a day for 11 days significantly increased nelfinavir mean Cmax (ratio (with/without coadministered drug) by 0.90-fold ; 90% confidence interval (CI), 0.81 to 1.01) and mean AUC by 0.85-fold (ratio, 0.85; 90% CI, 0.78 to 0.93) 12.
b) In a cohort of healthy subjects (n=12) was given nelfinavir 750 milligrams (mg) 3 times daily for 11 days, the concomitant administration of a single dose of azithromycin 1200 mg resulted in a 112% increase in azithromycin area under the concentration-time curve (AUC) and a 136% increase in azithromycin maximum serum concentration (Cmax) 3.
Common questions
Can I take Nelfinavir and Azithromycin together?
Increased azithromycin exposure, an increased risk of adverse effects (diarrhea, ototoxicity, hepatotoxicity) and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nelfinavir and Azithromycin interaction?
It is rated major. Potentially serious — often needs a change or close 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 "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Nelfinavir or Azithromycin 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 a safer alternative to one of these medications for me?
References (3)
- Product Information: ZMAX(R) oral extended-release suspension, azithromycin oral extended-release suspension. Pfizer Inc (per FDA), New York, NY, 2021. DailyMed
- Product Information: ZITHROMAX(R) oral tablets, oral suspension, azithromycin oral tablets, oral suspension. Pfizer Labs (per FDA), New York, NY, 2019. DailyMed
- Product Information: VIRACEPT(R) oral film coated tablets, oral powder, nelfinavir mesylate oral film coated tablets, oral powder. Pfizer Inc (per Dailymed), New York, NY, 2023. DailyMed
Keep reading about Nelfinavir
Keep reading about Azithromycin
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.
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