Nevirapine and St John's Wort: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Nevirapine
St John's Wort
No brand names on record
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
Reduced nevirapine exposure, reduced efficacy of nevirapine and an increased risk of antiretroviral resistance and loss of virologic response
Interaction Deep Dive
Oral clearance of nevirapine was found to be increased in patients treated for HIV taking St. John's Wort concomitantly5. St. John's Wort may induce CYP3A4 7 as well as P-glycoprotein 683, which are responsible for the metabolism and transport of nevirapine. The FDA advises against the concomitant use of St. John's Wort with non-nucleoside reverse transcriptase inhibitors (NNRTIs) 4. The combination may result in suboptimal antiretroviral drug concentrations, leading to inadequate virologic response and potential development of resistance or class cross-resistance 12.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of nevirapine; possible induction of P-gp drug transporter
Literature reports
2 reports — tap to read
a) The oral clearance of nevirapine was significantly increased with concomitant use of St. John's Wort in a retrospective analysis of HIV-positive patients. Five male patients (aged 34 to 53 years) had been treated with nevirapine plus 2 nucleoside analog reverse transcriptase inhibitors for at least 1 year, and had taken St. John's Wort for several months concomitantly. Nevirapine plasma concentrations were found to be reduced in these patients during routine clinical measurements. A non-linear mixed-effect modelling analysis (NONMEM) performed using 1330 nevirapine plasma concentrations from 176 patients measured over 789 visits, with concomitant use of St. John's Wort as a covariate for oral clearance, revealed a 35% increase in the oral clearance of nevirapine (p=0.02). Source and standardization of the St. John's Wort taken by patients was not reported. The mechanism of interaction is likely due to induction of the cytochrome P450 system by St. John's Wort 5.
b) St. John's Wort significantly increased P-gp expression and associated drug efflux in a randomized, single-blind, placebo-controlled trial of 22 healthy subjects (13 female, 9 male). Subjects received St. John's Wort (Good n' Natural, standardized to 0.15% hypericin) 600 mg (n=15) or placebo (n=7) three times daily for 16 days. P-gp expression in peripheral blood mononuclear cells increased 4.2-fold with St. John's Wort after 16 days (29.5 +/- 14.3 median fluorescence intensity (MFI, a measure of P-gp expression) versus 7 +/- 1.9 MFI, p less than 0.05, 95% confidence interval (CI): 13.5, 31.6). Individual variability occurred with a range of 1.09 to 9.06 MFI after St. John's Wort. No change in P-gp expression occurred in subjects receiving placebo. P-glycoprotein expression returned to baseline 16 days after discontinuing St. John's Wort. Efflux of the known P-gp substrate rhodamine was increased with St. John's Wort (p less than 0.05); no change in efflux occurred with placebo. Ritonavir (5 micromoles), known to reverse P-gp drug efflux, was significantly less effective in reducing rhodamine efflux in subjects treated with St. John's Wort (75.4 +/- 16.4% versus 23.9 +/- 15.3%, p less than 0.01, 95% CI: 43.7, 70.1). Three subjects receiving St. John's Wort withdrew from the study, one experienced adverse effects (nausea, dry mouth), and two needed potentially interacting medications. Analyses of 2 capsules from 3 batches of St. John's Wort with high performance liquid chromatography verified the hypericin content to be 0.15%, 0.14%, and 0.15% 6.
Common questions
Can I take Nevirapine and St John's Wort together?
Reduced nevirapine exposure, reduced efficacy of nevirapine and an increased risk of antiretroviral resistance and loss of virologic response Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nevirapine and St John's Wort interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
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 Nevirapine or St John's Wort 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 (8)
- Product Information: VIRAMUNE(R) oral suspension, nevirapine oral suspension. Boehringer Ingelheim Pharmaceuticals Inc (per FDA), Ridgefield, CT, 2024. DailyMed
- Product Information: VIRAMUNE XR(R) oral extended-release tablets, nevirapine oral extended-release tablets. Boehringer Ingelheim Pharmaceuticals Inc (per FDA), Ridgefield, CT, 2024. DailyMed
- Piscitelli S, Burstein A, Chaitt D, et al: Indinavir concentrations and St. John's Wort. Lancet 2000; 355:547-548. DOI
- Lumpkin MM: FDA Public Health Advisory: Risk of Drug Interactions with St John's Wort and Other Drugs. US Food and Drug Administration (FDA). Silver Spring, MD. 2013.
- de Maat MMR, Hoetelmans RMW, Mathot RAA, et al: Drug interaction between St. John's Wort and nevirapine. AIDS 2001; 15(3):420-421. PubMed
- Hennessy M, Kelleher D, Spiers JP, et al: St. John's Wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002; 53(1):75-82. DOI
- Moore LB, Goodwin B, Jones SA, et al: St. John's Wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Adac Sci U S A 2000; 97(13):7500-7502. DOI
- Durr D, Stiger B, Kullak-Ublick GA, et al: St. John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000; 68(6):598-604. PubMed
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Keep reading about St John's Wort
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