Liverpool HIV Interactions

Do Not Coadminister

Nevirapine (NVP)

St John's Wort

Quality of Evidence: Moderate

Summary:

Coadministration is not recommended in the product labels for nevirapine as St John's wort is expected to substantially decrease nevirapine concentrations and may result in sub-optimal levels. If patient is already taking St John's Wort check nevirapine and if possible viral levels and stop St John's Wort. Nevirapine levels may increase on stopping St John's Wort. The dose of nevirapine may need adjusting. The inducing effect may persist for at least 2 weeks after cessation of treatment with St John's Wort. However, a recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp). Coadministration may be considered with St John’s Wort formulations that clearly state the hyperforin content and which have a total daily hyperforin dose of 1 mg or less.

Description:

Herbal preparations containing St John's wort (Hypericum perforatum) must not be coadministered while taking nevirapine due to the risk of decreased plasma concentrations and reduced clinical effects of nevirapine. Serum levels of nevirapine can be reduced by concomitant use of the herbal preparation St John's Wort (Hypericum perforatum). This is due to induction of drug metabolism enzymes and/or transport proteins by St John's Wort. If patient is already taking St John's Wort check nevirapine and if possible viral levels and stop St John's Wort. Nevirapine levels may increase on stopping St John's Wort. The dose of nevirapine may need adjusting. The inducing effect may persist for at least 2 weeks after cessation of treatment with St John's Wort.

Viramune Summary of Product Characteristics, Boehringer Ingelheim Ltd, November 2019.

Concomitant use of St John's wort (Hypericum perforatum) or St John's wort containing products and nevirapine is not recommended. Co-administration of nevirapine with St John's wort is expected to substantially decrease nevirapine concentrations and may result in sub-optimal levels of nevirapine and lead to loss of virologic response and possible resistance to nevirapine or to the class of NNRTIs.

Viramune Prescribing Information, Boehringer Ingelheim Pharmaceuticals Inc, October 2019.

A study was conducted with 176 HIV+ outpatients who were using nevirapine as part of their antiretroviral drug regimen. Five of these patients also used St John's Wort concomitantly for several months. It was shown that the clearance of nevirapine was significantly increased by 35% thus lowering exposure to nevirapine.

Drug interaction between St John's wort and nevirapine. de Maat MMR, Hoetelmans RMW, Mathôt RAA, et al. AIDS, 2001, 15:420-421.

In a phase I, open-label, non-randomized, single-sequence study, a low-hyperforin St John’s wort extract was investigated using a drug cocktail in 20 healthy volunteers. No pharmacokinetic interactions were observed for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein, with AUC and Cmax of the probe drugs showing 90% confidence intervals well within the predefined bioequivalence range of 80-125% (GMR, drugs taken together with extract vs. probe drug alone). These data suggest that low hyperforin preparations of St John’s wort have a lower risk of drug-drug interactions than high hyperforin St. John’s wort preparations.

No clinically relevant interactions of St. John's Wort extract Ze 117 low in hyperforin with cytochrome P450 enzymes and P-glycoprotein. Zahner C, Kruttschnitt E, Uricher J, et al. Clin Pharmacol Ther, 2019, 106(2): 432-440.

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