Drug interaction between St John's wort and nevirapine

Maat, Monique M de; Hoetelmans, Richard M. W.; Gorp, Eric Cm van; Meenhorst, Pieter L.; Mulder, J.; Beijnen, Jos H.

doi:10.1097/00002030-200102160-00019

Cited by 162 publications

(79 citation statements)

References 5 publications

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“…The most widely recognized herb to interact with drugs is St. John's wort (Hypericum perforatum), which is a potent inducer of CYP3A4 and P-gp activity (18,19) and which has been related to significant decreases in exposure to different drugs, including the antiretrovirals indinavir and nevirapine (5,35). Additionally, numerous in vitro studies have shown that other botanical supplements are also capable of modulating CYP and P-gp activity and, thus, interact with drugs (3,22,25), although results from human in vivo studies have been less convincing (14,15,22,25).…”

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confidence: 99%

Effect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients

Moltó

Valle

Miranda

et al. 2012

Antimicrob Agents Chemother

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The aim of this open-label, fixed-sequence study was to investigate the potential of the botanical supplement milk thistle (silymarin) to interact with the boosted protease inhibitor combination darunavir-ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy with darunavir-ritonavir (600/100 mg twice daily) for at least 4 weeks were included. Silymarin (150 mg every 8 h) was added to the antiretroviral treatment from days 1 to 14. Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning dose of darunavirritonavir on day 0 and darunavir-ritonavir plus silymarin on day 14. Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 by means of the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 48 years (interquartile range, 44 to 50 years), and the median body weight was 70 kg (interquartile range, 65 to 84 kg). Silymarin was well tolerated, and all participants completed the study. The GMRs for darunavir coadministered with silymarin relative to darunavir alone were 0.86 (90% CI, 0.70 to 1.05) for the area under the concentration-time curve from 0 to 12 h, 0.83 (90% CI, 0.80 to 0.98) for the maximum concentration, and 0.94 (90% CI, 0.73 to 1.19) for the concentration at the end of the dosing interval. In summary, coadministration of silymarin with darunavirritonavir seems to be safe in HIV-infected patients; no dose adjustment for darunavir-ritonavir seems to be necessary.

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confidence: 99%

Effect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients

Moltó

Valle

Miranda

et al. 2012

Antimicrob Agents Chemother

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“…The most widely recognized botanical supplement associated with CYP450-mediated herbdrug interaction is St. John's wort (Hypericum perforatum). This herb may induce CYP3A4 activity, decreasing exposure to antiretroviral drugs such as indinavir or nevirapine (6,18) and putting patients at risk of treatment failure and subsequent development of viral resistance to antiretroviral drugs. Clinical pharmacokinetic interaction studies between antiretroviral agents and botanicals nonetheless remain scarce in the literature.…”

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confidence: 99%

Herb-Drug Interaction between Echinacea purpurea and Darunavir-Ritonavir in HIV-Infected Patients

Moltó

Valle

Miranda

et al. 2011

Antimicrob Agents Chemother

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The aim of this open-label, fixed-sequence study was to investigate the potential of Echinacea purpurea, a commonly used botanical supplement, to interact with the boosted protease inhibitor darunavir-ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy including darunavir-ritonavir (600/100 mg twice daily) for at least 4 weeks were included. E. purpurea root extract capsules were added to the antiretroviral treatment (500 mg every 6 h) from days 1 to 14. Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning dose of darunavir-ritonavir on days 0 (darunavir-ritonavir) and 14 (darunavir-ritonavir plus echinacea). Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 with the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 49 (range, 43 to 67) years, and the body mass index was 24.2 (range, 18.7 to 27.5) kg/m 2 . Echinacea was well tolerated, and all participants completed the study. The GMR for darunavir coadministered with echinacea relative to that for darunavir alone was 0.84 (90% CI, 0.63-1.12) for the concentration at the end of the dosing interval, 0.90 (90% CI, 0.74-1.10) for the area under the concentration-time curve from 0 to 12 h, and 0.98 (90% CI, 0.82-1.16) for the maximum concentration. In summary, coadministration of E. purpurea with darunavirritonavir was safe and well tolerated. Individual patients did show a decrease in darunavir concentrations, although this did not affect the overall darunavir or ritonavir pharmacokinetics. Although no dose adjustment is required, monitoring darunavir concentrations on an individual basis may give reassurance in this setting.

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“…8 Additionally, in as little as four to ten days SJW can cause some medications to metabolize too quickly thus lowering plasma concentrations and rendering treatment less effective or ineffectual. 5 Medications that SJW is known to adversely affect in this way include oral contraceptives, 9 antiretroviral medications used in the treatment of AIDS such as Nevirapine and Indinivar, 10,11 Digoxin, used to treat congestive heart failure, 12 and fexofenidine or Allegra, used to treat allergies. 13 Likewise, other herbal remedies used to treat mood disorders are thought to change the effects of prescription medications or exacerbate symptoms in dangerous ways.…”

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confidence: 99%

Concurrent herb-prescription medication use and health care provider disclosure among university students

McCrea¹,

Pritchard²

2011

Complementary Therapies in Medicine

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Drug interaction between St John's wort and nevirapine

Cited by 162 publications

References 5 publications

Effect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients

Effect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients

Herb-Drug Interaction between Echinacea purpurea and Darunavir-Ritonavir in HIV-Infected Patients

Concurrent herb-prescription medication use and health care provider disclosure among university students

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