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The effect of rilpivirine on the pharmacokinetics of methadone in HIV‐negative volunteers
Author(s) -
Crauwels Herta M.,
van Heeswijk Rolf P.G.,
Vandevoorde Ann,
Buelens Annemie,
Stevens Marita,
Hoetelmans Richard M.W.
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.222
Subject(s) - rilpivirine , methadone , medicine , pharmacokinetics , cmin , opiate , cmax , pharmacology , anesthesia , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy , virology , receptor
Antiretrovirals may influence methadone exposure in HIV‐1‐infected patients receiving methadone for opiate addiction. Rilpivirine is a non‐nucleoside reverse transcriptase inhibitor for treating HIV‐1 infection. In this open‐label trial (NCT00744770), 13 HIV‐negative volunteers continued on their regular stable methadone therapy (60 to 100 mg once daily; Days −14 to 12), with rilpivirine coadministration (Days 1 to 11). Methadone and rilpivirine pharmacokinetics and opiate withdrawal symptoms (Short Opiate Withdrawal Scale, Desires for Drugs Questionnaire, pupillometry) were evaluated. Rilpivirine decreased methadone minimum and maximum plasma concentrations (C min ; C max ) and area under the plasma concentration‐time curve versus methadone alone (least‐square mean ratio; 90% confidence interval) by 22% (0.78; 0.67, 0.91), 14% (0.86; 0.78, 0.95), and 16% (0.84; 0.74, 0.95), respectively (R‐methadone), and 21% (0.79; 0.67, 0.92), 13% (0.87; 0.78, 0.97), and 16% (0.84; 0.74, 0.96), respectively (S‐methadone). Rilpivirine pharmacokinetics with methadone were consistent with historic data. No clinically relevant opiate withdrawal symptoms were reported. Methadone and rilpivirine coadministration was generally well tolerated. No grade 3/4 adverse events (AEs), serious AEs, or discontinuations due to AEs were seen. No methadone dose adjustment is prompted by rilpivirine coadministration. Clinical monitoring for opiate withdrawal is recommended, as some patients may require adjustment of methadone maintenance therapy.