Treatment with rilpivirine does not alter plasma concentrations of the CYP3A substrates tadalafil and midazolam in humans
Abstract
Objectives: Antiretroviral combination therapy of patients infected with HIV has greatly increased their life expectancy. Hence, the treatment of HIV-related long-term complications and age-related comorbidities has become more important. Reported incidence rates of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH) are increasing in HIV-positive patients, potentially requiring treatment with phosphodiesterase 5 inhibitors such as sildenafil or tadalafil. In vitro, the NNRTI rilpivirine is both a pregnane X receptor agonist and cytochrome P450 (CYP) 3A inhibitor. Clinical data concerning the potential effects of rilpivirine coadministration on the pharmacokinetics of the CYP3A substrate tadalafil are lacking.
Methods: We enrolled 20 healthy volunteers in an open-label, two-part, one-arm Phase I clinical trial to investigate acute and chronic effects of multiple doses of 25 mg of oral rilpivirine on single-dose and steady-state pharmacokinetics of multiple oral 20 mg doses of tadalafil. CYP3A activity was measured simultaneously with the oral midazolam microdose test.
Results: We did not observe a change of tadalafil single-dose and steady-state exposure or of CYP3A activity measured at initiation, during maintenance and upon discontinuation of rilpivirine treatment after single-dose and chronic administration of rilpivirine.
Conclusions: Tadalafil can be combined with rilpivirine without dose adjustment or drug monitoring in HIV patients with ED or PAH.…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 20 participants or records.
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