Rilpivirine pharmacokinetics
Rilpivirine is a second-generation NNRTI. An optional 1-month oral lead
in phase (25 mg once daily) is also part of the product label prior to
use of the injectable formulation. For two-monthly dosing, 900mg/3ml is
administered as an IM injection, followed by a second 900mg injection a
month later and thereafter two-monthly. Injections must be given within
7 days of the planned injection date to avoid subtherapeutic exposures .
Oral rilpivirine bioavailability is affected by food intake and it
should be taken with a high fat meal to increase total exposures. Oral
rilpivirine absorption is also affected by gastric pH and proton pump
inhibitors can significantly reduce total exposure . Therefore, it is
important to provide adequate counselling to people initiating oral
rilpivirine. The peak plasma concentration is at 4 hours for oral
rilpivirine compared to 3-4 days for IM rilpivirine. LAI rilpivirine
reaches steady-date after 48 weeks. Rilpivirine is highly protein
(albumin)-bound (99.7%) and is hepatically metabolised with the main
clearance pathway being CYP3A4 and does not cause any major induction or
inhibition of transporters or enzymes . Elimination half-life of the LAI
formation is also driven by “flip-flop” pharmacokinetics and half-life
is 13-28 weeks, compared to 45 hours for oral rilpivirine . The
resistance risks associated with the prolonged pharmacokinetic tail also
apply to rilpivirine and appropriate cover with an alternative
antiretroviral must be used. No dose-adjustment is needed in renal
impairment or mild-moderate hepatic impairment .