Risk for gastrointestinal adverse events in the form of nausea motivates vigilance against insufficient intake of food, especially of carbohydrate.

A very common side effect that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack is nausea. Other common side effects are vomiting, abdominal pain, fatigue and increased transaminase.

Rilpivirine has been found to be an activator of hPXR and an inducer of CYP3A4. However, due to high plasma protein binding and a low free plasma concentration this is unlikely to be clinically relevant. No drug-drug interactions with rilpivirine as a perpetrator were found.

Diarylpyrimidine

Rilpivirine is an antiretroviral agent indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents.

Average steady-state plasma concentration of rilpivirine is 400 nM (Weiss 2013).

Rilpivirine is metabolised by CYP3A4 and the elimination half-life is approximately 45 hours (SPC). From in vitro studies, rilpivirine has been found to be an inhibitor of CYP3A4, CYP2C19 and CYP2B6 (Weiss 2013), and to be an activator of hPXR and an inducer of CYP3A4 (Sharma 2013, Weiss 2013). However, this is unlikely to be clinically relevant because the plasma protein binding of rilpivirine is so high, 99.7 % (SPC), and the free plasma concentration will therefore be very low, 1.2 nM (Weiss 2013). Rilpivirine does not affect the pharmacokinetics of ethinylestradiol and norethindorine (substrates of CYP3A4) when co-administrated, which indicates that it is not an inhibitor or an inducer of CYP3A4 (Crauwels 2014 and SPC). Rilpivirine was not found to have any clinically relevant effect on the exposure of several different co-administrated drugs (Crauvels 2013).