Urinary tract infections are very common in patients using ruxolitinib, and the risk of developing other opportunistic infections is also elevated. Since infections might trigger an acute porphyric attack, vigilance regarding signs and symptoms of an infection and/ or a porphyric attack is recommended.

Ruxolitinib is a substrate of hepatic CYP 3A4 and 2C9 but it is not an inducer or mechanism-based inhibitor of any major CYP enzymes, and therefore no pharmacokinetic porphyrinogenic effects are suspected.

Pyrrolopyrimidine

Ruxolitinib is a janus –associated kinase inhibitor used in the treatment of myelofibrosis and polycythemia vera. It is administered orally.

Ruxolitinib is metabolized mainly by CYP3A4, and to a minor extent by CYP2C9. Ruxolitinib is studied and described as a victim drug in drug-drug interaction information resources (Lexi-Interact, Shi 2012, SPC). At clinically relevant concentrations, ruxolitinib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or hepatic CYP3A4 and is not a potent inducer of CYP1A2, CYP2B6 or CYP3A4 based on in vitro studies. In vitro data indicate that ruxolitinib may inhibit intestinal CYP3A4, Pgp and BCRP (EMA). In a human in vivo study ruxolitinib did not inhibit the metabolism of the oral CYP3A4 substrate midazolam (SPC). In vitro data gives a weak indication that ruxolitinib may be a mild inducer of PXR regulated enzymes, but this is not expected to be clinically relevant (EMA). A drug-drug interaction study in healthy subjects was performed to investigate on ruxolitinibs potential CYP-inductive effects, but no effects on the pharmacokinetics of an oral contraceptive containing ethinylestradiol and levonorgestrel was seen (SPC). Ostojic and coworkers describes no evidence of inhibition and/or induction on CYP enzymes by ruxolitinib (Ostojic 2011). The mean elimination half-life of ruxolitinib is approximately 3 hours.