JAK Inhibitor Selection Should Be Guided by Comedications and Renal or Hepatic Impairment
While the three currently approved Janus kinase (JAK) inhibitors — tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq) — can be coprescribed for the most part without affecting other therapies, other drugs can affect their pharmacokinetics, according to a study published online in the journal Drug Safety.
“Assessment of the drug–drug interaction potential suggests that tofacitinib, baricitinib, and upadacitinib generally show a favorable disposition with no perpetrator activity,” researchers wrote. “However, as victim drugs, they show subtle pharmacokinetic differences that may be considered during polypharmacy.”
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JAK inhibitors provide an alternative to traditional drugs and expensive biologics for the treatment of rheumatoid arthritis. Researchers conducted their review to assess the drug–drug interaction potential of each JAK inhibitor in an attempt to guide prescribers in choosing the best option for patients with rheumatoid arthritis.
According to the review, cytochrome P450 3A4-related inhibition or induction altered the exposures, or area under the curve, of tofacitinib and upadacitinib, but not baricitinib. Meanwhile, the disposition of baricitinib, as compared with either tofacitinib or upadacitinib, was altered with certain transporter inhibitors.
The review also considered patients’ renal and hepatic impairment status.
As a patient’s renal impairment progresses from mild to severe, dosage adjustments are required for tofacitinib or baricitinib, but not upadacitinib, researchers advised. Meanwhile, dosage of tofacitinib, but not baricitinib or upadacitinib, needs to be adjusted for patients with moderate hepatic impairment.
—Jolynn Tumolo
Reference
Veeravalli V, Dash RP, Thomas JA, Babu RJ, Madgula LMV, Srinivas NR. Critical assessment of pharmacokinetic drug-drug interaction potential of tofacitinib, baricitinib and upadacitinib, the three approved Janus kinase inhibitors for rheumatoid arthritis treatment [published online ahead of print May 4, 2020]. Drug Saf. doi:10.1007/s40264-020-00938-z
