Tofacitinib

Tofacitinib tablets are Janus kinase (JAK) inhibitors. Tofacitinib tablets are indicated for the treatment of adult patients with: Moderately to severely active rheumatoid arthritis (RA), who have had an inadequate response or intolerance to one or more TNF blockers. Active psoriatic arthritis (PsA), who have had an inadequate response or intolerance to one or more TNF blockers. Active ankylosing spondylitis (AS), who have had an inadequate response or intolerance to one or more TNF blockers.

12.1 Mechanism of Action Tofacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.

Pharmacokinetic profiling of Tofacitinib demonstrates an elimination half-life of 3 hours terminal elimination (Tofacitinib SPL) with Estimated 71%–83% oral systemic absorption for Tofacitinib systemic bioavailability; clearance proceeds via hepatic oxidation via cyp3a4/cyp2c19 followed by renal and biliary excretion of tofacitinib metabolites, reaching clinical onset within peak plasma tmax within 0.5 hour (tofacitinib).

Titration schedules for Tofacitinib (1 mg/mL Solution → 10 mg/1 Tablet, Film Coated → 11 mg/1 Tablet, Extended Release → 5 mg/1 Tablet, Film Coated → 11 mg/1 Tablet, Film Coated, Extended Release) require excluding known hypersensitivity to tofacitinib or structurally related janus kinase inhibitor compounds; concomitant contra-labeled cyp/transporter therapies during active tofacitinib administration; real-world patient logs highlight headache (11.2% of reports), diarrhea (9.9% of reports), nausea (7.5% of reports) alongside a 86.00% Worth-It consensus.