Tofaticinib as a potential therapeutic agent: a review

Abstract

Tofacitinib is a Food and Drug Administration (FDA) approved second generation immunosuppressive disease-modifying anti-rheumatic drug (DMARD) that is used in the treatment of conditions like rheumatoid arthritis, ulcerative colitis polyarticular course juvenile idiopathic arthritis and psoriatic arthritis. Tofacitinib can be used to treat adult RA patients who are intolerant to methotrexate. At cellular level tofacitinib selectively inhibits Janus kinase (JAKs) in human genome and thereby stops the cytokine receptor-based signalling of interleukins viz., IL2, IL4, IL6, IL7, IL15, IL21, interferon alpha (IFNa) and IFNc in synovial fibroblasts and CD14 monocytes, thereby leading to disruption of immune and inflammatory responses. Tofacitinib is marketed as orally administered conventional tablets (5 mg and 10 mg doses) extended-release tablets (11 mg dose) and oral solutions (1 mg/ml dose). Tofacitinib is quickly absorbed after oral administration with systemic bioavailability of 74%. Tofacitinib is metabolized majorly by CYP3A4 and clearance is 70% via hepatic metabolism and 30% via renal excretion. Half-life of orally administered tofacitinib was observed to be 3 hours. Patients receiving tofacitinib therapy should be monitored for TB, renal impairment, hepatic impairment or any kind of bacterial, viral or fungal infections before initiating or during therapy. Most common reported adverse events of tofacitinib are headache, diarrhoea, nasopharyngitis, sore throat, hypertension and respiratory tract infections. Tofacitinib therapy should be cautiously used in females of reproductive age and in patients receiving renal transplant. Tofacitinib is not recommended with other immunosuppressants and vaccines. Thus, tofacitinib being a potential therapeutic agent the current review elaborates the history, detailed pharmacology, dosing, adverse events, interactions and contraindications of tofacitinib.