Tofacitinib

Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Common side effects include diarrhea, headache, and high blood pressure. Serious side effects may include infections, cancer, and pulmonary embolism. In May 2019 EMA’s safety committee (Pharmacovigilance Risk Assessment Committee / PRAC) has started a new review of Xeljanz (tofacitinib) and has recommended that doctors temporarily not prescribe the 10 mg twice-daily dose to patients at high risk for pulmonary embolism. The US Food and Drug Administration (FDA) has also released warnings about the risk of pulmonary embolism. It is in the janus kinase (JAK) inhibitor class, discovered and developed by the National Institutes of Health and Pfizer. In November 2012, the U.S. FDA approved tofacitinib citrate 'to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to, or who are intolerant of, methotrexate.' It was later approved in Japan, Switzerland and others (but not the EU). It is marketed as Xeljanz in all regions except for Russia where it will be marketed as Jakvinus or Jaquinus. In May 2018, the U.S. FDA approved tofacitinib citrate 'for the treatment of adult patients in the U.S. with moderately to severely active ulcerative colitis.' Tofacitinib citrate is the first oral JAK inhibitor approved for chronic use in ulcerative colitis (tofacitinib is a small molecule, not a biologic). Tofacitinib was initially not approved by European regulatory agencies because of concerns over efficacy and safety, although by 2018 the European Commission had approved it. Animal studies with tofacitinib conducted prior to human trials showed some carcinogenesis, mutagenesis, and impairment of fertility. The most commonly reported adverse reactions during the first three months in controlled clinical trials (occurring in greater than or equal to 2% of patients treated with tofacitinib citrate monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea, and nasopharyngitis (the 'common cold'). Tofacitinib is required by US FDA to have a boxed warning on its label about possible injury and death due to problems such as infections, Lymphoma and other malignancies which can arise from use of this drug. Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving tofacitinib. Epstein Barr Virus-associated post-transplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with tofacitinib while on immunosuppressive medications. Patients are warned to avoid use of tofacitinib citrate during an 'active serious infection, including localized infections.' Doctors are advised to use it with caution in patients that may be at increased risk of gastrointestinal perforations. Laboratory monitoring is recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids. Tofacitinib claims to have no contraindications, however doctors are advised to reduce the patient's dosage when combined with 'potent inhibitors of Cytochrome P450 3A4 (CYP3A4),' such as ketoconazole), or one or more combined medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 such as fluconazole. Furthermore, immunizations with live vaccines should be avoided by tofacitinib users. According to post-marketing research, tofacitinib may also increase the risk for pulmonary embolism. Prescribers should consider risk factors for pulmonary embolism before prescribing this medication. Risk factors include age, obesity, smoking and immobilization. Patients taking this medication, irrespective of indication or risk factors, should be monitored for signs and symptoms of pulmonary embolism.