S2288 Nausea and Hepatocellular Injury Associated With Tofacitinib 10 mg Tablets but Not 5 mg: A Case Report

Abstract

INTRODUCTION: Tofacitinib (tofa) is a non-selective Janus kinase inhibitor, approved for treatment of moderately to severely active ulcerative colitis (UC), and is available in 5mg and 10mg tablets (tabs). We present a case of a patient with UC who transitioned from tofa 5mg tabs to 10mg tabs with subsequent nausea and liver transaminase elevation and propose it is due to distinct ingredients in the 10mg tab formulation. CASE DESCRIPTION/METHODS: Our patient is a 42-year-old woman with a 12-year history of left-sided UC. She was previously treated with oral and rectal 5-ASA, infliximab, certolizumab, and vedolizumab. While on vedolizumab she developed a new synovitis of her fingers. In 2017, she was transitioned to tofa 5mg tab twice daily (BID) and achieved remission from her arthropathy and colitis. Two years later, she relapsed and subsequently dose escalated to tofacitinib 10mg BID, taken as two 5mg tabs BID. She was well with this formulation and dose for a year. A recent refill was transitioned to the 10mg tab formulation. After 3 doses of this formulation, she developed nausea. She continued the therapy for 5 additional doses. At this point, we advised stopping the therapy; the nausea resolved within 24 hours. On re-challenge with the 10mg formulation, nausea recurred after 2 doses, so liver enzymes were obtained. Her transaminases were double from baseline (AST = 45, ALT = 55, GGT = 25). Bilirubin, alkaline phosphatase and synthetic function remained normal. She denied any new drugs, herbal supplements or alcohol use. Her therapy was discontinued for two days; repeat labs were normal. After re-challenge with two 5 mg tabs BID and one week of follow-up, the patient’s transaminases remain normal and she is asymptomatic. DISCUSSION: We describe a UC patient who developed drug induced liver injury from the 10 mg formulation of tofa. We believe the drug-induced liver injury occurred from the excipient dyes (Brilliant Blue FCF Aluminum Lake and Indigo Carmine Aluminum Lake) found in the 10 mg formulation (and in the 22 mg XR formulation) but are not in the 5 mg formulation (or in the 11 mg XR formulation) (Table). Both dyes are triarylmethanes, which have been previously implicated in hepatocellular injury. Our suspicion was further confirmed by a positive de-challenge (discontinuation of the 10mg tabs) and successful re-challenge with the 5 mg tabs without recurrence of symptoms or chemistry abnormalities. Clinicians should be aware of this reaction and when it is suspected, consider the alternate formulation.Table.: Ingredients in tofacitinib (Xeljanz) tablets.