Drug Interaction Report

MONITOR: Coadministration of Janus kinase (JAK) inhibitors with corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or opioids may increase the risk of gastrointestinal (GI) perforation. Patients with a prior history of peptic ulceration or diverticular disease may also have an increased risk. Adverse events of diverticulitis and GI perforation have been infrequently reported in clinical studies and postmarketing use of JAK inhibitors such as baricitinib, ruxolitinib, tofacitinib, and upadacitinib. However, the role of JAK inhibition in these events has not been determined. In studies with rheumatoid arthritis and ulcerative colitis patients, many were receiving background therapy with NSAIDs or corticosteroids.

MANAGEMENT: Caution is recommended when using JAK inhibitors in patients with a history of peptic ulceration or diverticular disease and in patients receiving concomitant treatment with drugs associated with an increased risk of GI perforation such as corticosteroids, NSAIDs, and opioids. Patients should be advised to contact their healthcare provider if they experience signs and symptoms of GI perforation such as severe abdominal pain, fever, chills, nausea, or vomiting.

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.