Drug Interactions between lansoprazole / naproxen and tofacitinib

GENERALLY AVOID: Theoretically, proton pump inhibitors may decrease the gastrointestinal absorption of enteric-coated naproxen, which requires an acidic environment for dissolution. The proposed mechanism is an increase in gastric pH (i.e. decreased gastric acidity) induced by proton pump inhibitors. In patients treated with proton pump inhibitors, the possibility of a reduced or subtherapeutic response to enteric-coated naproxen should be considered.

MANAGEMENT: Concomitant use of these drugs is generally not recommended.

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.

ADJUST DOSE: Coadministration with one or more medications that may result in both moderate inhibition of CYP450 3A4 and potent inhibition of CYP450 2C19 may significantly increase the plasma concentrations of tofacitinib, which is primarily metabolized by the former isoenzyme with minor contribution from the latter. In study subjects, administration with the moderate CYP450 3A4 and potent CYP450 2C19 inhibitor fluconazole increased tofacitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 27% and 79%, respectively, compared to administration of tofacitinib alone. Side effects including lymphopenia, neutropenia, anemia, serious infections, and hyperlipidemia may be increased.

MANAGEMENT: The dosage of tofacitinib should be reduced by 50% when used concomitantly with one or more medications that may result in both moderate inhibition of CYP450 3A4 and potent inhibition of CYP450 2C19. For example, the dose for patients receiving 10 mg twice daily should be reduced to 5 mg twice daily and the dose for patients receiving 5 mg twice daily should be reduced to 5 mg once daily. For patients receiving 11 mg once daily of the extended-release formulation, the dose should be reduced to 5 mg once daily of the immediate-release formulation. The dose for patients receiving 3.2 mg twice daily should be reduced to 3.2 mg once daily and the dose for patients receiving 4 mg twice daily should be reduced to 4 mg once daily. Moderate inhibitors of CYP450 3A4 include amiodarone, aprepitant, ciprofloxacin, crizotinib, darunavir, dalfopristin-quinupristin, diltiazem, dronedarone, erythromycin, fluconazole, fusidic acid, grapefruit juice, imatinib, isavuconazonium, netupitant, and verapamil. Potent inhibitors of CYP450 2C19 include fluconazole, fluvoxamine, esomeprazole, lansoprazole, and omeprazole. Inhibitors of CYP450 2C19 alone are unlikely to substantially alter the pharmacokinetics of tofacitinib.