Drug Interaction Report

GENERALLY AVOID: Tofacitinib has been shown to decrease heart rate and prolong the PR interval of the electrocardiogram in some patients. Theoretically, coadministration with other agents that prolong the PR interval (e.g., beta-blockers, digoxin, alpha-2 adrenoceptor agonists) may result in elevated risk of conduction disturbances and atrioventricular block. In clinical trials, use of tofacitinib (10 to 20 mg daily; at steady-state) was associated with significant decreases in heart rate (4 to 7 bpm) and increases in PR interval (4 to 10 ms) compared with placebo.

MANAGEMENT: According to the manufacturer, concomitant use of tofacitinib with other agents that lower heart rate and/or prolong the PR interval should be avoided when possible. Caution is advised if concomitant use is necessary, particularly in patients with known conduction problems or severe cardiac disease. An ECG should be considered in these patients before initiating concomitant therapy and after titration to steady-state. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeats.

MONITOR: Grapefruit juice may increase the plasma concentrations of tofacitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Until more information is available, some authorities recommend avoiding consumption of grapefruit juice during tofacitinib therapy (Canada). Patients receiving tofacitinib therapy who ingest grapefruits or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.