Drug Interaction Report

GENERALLY AVOID: Based on in vitro inhibition data, a single topical application of abametapir lotion may increase plasma concentrations of drugs that are substrates of CYP450 3A4, CYP450 2B6, and CYP450 1A2 isoenzymes and increase their systemic concentrations. The proposed mechanism is high and prolonged systemic exposure to the metabolite abametapir carboxyl, which has been shown to be an in vitro inhibitor of CYP450 3A4, CYP450 2B6, and CYP450 1A2. The mean half-life of abametapir carboxyl in adults is estimated to be 71 hours or longer.

MANAGEMENT: Use of CYP450 3A4, CYP450 2B6, and CYP450 1A2 substrates should generally be avoided within 2 weeks after topical application of abametapir lotion. If this is not feasible, the manufacturer recommends avoiding use of abametapir lotion. If abametapir is used, monitor for increased toxicity of the CYP450 3A4, CYP450 2B6, and/or CYP450 1A2 substrate.

GENERALLY AVOID: Grapefruit, grapefruit juice or supplements containing grapefruit may increase the plasma concentrations of upadacitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit. In study subjects, administration with the potent CYP450 3A4 inhibitor ketoconazole increased upadacitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 70% and 75%, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Upadacitinib side effects including lymphopenia, neutropenia, anemia, serious infections, and hyperlipidemia may be increased.

MONITOR CLOSELY: Smoking during treatment with upadacitinib may increase the risk of major adverse cardiovascular events (MACE) and the risk of developing malignancies. During upadacitinib clinical studies, current or past smokers had an additional increased risk of overall malignancies. Also, upadacitinib may increase patients' risk of MACE, including myocardial infarction, stroke, and cardiovascular death.

MANAGEMENT: The manufacturer advises that concomitant use of upadacitinib with grapefruit, grapefruit juice, or supplements containing grapefruit should be avoided. Caution is advised if upadacitinib is prescribed to current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. The manufacturer recommends discontinuing upadacitinib in patients who have experienced a myocardial infarction or stroke.