Drug Interaction Report

Coadministration with inducers of CYP450 3A4 may decrease plasma concentrations (Cmax) and systemic exposure (AUC) of topical ruxolitinib, which is primarily metabolized by the isoenzyme. Following administration of rifampin (600 mg once daily for 10 days), a potent CYP450 3A4 inducer, healthy subjects then received a single dose of ruxolitinib (50 mg orally). The Cmax and AUC of ruxolitinib decreased 32% and 61% respectively, compared to healthy subjects receiving the oral ruxolitinib dose alone. However, the clinical significance of this effect on a topical formulation is unknown. Consultation with individual package labeling, as well as relevant institutional protocols, may be advisable for further guidance. Clinical data for less potent inducers are not available.

MONITOR CLOSELY: Smoking during treatment with topical ruxolitinib may increase the risk of major adverse cardiovascular events (MACE) and the risk of developing malignancies, including lymphomas. During clinical trials, patients who were current or past smokers and received oral Janus Kinase (JAK) inhibitors to treat inflammatory conditions had an additional increased risk of overall malignancies. Additionally, oral JAK inhibitors reportedly increase patients' risk of MACE, including cardiovascular death, myocardial infarction, and stroke, particularly in patients who are current or past smokers or patients with other cardiovascular risk factors.

MANAGEMENT: The potential risks and benefits of topical ruxolitinib should be carefully weighed prior to initiating therapy, particularly in patients with cardiovascular risk factors, as well as those with a history of malignancy, those who develop a malignancy while on treatment, and/or patients who are 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 topical ruxolitinib in patients who have experienced a myocardial infarction or stroke.

ADJUST DOSING INTERVAL: Certain penicillins may exhibit reduced gastrointestinal absorption in the presence of food. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: The interacting penicillin should be administered one hour before or two hours after meals. Penicillin V and amoxicillin are not affected by food and may be given without regard to meals.