Drug Interaction Report

GENERALLY AVOID: Coadministration of upadacitinib with other immunosuppressive agents may potentiate the risk of infections as well as lymphoma and other malignancies. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving upadacitinib, most of whom were taking concomitant immunosuppressants such as methotrexate or corticosteroids. The most common serious infections reported with upadacitinib treatment include pneumonia and cellulitis. Opportunistic infections include tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis. Lymphoma and other malignancies, including non-melanoma skin cancers, have also been observed with the use of upadacitinib and other Janus kinase (JAK) inhibitors.

MANAGEMENT: Concomitant use of upadacitinib with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended. Patients receiving upadacitinib should be closely monitored for the development of signs and symptoms of infection during and after treatment, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. If a serious or opportunistic infection develops, upadacitinib should be interrupted until the infection is controlled.

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.

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

MANAGEMENT: Caution is advised if deuruxolitinib 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 deuruxolitinib in patients that have experienced a myocardial infarction or stroke. Deuruxolitinib may be taken with or without food.