Drug Interaction Report

MONITOR: Coadministration of romosozumab with bisphosphonates, denosumab, angiogenesis inhibitors, or corticosteroids may increase the risk of developing osteonecrosis of the jaw (ONJ). The condition can occur spontaneously and is generally associated with tooth extraction and/or local infection with delayed healing. Other risk factors for ONJ include cancer, chemotherapy, radiotherapy to the head and neck, poor oral hygiene, preexisting dental disease or infection, anemia, and coagulopathy.

MANAGEMENT: Caution is advised when romosozumab is used with other agents that are also associated with osteonecrosis of the jaw. A routine oral examination should be performed by the prescriber prior to initiation of romosozumab treatment. For patients requiring invasive dental procedures, clinical judgment and risk-benefit assessment should guide the management plan of each patient based on their clinical circumstances. Patients should be advised to seek medical attention if they experience signs and symptoms of ONJ, such as: pain in the mouth, teeth, or jaw; swelling or sores inside the mouth; numbness or a feeling of heaviness in the jaw; loosening of a tooth; or exposure of bone in the jaw. Those who are suspected of having or who develop ONJ during romosozumab therapy should receive care by a dentist or an oral surgeon. In these patients, dental surgery to treat ONJ may exacerbate the condition. Discontinuation of romosozumab should be considered based on benefit-risk assessment.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of 21-desdeflazacort, the active metabolite of deflazacort that is formed by esterases after oral administration and further metabolized by CYP450 3A4 to several inactive metabolites. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism in the gut wall by certain compounds present in grapefruit. 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. Increased systemic exposure to 21-desdeflazacort may increase the risk of corticosteroid adverse effects such as hypercorticism, hyperglycemia, adrenal suppression, immunosuppression, hypertension, salt and water retention, electrolyte abnormalities, behavioral and mood disturbances, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.

MANAGEMENT: Deflazacort should not be administered with grapefruit juice.