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 pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.