Drug Interactions between Avastin and zoledronic acid

MONITOR: Osteonecrosis of the jaw (ONJ) has been reported with the use of angiogenesis inhibitors including denosumab, bevacizumab, and sunitinib. Concomitant exposure with other risk factors such as bisphosphonates (potency, route of administration, and cumulative dose), cancer, chemotherapy, corticosteroids, radiotherapy to the head and neck, dental disease, invasive dental procedures, or poor oral hygiene may increase the risk. Most reported cases with bevacizumab have occurred in patients who received prior or concomitant treatment with intravenous bisphosphonates or had a history of dental disease requiring invasive dental procedures. For denosumab, the majority of reported cases of ONJ in clinical trials occurred within 5 months after the last dose; in clinical trials, the incidence increased with duration of exposure. Clinical trials in patients with breast or prostate cancer with an extension treatment phase of open-label denosumab reported a patient-year adjusted incidence of confirmed ONJ of 1.1% in the first year of treatment, 3.7% in the second year, and 4.6% thereafter, with a median time to ONJ onset of approximately 20.6 months. ONJ has been rarely reported in clinical trials with the use of denosumab for osteoporosis.

MANAGEMENT: Caution is advised if bisphosphonates are used simultaneously or sequentially with denosumab or bevacizumab. Prior to initiating treatment, a thorough dental examination and appropriate preventive dentistry should be considered. If possible, invasive dental procedures should be avoided in patients who have previously received or are receiving intravenous bisphosphonates. Good oral hygiene practices should be maintained during treatment. Patients should be advised to seek medical attention if they experience signs and symptoms of osteonecrosis in the jaw, 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. Temporary interruption of treatment should be considered if clinically appropriate, until the condition resolves.

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