Interaction: Denosumab and Pamidronate

Availability

• Pamidronate Disodium 30mg Injection
• Denosumab 60mg/ml prefilled syringe

Rationale for Combination use

• Currently no available guidelines practices a combination use
• Agents are only used one after the other in cases of refractory to either one of the therapy

Interaction

• Category: Moderate
• 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
• 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.
• 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.

References:

1. www.drugs.com
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976858/