Contraindications to Romosozumab
Romosozumab is contraindicated in patients with hypocalcemia and in those with a history of systemic hypersensitivity to romosozumab or any component of the product formulation, as well as in patients who have had a myocardial infarction or stroke within the preceding year. 1
Absolute Contraindications
- Hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with romosozumab 1
- History of systemic hypersensitivity to romosozumab or any component of the product formulation (reactions have included angioedema, erythema multiforme, and urticaria) 1
- Recent myocardial infarction or stroke (within the preceding year) 1, 2, 3
Relative Contraindications/Use with Caution
- Cardiovascular risk factors: Consider whether benefits outweigh risks in patients with other cardiovascular risk factors due to increased risk of major adverse cardiac events (MACE) 1, 3
- Severe renal impairment (eGFR 15-29 mL/min/1.73 m²) or patients receiving dialysis: These patients are at greater risk of developing hypocalcemia and require close monitoring of serum calcium levels 1, 4
- Moderate fracture risk: In adults ≥40 years with moderate fracture risk, romosozumab is conditionally recommended against except in patients intolerant of other agents, due to risk of myocardial infarction, stroke, or death 5
- Solid organ transplants: Conditionally recommended against using romosozumab due to risk of myocardial infarction, stroke, or death 5
Special Considerations
- Males with CKD G4-G5D: Use is considered off-label in this population 5
- Pregnancy: Women who may become pregnant should use effective birth control during treatment 5
- Risk of osteonecrosis of the jaw (ONJ): Particularly in patients receiving concomitant medications associated with ONJ (chemotherapy, bisphosphonates, denosumab, angiogenesis inhibitors, and corticosteroids) 1
Monitoring Requirements
- Cardiovascular monitoring: Monitor for signs and symptoms of myocardial infarction and stroke; instruct patients to seek prompt medical attention if symptoms occur 1, 3
- Calcium levels: Monitor serum calcium levels, particularly in patients with severe renal impairment or those receiving dialysis 1, 4
- Oral examination: A routine oral examination should be performed prior to initiation of romosozumab treatment to assess risk of ONJ 1
Important Clinical Context
- Romosozumab is a potent bone-forming agent that both increases bone formation and decreases bone resorption 6, 3
- Treatment duration is limited to 12 monthly doses 1
- After romosozumab treatment, sequential therapy with an anti-resorptive agent is recommended to maintain bone mineral density gains 5, 3
- Despite concerns about cardiovascular risk, romosozumab has shown efficacy in patients with mild-to-moderate chronic kidney disease with a similar safety profile across different levels of kidney function 7
When considering romosozumab therapy, clinicians should carefully weigh the potential benefits of increased bone mineral density and fracture reduction against the risks, particularly cardiovascular risks, and ensure that absolute contraindications are not present before initiating treatment.