What is the indication and dosing regimen for Evenity (romosozumab) in postmenopausal women with osteoporosis?

Evenity (Romosozumab) for Postmenopausal Osteoporosis

Indication

Evenity is indicated for postmenopausal women with osteoporosis at very high risk of fracture, specifically those with a history of osteoporotic fracture, multiple risk factors for fracture, or who have failed or are intolerant to other osteoporosis therapies. 1, 2, 3

• Very high fracture risk is defined by: older age (typically >74 years), recent fracture within the past 12 months, history of multiple clinical osteoporotic fractures, multiple risk factors for fracture, or failure of other available osteoporosis therapy 2
• The American College of Physicians positions romosozumab as a conditional recommendation for this specific population (low-certainty evidence) 1

Dosing Regimen

The treatment consists of 210 mg administered as two separate 105 mg subcutaneous injections once monthly for exactly 12 months only. 2, 3

Administration Details:

• Two single-use prefilled syringes (105 mg each) are required for each monthly dose 3
• Inject one syringe after the other in the abdomen, thigh, or upper arm 3
• Must be administered by a healthcare provider 3
• Concurrent calcium and vitamin D supplementation is required throughout treatment 2, 3

Duration Limitation:

• Treatment is strictly limited to 12 monthly doses because the anabolic effect wanes after this period 1, 4
• Do not extend beyond 12 months 3

Sequential Therapy Requirement

After completing the 12-month romosozumab regimen, patients must immediately transition to an antiresorptive agent to maintain bone density gains and fracture risk reduction. 4, 2

• Bisphosphonates (particularly alendronate) are the preferred sequential therapy 2
• Failure to transition results in loss of bone density gains 4
• The sequential use of romosozumab followed by alendronate is more effective than alendronate alone in reducing hip fracture risk 4

Critical Safety Warnings

Cardiovascular Risk (FDA Black Box Warning):

Romosozumab is contraindicated in patients who have had a myocardial infarction or stroke within the preceding year. 3

• Romosozumab carries a higher risk of major adverse cardiovascular events compared to alendronate (2.5% vs 1.9%) 2
• The FDA analysis of adverse event reporting suggested higher risk for major cardiovascular events 1
• If a patient experiences MI or stroke during therapy, discontinue romosozumab immediately 3
• Carefully weigh benefits versus risks in patients with other cardiovascular risk factors 3

Other Contraindications:

• Hypocalcemia must be corrected before initiating treatment 3
• Known hypersensitivity to romosozumab 3

Additional Safety Considerations:

• Monitor for hypersensitivity reactions including angioedema, erythema multiforme, dermatitis, rash, and urticaria 3
• Risk of osteonecrosis of the jaw—monitor for symptoms and consider discontinuation based on benefit-risk assessment 3
• Risk of atypical femoral fractures—evaluate any new or unusual thigh, hip, or groin pain 3
• Patients with severe renal impairment or receiving dialysis are at greater risk of developing hypocalcemia and require closer monitoring 3

Common Adverse Reactions

The most common adverse reactions (≥5%) are arthralgia and headache 3