When is Evenity (romosozumab) contraindicated?

Contraindications for Evenity (Romosozumab)

Evenity (romosozumab) is contraindicated in patients with hypocalcemia, history of myocardial infarction or stroke within the preceding year, and history of systemic hypersensitivity to romosozumab or any component of the formulation. 1

Absolute Contraindications

1. Hypocalcemia

   • Pre-existing hypocalcemia must be corrected prior to initiating therapy 1
   • Patients with severe renal impairment (eGFR 15-29 mL/min/1.73m²) or on dialysis require careful monitoring and calcium supplementation 1

2. Hypersensitivity

   • History of systemic hypersensitivity to romosozumab or any component of the product formulation 1
   • Previous reactions have included angioedema, erythema multiforme, and urticaria 1

3. Recent Cardiovascular Events

   • Myocardial infarction or stroke within the preceding year 1, 2, 3
   • This is emphasized in the FDA black box warning due to increased risk of MACE (Major Adverse Cardiac Events) 3

Relative Contraindications/Use with Caution

1. High Cardiovascular Risk

   • Patients with multiple cardiovascular risk factors require careful risk-benefit assessment 1, 4
   • The ARCH trial showed higher risk of cardiovascular events in romosozumab-treated patients compared to alendronate 3, 4

2. Pregnancy and Breastfeeding

   • Use with caution in patients of child-bearing potential due to potential fetal harm 5
   • Avoid pregnancy for 5 months after the last dose 5

3. Open Growth Plates

   • Should be avoided in young adults with open growth plates 5

Patient Populations Where Alternative Therapies Are Preferred

1. Low Fracture Risk Patients

   • The 2022 American College of Rheumatology guidelines strongly recommend against osteoporosis medications in patients with low fracture risk due to known risks of harm and no evidence of benefit 5

2. Moderate Fracture Risk Patients

   • For moderate fracture risk, romosozumab is conditionally recommended against except in patients intolerant of other agents 5

3. Solid Organ Transplant Recipients

   • Conditionally recommended against in transplant recipients due to cardiovascular risk 5

Monitoring Requirements

If romosozumab is prescribed despite relative contraindications:

1. Calcium Levels

   • Monitor for signs and symptoms of hypocalcemia
   • Ensure adequate calcium and vitamin D supplementation (1000-1200 mg/day calcium and 600-800 IU/day vitamin D) 5, 6

2. Cardiovascular Monitoring

   • Monitor for signs and symptoms of myocardial infarction and stroke
   • Instruct patients to seek prompt medical attention if symptoms occur 1
   • Discontinue romosozumab if patient experiences myocardial infarction or stroke during therapy 1

Treatment Duration Limitations

• Romosozumab treatment is limited to 12 monthly doses 1
• After completion, patients should transition to an antiresorptive agent to maintain bone mineral density gains 3, 7

Practical Considerations

• Romosozumab should be reserved for postmenopausal women at highest risk for fracture with low cardiovascular risk 4, 7
• The ideal use in the therapeutic sequence is as first-line treatment in case of a recent major fracture in patients without cardiovascular contraindications 2
• For patients with high or very high fracture risk but cardiovascular concerns, alternative treatments such as PTH/PTHrP analogs or denosumab may be preferred 5

Remember that the risk-benefit assessment is particularly important with romosozumab, as it has demonstrated significant fracture reduction efficacy but carries cardiovascular safety concerns that require careful patient selection.