Understanding the FDA Box Warning
An FDA box warning, also called a “black box warning,” is the most severe warning required by the Food and Drug Administration to appear on a medication's label. This warning is reserved for drugs that carry significant safety concerns, highlighting a serious or life-threatening adverse effect. For romosozumab (Evenity), the box warning focuses on its cardiovascular risks.
The Specific Risks of the Romosozumab Box Warning
The box warning for romosozumab details an increased risk of major adverse cardiovascular events (MACE), specifically myocardial infarction (heart attack), stroke, and cardiovascular death. These risks were noted in clinical trials. In one study comparing romosozumab to alendronate, a higher rate of MACE, including heart attack and stroke, was seen in the romosozumab group during the first 12 months. This finding was significant enough for the FDA to issue the box warning.
Contraindications and Patient Selection
To mitigate these risks, romosozumab should not be started in patients who have had a myocardial infarction or stroke in the preceding year. For individuals with other cardiovascular risk factors, such as high blood pressure or diabetes, healthcare providers must carefully weigh the potential bone-strengthening benefits against the cardiovascular risks. This necessitates a thorough medical history and discussion between the patient and physician.
Action During Treatment and Other Serious Risks
If a patient experiences a heart attack or stroke while on romosozumab, the medication must be stopped immediately. Patients should be advised to seek immediate medical help if they develop symptoms of a heart attack or stroke.
Beyond the cardiovascular warning, romosozumab also has other potential serious side effects.
Other serious risks associated with Evenity include:
- Osteonecrosis of the Jaw (ONJ): Severe jaw bone issues, often linked to poor oral hygiene or dental disease. A dental exam before treatment is recommended.
- Atypical Femoral Fractures: Unusual thigh bone fractures. Patients should report any new hip, thigh, or groin pain.
- Hypocalcemia: Low blood calcium, particularly risky for those with severe kidney issues. This should be corrected before starting the drug.
Romosozumab vs. Alendronate: Cardiovascular Event Comparison
In the ARCH trial, a comparison of romosozumab and alendronate over 12 months, romosozumab showed a higher incidence of major adverse cardiovascular events (MACE).
| Event Type | Romosozumab Group | Alendronate Group |
|---|---|---|
| Myocardial Infarction | 0.8% | 0.2% |
| Stroke | 0.6% | 0.3% |
| Cardiovascular Death | 0.8% | 0.6% |
Data reflects events during the first year of the ARCH trial.
This difference in cardiovascular event rates contributed to the FDA's box warning for romosozumab. Although another trial (FRAME) didn't show a significantly higher MACE risk compared to placebo, the comparison to the active treatment alendronate in the ARCH trial was a key factor in the regulatory decision.
Conclusion
The box warning for romosozumab emphasizes the serious risks of heart attack, stroke, and cardiovascular death. It should not be used in patients with a history of these events within the past year. For other patients, a careful assessment of the potential benefits for bone health against the cardiovascular risks is crucial. Patients should report any concerning symptoms immediately, and if a cardiovascular event occurs during treatment, the medication should be stopped. More information is available from the manufacturer.
