FDA Issues Boxed Warning for Denosumab & Approves a Generic NSAID

New Denosumab Boxed Warning

On Jan. 19, the FDA issued a new boxed warning for denosumab (Prolia), a RANK ligand inhibitor. The warning states that patients with advanced chronic kidney disease (CKD)—especially those receiving hemodialysis—are at greater risk of developing severe hypocalcemia after receiving denosumab. Additionally, the label contains information to help reduce this risk, including how to appropriately select patients for treatment with denosumab, recommendations for increased monitoring of blood calcium levels and other strategies.¹

 In June 2010, denosumab was approved by the FDA to treat postmenopausal women with osteoporosis at high risk for fracture.² It was subsequently approved to treat:

• Men with osteoporosis at high risk for fracture;
• Glucocorticoid-induced osteoporosis in men and women at high risk for fracture;
• Men receiving androgen-deprivation therapy for non-metastatic prostate cancer at high risk for fracture; and
• Women receiving adjuvant aromatase inhibitor therapy for breast cancer at high risk for fracture.³

The Risks

Incidents of patients developing severe hypocalcemia, resulting in hospitalization, life-threatening events and fatalities have been reported. Patients with CKD-related mineral bone disorder have a significantly increased risk of hypocalcemia. Prior to starting denosumab, patients with advanced CKD should be evaluated for CKD-related mineral bone disorder. If these patients are treated with denosumab, they should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-related mineral bone disorder.¹

For patients with advanced CKD, especially those on dialysis, frequent blood calcium monitoring should be performed for the first two to 10 weeks after each denosumab injection.

Along with the boxed warning, the FDA is updating information in the patient Medication Guide and the denosumab Risk Evaluation and Mitigation Strategy, the FDA’s drug safety program.

New Generic NSAID

The U.S. Food & Drug Administration (FDA) approved an abbreviated new drug application for indomethacin oral suspension. This non-steroidal anti-inflammatory drug (NSAID) is a generic version of Indocin Oral Suspension.⁴

Indomethacin is approved to treat patients with rheumatoid arthritis, ankylosing spondylitis, severe osteoarthritis, acute painful shoulder (tendinitis and/or bursitis) and acute gouty arthritis. This suspension is advantageous for patients who are unable to swallow solid dosage forms.⁵

The current annual U.S. market for indomethacin oral suspension is approximately $4.1 million. This approval grants ANI Pharmaceuticals Inc. 180 days of market exclusivity.⁴

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Prolia (denosumab): Drug safety communication—FDA adds boxed warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney disease. U.S. Food & Drug Administration. 2024 Jan 19.
2. Biologics license application approval: Prolia (denosumab). U.S. Food & Drug Administration. 2010 Jun 1.
3. Highlights of prescribing information: Prolia (denosumab). U.S. Food & Drug Administration. 2024 Jan 19.
4. News release: ANI Pharmaceuticals announces FDA approval and launch of indomethacin oral suspension. ANI Pharmaceuticals Inc. 2024 Jan 16.
5. Highlights of prescribing information: Indocin (indomethacin) oral suspension. U.S. Food & Drug Administration. 2021 Apr 28.