Prolia "Black Box" Warning: Harm From Severe Hypocalcemia Ranges From Hospitalization For Life-threatening Events To Death
(Posted by Tom Lamb at Drug Injury Watch)
A January 2024 JAMA Original Investigation article, "Severe Hypocalcemia With Denosumab Among Older Female Dialysis-Dependent Patients", in summary, presents evidence of a Prolia increased risk of hypocalcemia in patients with chronic kidney disease (CKD) that can be 20-times higher than bisphosphonate pills.
From the "Key Points" beginning of this online JAMA article about Prolia and severe hypocalcemia, we get a clear picture of the great extent of this new Prolia side effect:
Question Is there a difference in risk of severe hypocalcemia among female dialysis-dependent Medicare patients treated for osteoporosis with [Prolia (denosumab)] vs oral bisphosphonates?
Findings In this cohort study of 1523 dialysis-dependent patients initiating [Prolia (denosumab)] and 1281 initiating oral bisphosphonates, the weighted cumulative incidence of severe hypocalcemia (ie, <7.5 mg/dL [1.88 mmol/L] or emergent care) at 12 weeks was 41.1% with [Prolia (denosumab)] , 60 mg, vs 2.0% with oral bisphosphonates (weighted risk difference, 39.1% [95% CI, 36.3%-41.9%]).
Meaning Treatment of older female dialysis-dependent patients with [Prolia (denosumab)] was associated with a statistically and clinically significant increased risk of severe hypocalcemia compared with oral bisphosphonates.
To make clear the significance of these findings, and why the FDA mandated a Prolia "Black-Box" warning, we turn to this January 19, 2024, MedPage Today news report, "Calcium Levels Quickly Become Critical for Many Denosumab-Treated Women on Dialysis":
Many women on dialysis quickly developed severe hypocalcemia after starting denosumab (Prolia) for osteoporosis, Medicare data showed.
During the first 12 weeks of treatment, 41.1% of women on [Prolia (denosumab)] developed severe hypocalcemia compared with 2.0% of those taking oral bisphosphonates, reported a group of largely FDA researchers led by Steven Bird, PhD, PharmD, of the agency offices in Silver Spring, Maryland.
This translated to more than a 20-times higher risk for incident severe hypocalcemia with [Prolia (denosumab)] (weighted risk ratio 20.7, 95% CI 13.2-41.2), according to the retrospective cohort study in JAMA.
Supported by these new findings, the FDA on Friday added a boxed warning over the risk of severe hypocalcemia in patients with advanced chronic kidney disease (CKD) taking [Prolia (denosumab)] for osteoporosis.
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We get some background about this Prolia - hypocalcemia safety issue from another January 19, 2024, MedPage Today news report, "FDA Slaps Boxed Warning on Osteoporosis Drug":
The label update comes after the FDA initially issued a safety alert in November 2022 about [Prolia's] potential hypocalcemia risk in dialysis-dependent women. The safety alert was prompted after interim results from maker Amgen's ongoing safety study -- required upon approval -- that indicated an increased risk of hypocalcemia in patients with advanced kidney disease.
[Prolia (denosumab)] was first approved in 2010 for postmenopausal women with osteoporosis at high risk for bone fracture and later picked up indications to treat men with osteoporosis, glucocorticoid-induced osteoporosis, and bone loss in those receiving androgen-deprivation therapy for prostate cancer and for women receiving aromatase inhibitor therapy for breast cancer. (Denosumab is also approved under the trade name Xgeva to reduce the risk of bone-related events in certain cancer patients.)
For more detailed information about the new "Black-Box" warning for this Prolia hypocalcemia side effect, we direct you to the January 19, 2024 "Drug Safety Communication: FDA adds Boxed Warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney disease taking osteoporosis medicine Prolia (denosumab)."
We will continue to monitor this still-developing Prolia drug safety issue involving severe hypocalcemia in Porlia patients with advanced chronic kidney disease (CKD) and share significant developments here on Drug Injury Watch.
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