FDA Slaps Boxed Warning on Osteoporosis Drug

The FDA added a boxed warning to the tag of the osteoporosis drug denosumab (Prolia) over the probability of severe hypocalcemia in patients with developed persistent kidney illness (CKD), the agency announced Friday.

After a overview of the evidence, including new records revealed in JAMA, the FDA sure that denosumab can elevate the probability for severe hypocalcemia in contrast with bisphosphonates in patients with developed CKD, especially those on dialysis. Patients on dialysis or with mineral and bone dysfunction (MBD) have the ideal probability of very low blood calcium ranges.

The brand new records, which alive to women on dialysis, confirmed that 41% developed severe hypocalcemia all around the first 12 weeks of denosumab medication, in contrast with 2.0% of those taking oral bisphosphonates.

The FDA’s “most prominent” warning, the boxed warning lists the aptitude for serious damage from severe hypocalcemia. This would per chance perchance furthermore encompass hospitalization, lifestyles-threatening events, and death in patients with developed CKD taking denosumab. Excessive hypocalcemia would perchance be asymptomatic or can fresh with signs admire confusion, seizures, irregular heart rhythm, fainting, face twitching, uncontrolled muscle spasms, or weak spot, tingling, or numbness in formulation of the physique.

As allotment of its new drug security dialog, the FDA instructed clinicians to fastidiously steal appropriate patients for this medication and elevate monitoring of blood calcium ranges, namely for the first 2 to 10 weeks after each and every injection. Calcium and food regimen D supplements would perchance be required.

Ahead of prescribing denosumab, clinicians can must mute assess their patients’ kidney goal and check the probability of severe hypocalcemia with denosumab within the context of diversified on hand therapies for osteoporosis for patients with developed CKD — especially those on dialysis.

“If Prolia is mute being thought of for these patients, for preliminary or persevered exercise, check their calcium blood ranges and assess them for evidence of CKD-MBD,” the FDA instructed.

Patients taking denosumab ought to not stop their treatment without first consulting with their healthcare provider.

The tag change comes after the FDA in the initiating issued a security alert in November 2022 about denosumab’s doubtless hypocalcemia probability in dialysis-dependent women. The safety alert changed into once introduced on after meantime results from maker Amgen’s ongoing security look — required upon approval — that indicated an elevated probability of hypocalcemia in patients with developed kidney illness.

The drug changed into once first accredited in 2010 for postmenopausal women with osteoporosis at high probability for bone crash and later picked up indications to treat males with osteoporosis, glucocorticoid-triggered osteoporosis, and bone loss in those receiving androgen-deprivation treatment for prostate cancer and for women receiving aromatase inhibitor treatment for breast cancer. (Denosumab is also accredited below the trade title Xgeva to gash the probability of bone-linked events in definite cancer patients.)

Administered via injection every 6 months, the medication works by blocking off the protein receptor activator of nuclear part kappa beta (RANK) and prevents osteoclasts from breaking down bone within the physique.

The FDA requested patients and healthcare mavens to anecdote unwanted side effects keen denosumab to the agency’s MedWatch program.