New Warnings for Bone Drug Denosumab (PROLIA)

On June 16, the Food and Drug Administration (FDA) approved revisions to the product label for the bone drug denosumab (PROLIA), adding two new warnings about potentially serious side effects.[1] Public Citizen’s Health Research Group designated this drug as Do Not Use soon after it was approved by the FDA in 2010, and these new warnings confirm this designation.

The first new denosumab warning states:[2]

In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking Prolia. ... The time to onset of symptoms varied from one day to several months after starting Prolia. Consider discontinuing use if severe symptoms develop.

We have previously written about atypical fractures in patients taking denosumab that could be a cause of pain in the thigh, hip or groin.[3] The pains related to the new warning are not caused by bone fractures.

The second new warning involves serious allergic reactions, also called hypersensitivity reactions.[4] The warning states that some patients taking denosumab have experienced anaphylaxis, a serious type of allergic reaction that can be fatal. Signs and symptoms have included low blood pressure, shortness of breath, throat tightness, swelling of the face and throat, itching, and rash. Patients having such reactions to denosumab require immediate medical treatment, and they should avoid taking the drug again.

The new alerts expand an already lengthy list of warnings about serious adverse events associated with denosumab treatment, including:[5]

• Dangerously low levels of blood calcium.
• Serious infections of the skin, abdomen, urinary tract and heart valves requiring hospitalization.
• Osteonecrosis of the jaw, a condition that involves destruction of the jaw bone.

Importantly, denosumab, which is administered by injection once every six months, remains in the body a long time after dosing — up to five months.[6] Some adverse reactions may therefore take a long time to improve, even after stopping the drug.

What You Can Do

If you are currently receiving treatment with denosumab, consult your health care provider about switching to alternative treatments, such as one of the following bisphosphonate drugs: alendronate (BINOSTO, FOSAMAX) and risedronate (ACTONEL, ATELVIA).

You should also contact your health care provider immediately if you are taking denosumab and develop any new moderate to severe muscle, bone or joint pain for which there is no other obvious cause, such as trauma, or if you experience any allergic symptoms.

If you have serious adverse events while taking drugs, be sure to report your experience to the FDA’s MedWatch adverse event reporting program at www.fda.gov/Safety/MedWatch/ or by calling 800-FDA-1088.

References

[1] Food and Drug Administration. Supplement Approval: Prolia. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/125320Orig1s150ltr.pdf. Accessed September 12, 2014.

[2] Ibid.

[3] Atypical fractures with an osteoporosis drug. WorstPills.org. https://www.worstpills.org/member/ealert.cfm?ea_id=86. Accessed September 12, 2014.

[4] Amgen Inc. Product labeling for Prolia (denosumab). Revised June 2014. http://pi.amgen.com/united_states/prolia/prolia_pi.pdf. Accessed September 12, 2014.

[5] Ibid.

[6] Ibid.