Intramuscular medroxyprogesterone and injection site necrosis and atrophy

HSA would like to inform healthcare professionals about overseas reports of injection site necrosis and atrophy associated with the use of intramuscular medroxyprogesterone.

Medroxyprogesterone acetate (Depo-Provera®, Pfizer Pte Ltd) is a synthetic progestin that is structurally related to the endogenous hormone progesterone. In Singapore, it is available as an intramuscular injection for use in contraception, treatment of endometriosis and menopausal vasomotor symptoms, adjunctive and/or palliative treatment of recurrent and/or metastatic endometrial or renal carcinoma as well as the treatment of hormonally-dependent, recurrent breast cancer in postmenopausal women.

Postmarketing reports of injection site necrosis and atrophy

As of 31 July 2012, a total of 103 medically confirmed global cases of injection site reactions associated with the intramuscular route of administration of medroxyprogesterone were reported to the company. Of these reports, 31 (30.1%) were serious. These injection site reactions described events such as injection site atrophy, atrophy, skin atrophy, lipoatrophy, injection site necrosis, necrosis, fat necrosis, injection site ulcer, and muscle necrosis.

In 46 cases (44.7%), there was insufficient information to allow a meaningful medical assessment. Missing information included site of reaction, site of administration, dates of therapy, dates of event onset, and/or the dose administered. There were 21 (20.4%) cases where intramuscular medroxyprogesterone injection was reported to be administered at the thigh region instead of the recommended deltoid or gluteal region. There were 10 (9.7%) cases where errors in the administration of intramuscular medroxyprogesterone were involved. For the remaining 26 cases (25.2%), the role of intramuscular medroxyprogesterone in the development of injection site atrophy, necrosis, lipoatrophy, skin atrophy, skin necrosis and injection site ulcer could not be ruled out.

HSA's advisory

HSA has not received any reports on injection site reactions associated with the use of intramuscular medroxyprogesterone. HSA is working with the company to further strengthen the warnings in the local package insert for Depo-Provera® to include injection site necrosis and skin atrophy as potential injection site reactions.

Healthcare professionals are reminded to take into consideration the above safety updates when prescribing intramuscular medroxyprogesterone and are encouraged to report any suspected reactions to the Vigilance Branch of HSA.