Denosumab (Prolia, Xgeva▼): reports of osteonecrosis of the external auditory canal

Denosumab is associated with a risk of osteonecrosis of the jaw, osteonecrosis of the external auditory canal has also been reported with denosumab.

Advice for healthcare professionals:

  • the possibility of osteonecrosis of the external auditory canal should be considered in patients receiving denosumab who present with ear symptoms including chronic ear infections or in those with suspected cholesteatoma
  • possible risk factors include steroid use and chemotherapy, with or without local risk factors such as infection or trauma
  • advise patients to report any ear pain, discharge from the ear, or an ear infection during denosumab treatment
  • report cases of osteonecrosis of any bone suspected to be associated with denosumab or any other medicine on a Yellow Card

Reports of osteonecrosis of the external auditory canal

In December 2015, we published a Drug Safety Update article about very rare reports of osteonecrosis of the external auditory canal with bisphosphonates. Since then, this possible risk has been kept under close review with denosumab, given that both denosumab and bisphosphonates are known to be associated with osteonecrosis of the jaw.

Worldwide, 5 reports of osteonecrosis of the external auditory canal have now been received for patients treated with 60 mg denosumab for osteoporosis.

The underlying possible pathological mechanism is considered to be similar to that for denosumab-related osteonecrosis of the jaw. As observed with bisphosphonates, the number of cases of osteonecrosis of the external auditory canal in association with denosumab is low compared with those of osteonecrosis of the jaw.

The product information for all denosumab-containing products is being revised to include a warning on the risk of osteonecrosis of external auditory canal. As for bisphosphonates, the risk of osteonecrosis at sites other than the jaw and the external auditory canal continues to be kept under close review.

Background

Denosumab is a human monoclonal IgG2 antibody. Denosumab 60 mg solution for injection (Prolia) is indicated for the treatment of osteoporosis in postmenopausal women and in men at increased risk of fractures, and for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures.

Denosumab 120 mg solution for injection (Xgeva▼) is indicated for the prevention of skeletal-related events (pathological fracture, radiation to bone, spinal cord compression, or surgery to bone) in adults with bone metastases from solid tumours, and for the treatment of adults and skeletally mature adolescents with giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

Article citation: Drug Safety Update volume 10 issue 11, June 2017: 1.

Published 21 June 2017