Gentamicin: potential for histamine-related adverse drug reactions with some batches

Some batches of gentamicin sulphate active pharmaceutical ingredient (API) used to manufacture gentamicin may contain higher than expected levels of histamine, which is a residual from the manufacturing process. Monitor patients for signs of histamine-related adverse reactions.

Advice for healthcare professionals:

  • monitor patients closely for potential adverse reactions associated with increased levels of histamine, including:
    • anaphylactoid reactions (for example, flushing, itching, urticaria, and shortness of breath)
    • hypotensive reactions
    • increased heart rate
  • heart rate and blood pressure should be monitored throughout administration of gentamicin
  • use caution when treating patients with gentamicin, especially if using at the same time as other drugs known to cause histamine release
  • paediatric patients and patients with severe renal impairment may be more susceptible to the effects of exogenous histamine, therefore these patients should be monitored more closely
  • report suspected adverse drug reactions to gentamicin on a Yellow Card

Background

We have been informed that some batches of the gentamicin sulphate active pharmaceutical ingredient (API), which is used to manufacture the antibiotic gentamicin, may contain higher than expected histamine levels. Histamine is a residual from the manufacturing process. Batches potentially affected were produced with the API between the second half of 2014 and June 2017.

On 17 October 2017, a Caution in Use alert was issued via the Central Alerting System. We are working with the Marketing Authorisation Holders for these products to investigate the issue further. A recall is not considered appropriate at this stage.

The following products are potentially affected:

Product Marketing Authorisation Holder
Gentamicin 1 mg/mL Solution for Infusion B Braun Melsungen AG
Gentamicin 3 mg/mL Solution for Infusion B Braun Melsungen AG
Cidomycin (Gentamicin) 80 mg/2 mL Solution for Injection Sanofi
Gentamicin 40 mg/mL Injection Hospira UK Limited
Gentamicin Intrathecal 5 mg/mL Solution for Injection Zentiva
Gentamicin Paediatric 20 mg/2 mL Solution for Injection Zentiva
Gentamicin 40 mg/mL Solution for Injection Amdipharm UK Limited
Gentamicin 10 mg/mL Solution for Injection or Infusion Wockhardt UK Limited
Gentamicin 40 mg/mL Solution for Injection or Infusion Wockhardt UK Limited

Call for reporting

Any suspected adverse drug reactions with gentamicin should be reported to us on a Yellow Card.

Further information

Caution in use alert - Class 4 medicines defect information: some batches of Gentamicin Sulphate Active Pharmaceutical Ingredient (API)

Article citation: Drug Safety Update volume 11 issue 4, November 2017: 1.

Published 24 November 2017