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.
Post-publication note: June 2018
Any batches of finished product with a date of manufacture of November 2017 onwards will have been made using API with levels of histamine that are within agreed limits. The agreed histamine limit is based on historical levels which are not known to cause adverse drug reactions, therefore routine vigilance may be resumed for these batches.
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
Article citation: Drug Safety Update volume 11 issue 4, November 2017: 1.