Gentamicin Injection USP (10 mg/mL and 40 mg/mL) – Potential for Adverse Reactions with 12 Lots Contaminated with Histamine

Starting date:

June 29, 2017

Posting date:

July 3, 2017

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Issue:

Important Safety Information

Audience:

Healthcare Professionals

Identification number:

RA-63768

• 
  Issue
• 
  Who is affected
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  Report health or safety concerns

Audience

Healthcare professionals including pediatricians, urologists, gynaecologists, respirologists, surgeons, internists, pharmacists, nurses, and emergency room staff.

Key messages

• Gentamicin Injection USP (10 mg/mL and 40 mg/mL) is indicated for the treatment of serious, potentially life-threatening, infections, in adults and children.
• Twelve lots of Gentamicin Injection USP manufactured at Sandoz Canada Inc. may contain traces of histamine.
• Histamine administered intravenously or intramuscularly could potentially lead to signs and symptoms of anaphylaxis, particularly in pediatric patients and patients with severe renal impairment.
• Although the likelihood of this adverse event is rare, healthcare professionals are advised, when administering Gentamicin Injection USP, to closely monitor all patients for adverse reactions associated with elevated levels of histamine.

Issue

Sandoz has identified histamine contamination in 3 Active Pharmaceutical Ingredient (API) batches used to manufacture 12 lots of Gentamicin Injection USP. The 3 API batches were tested for histamine levels. One batch had a level of 5 ppm (5 mcg/g), and the other 2 batches had a level less than the limit of quantification.

Products affected

Background information

Gentamicin Injection USP (10 mg/mL and 40 mg/mL), a medically necessary drug, is indicated for the treatment of serious, potentially life-threatening, infections, in adults and children.

Histamine, produced by certain white blood cells and found throughout connective tissues in the body, plays a key role in inflammatory responses, including anaphylactic reactions. Although no information on the safety of intramuscular histamine administration in humans was identified, the literature does suggest that as little as 7 mcg of histamine administered intravenously in adults can trigger vasodilatation and increased heart rate. Similar information could not be found for pediatric patients.  Based on the testing of the API batches, the amount of histamine that may be found in a daily adult dose of affected Gentamicin for Injection USP is expected to be below the 7 mcg level. 

Who is affected

Information for consumers

Gentamicin Injection USP is used only to treat serious and life-threatening infections that are proven or strongly suspected to be caused by certain bacteria. Gentamicin Injection USP is generally administered by healthcare professionals, either as an injection into a muscle or directly into a vein.

During the manufacturing of Sandoz Gentamicin Injection USP, some lots of the product were contaminated with a substance called histamine. When injected into the body, this could potentially lead to side-effects similar to those experienced during life-threatening allergic reactions. Sandoz and Health Canada are letting healthcare professionals know that they need to take extra precautions and to monitor patients when giving the medication.

Information for healthcare professionals

All patients being administered affected Gentamicin Injection USP lots should be monitored closely for potential adverse reactions associated with increased levels of histamine (see Products affected section). In particular, the daily amount of histamine that could trigger adverse reactions in the pediatric population is unknown. Additionally, patients with severe renal impairment may be more susceptible to the antihypertensive effects of exogenous histamine. Therefore, pediatric patients and patients with severe renal impairment should be monitored more closely.

Action taken by Health Canada

Health Canada is communicating this important safety information to healthcare professionals via the Recalls and Safety Alerts Database on the Healthy Canadians Web Site. This communication will be further distributed through the MedEffect e-Notice™ email notification system.

Health Canada continues to monitor the issue and the implementation of corrective and preventative actions by Sandoz Canada Inc.

Report health or safety concerns

Managing marketed health product-related side effects depends on health care professionals and consumers reporting them. Any case of serious or unexpected side effects in patients receiving Sandoz Gentamicin Injection USP (10 mg/mL and 40 mg/mL) should be reported to Sandoz Canada Inc. or Health Canada.

Sandoz Canada Inc.
145 Jules-Léger Street
Boucherville (Qc)
J4B 7K8
Email : medinfo@sandoz.com

To correct your mailing address or fax number, contact Sandoz Canada Inc..

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

• Calling toll-free at 1-866-234-2345; or
• Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

For other health product inquiries related to this communication, contact Health Canada at:

Regulatory Operations and Regions Branch
E-mail: dcviu_uvcem@hc-sc.gc.ca
Telephone: 1-800-267-9675
Fax: 1-613-946-5636

Original signed by

Daniel Abran
Sandoz Canada Inc. Executive Director, Quality ComOps
Novartis Canada, Quality Country Head