Primene 10% Amino Acid Solution, 250 mL - Compatibility Issue with Trace Elements - Update

Starting date:
November 23, 2015
Posting date:
November 23, 2015
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Drugs
Source of recall:
Health Canada
Issue:
Important Safety Information
Audience:
Healthcare Professionals, Hospitals
Identification number:
RA-55942

Audience

Health professionals who provide care for infants and children receiving total parenteral nutrition (TPN), or who prepare TPN for administration to this population in the following settings: Pediatric hospitals or units and associated inpatient pharmacy departments, Neonatal intensive care units, Pediatric nursing staff, Emergency departments, Compounding pharmacies, Homecare nursing agencies, and other relevant areas.

Key messages

  • This update on Primene 10% solution replaces the information previously communicated by Baxter Corporation on April 21, 2015, regarding a compatibility issue between Primene and trace elements.
  • Recent investigations conducted by Baxter indicated that, only after filtration, levels of particulate matter in 2 in 1 and 3 in 1 parenteral nutrition test solutions containing Primene admixed with trace elements were within USP limits for particulate matter.
  • To ensure optimal patient therapy and safety, Baxter is now requesting that customers adopt the following practice:
    • ALWAYS attach a filter prior to parenteral nutrition administration.
    • Use a 0.22 micron filter for 2 in 1 (amino acids and carbohydrates) parenteral nutrition solutions. Piggyback lipids for infusion to the patient below the filter (Y-site).
    • Use a 1.2 micron filter for 3 in 1 (lipid, amino acids, and carbohydrates) parenteral nutrition solutions, as the addition of lipids requires a larger filter.
    • Perform visual inspections for cloudiness or precipitation of the TPN solution, infusion set, catheter and in-line filter after compounding, prior to administration and periodically during administration.
    • If discoloration or precipitation is noted in the filter, it is not necessary to stop the infusion. Where medically relevant, perform blood levels of copper (or other trace elements).

       

Issue

There is potential for formation of a precipitate as a result of a suspected interaction between trace elements and cysteine. Formation of this precipitate may result in insufficient levels of cysteine and trace elements in TPN solutions. Deficiencies of cysteine or trace elements can lead to serious health consequences. Serious adverse effects may be associated with the infusion of particulate matter. Infusion of a precipitate may lead to serious adverse effects including phlebitis, thrombophlebitis, thrombosis and major organ dysfunction.

Products affected

The products of concern are:
Product Code Product Name DIN Lot Number
FCA3CG133C29D Primene 10% Amino Acid Injection, 250 mL
Pharmacy Bulk Pack
02236875 ALL

Background information

Primene 10% solution is indicated as nutritional support for infants (including those of low birth weight) and young children requiring total parenteral nutrition via either central or peripheral infusion routes.

Baxter Corporation has received reports from customers indicating that when certain trace elements are added to Primene 10% solution, a precipitate may form. Baxter’s investigations suggest that the precipitation and discoloration is due to the degradation of cysteine during terminal sterilization of Primene 10% solution that results in the formation of hydrogen sulfide. The hydrogen sulfide can then react with copper ions in the trace elements when compounded, and produce copper sulfide precipitate.

Recent investigations conducted by Baxter indicated that levels of particulate matter in 2 in 1 and 3 in 1 parenteral nutrition test solutions containing Primene admixed with trace elements were within acceptable USP <788> limits for particles/mL ≥ 10 µm and ≥ 25 µm1, only after filtration.  During the investigations, visible particulate matter was observed on the inlet side of an inline filter, and therefore the use of filters is required.

Baxter has not been made aware of any related adverse events or patient injury.

The Product Monograph for Primene 10% has been updated to reflect this safety concern.2

Who is affected

Information for consumers

For more information, caregivers of infants and children who receive TPN should contact their TPN provider.  Report serious adverse health consequences or other serious or unexpected side effects of Primene 10% solution to Health Canada. 

Information for health care professionals

The use of a final filter to administer Primene 10% Solution that has been compounded with trace elements is required.

  • Use a 0.22 micron filter for 2 in 1 (amino acids and carbohydrates) parenteral nutrition solutions.  Piggyback lipids for infusion to the patient below the filter (Y-site).
  • Use a 1.2 micron filter for 3 in 1 (lipid, amino acids, and carbohydrates) parenteral nutrition solutions, as the addition of lipids requires a larger filter.
  • Perform visual inspection for cloudiness or precipitation of the TPN solution, infusion set, catheter and of the in-line filter after compounding, prior to administration and periodically during administration.
  • If discoloration or precipitation is observed in the TPN solution, the infusion set, the catheter or at the filter, it is not necessary to stop administration. Where medically relevant, perform blood level checks for copper (or other trace elements).

Action taken by Health Canada

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

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 adverse health consequences or other serious or unexpected side effects in patients receiving Primene 10% solution should be reported to Baxter Corporation or Health Canada.

Baxter Corporation
Attn: Pharmacovigilance
7125 Mississauga Road
Mississauga, ON, L5N 0C2

To report an Adverse Reaction, health professionals and consumers may call toll free:
Phone: 1-800-387-8399 ext 6607
E-Mail: canada_pharmacovigilance@baxter.com
Fax: 1-855-767-4573

To correct your mailing address or fax number, contact Baxter Customer Care at 1- 888-719-9955.

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:
Marketed Health Products Directorate
E-mail: mhpd_dpsc.public@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

Sincerely,

Original signed by

Frank Shannon
Director, Quality
Baxter Corporation

References

1. USP <788> Particulate Matter Injections. In: United States Pharmacopeia-National Formulary (USP 38 – NF 33); pp550-553, 2015.
2. Primene 10% solution (amino acid injection). [Product Monograph Date of Revision October 8, 2015]. Baxter Corporation: Mississauga (ON), Canada L5N 0C2


For more information

The manufacturer advised Health Canada of the risk associated with this health product. Health Canada supports the actions taken by the manufacturer and as such a risk assessment was not required and a Summary Safety Review was not prepared.