Policy

Preparation, Expiration, and Storage of Compounded (Diluted or Mixed) Anesthetics and Analgesics for Animal Use

Type

Policy

Policy

Describes the process of preparing, setting expiration dates for, and storing analgesics and anesthetics for animal use for researchers and ACP-LAB (formerly DAR) veterinary staff

Background

Compounded drugs may change in efficacy and stability once mixed. In this policy we set a maximum expiration date of 6 months after mixing for compound drugs. We also set extended beyond-use dates (longer than manufacturer recommendations) for select drugs where performance standard studies demonstrate maintained sterility and strength/efficacy.

Definitions

Compounded – diluted or mixed.

Procedures

Preparation

  1. Gather supplies:
    • Alcohol swabs.
    • Sterile empty injection vial(s).
    • Appropriately sized sterile syringe and corresponding needle.
    • Sterile diluent (sterile saline or sterile water) if needed for dilution or mixture.
  2. Calculate and verify dilution or mixture amounts of each substance.
  3. Use the alcohol swab and clean the tops of all vials to be used.
  4. Using a sterile needle and syringe, extract the first substance to be mixed and inject into the sterile empty injection vial. Repeat using a new needle and syringe for each remaining component of the cocktail.
  5. Properly label the aliquot, dilution, or mixed cocktail with the components, concentration, total starting volume, mix date, and expiration date.

Setting Expiration Date

  1. Stock aliquots maintain the manufacturer expiration date printed on the bottle unless otherwise indicated. Some compounds expire a set number of days after puncture (e.g. carprofen, maropitant).
    • Performance standard literature may be used to set appropriate beyond-use dates
      • Stock carprofen can be maintained for up to 6 months when refrigerated and stored in glass vials, and protected from light (Xu., 2021).
  2. Dilutions or cocktail mixtures expire 6 months from mix date unless any component expires sooner.
    • Performance standard literature may be used to set appropriate beyond-use dates.
      • Diluted carprofen can be maintained for up to 6 months when refrigerated, stored in glass vials, and protected from light (Xu., 2021).
      • Ketamine-acepromazine-xylazine can be maintained for up to 6 months when protected from light and stored in glass vials (Taylor, 2009).
      • Diluted buprenorphine can be maintained for 6 months when protected from light and stored in glass vials (DenHerder 2017).

Storage and Use

  1. Products must be stored appropriately per their product label or conditions cited in performance standard literature to maintain appropriate expiration dates.
    • Many substances are sensitive to light, maintain stability under refrigeration, and are more stable in glass containers (vs plastic).
  2. Products should be visually examined for changes prior to use; color change, homogeneity, or precipitation indicate the product may no longer be safe for use even if it has not expired.

Note: Additional record keeping and documentation may be required for controlled drugs including additional witnesses, labeling of bottles, creation of controlled substance record card, storage in appropriate locked box, etc.

References

  • CFR, Title 21, Food and Drugs, Chapter II, Drug Enforcement Administration, Department of Justice
  • J Am Assoc Lab Anim Sci. 2021 Jul 1;60(4):470-474. doi: 10.30802/AALAS-JAALAS-20-000102. Epub 2021 May 10. Strength and Sterility of Stock and Diluted Carprofen Over Time. Xu, Jiajie J; Renner, Deanna M; Lester, Patrick A.
  • J Am Assoc Lab Anim Sci. 2009 Nov;48(6):718-26. Beyond-use dating of extemporaneously compounded ketamine, acepromazine, and xylazine: safety, stability, and efficacy over time. Brett J Taylor, Steven A Orr, Jennifer L Chapman, Diana E Fisher.
  • J Am Assoc Lab Anim Sci. 2017 Jul 1;56(4):457-461. Effects of Time and Storage Conditions on the Chemical and Microbiologic Stability of Diluted Buprenorphine for Injection. Johnathan M DenHerder, Ralph L Reed, Jennifer L Sargent, Gerd Bobe, Jan F Stevens, Helen E Diggs

Approved Date

Revised Date