17 août 2007

What Happens to Epinephrine After the Expiration Date?

Is it acceptable to use epinephrine that is older than the expiration date stamped on the container? What happens to it after that time?

The stability of a drug is defined as the time that the product will meet the specifications outlined in the drug monograph, including identity, strength, quality, and purity. The monograph specifications apply throughout the shelf life of the product, which is noted by the expiration date. Manufacturers must demonstrate that the products maintain their stability, under noted storage conditions, throughout the life of the product.

Stability includes considerations about the activity of the product and about its physical appearance. The stability of a product is influenced by storage conditions: light, temperature, air, humidity, and package components.

There are 5 general types of stability:

Chemical: Active ingredient(s) maintain chemical integrity and labeled potency, within specified limits.

Physical: Product retains the original appearance, palatability, uniformity, dissolution, and suspendability.

: The sterility/resistance to microbial growth is retained, and the microbial effect is within a specified range.

Therapeutic: The therapeutic effect of the product remains unchanged.

Toxicologic: There is no significant increase in toxicity.

Drugs degrade or decompose for various reasons, including chemical reactions, oxidation (exposure to air or chemicals), photochemical decomposition (exposure to light), and interaction with other package components. Epinephrine is one product that is readily oxidized, and it is packaged by the manufacturer to minimize oxidation.

Epinephrine, as labeled, contains between 90% and 115% of the labeled amount of drug. Several references note that the product should not be used if it is pink or brown or if it contains a precipitate. The change in color is evidence that oxidation has occurred. The basic formulation of epinephrine is buffered and contains antioxidants to maintain stability if protected from light, heat, and air.

Specific to your question, there is a warning note in Remington's to "not to use any epinephrine dosage form if it is brown or pink in color or contains a precipitate; a hallucinatory reaction may occur." Other references checked did not mention specific toxic effects of expired epinephrine.

When solutions of epinephrine oxidize in the presence of oxygen, especially in neutral or alkaline solutions, a red color is formed. This red substance is a pigment called adrenochrome. It has no medical use, but it is noted to have been used experimentally to produce psychic effects.

There are reports from the 1950s and 1960s referring to psychomimetic symptoms of adrenochrome, but they were not validated in the literature. In fact, these references would not meet the rigor of today's research. Overall, adrenochrome is not a very stable product, which would minimize any effects of exposure.

In summary, the manufacturer-provided expiration date reflects the shelf life of the product, during which it will meet the various specifications provided in the drug monograph. After this time, the product will still have some activity, but it is not proven to meet the given standards. The integrity of any product after the manufacturer's expiration date is questionable, and the product should not be used.

Tiré de Medscape

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