Tretinoin Storage, Stability & Shelf Life: How to Keep Your Retinoid Potent

What determines how long a tretinoin product lasts?

FDA describes an expiration date as the period during which a product is known to remain stable, keeping its strength, quality and purity, when it is stored according to its labeled storage conditions [1]. Applicants submit stability data with a proposed date and storage conditions, and FDA verifies that the date is supported by appropriate studies [1]. The appropriate conditions depend on the drug and may include temperature, humidity and exposure to light [1].

FDA also describes what can happen when a drug has degraded or was not stored as labeled: it may have a lower strength than intended, so it may not provide the intended benefit, and degradation can yield toxic compounds that could cause unintended side effects [1]. FDA's shelf-life extension program covers selected products in federal stockpiles under controlled storage. FDA notes that drugs held by consumers may have been stored under varied conditions, which makes testing to set meaningful, generally applicable expiration dates difficult [1].

How fast does light degrade tretinoin?

The sharpest numbers come from a 2000 laboratory study in the International Journal of Pharmaceutics. Brisaert and Plaizier-Vercammen placed a tretinoin lotion in front of a xenon lamp and measured the drug by HPLC: it fell to about 20% of its initial concentration within 30 minutes [2].

In this experiment, 420 nm appeared to be the most harmful wavelength, rather than 350 nm, where tretinoin absorbs most strongly [2]. Beta-cyclodextrin and certain surfactants did not change photodegradation, a UV-B sunscreen could not retard it, and a UV-A sunscreen had very little effect [2]. Yellow colorants that absorb around 420 nm did slow degradation, by amounts that depended on their concentration [2].

Why did one gel survive 24 hours of light when another did not?

A 2002 study in Cutis compared tretinoin gel microsphere 0.1% with a conventional tretinoin gel 0.025%, alone and combined with erythromycin-benzoyl peroxide topical gel, exposed to fluorescent light, incandescent light or darkness for up to 24 hours [3].

After 24 hours under fluorescent light, 98% of the initial tretinoin in the microsphere 0.1% gel was unchanged [3]. Combined with the erythromycin-benzoyl peroxide gel, 99% and 87% of the tretinoin was recovered after 4 and 24 hours [3]. The conventional 0.025% gel lost up to 69% of its tretinoin after 24 hours of fluorescent light, and up to 89% when it was combined with the erythromycin-benzoyl peroxide gel [3]. The authors concluded that the microsphere formulation offers marked protection against photodegradation [3].

That is two formulations in one laboratory experiment. It does not rank every cream against every gel, and it does not tell you how long a given tube stays potent on a shelf.

Does the container matter?

FDA's expiration-date information ties the date to the product's labeled storage conditions and does not address transferring a product to a different container [1]. Humidity and light are among the factors FDA lists as possibly relevant to storage [1].

What about heat, cold, a hot car or a warm delivery?

FDA's warning about drugs stored outside labeled conditions is general: lower strength than intended and possible toxic breakdown products [1]. The tretinoin-specific figures on this page come from a lotion under a xenon lamp [2] and gels under fluorescent light [3]. Those tests measured light exposure, not heat.

What about compounded tretinoin?

Compounded tretinoin is not FDA-approved, and FDA does not verify the safety, effectiveness or quality of compounded drugs before they are marketed [5]. Poor compounding practices can result in serious quality problems, such as contamination or a drug that contains too much or too little active ingredient [5].

Can color, texture or stinging tell you whether a tube has gone off?

Altreno's label describes its lotion as opaque and pale yellow [4]. Color alone does not establish how much tretinoin remains.

Local reactions are also listed as expected effects of use. The Renova label lists local reactions including erythema, peeling, dryness, burning, stinging and itching, and states that larger amounts of medication than recommended have not been shown to lead to more rapid or better results, while marked redness, peeling or discomfort may occur [6].

Can tretinoin be mixed with benzoyl peroxide?

The Cutis study is the main stability data here, and for at least one formulation the combination was not neutral under light. The conventional 0.025% gel lost up to 89% of its tretinoin after 24 hours of fluorescent light when combined with erythromycin-benzoyl peroxide gel, against up to 69% alone, while the microsphere 0.1% gel still had 87% of its tretinoin at 24 hours with the same combination [3].

Renova's label lists concomitant topical medications, medicated or abrasive soaps, strongly drying cosmetics and high-alcohol products among things that may increase irritation [6]. MedlinePlus lists benzoyl peroxide, hair removers, salicylic acid and dandruff shampoos containing sulfur or resorcinol among products that may interact with tretinoin [7].