Tretinoin cream vs gel: what the labels show

Tretinoin cream and tretinoin gel hold the same drug in different bases. The standard gel is 90 percent alcohol by weight, and a third form, the microsphere gel, is water based. One label says that comparable effectiveness of the microsphere gel and the cream "has not been established", and no source read for this hub ranks the forms for clearing acne. The prescriber picks the form along with the strength. For what the drug does, see the tretinoin guide.

Skinli gives general education and is not a doctor. Tretinoin is a prescription drug, and this page reports what the FDA-reviewed labels and a few named studies say about each form. Use it to prepare questions for the person who writes your prescription.

The forms of tretinoin on US labels

MedlinePlus, the patient site of the US National Library of Medicine, says: "Tretinoin comes as a lotion, cream, and gel." The labels on DailyMed, the library's database of drug labels, show more detail.

Form	Strengths on the label	What the label says about the base
Cream (generic and Retin-A)	0.025, 0.05 and 0.1 percent	A cream base. The generic cream lists stearic acid, isopropyl myristate, stearyl alcohol and purified water among its ingredients
Gel (generic and Retin-A)	0.01 and 0.025 percent	A gel base of hydroxypropyl cellulose, butylated hydroxytoluene and alcohol. The alcohol is 90 percent of the gel by weight
Microsphere gel (Retin-A Micro and a generic)	0.04, 0.06, 0.08 and 0.1 percent	"an aqueous gel", which means a water-based gel
Gel 0.05 percent (Atralin)	0.05 percent	The ingredient list includes purified water, glycerin, sodium hyaluronate and fish collagen hydrolyzates
Lotion (Altreno)	0.05 percent	The ingredient list includes glycerin, mineral oil, purified water, sodium hyaluronate and soluble collagen

Form and strength are separate choices, and the prescriber makes both.

Standard tretinoin gel is 90 percent alcohol

The generic gel and the Retin-A gel hold the same amount of alcohol. Both labels list alcohol at 90 percent of the gel by weight.

That much alcohol brings a fire warning, printed in capital letters on the generic label: "GELS ARE FLAMMABLE. AVOID FIRE, FLAME OR SMOKING DURING USE."

The two forms also have different storage limits. The guide on whether tretinoin expires lists the storage line for every product.

No label read for this hub says whether the alcohol gel dries the skin more than the cream. The generic label and the Retin-A label each cover the cream and the gel in one document, with one set of skin warnings for both forms and the fire warning for the gel.

What tretinoin microsphere gel is

A microsphere is a microscopic sphere. In this gel the spheres are made of an acrylic material. The Retin-A Micro label names it: "The formulation contains methyl methacrylate/glycol dimethacrylate crosspolymer (MICROSPONGE® System)". The label for a generic version explains the purpose: "The formulation uses acrylate copolymer microsphere system to enable inclusion of the active ingredient, tretinoin, in an aqueous gel."

In plain words, the spheres make it possible to put tretinoin in a gel made with water. The Retin-A Micro label gives the directions: apply it "to skin where acne lesions appear (cover the entire affected area), once daily in the evening." For the pump pack, the label says: "Store pump upright."

The generic microsphere label reports one comparison with the cream. In its irritation studies, done in people without acne, "tretinoin gel (microsphere), 0.1%, was statistically less irritating than tretinoin cream, 0.1%." The label then limits the finding twice:

• "The clinical significance of these irritation studies for patients with acne is not established."
• "Comparable effectiveness of tretinoin gel (microsphere), 0.1%, and tretinoin cream, 0.1%, has not been established."

Does one form irritate less?

Besides the microsphere label, two studies compare forms, and each has limits.

A 2001 study of retinoid gels. A study in the journal Cutis compared retinoid gels on the faces of volunteers with sensitive skin for up to 29 days. Its abstract reports: "Increases in facial dryness and erythema were comparable among all retinoids." Erythema is redness. The authors wrote that how well the skin tolerates a retinoid "depends more on the individual than on any major inherent differences in the irritant potential of these retinoids."

A 2022 study of lotion against cream. In the Journal of Drugs in Dermatology, "25 adult females with acne were randomized to apply lotion and cream to opposite cheeks once daily for 2 weeks." Randomized means that chance decided which cheek got which product. The abstract reports that "tretinoin 0.05% lotion was associated with less irritation and superior skin appearance/ sensation versus generic 0.05% cream". The study had 25 people, lasted 2 weeks and did not measure acne clearing. Its abstract shows no funding line, so the funder is unknown here.

Two labels also print side effect rates from their own trials. Read them with the warning that the Altreno label gives: "adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug". Each row below compares a product with its own base, and the two products were tested in separate trials.

Side effect reported	Atralin gel 0.05 percent (674 people)	Gel with no drug (487 people)	Altreno lotion 0.05 percent (767 people)	Lotion with no drug (783 people)
Dry skin	16 percent	2 percent	4 percent	Under 1 percent
Burning feeling (Atralin label), or stinging, burning or pain (Altreno label)	8 percent	2 percent	3 percent	Under 1 percent
Redness	7 percent	Under 1 percent	2 percent	Under 1 percent

The Atralin label also reports peeling in 12 percent of people on the gel and 1 percent on the gel with no drug. It says: "Most skin-related adverse reactions first appear during the first two weeks of treatment with Atralin Gel". For peeling with any retinoid, see retinoid dryness and peeling, and for the full list of reactions, see tretinoin side effects.

Do the gel and the cream work the same?

No source read for this hub tested the alcohol gel against the cream for clearing acne. For the microsphere gel, the label says comparable effectiveness with the cream "has not been established."

Three labels print acne results from their own 12-week trials. The trials used different measures, so the rows cannot rank the products.

Label	What was measured at week 12	With the drug	With the base alone
Retin-A Micro gel 0.1 percent, Study 1	Average drop in the count of acne spots, which the label calls lesions	45 percent	23 percent
Retin-A Micro gel 0.1 percent, Study 2	The same measure	32 percent	16 percent
Atralin gel 0.05 percent, Trials 1 and 2	People the label counts as a treatment success	21 and 23 percent	12 and 14 percent
Altreno lotion 0.05 percent, Trials 1 and 2	People rated clear or almost clear, with at least a 2-grade improvement	16.5 and 19.8 percent	6.9 and 12.5 percent

The labels give similar waiting times. The generic gel and cream label says: "Therapeutic results should be noticed after two to three weeks but more than six weeks of therapy may be required before definite beneficial effects are seen." The Retin-A Micro label says improvements "may be noticed after two weeks", and that "more than seven weeks of therapy may be needed for sustained benefit." The guide on how long tretinoin takes to work sets out the full timeline.

What light does to each gel

Two laboratory tests in the journal Cutis exposed the two gels to light. Both abstracts list a Johnson & Johnson consumer products company as the authors' workplace.

Test	Microsphere gel 0.1 percent	Standard gel 0.025 percent
24 hours of fluorescent light (2002)	98 percent of the tretinoin remained unchanged	Up to 69 percent of the tretinoin broke down
2 hours of simulated sunlight UV (2006)	94 percent remained stable	19 percent remained unchanged
6 hours of simulated sunlight UV (2006)	84 percent remained stable	10 percent remained unchanged

The 2006 authors state a limit: "simulated solar UV irradiation is not entirely reflective of actual conditions". These are tests of the product under artificial light, with no patients and no acne results. The microsphere label still directs use "once daily in the evening", and the tretinoin labels ask for sun protection, which the sunscreen with tretinoin guide covers.

How much gel to use, and what pilling means

The amount is small. The generic leaflet says to squeeze half an inch or less onto a fingertip, and the label says to use "enough to cover the entire affected area lightly."

The gel gives its own sign of too much. The generic label says: "Gel: Excessive application results in "pilling" of the gel, which minimizes the likelihood of over application by the patient." Pilling is the label's word for gel that dries into flakes on the skin. The Retin-A leaflet describes the same sign: "If it is still visible, or if dry flaking occurs from the gel within a minute or so, you are using too much."

So the label's answer to pilling is a smaller amount. The guide on how to use tretinoin lists the other steps.

Why the same form can feel different between makers

A generic cream from one maker can feel different from another maker's cream. The FDA explains why this is allowed: "small, allowable differences between the products manufactured by different companies (such as in certain inactive ingredients) can sometimes feel noticeable to patients." Inactive ingredients are everything in the tube except the drug. The Retin-A vs tretinoin guide compares the brand with the generic.

What the sources leave unanswered

Oily or dry skin. People search for whether gel suits oily skin and cream suits dry skin. No label, AAD page or NHS page read for this hub says so. Skinli therefore makes no claim about which form fits which skin type. The facts that the labels do give are the base, the strengths, the fire warning and the trial figures above.

A fish allergy. Two products list ingredients made from fish. The Altreno label says: "ALTRENO contains soluble fish proteins." The Atralin label lists "fish collagen hydrolyzates". Tell your prescriber about a fish allergy before either is prescribed.

When to ask about a different form

A change of form is the prescriber's decision. The generic label says that once acne has improved, "it may be possible to maintain the improvement with less frequent applications, or other dosage forms." A dosage form is the cream, the gel or the lotion.

Ask about a change, or about a pause, in these cases:

• Dryness that bothers you. The generic microsphere label says: "Patients should apply a topical moisturizer if dryness is bothersome." The moisturizer with tretinoin guide covers the options.
• Irritation that does not settle. The Altreno label tells prescribers to "instruct patients to use a moisturizer, reduce the frequency of the application of ALTRENO, or discontinue use."
• Severe or lasting irritation. The generic leaflet says: "If you are experiencing severe or persistent irritation, discontinue the use of tretinoin and consult your physician."
• No change after 12 weeks, or deep, painful lumps or scars. NICE, the guideline body in England, says to review acne treatment at 12 weeks. See a doctor or a dermatologist in person.