Tretinoin vs isotretinoin (Accutane): differences

Tretinoin and isotretinoin are two different prescription drugs from the same family. Tretinoin for acne is a cream, gel or lotion that goes on the skin. Isotretinoin, which many people still call Accutane, is a capsule taken by mouth for severe acne, and it comes with a pregnancy safety program called iPLEDGE. For each drug by itself, see the tretinoin guide and the Accutane guide.

Skinli gives general education and is not a doctor. Both drugs need a prescription, and the prescriber decides which one fits and at what strength or dose. This page stays with how the two differ.

Two related drugs, taken two ways

Both drugs are retinoids, which are drugs related to vitamin A. MedlinePlus, the National Library of Medicine's patient site, says: "Tretinoin is in a class of medications called retinoids." The label for Amnesteem, an isotretinoin capsule on DailyMed, calls isotretinoin "a retinoid" too.

The two chemicals are closely related. The Retin-A label gives tretinoin's other name, retinoic acid. The isotretinoin label says: "Chemically, isotretinoin is 13-cis-retinoic acid and is related to both retinoic acid and retinol (vitamin A)." It adds: "Retinoic acid and 13-cis-retinoic acid are geometric isomers and show reversible interconversion." Isomers are made of the same atoms arranged in a different shape. Reversible interconversion means each one can change into the other.

A study on the Altreno lotion label shows that change in people. After 20 people used the tretinoin lotion, researchers measured "tretinoin and its major metabolites (isotretinoin and 4-oxo-isotretinoin)" in their blood. A metabolite is a substance the body makes from a drug. So a tube of tretinoin holds no isotretinoin, and the body makes some from the tretinoin it absorbs.

Three names cause confusion:

• Accutane. The American Academy of Dermatology (AAD) says: "Some people refer to this medication as Accutane®. This is a brand of isotretinoin that is no longer available." Isotretinoin is still sold under other brand names, and Amnesteem is one of them.
• Retin-A. Retin-A is a brand of tretinoin for the skin. The guide to Retin-A vs tretinoin covers the brand names.
• Oral tretinoin. Tretinoin also exists as a capsule, and it is used for a different disease. MedlinePlus says those capsules treat acute promyelocytic leukemia, a cancer of the blood cells. Accutane is isotretinoin by mouth.

The two drugs compared

	Tretinoin	Isotretinoin
How it is used	A cream, gel or lotion on the skin, once a day	A capsule, "for oral use"
Use on the label	"the treatment of acne vulgaris" (generic cream)	"severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older"
Where the drug goes	The treated skin. A small share reaches the blood	The whole body
Length of treatment	Continued while the prescriber advises. Label trials measured results at week 12	"A course of treatment is 15 to 20 weeks."
Safety program	None named on the tretinoin labels read	Available only through iPLEDGE
Pregnancy	Wording differs by label	Must not be used. The label has a boxed warning

Acne vulgaris is the medical name for common acne. Recalcitrant means the acne has not responded to other treatment. Nodular acne has deep, firm lumps, and the label describes them as nodules "with a diameter of 5 mm or greater."

The length of treatment differs too. The generic tretinoin leaflet says: "Once your acne is under control you should continue regular application of tretinoin until your physician instructs otherwise." Isotretinoin is given as a course with an end. The AAD says one course takes four to five months, sometimes less and sometimes more, and that dermatologists fit the treatment to each patient.

Who each drug is for

Tretinoin is labelled for acne in general. The summary of the 2024 AAD acne guideline says: "Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline." Topical means applied to the skin, and tretinoin is one of the topical retinoids. NICE, the guideline body in England, lists a fixed combination of tretinoin with clindamycin among its first treatments "for any acne severity". The guide to prescription retinoids for acne lists the other retinoids that go on the skin.

Isotretinoin is reserved for acne that is harder to treat. Its label says the drug is "reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics." Systemic antibiotics are antibiotics taken by mouth. The AAD puts it in plain words: "When other treatments fail to clear the skin, isotretinoin may be an option." The guideline summary gives three situations: "Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy." Psychosocial burden means the acne harms a person's mood or daily life.

So the question of which drug is better or stronger has one practical answer: they are used for different acne. The guide on how to get Accutane explains who can prescribe it.

How each one works

MedlinePlus says tretinoin "works by increasing production of new skin cells and unclogging pores." The Retin-A Micro label is more careful: "The exact mechanism of action of topical tretinoin for treatment of acne vulgaris is unknown." Tretinoin acts where it is applied. The same label measured how much of the drug got through the skin into the blood, and the average was 0.82 percent of one application and 1.41 percent with daily use.

The isotretinoin label describes a different action. It says isotretinoin "inhibits sebaceous gland function", and sebaceous glands are the skin's oil glands. The label goes on: "Clinical improvement in nodular acne patients occurs in association with a reduction in sebum secretion." Sebum is skin oil. A capsule taken by mouth reaches the whole body, and the isotretinoin label lists side effects beyond the skin. The guide to Accutane side effects covers them.

The safety rules are different

Isotretinoin comes with strict rules. The label opens with a boxed warning, a warning printed inside a box, which says: "Amnesteem can cause life-threatening birth defects and is contraindicated in pregnancy." Contraindicated means the drug must not be used. The label continues: "Amnesteem is available only through a restricted program called the iPLEDGE REMS." REMS stands for Risk Evaluation and Mitigation Strategy, and the AAD says the FDA runs the program.

Under that program, the label says, "Prescribers must be certified with the REMS", and for patients who can get pregnant, "pregnancy testing is required prior to, during, and after Amnesteem treatment". The AAD says the dermatologist enrolls the patient, and that the patient is under close medical supervision during treatment. See Accutane and pregnancy for the full rules.

Tretinoin on the skin has no such program. Skinli searched eight DailyMed labels of products that contain tretinoin for the program's name and for the words "restricted program", and found neither. The side effects those labels list are reactions of the treated skin, such as dryness, redness and peeling. The guide to tretinoin side effects reports them.

Pregnancy still matters with tretinoin. Tell your prescriber if you are pregnant or planning a pregnancy, and read retinoids during pregnancy and breastfeeding for what each label says.

Tretinoin before or after isotretinoin

Before. Skin treatment usually comes first. NICE recommends "a 12-week course" of a first treatment, followed by a review, and it describes isotretinoin as a drug for "a severe form of acne that is resistant to adequate courses of standard therapy with systemic antibiotics and topical therapy". The AAD guideline also recommends isotretinoin for acne that is severe or scarring, so a dermatologist may suggest it sooner in those cases.

After. One small study tested tretinoin after a finished course. "Twenty males aged 18-45 years old were enrolled." Half used tretinoin 0.04 percent microsphere gel and half used a gel with no drug, for 24 weeks. The result: "there was a 38.7% lower lesion count with tretinoin 0.04% microsphere gel use versus vehicle." A lesion count is the number of pimples and clogged pores, and vehicle means the gel with no drug. The authors listed their limits: "the low number of patients enrolled, average age, and percentage of patients lost to follow-up." The AAD says more generally: "Dermatologists also may recommend a topical retinoid as a maintenance treatment." Maintenance treatment keeps skin clear once acne is under control. NICE says to consider maintenance treatment "in people with a history of frequent relapse after treatment."

At the same time. No source read for this guide says whether tretinoin can be used during a course of isotretinoin, or how long to wait after the last capsule. This is a question for the prescriber who manages the course.

When to see a doctor

See a doctor or a dermatologist if you have deep, painful lumps under the skin, acne that leaves scars, or acne that affects your mood. Those are the situations in which the AAD guideline recommends isotretinoin, and only a prescriber can assess them. The guide on when to see a dermatologist for severe acne explains what to expect.

For milder acne, give a treatment time before judging it. NICE reviews a first treatment at 12 weeks, and Skinli's own guidance is that skin needs 8 to 12 weeks to change. If a tretinoin product has not helped by then, go back to the prescriber. Stopping one drug and asking for the other is their decision to make with you.