Tretinoin side effects: what the labels list

The side effects on tretinoin labels are reactions of the treated skin: dryness, redness, peeling, itching, burning and stinging. They show up mostly in the first two weeks and ease for most people after that. This guide reports what the FDA-reviewed labels list, how often each effect happened in the label trials, and which signs mean a call to your prescriber. For the drug itself, see the tretinoin guide.

Skinli gives general education and is not a doctor. Tretinoin is a prescription drug, and your prescriber picks the strength and the schedule. If a reaction worries you, the person who prescribed the tube is the one to ask. Daily care for dry and flaking skin has its own page, retinoid dryness and peeling, so this guide stays with the label lists and the warning signs.

The side effects the labels list

The labels are published on DailyMed, the National Library of Medicine's database of drug labels. MedlinePlus is the same library's patient site.

Source	What it lists
Retin-A Micro gel label	It "can cause local skin irritation, including excessive dryness, redness, swelling, peeling, itching, blistering, burning, or stinging"
Retin-A Micro leaflet	"The most common side effects of RETIN-A MICRO include skin redness, pain, and itching."
Generic tretinoin cream label	A passing feeling of warmth or stinging when the cream goes on. Also: "Topical use may induce severe local erythema and peeling at the site of application." Erythema means redness
MedlinePlus, tell your doctor if severe or lasting	"dryness, itching, burning, stinging, peeling, swelling, redness, blistering, or flaky skin at the treatment area"
MedlinePlus, call your doctor immediately	"itching, rash, hives", and pain or discomfort at the treated area

Each item on these lists is on the skin where the medicine was applied. The American Academy of Dermatology (AAD) says of retinoid irritation: "Developing irritated skin doesn't typically mean that you have an allergy to this medication". The cream label agrees: "True contact allergy to topical tretinoin is rarely encountered."

How often they happened in trials

Each trial compared tretinoin with the same product made with no drug in it.

Label	What patients reported: tretinoin against no drug
Atralin gel 0.05 percent (674 and 487 people, as long as 12 weeks)	Dry skin 16 percent against 2. Peeling 12 against 1. Burning feeling 8 against 2. Redness 7 against under 1
Altreno lotion 0.05 percent (767 and 783 people)	Dryness 4 percent against under 1. Stinging, burning or pain 3 against under 1. Redness 2 against under 1

Examiners saw more than patients reported. In the Altreno trials, staff checked each face at each visit and recorded any sign of any grade:

Sign seen at any visit	Altreno lotion	Lotion with no drug
Redness	51 percent	44 percent
Scaling	49 percent	30 percent
Itching	35 percent	28 percent
Burning	30 percent	14 percent
Stinging	21 percent	8 percent
Darker patches	35 percent	35 percent

People on the lotion with no drug also had redness and itching at many visits, so part of what skin shows during a trial is unrelated to tretinoin.

A smaller share stopped treatment because of irritation. On the Retin-A Micro label, 6 percent of people on the 0.1 percent gel (14 of 224) stopped for that reason, and 1.3 percent on the 0.04 percent gel (3 of 225). In the trials of Renova cream 0.02 percent, a tretinoin cream for fine wrinkles, the label says "Almost all patients reported one or more local reactions such as peeling, dry skin, burning, stinging, erythema, and pruritus." Pruritus means itching. In 32 percent of those patients the irritation was severe, led to a pause, or led to a mild steroid cream for a short time.

A 2019 review of 54 trials of retinoids for acne, in the American Journal of Clinical Dermatology, reported that tretinoin 0.05 percent caused side effects in 62 percent of patients, compared with 19 percent for adapalene 0.1 percent. The Altreno label warns that rates from different trials "cannot be directly compared", so treat that difference with caution. See adapalene vs tretinoin.

When side effects start and how long they last

Time	What the sources say
Early days	"There may be some discomfort or peeling during the early days of treatment." (generic leaflet)
First 2 weeks	"Most skin-related adverse reactions first appear during the first two weeks of treatment" (Atralin label)
Week 2	Close to half of the 225 people on Retin-A Micro 0.04 percent gel had skin irritation. Fewer than 10 percent had moderate irritation, and none had severe irritation
After week 2	Irritation "peaked during the initial two weeks of therapy and decreased thereafter" (Retin-A Micro label)
Weeks 2 to 4	Early discomfort and peeling usually subside (generic leaflet)
Whole course	"In some subjects, the skin-related adverse reactions persist throughout the treatment period." (Atralin label)
Weeks 24 to 48	In a trial of tretinoin cream for sun-damaged skin, skin side effects were less common in the second 24 weeks than in the first

The cream label adds a line about stopping: "To date, all adverse effects of tretinoin have been reversible upon discontinuance of therapy".

Acne can also look worse at the start. MedlinePlus says that will probably happen during the first 7 to 10 days. The tretinoin purging guide covers early breakouts, and how long tretinoin takes to work gives the full timeline.

Burning and stinging: what is expected and what is too much

A short feeling of warmth or stinging when the cream goes on is on the label as a passing effect. The AAD says the same of prescription products in general: "Some products prescribed by a dermatologist may cause stinging or burning."

The labels name several things that make burning worse:

• Too much medicine. "If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur."
• Sensitive areas. The label says tretinoin "should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes." Mucous membranes are the moist linings inside the nose and mouth. See tretinoin under the eyes.
• Weather. "Weather extremes, such as wind or cold, also may be irritating to patients under treatment with tretinoin."
• Other acne products. The Retin-A Micro label says store-bought acne products "containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid" may raise the risk of irritation. See salicylic acid with tretinoin.
• Hair removal and other irritants. The Renova label says waxes, hair removal creams and electrolysis "should be used with caution".

Burning is too much when it is strong, when it lasts, or when the skin changes. The cream label says: "The skin of certain sensitive individuals may become excessively red, edematous, blistered, or crusted." Edematous means swollen. In that case the label gives the prescriber three options: "use the medication less frequently, discontinue use temporarily, or discontinue use altogether." The Altreno label adds moisturizer to that list.

The AAD lists the changes dermatologists use to reduce retinoid irritation: a smaller amount, less frequent use, and moisturizer first. It adds: "Only make these changes with your dermatologist's help."

Peeling

Peeling is on the label lists and the MedlinePlus list above. The leaflet calls early peeling "just your skin adjusting to tretinoin" and says it usually subsides within 2 to 4 weeks.

For peeling, the labels suggest moisturizer. The Retin-A Micro label says: "Apply a topical moisturizer." The Atralin label says a suitable moisturizer during the day may be helpful. The AAD says moisturizer every day can help skin tolerate these medicines. The guide to retinoid dryness and peeling explains what to do day by day, and moisturizer with tretinoin compares what each label says about timing.

Sun, skin color and who should take extra care

Sun. The leaflet says tretinoin "may make your skin more susceptible to sunburn and other adverse effects of the sun". It also says: "If you do become sunburned, stop your therapy with tretinoin until your skin has recovered." The Renova label asks for care with other medicines that make skin react to sunlight, and names five groups: thiazides, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides. Ask your pharmacist whether a medicine you take is in one of them. See sunscreen with tretinoin.

Skin color. The cream label says: "Temporary hyper- or hypopigmentation has been reported with repeated application of tretinoin." Those words mean darker patches and lighter patches. The leaflet says the color returned to normal when the skin adjusted or treatment stopped. The AAD says that in skin of color, irritation can trigger dark marks, which is one more reason to report irritation early.

Eczema. The labels differ in strength. The generic label says tretinoin "has been reported to cause severe irritation on eczematous skin and should be used with utmost caution". Retin-A Micro says to avoid areas affected by eczema, Altreno says to avoid applying it to such skin, and Atralin says the gel "should not be used" there.

Fish allergy. The Altreno label says the lotion "contains soluble fish proteins."

Swallowing. The cream label says tretinoin taken by mouth may cause the same side effects as too much vitamin A. The Retin-A Micro leaflet says to call the Poison Help line at 1-800-222-1222 if the gel is taken by mouth.

Pregnancy. Tell your prescriber if you are pregnant or planning a pregnancy. The guide to retinoids during pregnancy and breastfeeding covers what each label says.

Cancer and long-term safety

The leaflet states: "There is no evidence to date that tretinoin alone will cause the development of skin tumors in either laboratory animals or humans." The label also reports studies in mice. Those studies suggest that tretinoin may add to the tumor-causing effect of strong ultraviolet light from a lamp. The label says "the significance of these studies to humans is not clear" and that patients should keep sun and sunlamp exposure low.

In a 2009 report in the Archives of Dermatology, 1,131 veterans with a mean age of 71 used tretinoin 0.1 percent cream or a cream with no drug twice a day on the face and ears. The trial was stopped 6 months early because of more deaths in the tretinoin group. The authors wrote: "We observed an association of topical tretinoin therapy with death, but we do not infer a causal association that current evidence suggests is unlikely." In plain words, they saw the difference and did not conclude that the cream caused it.

Long-term use is covered in what happens if you stop tretinoin.

When to call your prescriber

Stop the medicine and call in these cases:

• Severe or lasting irritation. The leaflet says: "If you are experiencing severe or persistent irritation, discontinue the use of tretinoin and consult your physician."
• Blisters, crusts or swelling.
• A rash, hives, or pain where you applied it. MedlinePlus says to call your doctor immediately for these.
• Sunburn. Wait until the skin has recovered.
• Tretinoin swallowed. Call the Poison Help line.

Also see a doctor or a dermatologist in person if your acne is no better after 12 weeks, or if you get deep, painful lumps or scars. Side effects that stop you from using the medicine are a reason to ask about a different strength, form or drug, and that choice belongs to your prescriber.