Clindamycin and tretinoin together for acne

Clindamycin and tretinoin are used together for acne, most often as one prescription gel that holds both drugs. Clindamycin is an antibiotic and tretinoin is a retinoid, a drug related to vitamin A, so each one works on a different cause of acne. This guide covers what the combined gel contains, what its trials found, how its label says to use it, and the bowel warning that comes with clindamycin. For tretinoin by itself, see the tretinoin guide.

Skinli gives general education and is not a doctor. Both drugs need a prescription, and your prescriber picks the product, the strength and how long you use it. The other common clindamycin pair has its own page: clindamycin and benzoyl peroxide.

Two drugs that do different things

	Clindamycin on the skin	Tretinoin on the skin
Drug class (MedlinePlus)	"lincomycin antibiotics"	"retinoids"
What it does (MedlinePlus)	"slowing or stopping the growth of bacteria that cause acne and by decreasing swelling"	"increasing production of new skin cells and unclogging pores"
Forms sold alone (MedlinePlus)	Foam, gel, solution, lotion and single-use swabs	Lotion, cream and gel
How often, used alone (MedlinePlus)	Once or twice a day, depending on the product	Daily at bedtime

The American Academy of Dermatology (AAD) explains why the two kinds of drug are put in one product: "To reduce the risk of antibiotic resistance and increase how well each medication works, some acne treatments contain a topical antibiotic and another acne medication like benzoyl peroxide or a retinoid." Antibiotic resistance means bacteria stop responding to the drug. Topical means applied to the skin.

The 2024 acne guideline from the AAD makes strong recommendations for both topical retinoids and topical antibiotics. As good practice, it also recommends combining skin treatments that work in different ways.

The combined gel: what is in it and who it is for

The label for Ziana gel is published on DailyMed, the National Library of Medicine's database of drug labels. It calls the gel "a lincosamide antibiotic and retinoid combination product". Lincosamide is the name of clindamycin's drug family.

• Strengths. Clindamycin phosphate 1.2 percent and tretinoin 0.025 percent. Each gram holds 10 mg of clindamycin and 0.25 mg of tretinoin in a water-based gel.
• Use. "ZIANA Gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older." Acne vulgaris is the medical name for common acne.
• Brand names. The AAD's acne treatment page lists "Retinoid + antibiotic (Brand names include: Veltin, Ziana)". The Veltin label was not read for this guide, so the figures here come from the Ziana label.

NICE, the guideline body in England, places the pair among its first choices. It tells doctors to offer a 12-week course of one of several options, and one of them is "a fixed combination of topical tretinoin with topical clindamycin for any acne severity". Fixed combination means both drugs in one product.

Some people must not use the gel. The label says it is "contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis." The leaflet puts this in plain words: do not use it if you have Crohn's disease or ulcerative colitis, or if you developed colitis, an inflamed bowel, with past antibiotic use.

Two more limits are on the label. The gel "should not be used in combination with erythromycin-containing products". Laboratory tests showed the two antibiotics working against each other, and the label says the meaning of this for patients is not known. NICE says the combination is "Not for use during pregnancy or breastfeeding". The guide to retinoids during pregnancy and breastfeeding covers that topic.

What the trials on the label found

Three trials are on the Ziana label. Each lasted 12 weeks, and patients were 12 years and older. The first two compared four gels.

Result at week 12, two trials combined	Combined gel (845 people)	Clindamycin alone (426)	Tretinoin alone (846)	Gel with no drug (423)
Clear or almost clear	21 percent	16 percent	14 percent	8 percent
Average drop in inflamed pimples	48 percent	42 percent	39 percent	26 percent
Average drop in blackheads and whiteheads	36 percent	27 percent	31 percent	16 percent
Average drop in all acne spots	41 percent	34 percent	34 percent	20 percent

The combined gel had the highest figure in each row. Each single drug did better than the other on one measure: clindamycin on inflamed pimples, and tretinoin on blackheads and whiteheads. That pattern fits what each drug does.

The third trial enrolled 2,010 people with moderate or severe acne and compared the combined gel with clindamycin gel.

Result at week 12, third trial	Combined gel (1,008 people)	Clindamycin gel (1,002)
Improved by 2 grades or more	41 percent	34 percent
Average drop in inflamed pimples	61 percent	55 percent
Average drop in blackheads and whiteheads	50 percent	41 percent

A separate report agrees. In 2006 the Journal of the American Academy of Dermatology published two 12-week trials of a clindamycin and tretinoin gel in 2,219 people. Its abstract, the short published summary, states: "The combination demonstrated superior efficacy to clindamycin, tretinoin, and vehicle." Vehicle is the gel with no drug. The authors add a limit: 82.6 percent of the people had acne of grade 2 to 3 on the trials' severity scale at the start, so the results may not represent people with grades 4 to 5. The abstract shows no funding line.

These figures show the size of the gain. On the combined gel, 21 percent of people reached clear or almost clear skin in 12 weeks, so most people still had some acne at that point.

How the label says to use the gel

The leaflet gives a bedtime routine and a morning step.

1. Wash. "Wash your face gently with a mild soap and warm water."
2. Dry. Pat the skin dry.
3. Measure. Squeeze a pea-sized amount onto one fingertip.
4. Apply. The label says to "dot onto the chin, cheeks, nose, and forehead, then gently rub over the entire face."
5. Keep it off some areas. "Do not get ZIANA Gel in your eyes or mouth, on your lips, on the corners of your nose, or on open wounds."
6. Morning. "A sunscreen should be applied every morning and reapplied over the course of the day as needed."

The label tells patients "not to use more than the recommended pea-sized amount and not to apply more often than once daily", because more gel does not bring faster results and may increase irritation. The leaflet also says: "Do not wash your face more than 2 to 3 times a day."

Store the gel at room temperature, between 59° and 86°F. The label says "Protect from light", and the leaflet says "Do not freeze."

Some people are prescribed two separate products, a clindamycin product and a tretinoin product. No source read for this guide gives an order or a time of day for that case. MedlinePlus says clindamycin alone is applied once or twice a day depending on the product, and tretinoin goes on at bedtime, so ask your prescriber how to fit the two together. The label steps for tretinoin alone are in how to use tretinoin, and the SPF figures are in sunscreen with tretinoin.

Skin reactions and the bowel warning

Skin. The label lists redness, scaling, itching, burning and stinging. In the first two trials, irritation scores "peaked at 2 weeks of therapy" and decreased after that. Dry skin was reported as a side effect by 1 percent of the 1,853 people on the gel. The leaflet says the gel "may cause a temporary skin color change (lighter or darker)."

Bowel. This warning comes from the antibiotic. The label says absorption of clindamycin into the body has been shown after this gel is used on the skin, and that "Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin." Colitis is an inflammation of the bowel. The label describes the form linked to antibiotics as severe, lasting diarrhea and severe stomach cramps, sometimes with blood and mucus. The label says: "When significant diarrhea occurs, ZIANA Gel should be discontinued." The leaflet says of colitis: "This occurs rarely."

Longer use. The label reports that a 12-month safety study "showed a similar adverse reaction profile as seen in the 12-week studies", and that 18 of the 442 people in it, 4 percent, reported stomach or bowel symptoms.

Other products. The label asks for caution with medicated or abrasive soaps and cleansers and with products high in alcohol. MedlinePlus says the same products "may make the side effects of topical clindamycin worse." See cleanser for tretinoin.

How long it is used, and antibiotic resistance

The Ziana leaflet says: "Your doctor will tell you how long to use ZIANA Gel." NICE gives doctors three rules for that decision:

• Offer a 12-week course, then review.
• "Only continue a treatment option that includes an antibiotic (topical or oral) for more than 6 months in exceptional circumstances."
• Do not treat acne with "monotherapy with a topical antibiotic", meaning an antibiotic used as the only treatment.

The reason is resistance. The Ziana label says resistance of the acne bacterium to clindamycin "has been documented". The AAD says that when a topical antibiotic is part of a plan, "you'll use it along with an acne medication or wash that contains benzoyl peroxide", because this lowers the risk of resistance. Ask your prescriber whether that applies to you. The guide to retinoid with benzoyl peroxide covers how those two are combined.

NICE also tells doctors to review antibiotic treatment every 3 months "and stop the antibiotic as soon as possible." For the time after acne clears, the AAD says dermatologists "may recommend a topical retinoid as a maintenance treatment." Maintenance treatment is treatment that keeps skin clear once acne is under control. What happens if you stop tretinoin covers that stage.

When to call a doctor

Stop the gel and call your doctor in these cases, which the leaflet lists:

• Severe watery diarrhea, or bloody diarrhea.
• Skin that becomes swollen, blistered or crusted, or redness that is severe.
• A sunburn on treated skin. Stop until the skin has healed.

Tell your prescriber before you start if you are pregnant, planning a pregnancy or breastfeeding, and if you have ever had a bowel disease or colitis after an antibiotic. See a doctor or a dermatologist in person if your acne is no better after the 12-week course, or at any time if you get deep, painful lumps or scars.