Several types of prescription topical medicines are used to treat acne, including antibiotics, benzoyl peroxide, tretinoin, adapalene, and azelaic acid.

Antibiotics and azelaic acid help stop or slow the growth of bacteria and reduce inflammation.

Tretinoin, a type of drug called a retinoid that contains an altered form of vitamin A, is an effective topical medicine for stopping the development of new comedones. It works by unplugging existing comedones, thereby allowing other topical medicines, such as antibiotics, to enter the follicles. The doctor may also prescribe newer retinoids or retinoid-like drugs, such as tazarotene or adapalene, that help decrease comedo formation.

Like OTC topical medicines, prescription topical medicines come as creams, lotions, solutions, or gels. The doctor will consider the patient's skin type when prescribing a product. Creams and lotions provide moisture and tend to be good for people with sensitive skin. Gels and solutions are generally alcohol based and tend to dry the skin. Therefore, patients with very oily skin or those who live in hot, humid climates may prefer them. The doctor will tell the patient how to apply the medicine and how often to use it.

Some people develop side effects from using prescription topical medicines. Initially, the skin may look worse before improving. Common side effects include stinging, burning, redness, peeling, scaling, or discoloration of the skin. With some medicines, like retinoids, these side effects usually decrease or go away after the medicine is used for a period of time. Patients should report prolonged or severe side effects to their doctor. Between 4 and 8 weeks will most likely pass before acne patients see their skin improve.