Medications for Acne Treatment
For mild acne, start with a topical retinoid (adapalene 0.1-0.3% or tretinoin 0.025-0.1%) combined with benzoyl peroxide 2.5-5% applied once daily; for moderate-to-severe inflammatory acne, add doxycycline 100 mg or minocycline 100 mg once daily for a maximum of 3-4 months, always with concurrent benzoyl peroxide to prevent resistance. 1, 2
Topical Medications
First-Line Topical Agents
Topical retinoids are the foundation of acne treatment because they resolve microcomedones, are comedolytic, and have anti-inflammatory properties. 3, 1 Available options include:
- Tretinoin 0.025-0.1% cream or gel applied once nightly to dry skin 2, 4
- Adapalene 0.1% or 0.3% gel once nightly (0.1% available over-the-counter) 1, 2
- Tazarotene 0.05% or 0.1% cream, gel, or foam once nightly 3, 1
- Trifarotene (newer retinoid option) 1
Critical caveat: Tretinoin is photolabile and should be applied in the evening; it should not be used concurrently with benzoyl peroxide. 1 Adapalene is more photostable and can be combined with benzoyl peroxide. 2
Benzoyl Peroxide
Benzoyl peroxide 2.5-5% is an essential antimicrobial agent that releases free oxygen radicals and has mild comedolytic properties. 1, 2 No bacterial resistance has ever been reported with benzoyl peroxide. 1 Lower concentrations (2.5%) cause less irritation than higher concentrations while maintaining efficacy. 2
Warning: Benzoyl peroxide bleaches clothing and bedding—advise patients to wear old or white clothing. 5
Topical Antibiotics (Never as Monotherapy)
Topical antibiotics must always be combined with benzoyl peroxide to prevent bacterial resistance—never use as monotherapy. 1, 5, 2
- Clindamycin 1% gel, lotion, or solution twice daily 2
- Erythromycin 2-3% gel or solution twice daily 2
- Fixed-combination products enhance compliance: erythromycin 3%/BP 5%, clindamycin 1%/BP 5%, or clindamycin 1%/BP 3.75% 3, 1, 2
Additional Topical Options
- Azelaic acid 15-20% twice daily—particularly useful for post-inflammatory hyperpigmentation in darker skin types 3, 1, 2
- Topical dapsone 5% gel twice daily—especially effective for inflammatory acne in adult females 3, 1, 2
- Salicylic acid 0.5-2% over-the-counter—limited evidence but useful as adjunct 3, 1
- Clascoterone 1% cream twice daily—newer topical antiandrogen (high cost limits use) 1, 2
Systemic Medications
Oral Antibiotics
Systemic antibiotics are indicated for moderate-to-severe inflammatory acne and must be combined with topical retinoid plus benzoyl peroxide—never as monotherapy. 3, 1
First-line tetracycline-class antibiotics:
- Doxycycline 100 mg once or twice daily with food 3, 2
- Minocycline 100 mg once or twice daily 3, 2
- Doxycycline and minocycline are more effective than tetracycline and equally effective to each other 3
Critical limitation: Limit systemic antibiotics to 3-4 months maximum and re-evaluate to minimize bacterial resistance development. 3, 1, 2
Alternative antibiotics (restricted use):
- Erythromycin or azithromycin—only for patients who cannot use tetracyclines (pregnant women, children <8 years) 3
- Trimethoprim-sulfamethoxazole or trimethoprim—only for tetracycline-intolerant or treatment-resistant patients 3
Subantimicrobial doxycycline 20 mg twice daily to 40 mg daily has shown efficacy in moderate inflammatory acne. 3, 1
Hormonal Therapies (Female Patients)
Combined oral contraceptives (COCs) are effective for inflammatory acne in females, reducing inflammatory lesions by 62% at 6 months. 1, 6 Use at standard contraceptive dosing per product labeling. 2
Spironolactone 25-200 mg daily is useful for females with hormonal acne patterns, premenstrual flares, or those who cannot tolerate oral antibiotics. 1, 2 No potassium monitoring is needed in healthy patients without risk factors. 1, 2
Isotretinoin
Isotretinoin is the only drug affecting all four pathogenic factors of acne and is indicated for: 1
- Severe nodular or conglobate acne
- Moderate acne with scarring or significant psychosocial burden
- Treatment-resistant moderate acne after 3-4 months of appropriate therapy
Dosing: Start at 0.5 mg/kg/day, increase to 1.0 mg/kg/day as tolerated, targeting cumulative dose of 120-150 mg/kg. 1, 2 For moderate treatment-resistant acne, 0.25-0.4 mg/kg/day provides equal efficacy with fewer side effects. 2
Mandatory requirements: Pregnancy prevention through iPledge program for persons of pregnancy potential; monitor liver function tests and lipids (but not routine depression or inflammatory bowel disease screening). 1
Treatment Algorithm by Severity
Mild Acne
Topical retinoid monotherapy OR topical retinoid + benzoyl peroxide 1, 2
Moderate Acne
Fixed-dose combination topical retinoid + benzoyl peroxide as first-line 1
- Add topical antibiotic/BP combination for inflammatory lesions 1, 2
- Consider topical dapsone 5% gel, especially for adult females 1, 2
Moderate-to-Severe Acne
Triple therapy: oral antibiotic + topical retinoid + benzoyl peroxide 1, 2
Severe/Recalcitrant Acne
Isotretinoin for severe nodular acne or treatment-resistant cases 1, 6
Maintenance Therapy
After achieving clearance, continue topical retinoid once nightly indefinitely to prevent recurrence. 1, 5, 2 Add benzoyl peroxide 2.5-5% once daily if needed for more severe baseline disease. 2
Critical Pitfalls to Avoid
- Never use topical or oral antibiotics as monotherapy—resistance develops rapidly without concurrent benzoyl peroxide 1, 5, 2
- Never extend oral antibiotics beyond 3-4 months without re-evaluation—dramatically increases resistance risk 3, 1, 2
- Never stop treatment once acne clears—maintenance with topical retinoids is essential to prevent relapse 1, 5
- Never underestimate severity when scarring is present—warrants more aggressive treatment regardless of lesion count 1
- Apply retinoids to completely dry skin and avoid eyes, mouth, nose angles, and mucous membranes 4
- Daily sunscreen use is mandatory with retinoids due to photosensitivity 1, 5, 4