Isotretinoin ("Accutane") Dosing Options: Should You Go Low, Standard, or High?

The  FDA approved package insert recommends initiating isotretinoin at a dose of 0.5 to 1.0 mg/kg/day, divided into two doses taken with food—specifically a high-fat meal—to maximize absorption (which doubles when isotretinoin is taken with dietary fat). A typical course of treatment spans approximately 15 to 20 weeks (~4–5 months), targeting a cumulative dose of 120–140 mg/kg, which has been associated with durable remission. If acne persists or recurs, a second course may be considered, but it should not begin until at least 8 weeks after completing the first course to allow for continued post-treatment improvement.

Despite its efficacy, up to 70% of patients on isotretinoin may experience relapse (1), and many patients seek the benefits of the medication but are unable to tolerate its side effects. This has led to the development of various dosing strategies aimed at reducing relapse rates while minimizing adverse effects.

Two factors appear to strongly correlate with acne relapse following isotretinoin therapy. First is the total cumulative dose consumed over the course of treatment (4, 5). This is calculated by dividing the total number of milligrams (mg) ingested by the patient’s weight in kilograms (kg) (body weight in pounds divided by 2.2 = weight in kilograms). In general, cumulative doses of 120–150 mg/kg or greater are associated with lower relapse rates (1, 4, 5). The second key factor is the duration of time the patient remains clear while still on isotretinoin—ideally at least 1 to 2 months (5).

Different Dosing Regimens for Isotretinoin

Regimen	Cumulative Dose	Relapse Rate	Benefits	Drawbacks
High Dose	≥220 mg/kg	26.9%	Lower relapse, durable remission (4)	More retinoid dermatitis, higher mucocutaneous side effects
Standard Dose	≥120–150 mg/kg	~32–47%	Balanced efficacy/safety, guideline-recommended (1)	Moderate relapse, some side effects
Low Dose Daily	~0.1–0.3 mg/kg/day, <100 mg/kg total	~52%	Cost-effective, fewer side effects (2)	Higher relapse, longer duration
Pulsed Low Dose	e.g., 0.5 mg/kg/day 1 week/month	N/A	Economical, less toxicity (7)	Lower efficacy overall

To improve tolerability, low-dose regimens have been explored. Two systematic reviews have evaluated the safety and efficacy of low-dose isotretinoin (typically 0.1–0.4 mg/kg/day or 20 mg/day) for treating mild-to-moderate acne. These studies found that while low-dose regimens significantly improve acne severity and are associated with fewer side effects, they tend to result in higher relapse rates compared to conventional or high-dose regimens (2, 3). Although low-dose therapy is better tolerated and more cost-effective, relapse rates can reach up to 40% unless the cumulative dose is optimized (2). Although this may seem (and is) lower than the 70% quoted for conventional dosing, patients in low-dose studies generally have more mild acne, whereas standard-dose regimens have often been evaluated in patients with more severe disease. This discrepancy makes direct comparisons challenging. Additionally, mild acne combined with short follow-up periods may make low-dose regimens appear more effective than they might be over the long term (8).

A meta-analysis further confirmed that conventional doses (0.5–1 mg/kg/day, with a cumulative dose of 120–150 mg/kg) are more effective in achieving sustained remission and preventing relapse—especially when compared to both low-daily and pulsed dosing strategies (3). However, low-dose regimens may be appropriate for patients with milder acne who prioritize tolerability and are willing to accept a potentially higher risk of relapse. For instance, unblinded studies have reported relapse rates below 5% in patients with moderate acne treated with low-dose isotretinoin (0.3–0.4 mg/kg/day) (6). And, a partially blinded study comparing patients treated with 0.25–0.4 mg/kg/day showed relapse rates of 18%, compared to 13% in those receiving standard doses (0.5–0.7 mg/kg/day) (7).

In summary, while standard or higher-dose isotretinoin remains the most effective strategy for achieving long-term acne remission—particularly in moderate to severe cases—low-dose regimens represent a viable alternative for select patients. These lower-dose approaches may offer meaningful clinical improvement with fewer side effects, especially in individuals with mild-to-moderate acne who are unable or unwilling to tolerate the adverse effects of full-dose therapy. Ultimately, tailoring isotretinoin dosing to the severity of acne, patient preferences, and tolerability—while still aiming for an adequate cumulative dose and ensuring sufficient duration of clear skin on therapy—can help optimize both outcomes and patient satisfaction.

Dr. Ryan M. Trowbridge, MD, MS, MA

Harvard-Trained, Board-Certified Dermatologist and DermMythBuster

P.S. Have you come across any new or conflicting research on this topic? Please share—I’d love to explore it further with you!

Want an online acne consultation for isotretinoin? You can obtain one from Dr. Trowbridge at Bridge Dermatology if you currently reside in California, Connecticut, Illinois, or Nebraska.

References:

1. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1-1006.e30. doi:10.1016/j.jaad.2023.12.017​

2. Sadeghzadeh-Bazargan A, Ghassemi M, Goodarzi A, et al. Systematic review of low-dose isotretinoin for treatment of acne vulgaris: Focus on indication, dosage, regimen, efficacy, safety, satisfaction, and follow-up, based on clinical studies. Dermatol Ther. 2021;34(2):e14438. doi:10.1111/dth.14438​

3. Al Muqarrab F, Almohssen A. Low-dose oral isotretinoin for the treatment of adult patients with mild-to-moderate acne vulgaris: Systematic review and meta-analysis. Dermatol Ther. 2022;35(3):e15311. doi:10.1111/dth.15311​

4. Blasiak RC, Stamey CR, Burkhart CN, Lugo-Somolinos A, Morrell DS. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149(12):1392–1398. doi:10.1001/jamadermatol.2013.6746​

5. Tran PT, Berman HS, Leavitt E, Hogeling M, Cheng CE. Analysis of factors associated with relapse in patients on their second course of isotretinoin for acne vulgaris. J Am Acad Dermatol. 2021;84(3):856–858. doi:10.1016/j.jaad.2020.10.024​

6. Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006;54(4):644-646. doi:10.1016/j.jaad.2005.11.1061.

7. Lee JW, Yoo KH, Park KY, et al. Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study. Br J Dermatol. 2011;164(6):1369-1375. doi:10.1111/j.1365-2133.2010.10152.x.

8. Rademaker M, Wishart JM, Birchall NM. Isotretinoin 5 mg daily for low-grade adult acne vulgaris – a placebo-controlled, randomized double-blind study. J Eur Acad Dermatol Venereol. 2014;28(6):747-754. doi:10.1111/jdv.12170.