What is the appropriate dosing regimen for isotretinoin (13-cis-retinoic acid) in the treatment of acne?

From the Guidelines

Isotretinoin for acne is typically dosed at 0.5-1 mg/kg/day divided into two daily doses for a total cumulative dose of 120-150 mg/kg over a 15-20 week course, with the goal of achieving a cumulative dose of at least 120 mg/kg to minimize relapse rates, as supported by a prospective study of 180 patients with severe acne 1. The treatment usually begins at a lower dose (0.5 mg/kg/day) and may be increased after 4 weeks based on response and tolerability.

• The medication should be taken with food to enhance absorption, as it is highly lipophilic 1.
• A complete course of isotretinoin aims to achieve long-term remission of severe, recalcitrant nodular acne.
• Monthly monitoring of liver enzymes, lipids, and pregnancy tests for females is essential due to potential side effects.
• Common side effects include dry skin, lips, and eyes, which can be managed with moisturizers and eye drops.
• Isotretinoin is absolutely contraindicated in pregnancy due to severe birth defects, requiring two forms of contraception for female patients of childbearing potential.
• The medication works by reducing sebum production, decreasing inflammation, normalizing follicular keratinization, and reducing acne-causing bacteria.
• Treatment success is often determined by clearance of active acne lesions and prevention of scarring. Some studies have suggested that low-dose isotretinoin (0.2-0.4 mg/kg/day) may be effective in treating mild to moderate acne with reduced side effects, but these findings are based on limited follow-up and require further confirmation 1. Additionally, there is evidence that higher cumulative doses of isotretinoin are associated with decreased rates of relapse, with a prospective study finding that a cumulative dose of >220 mg/kg resulted in a lower relapse rate compared to lower doses 1. However, the optimal dosing strategy for isotretinoin remains a topic of debate, and further research is needed to determine the most effective and safe approach for different patient populations. It is also important to note that isotretinoin has been associated with various side effects, including inflammatory bowel disease and depressive symptoms, although the current evidence is insufficient to establish a causal relationship 1. Therefore, prescribing physicians should carefully monitor patients for these potential side effects and provide education on the risks and benefits of isotretinoin therapy.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Isotretinoin is a retinoid, which when administered in pharmacologic dosages of 0. 5 to 1 mg/kg/day (see DOSAGE AND ADMINISTRATION), inhibits sebaceous gland function and keratinization. The recommended dosing of isotretinoin for acne is 0.5 to 1 mg/kg/day.

• The dose should be taken with food to enhance absorption. Isotretinoin capsules should always be taken with food, as this increases the bioavailability of the drug without altering its disposition 2.

From the Research

Isotretinoin Dosing for Acne

• The standard dose of isotretinoin is 0.5-1 mg/kg/day for 4 months with a total dose of 120-140 mg/kg/day 3
• Low-dose isotretinoin (0.5 mg/kg/day for 1 week every 4 weeks for 6-months) could be effective and even comparable with high or optimal doses 3
• Daily doses between 0.1 and 0.3 mg/kg can be recommended for more than 6 months due to the occurrence of fewer side effects and more economical concerns 3
• A dose of 20 mg/day (approximately 0.3-0.4 mg/kg/day) for a period of 3 months was found to be effective in the treatment of moderate to severe acne vulgaris, with a low incidence of serious side effects 4
• A low-dose schema of 0.15-0.40 mg/kg per day was compared with a high-dose schema of 0.5-1.0 mg/kg per day, and the mean success rate of the low-dose schema was 69% 5
• The total dose up to 120 mg/kg should be followed for optimal results (success rate of 91%) and avoidance of relapses 5
• A low-dose isotretinoin capsule (0.25 mg/kg/day) was compared with a conventional dose of 0.5 mg/kg/day, and the low-dose isotretinoin can be considered in the treatment of acne due to fewer side effects and more patients' satisfaction 6

Side Effects and Efficacy

• Cheilitis was the most common side effect observed in 98% of the participants 4
• Elevated serum lipid levels were observed in 6% of the participants, and relapse occurred in 4% of the participants over a 6-month follow-up period 4
• The low-dose schema produced fewer adverse effects and offered a very beneficial effect on pre-existing scarring 5
• Nose dryness was the most common side effect in the low-dose group (17%), and hair thinning and loss in the conventional-dose group (33.2%) 6

Treatment Duration and Follow-up

• Three months of treatment with low-dose isotretinoin (20 mg/day) was found to be effective in the treatment of moderate to severe acne vulgaris 4
• Patients were followed up for 6 months to look for any relapse 4
• The patients received 6-month treatment, and their improvement was determined and compared at the end of the 6th month and 12th month (6 months after the end of the treatment) 6