Isotretinoin: Recommendations

What is the effectiveness and what are the potential side effects of isotretinoin in the treatment of adult acne and acne vulgaris in adolescents to adults?


  • Oral isotretinoin is recommended for the treatment of severe nodular acne.
  • Oral isotretinoin is appropriate for the treatment of moderate acne that is treatment-resistant or for the management of acne that is producing physical scarring and/or psychosocial distress.
  • Low-dose isotretinoin can be used to effectively treat acne and reduce the frequency and severity of medication-related side effects.  Intermittent dosing of isotretinoin is not recommended.
  • Routine monitoring of liver function tests, serum cholesterol and triglycerides at baseline and again until response to treatment is established is recommended. Routine monitoring of complete blood count is not recommended.
  • All patients treated with isotretinoin must adhere to the iPLEDGE risk management program.
    Females of child-bearing potential taking isotretinoin should be counseled regarding various contraceptive methods including user-independent forms.
  • Prescribing physicians also should monitor their patients for any indication of IBD and depressive symptoms and educate their patients about the potential risks with isotretinoin.
  Strength of Recommendation  Level of Evidence 
Conventional dosing  I,II 
Low-dose treatment for moderate acne  I,II 
Monitoring  II 
iPLEDGE and contraception  II 

Review prescribing information for recommended acne treatments.

Oral isotretinoin, an isomer of retinoic acid, has been used in the United States for the treatment of acne for >30 years and is approved by the FDA for the treatment of severe recalcitrant AV. Its use has proven successful for most patients with severe acne, resulting in decreased sebum production, acne lesions, and acne scarring, along with a decrease in symptoms of anxiety and depression.107-117,274-277 It has also been effectively used in the treatment of moderate acne that is either treatment-resistant or that relapses quickly after the discontinuation of oral antibiotic therapy.32,134-138 It is the consensus of the current working group that the presence of moderate acne that is either treatment-resistant, or that produces physical scarring or significant psychosocial distress, is an indication for treatment with oral isotretinoin. 

When used for severe AV, isotretinoin is commonly initiated at a starting dose 0.5 mg/kg/day for the first month, then increased to 1.0 mg/kg/day thereafter as tolerated by the patient.118 In extremely severe cases, even lower starting doses, with or without the concomitant use of oral steroids, may be needed. In earlier studies of optimal dosing of isotretinoin in patients with severe AV, doses ranging from 0.1 mg/kg/day to 1.0 mg/kg/day were most commonly used. Some efficacy was generally seen at all doses, along with a dose-dependent decrease in sebum production.109 While there was not a significant difference in the improvement of acne by the end of the treatment course between doses of 0.5 and 1.0 mg/kg/day in most of the studies, there was a significant difference in relapse rates and the need for retreatment; patients treated with approximately 1.0 mg/kg/day had a significantly lower relapse rate and a lower rate of retreatment with isotretinoin than those treated with 0.5 mg/kg/day.110,112,116 Similarly, a lower relapse rate was seen for those treated with a cumulative dose of >120 mg/kg compared to those treated with <120 mg/kg.110,119 It has been suggested that this dose-dependent therapeutic benefit plateaus beyond 150 mg/kg.119 Therefore, in patients with severe AV, the work group supports initiation of isotretinoin at 0.5 mg/kg/day when appropriate, subsequently increasing to a full dose of 1 mg/kg/day after the first month as tolerated, with a goal cumulative dose between 120 and 150 mg/kg. One recent study of 116 patients found that a cumulative dose of 220 mg/kg or more may result in lower relapse rates, but confirmation will require study in larger populations.278

Isotretinoin treatment has been studied in patients with treatment-resistant or quick-relapsing, moderate AV. In this patient population, multiple studies have found that low-dose isotretinoin (0.25-0.4 mg/kg/day) is effective in the treatment of acne, and that this efficacy is comparable to the use of more conventional dosing.32,107,134,135,279 This may also be true for a low cumulative dose regimen.136 In addition, low-dose regimens are associated with a decreased rate of medication-related adverse effects, thereby leading to improved tolerability and increased patient satisfaction.107,134,135,279,280 Unlike in patients with severe acne, relapse rates in patients with moderate acne treated with low-dose isotretinoin are equal to relapse rates in those treated with conventional dosing.32,279 Intermittent dosing, however, is not as effective and is associated with higher relapse rates; therefore, it is not recommended.32,134,135,276

Isotretinoin is highly lipophilic and is best absorbed when taken with food.115,120,121 Patients should be instructed to take isotretinoin with meals. One formulation, isotretinoin with lidose, uses lipid agents to encase the medication, bypassing the need for food, and can be taken on an empty stomach.121

 


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