Side Effects of Accutane (Isotretinoin)
Almost all patients treated with isotretinoin will experience mucocutaneous side effects, with cheilitis (dry lips) affecting up to 78% of users, which can typically be managed with liberal emollient use. 1, 2
Common Side Effects
Mucocutaneous Effects
- Cheilitis (dry lips) - most common side effect, occurring in 78% of patients and up to 96% of those on higher doses 3
- Dry skin, xerosis - very common 1, 2
- Dry eyes, xerophthalmia, conjunctivitis - may require ocular lubricants 1
- Dry nasal passages - may lead to epistaxis (nosebleeds) 1, 2
- Eczematous reactions - reported in approximately 12% of users 3
- Photosensitivity - increased susceptibility to sunburn 2
Laboratory Abnormalities
- Hypertriglyceridemia - occurs in 25-50% of patients, dose-dependent 1, 2
- Mild elevations in liver enzymes - seen in 13-16% of patients 1
- Rarely, severe abnormalities in lipids that could lead to pancreatitis 1
Musculoskeletal Effects
- Myalgias - reported in up to 25% of patients on high-dose isotretinoin 1
- Arthralgias - more common in pediatric patients 2
- Back pain - more common in pediatric patients 2
Serious Side Effects
Teratogenicity
- Retinoid embryopathy - severe and well-documented complication during pregnancy 1
- Requires mandatory enrollment in iPLEDGE program for women of childbearing potential 1, 2
- Women must avoid pregnancy for at least one month after discontinuation 2
Psychiatric Effects
- The relationship between depression and isotretinoin use remains uncertain 1
- A recent meta-analysis found no association between isotretinoin and increased risk of depression 1
- Most studies show isotretinoin improves mood as acne improves 1
- However, there are reports of mood changes with positive dechallenge and rechallenge responses 1
- Monitoring for depression symptoms during treatment is recommended 1
Inflammatory Bowel Disease
- Early reports suggested a possible association 1
- Recent meta-analyses and studies controlling for confounders have not confirmed such a risk 1
- The American Academy of Dermatology states that "current evidence is insufficient to prove either an association or causal relationship between isotretinoin use and IBD" 1
Other Rare Side Effects
- Pseudotumor cerebri - rare but serious complication 2
- Decreased night vision - may persist after discontinuation 2
- Corneal opacities 2
- Hearing impairment 2
Dose-Dependent Effects
- Side effects are clearly dose-dependent 3
- Low-dose regimens (0.2-0.4 mg/kg/day) have similar effectiveness with reduced side effects compared to higher doses 1
- At doses under 0.25 mg/kg/day, cheilitis affects 47% of patients (vs. 96% at >0.75 mg/kg/day) 3
- Eczema occurs in 7% at low doses (vs. 16% at high doses) 3
- Fatigue/tiredness affects 5% at low doses (vs. 18% at high doses) 3
Management of Side Effects
- Mucocutaneous dryness can be managed with liberal emollient use or topical steroids if needed 1
- Omega-3 supplements (1g/day) can reduce mucocutaneous side effects 1
- Ocular lubricants should be considered for patients with conditions that impair corneal wetting 1
- Monitoring of triglycerides and liver enzymes at baseline and two months into treatment is recommended 1
- More frequent monitoring is needed with dose changes or as clinically indicated 1
Discontinuation Rates Due to Side Effects
- Only 1.4% of patients stop isotretinoin because of adverse effects 3
- The most common reasons for discontinuation are cheilitis, mood changes, tiredness, and eczema 3
Special Considerations
- Routine monitoring of complete blood count is not warranted based on recent evidence 1
- Procedures other than mechanical dermabrasion and fully ablative laser treatments do not need to be delayed 1
- Patients with contact lenses should be counseled about potential ocular complications 1
- Younger patients (<16 years) have higher relapse rates and may require additional monitoring 1