Based on the textbook sources, here is a clear answer:

1. Both stress the liver Isotretinoin already causes elevated liver enzymes (transaminases) in up to 15% of patients, and liver function must be regularly monitored during treatment. Alcohol is independently hepatotoxic. Combining the two amplifies the risk of liver damage. — Fitzpatrick's Dermatology, p. 1437

2. Worsens triglyceride elevation Isotretinoin raises serum triglycerides in roughly 20–50% of patients — a dose-dependent effect that typically emerges within the first 4–8 weeks. Alcohol is itself a well-established cause of hypertriglyceridemia. Drinking while on isotretinoin can push triglyceride levels into dangerous ranges (>700–800 mg/dL), risking acute pancreatitis and eruptive xanthomas. — Fitzpatrick's Dermatology, p. 1437; Dermatology 2-Volume Set 5e, p. 731

3. The acitretin confusion (important distinction) A common warning about "retinoids and alcohol" stems from acitretin (a related retinoid used for psoriasis), not isotretinoin directly. With acitretin, alcohol converts the drug into etretinate — a far more teratogenic compound with a half-life of 80–160 days. This is the reason women on acitretin must avoid alcohol entirely and avoid pregnancy for 3 years after stopping. Isotretinoin does not undergo this same conversion, so the teratogenicity concern from alcohol is specific to acitretin. — Goodman & Gilman's Pharmacological Basis of Therapeutics, p. 1501

4. Central nervous system effects Both alcohol and isotretinoin can independently affect mood and cognition. Although no causal link between isotretinoin and depression has been firmly established, combining alcohol (a CNS depressant) with a drug already being monitored for psychiatric effects is inadvisable.

The bottom line: Alcohol is not absolutely contraindicated with isotretinoin the way it is with acitretin, but drinking during treatment is strongly discouraged because it worsens two of the drug's most monitored risks — liver toxicity and hypertriglyceridemia. Most clinicians advise complete abstinence or at minimum very minimal alcohol intake for the full duration of therapy.