Accutane (Isotretinoin) and Alcohol: Full Interaction Profile

What the prescribing information says about alcohol

The Absorica label's contraindications are pregnancy and hypersensitivity to isotretinoin, vitamin A or a capsule component; alcohol is not among them [4]. Its drug interactions section covers vitamin A supplements, tetracyclines and oral contraceptives, and alcohol does not appear there either [4].

Alcohol does appear in the lipid warning of the Accutane label. It says especially careful consideration must be given to risk and benefit for patients at high risk, including patients with diabetes, obesity, increased alcohol intake, a lipid metabolism disorder or a family history of one, and that if treatment goes ahead, more frequent checks of lipids and/or blood sugar are recommended [1]. The same warning notes that some patients reversed triglyceride elevation through weight reduction, restriction of dietary fat and alcohol, and a dose reduction while continuing treatment [1].

Why triglycerides get the attention

The Accutane label reports marked serum triglyceride elevations in approximately 25% of patients in clinical trials, a decrease in high-density lipoprotein cholesterol in about 15%, and a rise in cholesterol in about 7%; the effects were reversible when treatment stopped [1]. Triglyceride elevations above 800 mg/dL have been reported in treated patients [1]. The label says blood lipids should be checked before treatment and then at intervals until the lipid response is established, which usually occurs within 4 weeks [1].

A retrospective cohort of 13,772 patients treated in a Northern California managed care plan between 1995 and 2002 found new abnormalities in 44% of patients who started with normal triglycerides, 31% for total cholesterol and 11% for transaminases; moderate to severe abnormalities were generally transient and reversible [2]. A 2016 JAMA Dermatology meta-analysis of 26 studies (1,574 patients) reported mean on-treatment values of 119.98 mg/dL for triglycerides and 184.74 mg/dL for total cholesterol [3]. These are averages across patients, not measurements of the effect of drinking.

Liver enzymes: what is monitored, what is reported

The Absorica label carries a hepatotoxicity warning and directs that liver function tests be done before and during treatment [4]. Transaminase, alkaline phosphatase, GGTP and LDH elevations appear among the laboratory abnormalities listed for isotretinoin [1]. In the cohort, 11% of patients with normal baseline transaminases developed a new abnormality; the report says transaminase elevations were generally mild [2].

Research on vitamin A and alcohol raises a separate concern, but these findings do not establish what happens when a person drinks while taking isotretinoin [8][9]. In a 1999 review, Leo and Lieber describe how prolonged alcohol use accelerates the breakdown of retinol and potentiates retinol's own liver toxicity, narrowing the therapeutic window for retinol in people who drink [8]. In rats fed a fivefold vitamin A diet with ethanol, the combination produced far more striking liver lesions, including giant mitochondria and depressed fatty acid oxidation, than either alone [9].

The vitamin A overlap

The Absorica label says to avoid supplements containing vitamin A because isotretinoin is closely related to vitamin A and combined use may lead to isotretinoin-associated adverse reactions [4]. The 1999 review also describes competition between ethanol and retinoic acid precursors and hepatotoxicity when beta-carotene was combined with ethanol in experimental work [8].

Pancreatitis

The Accutane label warns that acute pancreatitis has been reported in isotretinoin patients with either elevated or normal serum triglycerides, and that fatal hemorrhagic pancreatitis has occurred in rare instances. It says the drug should be stopped if hypertriglyceridemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur [1].

Is there a safe amount of alcohol?

The Accutane label does not specify a safe number of drinks during treatment [1]. It does name increased alcohol intake as a risk factor when weighing treatment and lipid monitoring [1]. NIAAA counts a standard drink as 14 g of pure alcohol and defines binge drinking as five or more drinks for men or four or more for women in about two hours [5].

iPLEDGE and alcohol

None of the iPLEDGE requirements described by FDA or in the Absorica label concerns alcohol. They cover enrollment of every patient, pregnancy testing in patients who can get pregnant, contraception counseling, collection of the prescription within 7 days of a pregnancy test, no sharing of the drug and no blood donation [4][6][7].