Prometrium and Alcohol: What the Drug Label and Clinical Data Actually Say

Does the Prometrium label say anything about alcohol?

The label has no separate drug-interactions section, and its drug-interaction text is short. It reports an in-vitro finding that ketoconazole, a known CYP3A4 inhibitor, blocked progesterone metabolism by human liver microsomes, with the note that the clinical relevance of that in-vitro finding is unknown. It then reports a 12-day study in 29 postmenopausal women in which conjugated estrogens were given with Prometrium, raising total estrone and total equilin concentrations [2]. Alcohol is not part of either item. The label also does not name the enzyme responsible for progesterone's main metabolism [2].

What the label does warn about

The label's relevant warning is about sedation, not alcohol. It states that Prometrium 'may cause transient dizziness and drowsiness and should be used with caution when driving a motor vehicle or operating machinery,' and the dose is given as a single daily dose at bedtime [1]. During initial therapy, a few women have had a cluster of symptoms including extreme dizziness or drowsiness, blurred vision, slurred speech, difficulty walking, loss of consciousness, vertigo, confusion, disorientation, feeling drunk, and shortness of breath [2]. Postmarketing reports listed in the label include sedation, stupor, disorientation, depressed consciousness, and syncope [2].

Two label trials give rates. In the 3-year postmenopausal study, dizziness was reported by 15% of women taking cyclic Prometrium 200 mg with conjugated estrogens 0.625 mg and by 9% of those on placebo; the active arm also took estrogen, so that number is not progesterone alone [2]. In the secondary-amenorrhea study of 25 women on Prometrium 400 mg and 24 on placebo, dizziness was reported by 24% and 4% respectively [2].

Would alcohol add to the drowsiness?

The label does not say. A 2024 review discusses progesterone and allopregnanolone as neuroactive pregnane steroids that modulate excitatory and inhibitory transmission and the effects of alcohol, but it does not show that alcohol and oral Prometrium cause additive drowsiness or impairment in patients [3]. The label's sedation warning applies to Prometrium on its own.

Does alcohol change progesterone blood levels?

After an oral dose, the label reports peak serum progesterone within 3 hours; in postmenopausal women taking 200 mg daily, mean Tmax was 2.3 hours and mean Cmax was 38.1 ng/mL [2]. The label does not report progesterone levels measured with alcohol present, and it does not establish how long any alcohol-related overlap or impairment would last.

Two general observations were not made in Prometrium users. Heavy drinking induces the ethanol-metabolizing enzyme CYP2E1, and that induction is accompanied by increased activity of other cytochrome P450 enzymes and faster metabolism of some other drugs [4]. This is not a finding about progesterone, and the label names no enzyme for its main metabolism [2]. Separately, a meta-analysis of 45,431 premenopausal and 173,476 postmenopausal women found alcohol intake weakly and positively associated with several hormones, with progesterone in premenopausal women the exception [5]; that concerns the body's own progesterone, not the capsules.

Known liver dysfunction or liver disease is one of the label's contraindications, and the label notes that progesterone pharmacokinetics have not been studied in hepatic impairment [1][2].