What medications should be avoided with alcohol?

Medications to Avoid with Alcohol

Alcohol should be strictly avoided with benzodiazepines (e.g., diazepam), metronidazole, and medications for alcohol use disorder (particularly disulfiram), while caution is warranted with opioids, CNS depressants, and certain other medication classes due to additive effects and potential toxicity.

High-Risk Combinations Requiring Strict Avoidance

Benzodiazepines

• Concomitant use of benzodiazepines and alcohol is not recommended due to significant enhancement of sedative effects and increased risk of respiratory depression 1
• The combination produces additive CNS depression through actions at different receptor sites (benzodiazepines at GABA-A sites, alcohol as a GABA agonist) 1, 2
• This interaction increases risks of oversedation, respiratory depression, and impaired motor function 2, 3
• Patients taking diazepam or other benzodiazepines should be explicitly advised against simultaneous alcohol ingestion 1

Metronidazole

• Alcoholic beverages should not be consumed during metronidazole therapy and for at least one day afterward due to risk of disulfiram-like reactions 4
• Reported reactions include abdominal cramps, nausea, vomiting, headaches, and flushing 4
• However, recent research suggests the evidence for this interaction may be weaker than traditionally believed, with no convincing in-vitro studies, animal models, or clinical trials demonstrating a clinically relevant disulfiram-like effect 5
• Despite limited evidence, the FDA label maintains this warning, and clinical practice should follow this guidance 4

Disulfiram and Alcohol Use Disorder Medications

• Disulfiram should be avoided entirely in pregnant women with alcohol-related liver disease who cannot achieve abstinence 6
• Metronidazole should not be given to patients who have taken disulfiram within the last two weeks due to risk of psychotic reactions 4
• Alternative medications for alcohol use disorder (naltrexone, acamprosate) require careful risk-benefit assessment when used with ongoing alcohol consumption 6

Medications Requiring Caution with Alcohol

Opioids

• The concomitant use of opioids and alcohol increases the risk of respiratory depression through actions at different CNS receptor sites 1
• Limit dosage and duration when combining these substances, and monitor closely for respiratory depression and sedation 1
• The combination significantly worsens opioid-related respiratory depression 1

Other CNS Depressants

• Multiple CNS-active drugs combined with alcohol increase risk of falls and additive CNS depression, including antidepressants, antipsychotics, anticonvulsants, sedative antihistamines, barbiturates, and MAO inhibitors 1, 7
• Patients should be cautioned against engaging in hazardous activities requiring complete mental alertness (operating machinery, driving) when combining alcohol with any CNS depressant 1

Anticoagulants (Warfarin)

• Metronidazole potentiates the anticoagulant effect of warfarin and other oral coumarins, resulting in prolonged prothrombin time 4
• Alcohol itself can interact with anticoagulants, creating a compounded risk 7, 3

Medications Affected by Liver Metabolism

• Acute alcohol consumption can inhibit drug metabolism, while chronic alcohol use induces cytochrome P450 enzymes (particularly CYP2E1), altering drug pharmacokinetics 3, 8
• Drugs metabolized by CYP3A4 and CYP2C19 may have altered levels when combined with alcohol 3, 8
• Examples include phenytoin (decreased elimination when combined with diazepam and potentially affected by alcohol) 1, 4

Special Clinical Contexts

Hepatitis C Treatment

• Patients should be counseled to abstain from alcohol during antiviral therapy for hepatitis C 6
• Patients with ongoing alcohol consumption during HCV treatment should receive additional support 6
• Alcohol consumption impacts treatment adherence and should be addressed before starting therapy 6

Gout Management

• Gout patients should reduce alcohol consumption (particularly beer, but also wine and spirits) and avoid alcohol overuse 6
• Complete abstinence from alcohol is recommended during periods of active gout arthritis, especially with inadequate medical control 6

Cancer Survivors

• Alcohol should be avoided or limited among cancer survivors with oral mucositis, as even small amounts in mouthwashes can be irritating 6
• Alcohol intake increases risk of new primary cancers of the mouth, larynx, esophagus, liver, breast, and possibly colon 6

Acitretin (Retinoid) Therapy

• Women of childbearing age taking acitretin should abstain from alcohol, as it increases metabolism of acitretin to etretinate (which has a much longer half-life and teratogenic potential) 6
• Strict contraception must be maintained for 3 years after acitretin cessation due to this alcohol-mediated conversion 6

Common Pitfalls to Avoid

• Do not assume all reported alcohol-drug interactions have strong evidence: The metronidazole-alcohol interaction, while widely taught, lacks robust clinical evidence despite FDA warnings 4, 5
• Consider both acute and chronic alcohol use patterns: Acute alcohol inhibits metabolism while chronic use induces enzymes, creating opposite pharmacokinetic effects 3, 8
• Account for pharmacodynamic interactions beyond pharmacokinetics: Additive sedation with benzodiazepines and antihistamines represents a major clinical risk even without altered drug levels 1, 2, 3
• Remember that alcohol itself has anxiolytic effects: Anxious patients on benzodiazepines may self-medicate with alcohol, creating dangerous combinations 2
• Monitor for hypoglycemia risk: Alcohol impairs gluconeogenesis and increases hypoglycemia risk with antidiabetic medications 6, 3
• Assess gastrointestinal bleeding risk: NSAIDs combined with alcohol significantly increase risk of GI hemorrhage 3