Alcohol-Medication Interactions: Potentially Dangerous Mixes

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    Takeaways

    • Combining alcohol with certain medications, particularly those with sedative effects, can increase the risk of adverse events, including falls, driving accidents, and fatal overdoses.
    • Alcohol can alter the metabolism and pharmacological effects of many common medications, and conversely, many medications can alter the absorption and metabolism of alcohol.
    • People aged 65 and older are at particularly high risk for harm, due in part to age-related changes in their physiology and in part to their increasing use of medications that could interact with alcohol.
    • The potential for harmful medication-alcohol interactions is a compelling reason for healthcare professionals to talk with their patients about their alcohol use when prescribing medications.

    Dozens of common medications have the potential to interact in dangerous ways with alcohol.1 Consequences can range from gastrointestinal bleeding and liver damage to falls, traffic accidents, and overdose deaths.1 By one estimate, 40% of adults took a medication in the past year that could interact negatively with alcohol.1 For example, about 5-6% of people who drink regularly are prescribed a sedative hypnotic or opioid for at least 30 days,2 the combination of which can be deadly.

    People over age 65 are at particularly high risk for harm, in part because of age-related changes in how the body responds to both alcohol and medications, and in part because older adults often take multiple medications with the potential to interact with alcohol.3 About 80 percent of people aged 65 and older took a medication in the past year that could interact with alcohol.1 Both the size of this patient age group and the percentage taking alcohol-interactive medications is increasing.4

    Fortunately, educating patients about the risks of combining medications with alcohol may help them avoid negative outcomes. Here, we describe briefly how alcohol and medications can interact, and we provide a few examples of common medications that could interact negatively with alcohol. We provide links to resources to help you mitigate these risks, including a consensus-developed list of potentially serious alcohol-medication interactions in older adults.

    A note on drinking level terms in this Core article: Binge drinking brings a person’s blood alcohol concentration to 0.08 percent or more, which typically happens if a woman has 4 or more drinks, or a man has 5 or more drinks, within about 2 hours. Heavy drinking includes binge drinking and has been defined for women as 4 or more drinks on any day or 8 or more per week, and for men as 5 or more drinks on any day or 15 or more per week.

    Types of alcohol-medication interactions

    Alcohol and medications have the potential to interact in three main ways:

    • Alcohol can alter the metabolism of a medication, speeding or slowing the clearance of the medication from the body and thus lowering or raising the blood levels of the medication.
    • A medication can influence the absorption and metabolism of alcohol, potentially resulting in higher blood alcohol concentrations (BACs) and other adverse effects. (See Core article on the basics for a brief overview of how the body metabolizes ethanol, the type of alcohol in alcohol beverages.)
    • Alcohol can alter the pharmacological effects of the medication, which can increase or decrease the effect of the medication on the body.

    Checking alcohol-medication interactions

    Whether and how alcohol affects a medication’s safety and effectiveness should be noted on the medication’s prescribing label. Labels for medications are available from the DailyMed website provided by the NIH’s National Library of Medicine as well as from Drugs@FDA. In addition, online interaction checkers allow one to search easily for interactions between alcohol and most medications. For reviews of interaction checkers for healthcare professionals, see this 2016 article, which compares the accuracy and completeness of five common software programs, and this 2021 article, which compares the scope, completeness, and consistency of eight drug interaction resources.5 6,7 8,9 10-12 10,12,13 14-16 17 18 19 20,21 22 23

    Examples of Potentially Deadly Interactions

    Some medications can have life threatening consequences when combined with alcohol by increasing dangerous side effects or by decreasing the beneficial effects of medications. Two examples follow:

    • Overdose risk from alcohol combined with opioids or benzodiazepines. Alcohol plays a role in about 1 in 5 overdose deaths related to both prescription opioids (22.1%) and benzodiazepines (21.4%) each year.5 Any combination of alcohol, opioids, and benzodiazepines is particularly dangerous because they may have synergistic rather than additive effects on brain circuits involved in vital physiological functions.6,7 Specifically, alcohol, opioids, and benzodiazepines each suppress activity in respiratory circuits in the brainstem through actions on different receptor systems: opioids via mu-opioid receptors,8,9 benzodiazepines via GABA-A receptors,10–12 and alcohol via GABA-A and NMDA receptors.10,12,13 It is important to educate all patients prescribed opioids and benzodiazepines about the risks of combining them with alcohol.
    • Suicide risk. According to data from 2000 to 2018, depression, suicide attempts, and antidepressant use have all been increasing in the U.S.14–16 People commonly drink alcohol to cope with depression, but alcohol worsens depression over time,17 and those who report binge drinking are twice as likely to have suicidal ideation in the past year compared to non-drinkers (6.3% vs 3.4%).18 Of those who die by suicide, 1 in 5 (21%) had a BAC of 0.10% or higher at the time of death.19 The combination of alcohol and certain medications may potentiate suicide risk:
      • Antidepressants: In patients being treated for depression, even low levels of drinking may be problematic because alcohol may reduce antidepressant response and decrease patient adherence,20,21 while promoting impulsivity,22 all of which may potentiate suicide risk.
      • Sedative, anxiolytic, or opioid medications: In suicidal patients taking sedative, anxiolytic, or opioid medications, there is an increased short-term risk of suicide attempt with these medications, especially in combination with alcohol.23

    Examples of common medications known to interact negatively with alcohol

    Below are a few examples of commonly prescribed medications that may interact with alcohol to cause negative side effects:

    • Psychotropic medications: Injuries, overdose, and other potential risks
      • Benzodiazepines. Commonly prescribed for anxiety and sleep, benzodiazepines include alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), and lorazepam (Ativan).
        • Risk of death. Overdose deaths with benzodiazepines alone are rare, but as noted in the box above, combining alcohol and benzodiazepines can increase the likelihood of death due to respiratory depression.13 Taking even therapeutic doses of the medication tenazepam (Restoril), for example, lowers the threshold for alcohol levels found in fatal overdoses by 20%, compared with overdoses caused by alcohol alone.24 Alcohol plays a causal role in nearly 1 in 5 (18.5%) benzodiazepine overdose deaths each year.25
        • Risk of injuries. Alcohol increases the sedative effects of benzodiazepines, as well as the impairments in balance, reaction time, and motor coordination caused by these medications.26 The combination of alcohol and benzodiazepines increases the risk for driving accidents beyond the risks of alcohol alone.26 In older adults, benzodiazepines raise the risk for injuries and deaths from falls,27,28 and alcohol has the potential to heighten those risks. Patients with alcohol use disorder (AUD) are more than twice as likely to receive prescriptions for benzodiazepines29 and may be more prone to use benzodiazepines in ways other than prescribed, which increases the risks of harm.30
        • Risk of memory issues. Alcohol and benzodiazepines impair memory formation and are capable of producing mild to complete memory “blackouts,” amnesia for events that occurred while under the influence.31–35 Prescribing information for benzodiazepines commonly lists memory impairments as a side effect (e.g., see Xanax prescribing information). In laboratory studies, synergistic effects of alcohol and benzodiazepines on memory have been noted.36
      • “Z-drugs” for insomnia. The FDA warns against drinking alcohol before or while taking “Z-drug” insomnia medications such as eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Edluar, and Zolpimist) because of the increased risk of side effects.37 For example, on its own, zolpidem can impair motor coordination and increase fall risk;38 produce memory impairments, including memory blackouts;39 and promote behaviors during sleep for which patients have no recall, such as driving.40 Combining zolpidem with alcohol could increase these risks.40,41 Zolpidem overdose is linked with alcohol consumption and often warrants admission to intensive care in the emergency department.42
      • Antidepressants. Alcohol may increase the side effects of antidepressants on the central nervous system, such as drowsiness and dizziness.43 Alcohol may also reduce antidepressant response and patient adherence.20,21 Tranylcypromine (Parnate), phenelzine (Nardil), and other antidepressants in the class of monoamine oxidase inhibitors may cause a dangerous rise in blood pressure when mixed with tyramine, a byproduct found in beer and wine, particularly red wine.44,45 Buproprion (Wellbutrin) may lower the threshold for seizures, and alcohol may further increase seizure risk.43,46 Duloxetine (Cymbalta) may cause liver damage and combining it with alcohol may further raise the risk of liver toxicity.47 In addition, a study found that combining alcohol with venlafaxine (Effexor) may lower the threshold for fatal alcohol overdoses.48 (See also the text box above.)
    • Opioids: Respiratory suppression and overdose
      • All opioids, such as morphine, methadone, oxycodone, fentanyl, and hydrocodone, when combined with alcohol, could increase the risk of overdose leading to death via suppression of the respiratory centers in the brain. Alcohol plays a significant role in roughly 15-20% of all opioid-related deaths and the risk begins at low doses of both substances.49 In a 2017 study, 20mg of oxycodone alone reduced respiration by 28%.7 When participants had enough alcohol to reach a BAC of 0.1%, respiration dropped by another 19%, and apneic episodes increased in older participants.7 Like alcohol, prescription opioids cause sedation and increase reaction time. Prescription opioids and alcohol, when combined, have additive effects on the risk of fatal car crashes.50,51 (See also the text box above.)
      • Buprenorphine preparations, when combined with alcohol, can lead to hypotension, respiratory depression, profound sedation, and coma.52–55 Post-mortem studies suggest alcohol lowers the threshold for levels of buprenorphine found in fatal accidental overdose cases.56
    • Over-the-counter pain relievers: Liver damage and gastrointestinal bleeding
      • Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and aspirin, are associated with an increased risk of gastrointestinal bleeding on their own. Combining them with alcohol significantly increases the risk.57 Consuming up to 1 drink per day increases the risk of gastrointestinal bleeding associated with NSAID use by about 37%58 (see Core article on medical complications).
      • Acetaminophen (Paracetamol, Tylenol) is the most widely used over-the-counter analgesic. Acetaminophen toxicity accounts for almost 50% of cases of acute liver failure in North America and approximately 20% of liver transplant cases in the U.S.59,60 Acetaminophen interacts with alcohol in complex, potentially lethal, ways.61,62 One pathway to potential toxicity involves the CYP450 enzyme system. Acetaminophen is partially metabolized by CYP2E1, forming a metabolite, NAPQI, that is toxic to the liver.63 The same enzyme assumes an important role in metabolizing alcohol in people who drink heavily.64,65 Chronic, heavy alcohol consumption leads to an increase in CYP2E1 activity.63 When acetaminophen is taken on its own after chronic alcohol use, formation of the toxic metabolite NAPQI increases, thereby increasing the risk of damage to the liver.66,67 The exact amounts and timing of alcohol and acetaminophen intake that could lead to liver damage are unknown. The FDA asks healthcare professionals to advise patients not to drink alcohol when taking medicines that contain acetaminophen.68
    • Anticoagulant and cardiovascular medications: Bleeding risk, elevated blood alcohol, and lowered blood pressure
      • Warfarin (Coumadin, Jantoven) is an anticoagulant used to prevent blood clotting events including heart attack and stroke. Alcohol use is among the strongest risk factors for major bleeding while on warfarin. At particularly increased risk are patients who screen positive for heavy drinking (see Core article on screening) and either have been taking warfarin for more than one year or have genetic variants that influence warfarin metabolism.69
      • Verapamil (Verelan, Calan) is a calcium channel antagonist used to treat arrhythmia, high blood pressure, and angina. Verapamil significantly inhibits alcohol metabolism, which leads to prolonged elevated BACs when alcohol and verapamil are consumed together.70
      • Propranolol (Inderal, InnoPran, Hemangeol) is a beta blocker used to treat hypertension and other cardiac conditions. Alcohol consumption may increase plasma levels of propranolol71 and increase the medication’s side effects including dizziness, lightheadedness, fainting, and changes in heart rate. In addition, acute alcohol ingestion can cause an initial drop in blood pressure, which could add to the blood-pressure-lowering effects of propranolol.71,72
    • Antimicrobials: Reduced efficacy, liver toxicity, and flushing reactions

      A 2020 systematic review evaluated the evidence behind alcohol warnings for common antimicrobials and drew conclusions including the following:73

      • Erythromycin and doxycycline—Reduced efficacy: Erythromycin may be less effective in people who drink alcohol and may increase BACs. Doxycycline may have reduced efficacy in those with long-term, heavier drinking levels.
      • Ketoconazole, griseofulvin, isoniazid, and others—Liver toxicity: Alcohol should be avoided by patients taking ketoconazole, griseofulvin, and isoniazid because of an additive potential for liver toxicity. In addition, data indicate a possible risk of added liver toxicity with pyrazinamide, ethionamide, and rifampin, warranting avoidance or close monitoring of liver function.
      • Cefotetan, ceftriaxone, and others—Disulfiram-like reactions: Alcohol should be avoided when taking certain cephalosporins (those with a methylthiotetrazole side chain, such as cefotetan, or a methylthiodioxotriazine ring, such as ceftriaxone), and as noted above, when taking ketoconazole and griseofulvin. Much like disulfiram, an FDA-approved medication for AUD that blocks the enzyme acetaldehyde dehydrogenase (see Core article on the basics), consuming these antimicrobial medications with alcohol can cause facial flushing, nausea, vomiting, headache, rapid heartrate, and low blood pressure.73 Disulfiram-like reactions have also been associated with metronidazole and trimethoprim-sulfamethoxazole, but supporting evidence is limited.

    Important: Prescribing presents an alcohol screening opportunity

    When you recommend or prescribe a medication that can interact with alcohol, this scenario presents a natural opening to review or inquire about a patient’s alcohol intake. Asking basic screening questions about a patient’s alcohol use provides opportunities to discuss the potential for negative interactions with medications, make recommendations to cut back or quit drinking, and connect patients with further resources if warranted. The potential for a harmful interaction may provide a compelling reason for patients to cut down or quit drinking when warranted (see Core articles on screening and brief intervention).

    For further information about alcohol-medication interactions

    Beyond the examples noted above, alcohol has the potential to interact negatively with many other commonly prescribed medications. The resources below can help alert you and your patients to important potential risks.

    • For older adults: If you are treating older adults, you may wish to view a 2017 consensus-validated list [PDF – 295 KB] of potentially serious alcohol-medication interactions in older adults.74 Through a rigorous consensus process, a panel of 19 physicians, pharmacologists, and pharmacists developed a list of 38 medications with the potential for serious interactions with “any” or “heavy” alcohol use in older adults.
    • From NIAAA: The webpage Harmful Interactions: Mixing Alcohol with Medicines includes the medications listed above and describes additional possible interactions with medications for:
      • Allergies, colds, and flu
      • Angina
      • Arthritis
      • Attention-deficit/hyperactivity disorder
      • Cough
      • Diabetes
      • Enlarged prostate
      • Epilepsy
      • Heartburn
      • High cholesterol
      • Hypertension
      • Muscle pain
      • Nausea
      • And more

    In closing, combining alcohol with certain medications, particularly those with sedative effects, can increase the risk of adverse events, including falls, driving accidents, and fatal overdoses. The more alcohol a patient consumes, the greater the risk for alcohol and medication interactions. Universal screening, careful prescribing choices, and patient education can help minimize the risks of combining alcohol with certain medications. Asking patients about their alcohol use provides opportunities to discuss potential interactions with medications, to advise changes in their drinking if indicated, and to connect them with further resources as needed.

    Resources

    Medication Labeling

    Alcohol-Medication Interactions

    More resources for a variety of healthcare professionals can be found in the Additional Links for Patient Care.

     

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    Earn CME/CE Credit

    We invite healthcare professionals including physicians, physician assistants, nurses, pharmacists, and psychologists to complete a post-test after reviewing this article to earn FREE continuing education (CME/CE) credit. This CME/CE credit opportunity is jointly provided by the Postgraduate Institute for Medicine and NIAAA.

    CME/CE Activity — Alcohol-Medication Interactions: Potentially Dangerous Mixes

    Released on 5/6/2022
    Expires on 5/10/2024

    FREE

    This activity provides 0.75 CME/CE credits for physicians, physician assistants, nurses, pharmacists, and psychologists.
    Learn more about credit designations here.

    Complete CME/CE Post-Test

    Please note that you will need to log into or create an account on CME University in order to complete this post-test.

    Learning Objectives

    After completing this activity, the participant should be better able to:

    • Identify specific adverse events for which combining alcohol and certain medications can increase risk.
    • Describe why older adults are at increased risk for harms from combining alcohol and some medications.
    • Recognize at least three ways that alcohol and medications can interact. 

    Contributors

    Contributors to this article for the NIAAA Core Resource on Alcohol include the writer for the full article, content contributors to subsections, reviewers, and editorial staff. These contributors included both experts external to NIAAA as well as NIAAA staff.

    NIAAA Writer

    Aaron White, PhD
    Senior Scientific Advisor to
    the NIAAA Director, NIAAA

    NIAAA Content Contributors

    Raye Z. Litten, PhD
    Editor and Content Advisor for the Core Resource on Alcohol,
    Director, Division of Treatment and Recovery, NIAAA

    Laura E. Kwako, PhD
    Editor and Content Advisor for the Core Resource on Alcohol,
    Health Scientist Administrator,
    Division of Treatment and Recovery, NIAAA

    Maureen B. Gardner
    Project Manager, Co-Lead Technical Editor, and
    Writer for the Core Resource on Alcohol,
    Division of Treatment and Recovery, NIAAA

    External Reviewers

    Douglas Berger MD, MLitt
    Staff Physician, VA Puget Sound,
    Associate Professor of Medicine,
    University of Washington, Seattle, WA

    Leonard Koda, PhD
    Pharmacist-in-Charge
    California State University, San Marcos, CA

    Lewei (Allison) Lin MD, MS
    Assistant Professor, Department of
    Psychiatry, University of Michigan,
    Ann Arbor, MI

    Chitra D. Mandyam PhD
    Professor, Department of Anesthesiology,
    University of California San Diego,
    La Jolla, CA

    Renata C. N. Marchette, PhD, PharmD
    Postdoctoral Fellow, National Institute on
    Drug Abuse, Baltimore, MD

    Mack C. Mitchell, MD
    Nancy and Jeremy Halbreich Professor of
    Gastroenterology, UT Southwestern Medical
    Center, Dallas, TX

    Arun J. Sanyal, MD
    Reno Vlahcevic Professor of Medicine,
    Director, Institute of Liver Disease and
    Metabolic Health, Virginia Commonwealth
    University School of Medicine
    Richmond, VA

    Kimberly Tallian, PharmD, APh, BCPP, FASHP, FCCP, FCSHP
    Advance Practice Pharmacist, Psychiatry,
    Scripps Mercy Hospital;
    Adjunct Clinical Professor, School of Pharmacy
    and Pharmaceutical Sciences,
    University of California San Diego,
    La Jolla, California

    NIAAA Reviewers

    George F. Koob, PhD
    Director, NIAAA

    Patricia Powell, PhD
    Deputy Director, NIAAA

    Lorenzo Leggio, MD, PhD
    NIDA/NIAAA Senior Clinical Investigator and Section Chief;
    NIDA Branch Chief;
    NIDA Deputy Scientific Director;
    Senior Medical Advisor to the NIAAA Director

    Falk W. Lohoff, MD
    Lasker Clinical Research Scholar;
    Chief, Section on Clinical Genomics and Experimental Therapeutics, NIAAA

    Aaron White, PhD
    Senior Scientific Advisor to
    the NIAAA Director, NIAAA

    Editorial Team

    NIAAA

    Raye Z. Litten, PhD
    Editor and Content Advisor for the Core Resource on Alcohol,
    Director, Division of Treatment and Recovery, NIAAA

    Laura E. Kwako, PhD
    Editor and Content Advisor for the Core Resource on Alcohol,
    Health Scientist Administrator,
    Division of Treatment and Recovery, NIAAA

    Maureen B. Gardner
    Project Manager, Co-Lead Technical Editor, and
    Writer for the Core Resource on Alcohol,
    Division of Treatment and Recovery, NIAAA

    Contractor Support

    Elyssa Warner, PhD
    Co-Lead Technical Editor,
    Ripple Effect

    Daria Turner, MPH
    Reference and Resource Analyst,
    Ripple Effect

    Kevin Callahan, PhD
    Technical Writer/Editor,
    Ripple Effect

    To learn more about CME/CE credit offered as well as disclosures, visit our CME/CE General Information page. You may also click here to learn more about contributors.

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