Alcohol-Medication Interactions: Potentially Dangerous Mixes

Dozens of common medications have the potential to interact in dangerous ways with alcohol.^1,2 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 drug for at least 30 days,³ 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.⁴ About 80% 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.⁵

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.

Types of alcohol-medication interactions

Alcohol and medications have the potential to interact in three main ways:^6–8

• 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.

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). The effects of alcohol and benzodiazepines on central nervous system function are additive and possibly synergistic.²
    • 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.¹⁷ 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.²⁸ Alcohol plays a causal role in nearly 1 in 5 (18.5%) benzodiazepine overdose deaths each year.²⁹
    • 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.³⁰ The combination of alcohol and benzodiazepines increases the risk for driving accidents beyond the risks of alcohol alone.³⁰ In older adults, benzodiazepines raise the risk for injuries and deaths from falls,^31,32 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 benzodiazepines³³ and may be more prone to use benzodiazepines in ways other than prescribed, which increases the risks of harm.³⁴
    • Risk of memory impairment. 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.^35–39 Prescribing information for benzodiazepines commonly lists memory impairments as a side effect (e.g., see Xanax prescribing information) and synergistic effects of alcohol and benzodiazepines on memory have been noted.⁴⁰
    In addition, alcohol inhibits metabolism of some benzodiazepines (e.g., alprazolam, clonazepam, and diazepam, but not lorazepam), leading to higher plasma levels and prolonged rates of elimination, which can also contribute to the functional effects listed above.²
  • “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.⁴¹ For example, on its own, zolpidem can impair motor coordination and increase fall risk;⁴² produce memory impairments, including memory blackouts;⁴³ and promote behaviors during sleep for which patients have no recall, such as driving.⁴⁴ Combining zolpidem with alcohol could increase these risks.^44,45 Zolpidem overdose is linked with alcohol consumption and often warrants admission to intensive care in the emergency department.⁴⁶
  • Antidepressants. Alcohol may increase the side effects of antidepressants on the central nervous system, such as drowsiness and dizziness.⁴⁷ Alcohol may also reduce antidepressant response and patient adherence.^24,25 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.^48,49 Buproprion (Wellbutrin) may lower the threshold for seizures, and alcohol may further increase seizure risk.^47,50 Duloxetine (Cymbalta) may cause liver damage, and combining it with alcohol may further raise the risk of liver toxicity.⁵¹ In addition, a study found that combining alcohol with venlafaxine (Effexor) may lower the threshold for fatal alcohol overdoses.⁵² (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 system. Alcohol plays a significant role in roughly 15-20% of all opioid-related deaths, and the risk begins at low doses of both substances.⁵³ In a 2017 study, 20mg of oxycodone alone reduced respiration by 28%.¹¹ When participants had enough alcohol to reach a BAC of 0.1%, respiration dropped by another 19%, and apneic episodes increased in older participants.¹¹ 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.^54,55 (See also the text box above.)
  • Buprenorphine preparations, when combined with alcohol, can lead to hypotension, respiratory depression, profound sedation, and coma.^56–59 Post-mortem studies suggest that alcohol lowers the threshold for levels of buprenorphine found in fatal accidental overdose cases.⁶⁰ When caring for a patient who has opioid use disorder and drinks heavily, assess the risks and benefits of prescribing buprenorphine while keeping in mind the risks of untreated opioid use disorder.⁶¹
• 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.⁸ Consuming up to 1 drink per day increases the risk of gastrointestinal bleeding associated with NSAID use by about 37%.⁶² (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.^63,64 Acetaminophen interacts with alcohol in complex, potentially lethal, ways.^65,66 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.⁶⁷ The same enzyme assumes an important role in metabolizing alcohol in people who drink heavily.^68,69 Chronic, heavy alcohol consumption leads to an increase in CYP2E1 activity.⁶⁷ 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.^70,71 The exact amounts and timing of alcohol and acetaminophen intake that could lead to liver damage are unknown, although the FDA requires that acetaminophen products have a label that states that “severe liver damage may occur if an adult has 3 or more alcoholic drinks everyday while using this product.”⁷² Out of an abundance of caution, however, the FDA also asks healthcare professionals to advise patients not to drink alcohol when taking medicines that contain acetaminophen.^73,74
• 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.⁷⁵
  • 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.⁷⁶
  • Propranolol (Inderal, InnoPran, Hemangeol) is a beta blocker that has been used to treat hypertension, other cardiac conditions, and anxiety disorders. Alcohol consumption may increase plasma levels of propranolol⁷⁷ 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.^77,78
• 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:⁷⁹
  • 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. Disulfiram-like reactions have also been associated with metronidazole and trimethoprim-sulfamethoxazole, but supporting evidence is limited.
  A 2022 review on interactions between antiretroviral drugs and alcohol was unable to draw general recommendations, as it found only scarce data limited to individual medications.⁸⁰

Important: Prescribing presents an alcohol screening opportunity

When you recommend or prescribe a medication that can interact with alcohol, you have 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. (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.⁸¹ 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:

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.