Just in Time for the Holidays: Mixing Alcohol With Some Medicines Is a Bad Idea

Sixty-five years ago, always an inquisitive child, my mother decided to tell me why we had so much booze, hidden on all of the shelves in the large breakfront and taken out for frequent parties. She said that the neighbor worked in Customs. Sometimes, when nobody was looking, he’d make what he had to carry lighter by “borrowing” bottles of whiskey and liqueurs.

My father and a few of the neighbor’s friends would buy it from him at an enormous discount. Everybody was happy, the neighbor who sold and the customers who bought. 

With neither of my parents as alcoholics, they were glad to share it with their friends (three of them were alcoholics and they, too, were deliriously delighted). 

Maybe I didn’t turn out as an alcoholic because the booze was already there since before I was born, and I was used to seeing the intoxicating beverage. And I said my prayers. But I don’t really know. 

Anyway, as I aged, now 75, I took medicines–for the ache in my back, for allergies, for ear infections, and for so many more maladies–and I began to see articles on mixing alcohol with drugs more over the years, with increasing frequency.

So the time is as good as any (maybe better with the holidays, beginning with Thanksgiving, just around the corner) to write about mixing alcohol with drugs. I hope you’re safer having read the contents of this blog.

Coming from the National Institute and Alcohol Abuse and Alcoholism (NIAAA) are examples of common medications known to interact negatively with alcohol.

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.
• 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. Alcohol plays a causal role in nearly 1 in 5 (18.5%) benzodiazepine overdose deaths each year.
• 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.
• The combination of alcohol and benzodiazepines increases the risk for driving accidents beyond the risks of alcohol alone. In older adults, benzodiazepines raise the risk for injuries and deaths from falls, 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 benzodiazepines and may be more prone to use benzodiazepines in ways other than prescribed, which increases the risks of harm.
• 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. Prescribing information for benzodiazepines commonly lists memory impairments as a side effect.  

“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.
• For example, on its own, zolpidem can impair motor coordination and increase fall risk; produce memory impairments, including memory blackouts; and promote behaviors during sleep for which patients have no recall, such as driving.
• Combining zolpidem with alcohol could increase these risks.
• Zolpidem overdose is linked with alcohol consumption and often warrants admission to intensive care in the emergency department.

Antidepressants. Alcohol may increase the side effects of antidepressants on the central nervous system, such as drowsiness and dizziness.

• Alcohol may also reduce antidepressant response and patient adherence.
• 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.
• Buproprion (Wellbutrin) may lower the threshold for seizures, and alcohol may further increase seizure risk.
• Duloxetine (Cymbalta) may cause liver damage and combining it with alcohol may further raise the risk of liver toxicity.
• In addition, a study found that combining alcohol with venlafaxine (Effexor) may lower the threshold for fatal alcohol overdoses. 

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.
• In a 2017 study, 20mg of oxycodone alone reduced respiration by 28%. When participants had enough alcohol to reach a Blood Alcohol Content (BAC) of 0.1%, respiration dropped by another 19%, and apneic (apnea-like) episodes increased in older participants, blocking airflow.
• 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.
• Buprenorphine preparations, when combined with alcohol, can lead to hypotension (low blood pressure), respiratory depression, profound sedation, and coma.
• Post-mortem studies suggest alcohol lowers the threshold for levels of buprenorphine found in fatal accidental overdose cases.

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.
• Consuming up to 1 drink per day increases the risk of gastrointestinal bleeding associated with NSAID use by about 37%.
• 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.
• Acetaminophen interacts with alcohol in complex, potentially lethal, ways.
• 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.

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 and either have been taking warfarin for more than one year or have genetic variants that influence warfarin metabolism.
• Verapamil (Verelan, Calan) is a calcium channel antagonist used to treat arrhythmia, high blood pressure, and angina. Verapamil significantly inhibits alcohol metabolism, when alcohol and verapamil are consumed together.
• Propranolol (Inderal, InnoPran, Hemangeol) is a beta blocker used to treat hypertension and other cardiac conditions. Alcohol consumption may increase plasma levels of propranolol 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.

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:

• Erythromycin and doxycycline—Reduced efficacy: Erythromycin may be less effective in people who drink alcohol and may increases 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) when taking ketoconazole and griseofulvin.
• Much like disulfiram, an FDA-approved medication for AUD that blocks the enzyme acetaldehyde dehydrogenase, 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.

If you plan to drink alcohol and are taking any medicine whether prescribed or over the counter and even if it’s not listed in this blog, you should check with the pharmacy if memory serves regardless. They’ll have the answer, even if it’s not listed as a precaution on the bottle. 

Happy Thanksgiving from our home to yours. Stay safe, my dear readers, drinking or otherwise!