Alcohol and medication: which combinations carry risk

Most medicines tolerate a glass perfectly well. A handful do not, and those combinations are common ones: painkillers, sleeping pills, sedatives. In a US population survey, 41.5 percent of current drinkers were taking a medicine that interacts with alcohol, rising to 77.8 percent among those over 65 (PMID 25597432).

Below is what is known per group, and what the Dutch Farmacotherapeutisch Kompas says about it. For your own medication, your pharmacist remains the right address.

Why is mixing alcohol and medication risky?

There are two routes. Alcohol and the medicine can do the same thing, for instance both dampening your breathing and alertness, so the effects add up. Or they compete for the same breakdown pathway in the liver, leaving more active substance or more toxic byproduct in your blood.

The second route is the insidious one. You notice nothing until something goes wrong.

Can you take paracetamol with alcohol?

For occasional use at a normal dose, this is not a problem for most people. With regular drinking the picture changes. The liver then breaks paracetamol down via a route that produces a liver-toxic intermediate. On top of that, the protective glutathione reserve is often lower in drinkers.

This is not theory. Researchers examined 67 patients with severe liver injury after taking paracetamol with therapeutic intent. In 40 percent of them the dose was within the recommended 4 grams per day (PMID 7657281). Almost 20 percent died.

That is no reason to panic about one paracetamol after one glass. It is a reason to take the leaflet seriously if you drink often.

How much time should there be between paracetamol and alcohol?

There is no official Dutch interval for this, and I would be sceptical of any site that names a precise number of hours. What the leaflet and the Farmacotherapeutisch Kompas do say is that paracetamol should not be combined with regular, heavy alcohol use.

The risk sits in the pattern, not in the clock. If in doubt, ask your pharmacist, who can see your whole medication list.

And ibuprofen with alcohol?

Here the risk is of a different kind: not the liver, but the stomach. Alcohol and NSAIDs such as ibuprofen both damage the stomach lining. Together those effects add up.

A case-control study followed more than 1,200 people with major upper gastrointestinal bleeding. The relative risk rose to 2.8 at 21 or more drinks per week (PMID 10566713). Among drinkers using ibuprofen regularly it was 2.7. With regular aspirin above 325 mg it reached 7.0.

Which medicines amplify the effect of alcohol?

Mainly those acting on the same system. Benzodiazepines, opioids, some antidepressants and antihistamines all dampen the central nervous system, just as alcohol does. The sum is more than the two parts separately.

Across almost 400,000 opioid poisoning deaths in the United States, alcohol was involved in 14.7 percent by 2017, and benzodiazepines in 21.0 percent (PMID 32271389).

Say you take oxazepam and drink 2 glasses alongside it. The sedation adds up. A screen will then correctly show benzodiazepines. That is not a false positive, it is a true one. Which substances do cause an incorrect result is covered in false-positive drug test.

Must you really avoid alcohol on metronidazole?

That warning is everywhere, but the evidence is thinner than its reputation. In an experimental study, metronidazole did not raise blood acetaldehyde. The combination produced no objective or subjective adverse effects either (PMID 12022894). A more recent study matched 18 patients on metronidazole who had detectable blood alcohol. Not one documented disulfiram-like reaction turned up (PMID 37494646).

A review concludes that the reaction occurs "with uncertain frequency and with varied severity" (PMID 31871085). That same review does confirm a genuine risk with certain cephalosporins, ketoconazole and griseofulvin.

I raise this not to encourage anyone to drink on a course of antibiotics. I raise it because a warning that does not hold up undermines trust in the warnings that do.

Can medication affect an alcohol test?

For CDT this is barely an issue, which is exactly why that marker carries so much weight in assessments. For liver values it is different: gamma-GT rises with a range of medicines without any alcohol involved. That difference determines how you should read a result, which is the subject of gamma-GT too high.

The full overview of what CDT, EtG and a blood test show sits in detecting alcohol. If you want to know your own CDT value, a CDT test for alcohol will quantify it for you.

Every blood test result at Zuivertest includes a professional assessment by a BIG-registered doctor. Discuss your results with your GP or pharmacist before making treatment decisions.

Sources

• Breslow R.A. et al., "Prevalence of alcohol-interactive prescription medication use among current drinkers: United States, 1999 to 2010", Alcoholism: Clinical and Experimental Research, 2015 (PMID 25597432)
• Zimmerman H.J. and Maddrey W.C., "Acetaminophen hepatotoxicity with regular intake of alcohol", Hepatology, 1995 (PMID 7657281)
• Kaufman D.W. et al., "The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption", American Journal of Gastroenterology, 1999 (PMID 10566713)
• Tori M.E. et al., "Alcohol or Benzodiazepine Co-involvement With Opioid Overdose Deaths in the United States, 1999-2017", JAMA Network Open, 2020 (PMID 32271389)
• Visapää J.P. et al., "Lack of disulfiram-like reaction with metronidazole and ethanol", Annals of Pharmacotherapy, 2002 (PMID 12022894)
• Feldman R. et al., "Can Metronidazole Cause a Disulfiram-Like Reaction?", Wisconsin Medical Journal, 2023 (PMID 37494646)
• Mergenhagen K.A. et al., "Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions", Antimicrobial Agents and Chemotherapy, 2020 (PMID 31871085)
• Farmacotherapeutisch Kompas, monographs on paracetamol, ibuprofen and metronidazole (farmacotherapeutischkompas.nl)
• Thuisarts, information on medicines and alcohol (thuisarts.nl)