10 Common Drug Combinations You Should Never Mix
Drug interactions send over 125,000 Americans to the hospital every year. Many involve common medications you can buy without a prescription. Here are ten dangerous combinations that too many people don't know about.
Warfarin, Eliquis, or Xarelto combined with ibuprofen, naproxen, or aspirin
Risk: Dramatically increased bleeding risk — including life-threatening internal bleeding. NSAIDs also irritate the stomach lining, compounding the danger.
Sertraline (Zoloft) + Fluoxetine (Prozac), or any SSRI with Duloxetine (Cymbalta)
Risk: Serotonin syndrome — a potentially fatal condition causing rapid heart rate, high blood pressure, fever, muscle rigidity, and seizures.
Lisinopril or Enalapril + potassium supplements or salt substitutes
Risk: Dangerously high potassium levels (hyperkalemia) — can cause fatal heart arrhythmias. ACE inhibitors already raise potassium levels.
Atorvastatin (Lipitor), Simvastatin (Zocor), or Lovastatin + grapefruit juice
Risk: Grapefruit blocks the enzyme that breaks down certain statins, dramatically increasing drug levels in your blood — leading to muscle breakdown (rhabdomyolysis) and kidney damage.
Oxycodone or Hydrocodone + Alprazolam (Xanax) or Diazepam (Valium)
Risk: Both suppress breathing. Together, they can cause fatal respiratory depression. The FDA issued a boxed warning about this combination in 2016.
Metformin + excessive alcohol consumption
Risk: Lactic acidosis — a rare but serious condition where lactic acid builds up in the blood. Alcohol intensifies this risk by impairing the liver's ability to clear lactate.
Sertraline or any SSRI/SNRI + Sumatriptan (Imitrex)
Risk: Serotonin syndrome. Both drug classes increase serotonin levels. Together, they can push levels dangerously high.
Tylenol + cold medicine, sleep aids, or prescription painkillers that also contain acetaminophen
Risk: Liver failure. Acetaminophen is hidden in over 600 products. Taking multiple products can easily push you over the safe daily limit (3,000-4,000mg) without realizing it.
Lisinopril, Losartan, or Amlodipine + Ibuprofen or Naproxen
Risk: NSAIDs can reduce the effectiveness of blood pressure medications and worsen kidney function. Regular use can raise blood pressure by 3-6 mmHg.
Warfarin (Coumadin) + Ciprofloxacin, Metronidazole, or Fluconazole
Risk: Many antibiotics and antifungals dramatically increase warfarin's blood-thinning effect, raising the risk of serious bleeding events. INR monitoring is essential during any antibiotic course.
How to Protect Yourself
Use one pharmacy. When all your prescriptions go through one pharmacy, their system automatically checks for interactions.
Read labels. Always check active ingredients in OTC products — especially cold medicines, sleep aids, and pain relievers.
Tell every doctor every medication. Including supplements, vitamins, and OTC drugs.
Ask your pharmacist. They're trained specifically in drug interactions and are often more accessible than your doctor.