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5 Over-the-Counter Medicines You Should Never Take Together

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You can buy over-the-counter drugs without a prescription, but they still have risks—especially if you treat yourself with more than one at a time. 

Even people who read labels closely don’t always spot potential problems, such as two OTC meds with the same active ingredient, according to a recent study in the Journal of Public Policy & Marketing. Keep yourself safe while getting healthy. Use the following tips to avoid these potentially perilous pairs.

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1. Dangerous duo: Tylenol and multi-symptom cold medicines
Many cough, cold, and flu combos contain acetaminophen to relieve sore throats, headaches, and fevers. Take Tylenol—which is also acetaminophen—on top of them and you might exceed the 4-gram (g) daily upper limit for this drug, says Jesse R. Catlin, Ph.D., of California State University, Sacramento, and the Journal of Public Policy & Marketing study author. 

The risk: liver damage that can ultimately require transplantation or even kill you. (The threat of severe overdose is greatest if you consume 7g or more a day, but even just one day of exceeding 4g can be dangerous.)  

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Also, watch for abbreviations of acetaminophen like APAP, AC, or Acetam, along with the word paracetamol—that’s what acetaminophen goes by in most other countries. 

2. Dangerous duo: Any combo of ibuprofen, naproxen, and aspirin
Drugs known by brand names like Advil, Aleve, and Bayer fall into a class called non-steroidal anti-inflammatories (NSAIDs), Catlin says. Because they work via the same underlying pathways, taking more than one boosts your risk of side effects. These range from mild nausea to severe gastrointestinal bleeding, says Tim Davis, Pharm.D., a member of the National Community Pharmacists Association.

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3. Dangerous duo: Antihistamines and motion-sickness medications
Use caution when combining antihistamine allergy meds like Benadryl with nausea-busting treatments like Dramamine. Their similar active ingredients— diphenhydramine to treat sniffles, red eyes, and sneezing, and dimenhydrinate to ease motion sickness—can add up to excess drowsiness. “I’ve heard about people sleeping through their flight connection because they took too much antihistamine,” Gattas says.

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4. Dangerous duo: Anti-diarrheal medicine and calcium supplements

Products containing loperamide, such as Imodium, tame the trots. But take them alongside a calcium supplement, and you risk the opposite problem. Calcium firms your stool, so combining it with an anti-diarrheal can stop up your system, Davis says.

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5. Dangerous duo: St. John’s wort and cough medicine

The herbal supplement St. John’s wort claims to ease anxiety and depression. Dextromethorphan, a cough suppressant, quiets your hacking. But pairing them up may trigger a dangerous condition called serotonin syndrome, Davis says. Too much of the neurotransmitter serotonin builds up in your system, causing sweating, feelings of confusion and discomfort, trouble controlling your movements, and in rare cases, even death.

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When in doubt about how a particular cold, cough, and flu formula combines with any other medicine or supplement you’re taking, ask a pharmacist, either in person or on the phone, Gattas says.

You can also soothe hacking by using a cool-mist humidifier, drinking plenty of water, and popping a cough drop or even a hard candy to calm the cough reflex, Gattas says. Swallowing one-half to 2 teaspoons honey before bed might decrease nighttime coughing and improve sleep.

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