Mucinex DM (guaifenesin/dextromethorphan) and Nyquil Cold and Flu (acetaminophen/dextromethorphan/doxylamine) are both over-the-counter medications used to treat cold and flu symptoms. But they have several differences. Mucinex DM combines guaifenesin, an expectorant that loosens mucus, and dextromethorphan, a cough suppressant. It is available in various forms, including tablets, liquids, and dissolvable granules, and is typically taken every 4 to 12 hours depending on the formulation. Nyquil Cold and Flu, on the other hand, includes acetaminophen for pain and fever relief, dextromethorphan for cough suppression, and doxylamine, an antihistamine that helps with runny nose and sneezing. Nyquil is available as a liquid or capsules and is usually taken every 6 hours. While both medications contain dextromethorphan, Nyquil also addresses pain, fever, and allergy symptoms, making it more comprehensive for nighttime relief. However, Nyquil can cause significant drowsiness due to doxylamine, whereas Mucinex DM may cause less drowsiness. You should not take these medications together because of the risk of dextromethorphan overdose. Always check with your prescriber or pharmacist to ensure you are using these medications safely.