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Guaifenesin, in my opinion. Usually multiple over-the-counter (OTC) medicines are needed to treat all the symptoms of flu-like illnesses. Consulting the pharmacist in the drug store for suggestions of the best choices available to meet your needs is always a good thing to do when purchasing OTC remedies. When products contain multiple active ingredients for multiple symptoms, I prefer to take only the ones that have exactly what I need so I don't take unneeded preparations. The pharmacist can best help you select those. See the related questions in the related question section for this Q&A for a more comprehensive answer to how cold and flu are treated.

But, if picking the "best" of a single OTC product to help the symptoms of the flu, I would pick the ones that help expectoration and cough, since lung secretions that are not coughed up are part of the problem in development of secondary pneumonia from the flu, which can be a life-threatening complication. Other remedies may make you more comfortable, but could be less important in preventing complications. My personal choice for the best of the cough/expectorant OTC medicine would be any cough preparations that contain Guaifenesin as the primary active ingredient. This is made from a natural product with centuries, if not longer, safe and effective use for this purpose, and it loosens congestion and sputum better than other choices for me to help clear my lungs and airway.

Guaifenesin is available OTC in generic and store brand cough medicines at very reasonable prices, and in brand name OTC cough and expectorant treatments, such as Robitussin and Mucinex. I usually prefer to use cough medicines that do not also contain decongestants, because they are not needed every time you need an expectorant or cough medicine and can be taken separately when they are really needed. Also consult your pharmacist for choosing OTC medicines that can be taken safely together.

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Q: What is the best OTC medicine for flu like symptoms?
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