Key takeaways:
Dextromethorphan is a popular over-the-counter (OTC) cough suppressant. It’s found in products such as Delsym, Mucinex DM, and many others.
Dextromethorphan interactions include alcohol, monoamine oxidase inhibitors (MAOIs), and other cough suppressants. You should also check with your prescriber before taking dextromethorphan with antidepressant medications.
Taking the recommended dose of dextromethorphan can help reduce the risk of serious interactions. Be sure to check OTC product labels for dosage information and to help avoid doubling up on ingredients.
Save on related medications
Dextromethorphan is one of the most common ingredients in over-the-counter (OTC) cough medications, such as Delsym. You’ll often find it in products that have “DM” in the name, such as Mucinex DM, Robitussin Cough+Chest Congestion DM, and others.
It can be hard to know if OTC products like dextromethorphan are safe to take with your other medications. Here, we’ll review four dextromethorphan interactions to be aware of before taking it. Keep in mind that this isn’t a complete list, so it’s best to read the product label or talk to a healthcare professional to make sure dextromethorphan is safe for you.
1. Alcohol
It’s best to avoid alcohol while taking dextromethorphan. Dextromethorphan side effects may include drowsiness, dizziness, or nausea. These same side effects can happen when you drink alcohol. So the combination can raise your risk of excessive dizziness or sedation.
What’s more, drinking alcohol when you’re sick — especially in large amounts — can make it harder for you to recover. That’s because alcohol can weaken your immune system.
Good to know: Some OTC liquid cough and cold medications contain alcohol. If you drink alcohol while taking one of these products, your risk of side effects and intoxication goes up. Be sure to check the product labels and choose one that's alcohol free if this is a concern for you.
2. Monoamine oxidase inhibitors (MAOIs)
You should not take dextromethorphan if you currently take a monoamine oxidase inhibitor (MAOI). You should wait at least 2 weeks after your last MAOI dose before taking dextromethorphan.
MAOIs are a class of medications that treat conditions such as Parkinson's disease and depression. Some examples include:
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Rasagiline (Azilect)
Selegiline (Zelapar, Emsam)
Dextromethorphan and MAOIs both raise serotonin levels in the body. Combining them can lead to serotonin syndrome — a serious condition that happens when serotonin levels are too high. If you’re taking an MAOI, talk to your pharmacist or prescriber about a safer option to treat your cough.
3. Some antidepressants
Some antidepressants increase serotonin levels in the body. Common examples include:
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and sertraline (Zoloft)
Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor XR) and duloxetine (Cymbalta)
Tricyclic antidepressants (TCAs), such as amitriptyline and nortriptyline
As mentioned, dextromethorphan can also raise serotonin levels. So combining it with antidepressants can raise your risk of serotonin syndrome. This interaction is more likely if you take too much dextromethorphan. It isn’t common with recommended dextromethorphan dosages.
If you take an antidepressant, check with your healthcare team before taking dextromethorphan. If they OK the combination, be sure to take the lowest effective dose of dextromethorphan for the shortest amount of time needed. Seek emergency care if any signs or symptoms of serotonin syndrome appear, such as:
Excessive sweating
Muscle spasms
Agitation
Confusion
Is your cough serious? Most coughs go away on their own. But sometimes they can be a sign of a serious health condition, like pneumonia or heart problems. Learn when to see a healthcare professional for your cough.
Dextromethorphan side effects: Learn about potential dextromethorphan side effects and how to manage them if they occur.
Choosing the best cough medicine: With so many prescription and over-the-counter cough medications to choose from, it can be hard to know which ones work best. Here’s what studies say are the most effective cough medicines.
Good to know: St. John's wort is an herbal supplement that’s often marketed for depression symptoms. This herb can increase serotonin levels and may raise the risk of serotonin syndrome if you take it with dextromethorphan. Check with a healthcare professional before taking St. John’s wort and dextromethorphan at the same time.
4. Other cough suppressants
Taking more than one cough suppressant at the same time isn’t recommended unless your prescriber tells you to. Doing so can raise the risk of side effects, such as dizziness and drowsiness.
If OTC dextromethorphan isn’t effective, your prescriber may switch you to a prescription cough medication. Examples include benzonatate (Tessalon) or Virtussin AC (guaifenesin / codeine). In this case, you should stop taking OTC dextromethorphan before starting the new medication, unless your prescriber tells you otherwise.
It’s also good to be aware that dextromethorphan is often included in combination cough and cold products. So be sure to read product labels to avoid taking more than one product with the same ingredient. This could lead to taking more dextromethorphan than recommended.
Keep in mind that it’s fine to take dextromethorphan with guaifenesin (Mucinex) or an antihistamine such as diphenhydramine (Benadryl). These medications work in different ways to help manage a cough and don’t interact with dextromethorphan in a harmful way.
Frequently asked questions
Yes, it’s fine to take dextromethorphan and Benadryl, or diphenhydramine, at the same time. In fact, several OTC combination cough and cold medicines contain both of these ingredients. Just be aware that since both medications cause drowsiness, the combination is likely to make you sleepy. And it’s best to avoid other sedating medications if you’re taking dextromethorphan and Benadryl at the same time. Combining them can cause excessive drowsiness.
Yes, it’s generally safe to take dextromethorphan with ibuprofen (Advil, Motrin) or acetaminophen (Tylenol) if needed. But if dextromethorphan is part of a combination cough and cold medicine, be sure to check the OTC label. It may already include a pain or fever reducer, so you likely won’t need to take another one.
Yes, it’s fine to take dextromethorphan and Benadryl, or diphenhydramine, at the same time. In fact, several OTC combination cough and cold medicines contain both of these ingredients. Just be aware that since both medications cause drowsiness, the combination is likely to make you sleepy. And it’s best to avoid other sedating medications if you’re taking dextromethorphan and Benadryl at the same time. Combining them can cause excessive drowsiness.
Yes, it’s generally safe to take dextromethorphan with ibuprofen (Advil, Motrin) or acetaminophen (Tylenol) if needed. But if dextromethorphan is part of a combination cough and cold medicine, be sure to check the OTC label. It may already include a pain or fever reducer, so you likely won’t need to take another one.
The bottom line
Dextromethorphan is a common over-the-counter (OTC) cough medication. It is found in products such as Delsym, Mucinex DM, and many others. Dextromethorphan interactions include alcohol, monoamine oxidase inhibitors (MAOIs), and other cough suppressants. It’s also best to check with your prescriber before taking it with antidepressants.
Staying within the recommended dextromethorphan dosages can help reduce the risk of serious interactions. Be sure to read OTC product labels carefully. This can help you to avoid duplicate ingredients and understand the proper dosage directions.
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References
AMZ789. (2025). DEXTROMETHORPHAN HBR 15 MG capsule, liquid filled [package insert]. DailyMed.
Journey, J. D., et al. (2023). Dextromethorphan toxicity. StatPearls.
Schwartz, A. R., et al. (2008). Dextromethorphan-induced serotonin syndrome. Clinical Toxicology.
