What Medications Cannot Be Taken With Dextromethorphan?

October 11, 2025 •

4 min read

According to the U.S. Pharmacist, a deadly interaction between dextromethorphan and MAO inhibitors was reported as early as 1992. It is critical to understand what medications cannot be taken with dextromethorphan to prevent potentially life-threatening side effects, most notably serotonin syndrome.

Quick Summary

Serious interactions can occur when combining dextromethorphan with other medications. The most severe is serotonin syndrome, which is triggered by MAOIs, SSRIs, and other serotonergic drugs. Avoiding CNS depressants, alcohol, and grapefruit is also advised to prevent adverse effects.

Key Points

Avoid MAOIs: The combination of dextromethorphan and Monoamine Oxidase Inhibitors (MAOIs) can cause fatal serotonin syndrome and must be avoided at all costs, with a 14-day washout period required.
Beware of Serotonergic Drugs: Many common antidepressants, including SSRIs, SNRIs, and TCAs, increase serotonin levels and should be used cautiously with dextromethorphan to prevent serotonin syndrome.
Limit CNS Depressants: Combining dextromethorphan with alcohol, opioids, and other sedatives can dangerously increase drowsiness and the risk of respiratory depression.
Consider Food and Supplements: Grapefruit juice can increase dextromethorphan levels in your body, while St. John's Wort can contribute to the risk of serotonin syndrome.
Prevent Accidental Overdose: Many over-the-counter cold and flu products contain dextromethorphan. Always check labels carefully to avoid taking multiple products with the same active ingredient.
Check for Metabolism Inhibitors: Some medications, including heart rhythm drugs (quinidine) and certain antidepressants (fluoxetine), inhibit the enzyme that breaks down dextromethorphan, increasing the risk of adverse effects.

Dextromethorphan (DXM) is a common, over-the-counter cough suppressant found in a wide range of cold and flu medications, often listed as "DM" on product labels. While generally safe when used as directed, it is crucial to be aware of potentially dangerous drug interactions. Taking dextromethorphan with certain prescription or even other over-the-counter drugs can lead to severe or life-threatening reactions, such as serotonin syndrome.

The Critical and Dangerous Interaction with MAO Inhibitors

The most severe and well-documented interaction involves Monoamine Oxidase Inhibitors, or MAOIs. MAOIs are a class of antidepressants used to treat depression and other psychiatric conditions. Combining dextromethorphan with an MAOI is strictly contraindicated and can lead to a fatal condition known as serotonin syndrome.

Serotonin syndrome is caused by an excess of serotonin in the brain, which can trigger symptoms like agitation, hallucinations, a rapid heart rate, high blood pressure, and seizures. This is because MAOIs prevent the breakdown of serotonin, while dextromethorphan also increases serotonin levels through its reuptake inhibition properties. The combination creates a dangerous buildup of serotonin.

To prevent this, healthcare professionals advise a mandatory 14-day washout period. This means a person must stop taking the MAOI for at least two weeks before starting any medication containing dextromethorphan. Common MAOIs to avoid include:

Isocarboxazid (Marplan)
Phenelzine (Nardil)
Selegiline (Eldepryl, Zelapar)
Tranylcypromine (Parnate)
The injectable antibiotic linezolid and methylene blue injection are also considered MAOIs in this context.

Other Serotonergic Agents to Avoid or Use with Caution

Beyond MAOIs, many other medications also increase serotonin levels and should be used with caution or avoided altogether with dextromethorphan to mitigate the risk of serotonin syndrome.

Selective Serotonin Reuptake Inhibitors (SSRIs): Common antidepressants like fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro) all work by increasing serotonin in the brain. Taking them with dextromethorphan can lead to serotonin syndrome, especially at higher doses.
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Drugs such as venlafaxine (Effexor XR) and duloxetine (Cymbalta) also carry this risk.
Tricyclic Antidepressants (TCAs): Older antidepressants like amitriptyline and nortriptyline can also increase serotonin levels.
Triptans: These medications, used to treat migraines (e.g., sumatriptan), can increase serotonin levels and pose a risk when combined with DXM.
Herbal Supplements: St. John's Wort is a natural supplement that increases serotonin. Its combination with dextromethorphan is not recommended.
Other Antidepressants: Mirtazapine and bupropion (Wellbutrin) also carry a risk of interaction.

Medications That Increase Dextromethorphan Levels

Certain medications can interfere with the liver enzyme (CYP2D6) that metabolizes dextromethorphan. When this enzyme is inhibited, DXM levels build up in the body, which can increase side effects and the risk of serotonin syndrome even at therapeutic doses.

Certain Antidepressants: As noted, some SSRIs like fluoxetine and paroxetine are potent CYP2D6 inhibitors.
Heart Rhythm Medications: Antiarrhythmics such as quinidine and amiodarone are known to inhibit this enzyme.
HIV Medications: Some medications used to treat HIV, like cobicistat, can significantly increase dextromethorphan levels.

Other Interactions to Note

Central Nervous System (CNS) Depressants: Alcohol, opioids (e.g., morphine, codeine), benzodiazepines (e.g., Xanax), and sedatives can have an additive effect with dextromethorphan, increasing drowsiness, dizziness, and risk of slowed breathing.
Grapefruit Juice: Compounds in grapefruit can inhibit the same liver enzyme that breaks down dextromethorphan, potentially increasing its concentration and side effect risk.
Other Cold & Cough Products: Many over-the-counter products contain dextromethorphan. Taking multiple products simultaneously can lead to an accidental overdose, significantly raising the risk of severe side effects. Always check the active ingredients list on all cold and flu medications before use.

Comparison Table: Dextromethorphan Interactions


Interacting Agent	Examples	Risk	Recommendation
Monoamine Oxidase Inhibitors (MAOIs)	Phenelzine (Nardil), Selegiline (Eldepryl)	High: Life-threatening Serotonin Syndrome	Do not combine. Wait 14 days after stopping MAOI.
SSRIs	Fluoxetine (Prozac), Sertraline (Zoloft)	Moderate to High: Serotonin Syndrome	Avoid combination, especially at high doses. Discuss with a healthcare provider.
SNRIs	Venlafaxine (Effexor XR), Duloxetine (Cymbalta)	Moderate to High: Serotonin Syndrome	Use with caution. Consult a doctor.
Other Antidepressants	Bupropion (Wellbutrin), Mirtazapine (Remeron)	Moderate: Increased side effects or Serotonin Syndrome	Use with caution. Consult a doctor.
Triptans (Migraine)	Sumatriptan (Imitrex)	Moderate: Serotonin Syndrome	Use with caution. Consult a doctor.
Herbal Supplements	St. John's Wort	Moderate: Serotonin Syndrome	Avoid combination.
CNS Depressants	Alcohol, Opioids, Benzodiazepines	Moderate: Increased drowsiness, respiratory depression	Avoid combining.
Grapefruit Juice	-	Moderate: Increased dextromethorphan levels and side effects	Avoid consumption.
Other Dextromethorphan Products	Multi-symptom cold medicines	High: Accidental overdose	Always check labels to avoid doubling up.

Conclusion

While dextromethorphan is an effective treatment for coughs, its potential for dangerous interactions with other medications cannot be overlooked. The most critical risk is serotonin syndrome, which can be life-threatening and is most strongly associated with combining DXM with MAOIs and other serotonergic drugs. Other interactions can lead to increased side effects like drowsiness or accidental overdose. Always consult with a pharmacist or doctor before taking dextromethorphan, especially if you are on other medications or supplements, to ensure it is safe for you. Checking labels and avoiding combination products that contain the same active ingredients are simple steps that can prevent a serious medical event.

For more detailed information on dextromethorphan, consult the MedlinePlus drug information page.

Frequently Asked Questions

Serotonin syndrome is a potentially life-threatening drug reaction caused by an excess of serotonin in the brain. Symptoms can range from mild (agitation, rapid heart rate) to severe (seizures, coma) and require immediate medical attention.

MAOIs are a class of powerful antidepressants. Combining them with dextromethorphan is dangerous because both substances increase serotonin levels in the brain. The combined effect can lead to a severe and potentially fatal form of serotonin syndrome.

Combining dextromethorphan with an SSRI (like Prozac or Zoloft) is not recommended due to the increased risk of serotonin syndrome. You should consult your doctor or pharmacist for a safe alternative or to discuss your specific medication regimen.

Yes, aside from serotonin syndrome, combining dextromethorphan with other CNS depressants like alcohol or opioids can heighten sedative effects, increasing drowsiness, dizziness, and the risk of respiratory depression.

No, you should avoid drinking alcohol while taking dextromethorphan. The combination can increase the sedative effects of both substances and significantly raise your risk of dizziness, impaired coordination, and overdose.

Always check the active ingredients of any multi-symptom cold or flu product you purchase. If you are already taking a cough medicine containing dextromethorphan (often labeled as DM), do not take a second product that also contains it.

If you experience symptoms of serotonin syndrome (agitation, confusion, high fever, shivering) or overdose (severe drowsiness, seizures), seek emergency medical attention immediately. It is crucial to inform healthcare providers about all medications and supplements you have taken.