What are the contraindications of dextromethorphan?

October 10, 2025 •

4 min read

In the United States, adults experience an average of two to three colds each year, often turning to over-the-counter (OTC) remedies [1.7.3]. A primary component in many of these is dextromethorphan, but it's crucial to understand: what are the contraindications of dextromethorphan?

Quick Summary

This article details the absolute and relative contraindications for the cough suppressant dextromethorphan. It covers dangerous drug interactions, particularly with MAOIs and SSRIs, risks for specific patient populations, and signs of toxicity.

Key Points

MAOI Interaction: Dextromethorphan is absolutely contraindicated with or within 14 days of using MAOI antidepressants due to a high risk of serotonin syndrome [1.3.3, 1.6.5].
Serotonin Syndrome Risk: Combining dextromethorphan with other serotonergic drugs like SSRIs, SNRIs, and tricyclic antidepressants can also trigger serotonin syndrome [1.6.4].
Respiratory Conditions: Use with caution in patients with asthma, emphysema, or a chronic cough with excessive phlegm [1.3.2, 1.3.3].
Liver Impairment: Patients with severe liver disease should be cautious, as the drug is metabolized by the liver and levels can increase, raising toxicity risk [1.9.1, 1.4.1].
CNS Depressant Effects: Dextromethorphan can amplify the sedative effects of alcohol, antihistamines, and other CNS depressants [1.2.4].
Pediatric Use: The safety and efficacy are not established for children under four; careful dosing is critical for older children [1.10.1, 1.9.2].
Abuse Potential: At high doses, dextromethorphan has dissociative effects and a potential for abuse, especially among adolescents [1.11.1, 1.11.4].

Understanding Dextromethorphan (DXM)

Dextromethorphan (DXM) is a synthetically produced drug that is chemically related to codeine and is one of the most widely used cough suppressants in the United States [1.11.3]. It acts on the cough center in the brain to elevate the threshold for coughing [1.8.4]. Found in more than 140 over-the-counter (OTC) cough and cold remedies, it is available in various forms, including liquids, capsules, lozenges, and tablets [1.11.3]. While generally safe at recommended therapeutic doses, DXM is not without significant risks and contraindications [1.9.2, 1.11.3]. It acts as a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor and is also a nonselective serotonin reuptake inhibitor, which is key to understanding its interaction profile [1.8.4, 1.8.1].

Absolute Contraindications

An absolute contraindication is a situation that makes a particular treatment or procedure absolutely inadvisable. For dextromethorphan, the most critical contraindication is its use with or within 14 days of taking monoamine oxidase inhibitors (MAOIs) [1.3.3, 1.6.5].

Monoamine Oxidase Inhibitors (MAOIs): This class of drugs is used to treat depression and includes medications like phenelzine (Nardil), isocarboxazid (Marplan), selegiline (Eldepryl, Emsam), and tranylcypromine (Parnate) [1.3.3]. Combining DXM with an MAOI significantly increases the risk of developing serotonin syndrome, a potentially life-threatening condition caused by excessive serotonergic activity in the nervous system [1.6.5, 1.8.2]. Symptoms can range from mild (agitation, sweating, restlessness) to severe (high fever, seizures, irregular heartbeat, unconsciousness) [1.9.4].
Known Hypersensitivity: Patients with a known allergy or hypersensitivity to dextromethorphan or any components in the formulation should not take the medication [1.3.1, 1.2.5]. Some products may contain ingredients like sulfites or aspartame, which can cause reactions in susceptible individuals, such as those with phenylketonuria (PKU) [1.3.3].

Relative Contraindications and Precautions

Relative contraindications mean that caution should be used when two drugs or procedures are used together. It is not strictly forbidden, but requires careful medical consideration.

Medical Conditions

Certain pre-existing medical conditions warrant caution:

Respiratory Conditions: Patients with conditions like asthma, emphysema, chronic bronchitis, or a cough that produces a large amount of mucus should consult a doctor before using dextromethorphan [1.3.2, 1.3.3]. The cough reflex is a protective mechanism, and suppressing it can be harmful in these cases.
Liver Disease: Dextromethorphan is extensively metabolized by the liver, primarily via the CYP2D6 enzyme [1.4.1, 1.8.4]. Patients with severe liver impairment may have higher blood levels of the drug, increasing the risk of side effects and toxicity [1.9.1, 1.4.1]. While some labels do not recommend specific dosage adjustments, caution is strongly advised [1.4.1, 1.4.2].
Debilitated Patients or Those with Limited Respiratory Reserve: These individuals should use DXM with caution as it can depress respiration.
History of Substance Abuse: Because DXM can produce euphoric and dissociative effects at high doses, it has a potential for abuse [1.11.1, 1.11.4]. Individuals with a history of drug abuse or dependence may be more likely to misuse it [1.9.1].

Significant Drug Interactions

Beyond MAOIs, DXM interacts with numerous other drugs, primarily those affecting serotonin levels or the CYP2D6 enzyme.

SSRIs and SNRIs: Taking dextromethorphan with selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac) and sertraline (Zoloft), or serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine (Effexor XR), can increase the risk of serotonin syndrome [1.2.4, 1.6.4, 1.6.5].
Tricyclic Antidepressants (TCAs): Medications like amitriptyline and imipramine can also lead to serotonin syndrome when combined with DXM [1.2.4, 1.6.5].
CYP2D6 Inhibitors: Drugs that inhibit the CYP2D6 enzyme—such as certain antidepressants (bupropion, fluoxetine, paroxetine), the heart medication quinidine, and antipsychotics—can slow the metabolism of DXM. This increases its concentration in the body and heightens the risk of side effects [1.8.4, 1.3.5]. The combination product Nuedexta, used for pseudobulbar affect, intentionally uses quinidine to inhibit DXM metabolism [1.8.4].
CNS Depressants: Dextromethorphan can enhance the effects of other central nervous system (CNS) depressants, including alcohol, antihistamines, sedatives, and prescription pain medication. This can lead to increased drowsiness, dizziness, and impaired coordination [1.2.4, 1.10.3].


Drug Class	Examples	Potential Interaction with Dextromethorphan
MAOIs	Phenelzine, Selegiline	High risk of life-threatening serotonin syndrome [1.6.5]. Do not use together.
SSRIs/SNRIs	Fluoxetine, Sertraline, Duloxetine	Increased risk of serotonin syndrome [1.6.4, 1.10.4].
Tricyclic Antidepressants	Amitriptyline, Nortriptyline	Increased risk of serotonin syndrome [1.2.4, 1.6.5].
CYP2D6 Inhibitors	Bupropion, Quinidine, Haloperidol	Increased DXM levels, raising risk of side effects and toxicity [1.8.4].
CNS Depressants	Alcohol, Benzodiazepines, Opioids	Additive effects leading to increased drowsiness, dizziness, and respiratory depression [1.2.4].

Special Populations

Pediatric Use: The safety and efficacy of dextromethorphan in children under four years old have not been well established [1.10.1]. Overdoses in children often result from accidental ingestion or medication errors [1.7.4]. Parents should always use the provided measuring device and follow age-specific dosing instructions carefully [1.9.2].
Pregnancy and Breastfeeding: Standard doses of dextromethorphan are generally considered acceptable during pregnancy, though research is limited [1.5.2, 1.5.1]. It is recommended to avoid alcohol-containing formulations [1.5.2]. Very low amounts of DXM are excreted in breast milk, and adverse effects on the infant are not expected, though products with high alcohol content should be avoided [1.5.5, 1.5.2]. It is always best to consult a healthcare provider before use during pregnancy or breastfeeding [1.5.3].

Conclusion

Dextromethorphan is an effective cough suppressant for many, but its use is restricted by a number of important contraindications. The absolute prohibition against its use with MAOIs is paramount due to the risk of severe serotonin syndrome [1.6.5]. Caution is also essential for individuals taking other serotonergic drugs like SSRIs and those with conditions such as severe liver disease or chronic respiratory illnesses [1.4.2, 1.3.3]. Understanding these contraindications and potential interactions is vital for the safe use of this common over-the-counter medication. Always consult a doctor or pharmacist to discuss your health history and current medications before taking dextromethorphan [1.3.3].

For more detailed information from a certified authority, you can visit the MedlinePlus page on Dextromethorphan.

Frequently Asked Questions

It depends on the type of antidepressant. You should NOT take dextromethorphan if you have taken a Monoamine Oxidase Inhibitor (MAOI) within the last 14 days due to the risk of life-threatening serotonin syndrome [1.3.3, 1.6.5]. If you take an SSRI or SNRI, you should consult your doctor as the combination can also increase the risk of serotonin syndrome [1.6.4].

No, you should avoid drinking alcohol while taking dextromethorphan. Alcohol is a CNS depressant, and combining it with dextromethorphan can increase side effects like drowsiness, dizziness, and impaired coordination [1.2.4, 1.10.3].

Symptoms of serotonin syndrome can include agitation, restlessness, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity or twitching, heavy sweating, and in severe cases, high fever, seizures, and loss of consciousness [1.9.4, 1.6.1].

You should talk to a doctor before using dextromethorphan for a productive cough (one with a lot of phlegm or mucus). Suppressing this type of cough may be harmful as the cough reflex helps clear the airways [1.3.3].

Caution is advised for patients with severe liver disease. Dextromethorphan is metabolized by the liver, and impaired function can lead to higher levels of the drug in your body, increasing the risk for side effects and toxicity [1.9.1, 1.4.1].

Dextromethorphan has a potential for abuse, particularly among teenagers, who may take large doses to experience euphoric or hallucinogenic effects, a practice known as 'robo-tripping' or 'skittling' [1.11.2, 1.11.3]. This can lead to overdose and serious side effects [1.11.4].

You should not treat yourself for a cough with dextromethorphan for more than one week without consulting a healthcare provider. If your cough persists, returns, or is accompanied by fever, rash, or a persistent headache, you should see your doctor [1.3.2, 1.9.2].