What should you not combine with gabapentin? A guide to drug interactions

October 9, 2025 •

4 min read

In 2019, the FDA required new warnings on gabapentinoids about the risk of severe respiratory distress, especially when combined with other central nervous system depressants. Understanding what you should not combine with gabapentin is crucial for patient safety and to ensure the medication works as intended, reducing the risk of severe side effects.

Quick Summary

This article details the critical interactions to avoid when taking gabapentin. Learn about the dangers of combining it with central nervous system depressants like opioids and alcohol, how antacids can reduce its effectiveness, and risks associated with certain supplements.

Key Points

Avoid CNS Depressants: Never combine gabapentin with opioids, alcohol, or benzodiazepines, as this can lead to severe respiratory depression and potentially fatal consequences.
Time Antacids Correctly: Separate aluminum or magnesium-containing antacids from gabapentin by at least two hours to ensure the medication is properly absorbed.
Check OTC Ingredients: Be cautious with over-the-counter cold and allergy medications, as sedating antihistamines like Benadryl can worsen gabapentin's sedative effects.
Disclose all Supplements: Inform your doctor about all herbal and dietary supplements you take, particularly ginkgo biloba, which can interfere with gabapentin's anticonvulsant properties.
Watch for Breathing Problems: Patients, especially older adults or those with respiratory issues, should be closely monitored for slowed or shallow breathing when combining gabapentin with other CNS depressants.
Do Not Stop Abruptly: Never stop taking gabapentin suddenly without a doctor's guidance, as this can cause withdrawal symptoms or increase the risk of seizures.
Prioritize Medical Guidance: Always consult your healthcare provider or pharmacist about any medication changes, including OTC products, to avoid harmful interactions.

Dangerous Interactions: Central Nervous System (CNS) Depressants

Gabapentin is a CNS depressant, meaning it slows down brain function. Combining it with other CNS depressants can have a compounding, or synergistic, effect that significantly increases the risk of severe drowsiness, dizziness, and life-threatening respiratory depression. In 2019, the FDA issued a warning about the risk of serious breathing problems when combining gabapentin with other CNS depressants. This risk is heightened for older adults and individuals with pre-existing lung conditions like COPD.

Opioids

Combining gabapentin with opioids is a particularly dangerous interaction. Studies have shown that a high percentage of fatal overdoses involving gabapentin also involved opioids. Both drugs individually cause respiratory depression and sedation, and when combined, these effects are dramatically amplified. Taking this combination substantially increases the risk of overdose, coma, and death. If you are prescribed both, it is crucial to use them only under strict medical supervision and to be aware of symptoms like extreme sleepiness or slowed breathing.

Alcohol

Alcohol also acts as a powerful CNS depressant. When mixed with gabapentin, it can worsen side effects like dizziness, drowsiness, and impaired coordination. This combination can severely impair judgment and motor skills, increasing the risk of accidents and falls. Avoiding or limiting alcohol consumption is essential while on gabapentin to prevent these amplified effects. In high doses, the combination can lead to severe respiratory depression and overdose.

Benzodiazepines and Other Sedatives

Other prescription medications, including benzodiazepines (e.g., alprazolam, lorazepam) and other sedatives or sleep aids (e.g., zolpidem), can also cause severe drowsiness and impaired coordination when combined with gabapentin. Muscle relaxants like cyclobenzaprine can also contribute to this excessive sedation. If co-prescribed, a healthcare provider may need to adjust doses to minimize risk.

Common OTC and Supplement Interactions

Certain over-the-counter (OTC) products and dietary supplements can also interact with gabapentin, either by reducing its effectiveness or increasing side effects.

Antacids and Mineral Supplements

Antacids containing aluminum or magnesium hydroxide (e.g., Maalox, Mylanta) can significantly reduce the absorption of gabapentin in the body, making it less effective. To prevent this, it is recommended to take gabapentin at least two hours after taking these antacids. This timing is also advised for magnesium supplements.

Certain Herbal Supplements

While gabapentin has a relatively low interaction profile with many supplements, certain ones should be avoided. For instance, high amounts of ginkgo biloba may increase the risk of seizures and reduce the anticonvulsant effects of gabapentin. Other herbal remedies and supplements that cause drowsiness could worsen gabapentin's sedative side effects. It is important to disclose all supplement use to your healthcare provider.

Other OTC Medications

Certain OTC cold, cough, and allergy products containing sedating antihistamines, such as diphenhydramine (Benadryl), can increase the sedative effects of gabapentin. Opting for non-drowsy alternatives is often recommended.

Other Medications to Watch For

Other Anticonvulsants: While gabapentin is often prescribed alongside other anti-seizure medications, combining it with pregabalin (Lyrica) is generally not recommended due to duplication of therapy. Phenytoin concentration may also be affected.
Mefloquine (Antimalarial): This drug can increase the risk of seizures and may need to be avoided or managed with caution in people on gabapentin.
Cimetidine (Stomach Acid Reducer): Cimetidine can increase the concentration of gabapentin in the blood.
NSAIDs (e.g., Naproxen): Some NSAIDs have been noted to interact with gabapentin, and caution should be exercised.
Excessive Caffeine: Animal studies suggest excessive caffeine intake might reduce the anticonvulsant effects of gabapentin, though this is less of a concern with normal use.

Comparison of Gabapentin Interactions


Substance Category	Key Examples	Primary Risk	Action to Take
CNS Depressants	Alcohol, Opioids (morphine), Benzodiazepines (alprazolam)	Severe sedation, respiratory depression, overdose, and death	Avoid completely or use only under strict medical supervision
Antacids with Aluminum/Magnesium	Maalox, Mylanta, Magnesium Supplements	Reduced gabapentin absorption and effectiveness	Separate doses by at least two hours
Sedating Antihistamines	Diphenhydramine (Benadryl)	Increased drowsiness and dizziness	Use non-sedating alternative or exercise caution
Herbal Supplements	Ginkgo biloba, drowsiness-causing herbs	Reduced anticonvulsant effects, increased sedation	Discuss with a healthcare provider before use

Conclusion

While gabapentin is a widely used and effective medication for conditions like nerve pain and seizures, it is crucial to be aware of and avoid dangerous drug interactions. Combinations with CNS depressants like opioids, alcohol, and benzodiazepines carry a significant and potentially life-threatening risk of respiratory depression and excessive sedation. Other common interactions, such as with antacids, can diminish gabapentin's effectiveness and should be managed with proper timing. Always provide your healthcare provider with a complete list of all medications, including OTC drugs and supplements. Never stop taking gabapentin abruptly without consulting a doctor, as this can lead to serious withdrawal effects or increased seizure risk. Adhering to these safety precautions can help you manage your condition effectively and safely.

Important Disclaimer: The information provided is for educational purposes only and should not be considered a substitute for professional medical advice. Always consult your healthcare provider or pharmacist regarding medication interactions.

For more information on gabapentin safety and interactions, visit the U.S. Food and Drug Administration (FDA) website. [https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin]

Frequently Asked Questions

No, it is highly recommended to avoid alcohol while taking gabapentin. Both are central nervous system depressants, and combining them can cause severe drowsiness, dizziness, impaired coordination, and a life-threatening risk of respiratory depression.

Combining gabapentin with opioids dramatically increases the risk of severe respiratory depression, overdose, and death. Both medications slow down breathing, and this effect is compounded when taken together. This combination should only be used under strict medical supervision.

Yes, antacids containing aluminum or magnesium (e.g., Maalox, Mylanta) can decrease gabapentin's absorption and make it less effective. To prevent this, take your gabapentin dose at least two hours after taking the antacid.

You should inform your doctor of all supplements you take. Specifically, avoid ginkgo biloba, as it may reduce the anticonvulsant effects of gabapentin. Any supplement that causes drowsiness could also worsen gabapentin's sedative side effects.

Combining gabapentin with benzodiazepines can significantly increase sedation, dizziness, and the risk of respiratory depression. This combination should be approached with extreme caution and only under a doctor's guidance, as it can be dangerous.

Signs of a dangerous interaction, especially with CNS depressants, include extreme sleepiness, confusion, unusual dizziness, slowed or shallow breathing, and unresponsiveness. Seek immediate medical attention if these symptoms occur.

It is crucial because many different types of medications and supplements can interact with gabapentin and increase side effects or decrease its effectiveness. Disclosing everything allows your doctor to make informed decisions and prevent potentially dangerous combinations.