Diphenhydramine with Gabapentin Interaction Details

Brand Names Associated with Diphenhydramine

Brand Names Associated with Gabapentin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 24, 2023

Interaction Effect

Respiratory depression

Interaction Summary

Concomitant use of gabapentin and other CNS depressants has resulted in serious, life-threatening, or fatal respiratory depression. If gabapentin is coadministered with another CNS depressant, especially with an opioid and in patients with underlying respiratory impairment, monitor for symptoms of respiratory depression and sedation, and consider initiating gabapentin at a low dose. Manage respiratory depression with close observation, supportive measures, and reduction or withdrawal of CNS depressants (including gabapentin).

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of gabapentin and other CNS depressants has resulted in serious, life-threatening, or fatal respiratory depression. If gabapentin is coadministered with another CNS depressant, especially with an opioid and in patients with underlying respiratory impairment, monitor for symptoms of respiratory depression and sedation, and consider initiating gabapentin at a low dose. Manage respiratory depression with close observation, supportive measures, and reduction or withdrawal of CNS depressants (including gabapentin).

Mechanism Of Interaction

Additive CNS depression

Literature Reports

A) According to the FDA Adverse Event Reporting System (FAERS) database, between January 1, 2012 and October 26, 2017, 49 cases of respiratory depression occurred with gabapentinoids (gabapentin n=15; pregabalin n=34). A respiratory risk factor, including age-related loss of lung function or the use of a CNS depressant, was reported in 92% of cases. Twelve deaths occurred (24%) and all deaths reported at least 1 respiratory risk factor. Small, randomized trials of healthy volunteers have demonstrated that gabapentinoids alone and in combination with opioids depress respiratory function. End-tidal CO(2) increased with additive effect with exposure to pregabalin plus remifentanil, and hourly apneic episodes were more frequent during gabapentin exposure than placebo exposure. Observational studies suggest an increased risk of postoperative respiratory depression with the use of preoperative gabapentinoids compared with no preoperative gabapentinoid exposure .

B) Increased somnolence or sedation, dizziness, and nausea occurred per visual analog scale measurement when a single gabapentin enacarbil 600 mg dose was given 2 hours after a single 60 mg dose of morphine sulfate extended-release was administered to 18 subjects compared to the agents alone. No changes in Cmax or AUC of gabapentin, morphine, or morphine's active metabolite occurred .

C) In a study of 12 volunteers, a single oral dose of 60 mg controlled-release morphine was administered 2 hours prior to a single oral dose of 600 mg immediate-release gabapentin. The mean gabapentin AUC value in these patients was 44% greater compared with administration of gabapentin alone. The pharmacokinetics of morphine were not altered .

Diphenhydramine Overview

• Diphenhydramine is used to relieve red, irritated, itchy, watery eyes; sneezing; and runny nose caused by hay fever, allergies, or the common cold. Diphenhydramine is also used to relieve cough caused by minor throat or airway irritation. Diphenhydramine is also used to prevent and treat motion sickness, and to treat insomnia (difficulty falling asleep or staying asleep). Diphenhydramine is also used to control abnormal movements in people who have early stage parkinsonian syndrome (a disorder of the nervous system that causes difficulties with movement, muscle control, and balance) or who are experiencing movement problems as a side effect of a medication.

• Diphenhydramine will relieve the symptoms of these conditions but will not treat the cause of the symptoms or speed recovery. Diphenhydramine should not be used to cause sleepiness in children. Diphenhydramine is in a class of medications called antihistamines. It works by blocking the action of histamine, a substance in the body that causes allergic symptoms.

Gabapentin Overview

• Gabapentin capsules, tablets, and oral solution are used along with other medications to help control certain types of seizures in people who have epilepsy. Gabapentin capsules, tablets, and oral solution are also used to relieve the pain of postherpetic neuralgia (PHN; the burning, stabbing pain or aches that may last for months or years after an attack of shingles). Gabapentin extended-release tablets (Horizant) are used to treat restless legs syndrome (RLS; a condition that causes discomfort in the legs and a strong urge to move the legs, especially at night and when sitting or lying down). Gabapentin is in a class of medications called anticonvulsants. Gabapentin treats seizures by decreasing abnormal excitement in the brain. Gabapentin relieves the pain of PHN by changing the way the body senses pain. It is not known exactly how gabapentin works to treat restless legs syndrome.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.