Alprazolam with Pregabalin Interaction Details


Brand Names Associated with Alprazolam

  • Alprazolam
  • Niravam®
  • Xanax®
  • Xanax® XR

Brand Names Associated with Pregabalin

  • Lyrica CR®
  • Lyrica®
  • Pregabalin

Medical Content Editor
Last updated Feb 27, 2024


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Interaction Effect

Respiratory depression


Interaction Summary

Concomitant use of pregabalin and CNS depressants has resulted in respiratory depression with an increased risk in patients with conditions that reduce lung function (eg, COPD) and in the elderly. Initiate pregabalin at lowest dose and monitor for symptoms of respiratory depression and sedation[1].


Severity

Major


Onset

Unspecified


Evidence

Theoretical


How To Manage Interaction

Concomitant use of pregabalin and CNS depressants has resulted in respiratory depression with an increased risk in patients with conditions that reduce lung function (eg, COPD) and in the elderly. Initiate pregabalin at lowest dose and monitor for symptoms of respiratory depression and sedation[1].


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 CO2 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 [1].

B) Increased somnolence or sedation, dizziness, and nausea occurred per visual analog scale measurement when a single gabapentin enacarbil 600 mg dose (another gabapentinoid) 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 [2].

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 (another gabapentinoid). The mean gabapentin AUC value in these patients was 44% greater compared with administration of gabapentin alone. The pharmacokinetics of morphine were not altered [3][4].

References

    1 ) US Food and Drug Administration (FDA): Drug Safety Communications: FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) when used with CNS depressants or in patients with lung problems. US Food and Drug Administration (FDA). Silver Spring, MD. 2019. Available from URL: https://www.fda.g... . As accessed 2019-12-19.

    2 ) Product Information: HORIZANT(R) oral extended-release tablets, gabapentin enacarbil oral extended-release tablets. GlaxoSmithKline (per FDA), Research Triangle Park, NC, 2013.

    3 ) Product Information: Neurontin(R) oral capsules, tablets, solution, gabapentin oral capsules, tablets, solution. Parke-Davis, New York, NY, 2010.

    4 ) Product Information: GRALISE(R) oral tablets, gabapentin oral tablets. Abbott Laboratories, North Chicago, IL, 2011.

Alprazolam Overview

  • Alprazolam is used to treat anxiety disorders and panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks). Alprazolam is in a class of medications called benzodiazepines. It works by decreasing abnormal excitement in the brain.

See More information Regarding Alprazolam

Pregabalin Overview

  • Pregabalin capsules, oral solution (liquid), and extended-release (long-acting) tablets are used to relieve neuropathic pain (pain from damaged nerves) that can occur in your arms, hands, fingers, legs, feet, or toes if you have diabetes and postherpetic neuralgia (PHN; the burning, stabbing pain or aches that may last for months or years after an attack of shingles). Pregabalin capsules and oral solution are also used to relieve neuropathic pain that can occur after a spinal cord injury and to treat fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep). Pregabalin capsules and oral solution are used along with other medications to treat certain types of seizures in adults and children 1 month of age and older. Pregabalin is in a class of medications called anticonvulsants. It works by decreasing the number of pain signals that are sent out by damaged nerves in the body.

See More information Regarding Pregabalin

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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:

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.