Alprazolam with Primidone Interaction Details

Brand Names Associated with Alprazolam

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

Brand Names Associated with Primidone

  • Desoxyphenobarbital
  • Mysoline®
  • Primaclone
  • Primidone

Medical Content Editor
Last updated Feb 27, 2024

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Interaction Effect

An increased risk of CNS and respiratory depression

Interaction Summary

When used in combination, these drugs may have additive CNS and respiratory depressant effects[1][2][3][4][5].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

When used in combination, these drugs may have additive CNS and respiratory depressant effects[1][2][3][4][5].

Mechanism Of Interaction

Additive CNS depression

Literature Reports

A) It has been noted in several studies that combinations of clonazepam and primidone or phenobarbital tend to produce more severe side effects (drowsiness, irritability, hyperactivity), while clonazepam in combination with hydantoins or carbamazepine are better tolerated [1][2][3][4][5].

B) Concomitant administration of intravenous midazolam and thiopental resulted in synergistic (supraadditive) effects during induction of anesthesia [6]. The combination of intravenous thiopental and midazolam had 1.8 times the expected potency of the individual drugs, and the dose of thiopental required to produce anesthesia was reduced by 50% in another study [7]. A 15% reduction in the thiopental induction dose requirement has been observed if it follows intramuscular premedication with midazolam [8]. The interaction between midazolam and thiopental may in part be dependent on thiopental dosing [9].

References

    1 ) Birket-Smith E & Mikkelsen B: Preliminary observations on the effect of a new benzodiazepine (RO-5-4023) in epilepsy. Acta Neurol Scand 1972; 48(suppl):385-395.

    2 ) Aarli J: Effect of clonazepam (RO5-4023) on epileptic seizures. Acta Neurol Scand 1973; 49(suppl 53):11.

    3 ) Mikkelsen B & Birket-Smith E: A clinical study of the benzodiazepine RO5-4023 (clonazepam) in the treatment of epilepsy. Acta Neurol Scand 1973; 49(suppl 53):91-96.

    4 ) Munthe-Kaas A: Clonazepam in the treatment of epileptic seizures. Acta Neurol Scand 1973; 49(suppl 53):97.

    5 ) Hooshmond H: Trial of a new anticonvulsant for uncontrollable minor motor seizures. Epilepsia 1971; 12:277.

    6 ) Tverskoy M, Fleyshman G, Bradley EL, et al: Midazolam-thiopental anesthetic interaction in patients. Anesth Analg 1988; 67:342-345.

    7 ) Short TG, Galletly DC, & Plummer JL: Hypnotic and anaesthetic action of thiopentone and midazolam alone and in combination. Br J Anaesth 1991; 66:13-19.

    8 ) Product Information: Versed(R), midazolam. Roche Laboratories Inc., Nutley, NJ, 2000.

    9 ) Wilder-Smith OHG, Ravussin PA, Decosterd LA, et al: Hypnotic and anaesthetic action of thiopentone and midazolam alone and in combination. Br J Anaesth 1999; 83:590-595.

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

Primidone Overview

  • Primidone is used alone or with other medications to control certain types of seizures. Primidone is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.

See More information Regarding Primidone

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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.