Alprazolam with Ivacaftor Interaction Details

Brand Names Associated with Alprazolam

Brand Names Associated with Ivacaftor

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 27, 2024

Interaction Effect

Increased ALPRAZolam exposure

Interaction Summary

Concomitant use of ALPRAZolam (CYP3A4 substrate) with a moderate or weak CYP3A inhibitor should be avoided as it may increase the concentration of ALPRAZolam and increase the risk of adverse reactions. If concomitant use is necessary, consider appropriate dose reduction of ALPRAZolam. In pharmacokinetic analyses, coadministration of ALPRAZolam with moderate or weak CYP3A inhibitors resulted in increased AUC, Cmax, and t(1/2)[1][2] and reduced clearance [1][2][3][4].

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Concomitant use of ALPRAZolam (CYP3A4 substrate) with a moderate or weak CYP3A inhibitor should be avoided as it may increase the concentration of ALPRAZolam and increase the risk of adverse reactions. If concomitant use is necessary, consider appropriate dose reduction of ALPRAZolam[1][2].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of ALPRAZolam

Literature Reports

A) In in-vivo drug interactions studies, concomitant use of ALPRAZolam with weak or moderate CYP3A4 inhibitors increased ALPRAZolam AUC as follows: fluvoxaMINE by 1.96-fold and erythromycin by 1.61-fold [1][2].

B) Coadministration of cimetidine (CYP3A inhibitor) with ALPRAZolam increased ALPRAZolam Cmax by 82% and t(1/2) by 16% and decreased clearance by 42% [1][2].

C) The influence of cimetidine on ALPRAZolam pharmacokinetics was evaluated in healthy subjects who ingested 1 mg ALPRAZolam with and without concurrent cimetidine 300 mg every 6 hours. The clearance of ALPRAZolam was significantly reduced from 1.66 mL/min/kg to 1.05 mL/min/kg [3]. In a separate pharmacokinetic analysis, the clearance of ALPRAZolam was markedly reduced with concurrent cimetidine administration [4].

D) When fluvoxaMINE maleate (100 mg once a day) and ALPRAZolam (1 mg four times a day) were coadministered to steady state, plasma concentrations and other pharmacokinetic parameters (AUC, Cmax, t1/2) of ALPRAZolam were approximately twice those observed when ALPRAZolam was administered alone; oral clearance was reduced by about 50%. This interaction, may be more pronounced if a 300 mg daily dose is coadministered, particularly since fluvoxaMINE exhibits non-linear pharmacokinetics over the dosage range 100-300 mg [5].

References

1 ) Product Information: XANAX(R) oral tablets, alprazolam oral tablets. Pharmacia & Upjohn Co (per FDA), New York, NY, 2021.

2 ) Product Information: Xanax(R) XR oral extended-release tablets, alprazolam oral extended-release tablets. Pharmacia & Upjohn Co (per FDA), New York, NY, 2021.

3 ) Abernethy DR, Greenblatt DJ, Divoll M, et al: Interaction of cimetidine with the triazolobenzodiazepines alprazolam and triazolam. Psychopharmacology 1983; 80:275-278.

4 ) Pourbaix S, Desager JP, Hulhoven R, et al: Pharmacokinetic consequences of long term coadministration of cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects. Int J Clin Pharmacol Ther Toxicol 1985; 23:447-451.

5 ) Product Information: Fluvoxamine maleate oral tablets, fluvoxamine maleate oral tablets. ANI Pharmaceuticals Inc (per FDA), Baudette, MN, 2023.

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.

Ivacaftor Overview

• Ivacaftor is used to treat certain types of cystic fibrosis (an inborn disease that causes problems with breathing, digestion, and reproduction) in adults and children 4 months of age and older. Ivacaftor should be used only in people with a certain genetic make-up. Your doctor may order a blood test to help decide if this medication is right for you. Ivacaftor is in a class of medications called cystic fibrosis transmembrane conductance regulator (CFTR) potentiators. It works by improving the function of a protein in the body to decrease the build-up of thick mucus in the lungs and improving other symptoms of cystic fibrosis.

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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.