Alprazolam with Ritonavir Interaction Details

Brand Names Associated with Alprazolam

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

Brand Names Associated with Ritonavir

  • Norvir®
  • Ritonavir
  • RTV

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Last updated Feb 27, 2024

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Interaction Effect

Increased alprazolam exposure with short-term use

Interaction Summary

Interactions involving ritonavir (strong CYP3A4 inhibitor) and alprazolam (CYP3A4 substrate) are complex and time-dependent. Short-term administration of ritonavir increases alprazolam exposure. Following long-term treatment with ritonavir (greater than 10 to 14 days), CYP3A4 induction offsets CYP3A4 inhibition and alprazolam exposure is not meaningfully affected. When ritonavir and alprazolam are initiated concomitantly or when ritonavir is added to a stable alprazolam regimen, reduce the usual alprazolam dosage by 50%. After 10 to 14 days of concomitant use, increase alprazolam to target dose. No dosage adjustment of alprazolam is necessary in patients receiving ritonavir for more than 10 to 14 days. Concomitant use of alprazolam with other strong CYP3A4 inhibitors, excluding ritonavir, is contraindicated[1][2].

Severity

Major

Onset

Rapid

Evidence

Established

How To Manage Interaction

Interactions involving ritonavir (strong CYP3A4 inhibitor) and alprazolam (CYP3A4 substrate) are complex and time-dependent. Short-term administration of ritonavir increases alprazolam exposure. Following long-term treatment with ritonavir (greater than 10 to 14 days), CYP3A4 induction offsets CYP3A4 inhibition and alprazolam exposure is not meaningfully affected. When ritonavir and alprazolam are initiated concomitantly or when ritonavir is added to a stable alprazolam regimen, reduce the usual alprazolam dosage by 50%. After 10 to 14 days of concomitant use, increase alprazolam to target dose. No dosage adjustment of alprazolam is necessary in patients receiving ritonavir for more than 10 to 14 days. Concomitant use of alprazolam with other strong CYP3A4 inhibitors, excluding ritonavir, is contraindicated[1][2].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of alprazolam

Literature Reports

A) Interactions involving HIV protease inhibitors (eg, ritonavir) and alprazolam are complex and time dependent. Short-term low doses of ritonavir (4 doses of 200 mg) increased mean AUC of alprazolam by about 2.5-fold, and did not significantly affect Cmax of alprazolam. The elimination t(1/2) was prolonged (30 hours versus 13 hours). However, upon extended exposure to ritonavir (500 mg, twice daily for 10 days), CYP3A induction offset this inhibition. Alprazolam AUC and Cmax were reduced by 12% and 16%, respectively, in the presence of ritonavir. The elimination t(1/2) of alprazolam was not significantly changed [1][2].

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.

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

Ritonavir Overview

  • Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

See More information Regarding Ritonavir

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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.