Venetoclax with Posaconazole Interaction Details
Brand Names Associated with Venetoclax
- Venclexta®
- Venetoclax
Brand Names Associated with Posaconazole
- Noxafil PowderMix®
- Noxafil®
- Posaconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased venetoclax exposure
Interaction Summary
Venetoclax is a sensitive CYP3A substrate, and coadministration with posaconazole, a strong CYP3A inhibitor, during drug interaction studies resulted in significantly increased venetoclax exposure. Concomitant use of venetoclax with posaconazole is contraindicated at venetoclax initiation and during ramp-up phase when treating chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL). For patients who have completed the CLL/SLL ramp-up phase, are on a steady venetoclax dosage, and require concomitant posaconazole, reduce venetoclax to 70 mg daily. For patients with acute myeloid leukemia, coadministration with posaconazole requires venetoclax dosage reduction during initiation and ramp-up to 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, and after ramp-up phase, give venetoclax 70 mg daily thereafter. In all patients, 2 to 3 days after discontinuation of concurrent posaconazole, resume the venetoclax dosage that was used prior.
Severity
Contraindicated
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant use of posaconazole with venetoclax is contraindicated at initiation and during ramp-up phase when treating chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL). For patients who have completed the CLL/SLL ramp-up phase, are on a steady venetoclax dosage, and require a concomitant posaconazole, reduce venetoclax to 70 mg daily. For patients with acute myeloid leukemia, coadministration with posaconazole requires venetoclax dosage reduction during initiation and ramp-up to 10 mg on day 1, 20 mg on day 2, 50 mg on day 4, and after ramp-up phase give venetoclax 70 mg daily thereafter. In all patients, 2 to 3 days after discontinuation of concurrent posaconazole, resume the venetoclax dosage that was used prior.
Mechanism Of Interaction
Inhibition of CYP3A-mediated venetoclax metabolism by posaconazole
Literature Reports
A) In a drug interaction study, coadministration of venetoclax 50 mg or 100 mg daily with posaconazole (strong CYP3A and P-gp inhibitor) 300 mg once daily for 7 days increased venetoclax Cmax by 61% and 86% and venetoclax AUC(24) increased by 90% and 144%, respectively, compared with venetoclax 400 administered alone .
Venetoclax Overview
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Venetoclax is used alone or in combination with obinutuzumab (Gazyva) or rituximab (Rituxan) to treat certain types of chronic lymphocytic leukemia (CLL; a type of cancer that begins in the white blood cells) or certain types of small lymphocytic lymphoma (SLL; a type of cancer that begins mostly in the lymph nodes). It is also used in combination with either azacitidine (Vidaza), decitabine (Dacogen), or cytarabine as a first treatment for acute myeloid leukemia (AML; a type of cancer that begins in the white blood cells) in people 75 years of age or older, or in adults who have medical conditions that prevents them from being treated with other chemotherapy medications. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It works by blocking the action of a certain protein in the body that helps cancer cells survive. This helps to kill cancer cells.
Posaconazole Overview
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Posaconazole is used to prevent serious fungal infections that can spread throughout the body in adults and children 2 years of age and older with a weakened ability to fight infection. Posaconazole delayed-release tablets are used to treat invasive aspergillosis (a serious fungal infection that begins in the lungs and spreads through the bloodstream to other organs) in adults and teenagers 13 years of age and older. Posaconazole oral suspension is also used to treat yeast infections of the mouth and throat including yeast infections in adults and teenagers 13 years of age and older that could not be treated successfully with other medications. Posaconazole is in a class of medications called azole antifungals. It works by slowing the growth of fungi that cause infection.
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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.