Venetoclax with Conivaptan Interaction Details
Brand Names Associated with Venetoclax
- Venclexta®
- Venetoclax
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 strong CYP3A inhibitors (eg, ritonavir, ketoconazole) during drug interaction studies significantly increased venetoclax exposure. Conivaptan is a strong CYP3A inhibitor and use with CYP3A substrates (eg, midazolam, simvastatin, amlodipine) resulted in increased substrate AUC . Concurrent conivaptan with venetoclax is contraindicated at venetoclax initiation and during ramp-up phase when treating CLL/SLL . A CYP3A substrate may be initiated no sooner than 1 week after completion of conivaptan therapy . For patients who have completed CLL/SLL ramp-up phase, are on a steady venetoclax dosage, and require concurrent use, reduce venetoclax to 100 mg daily. For patients with AML, coadministration with a strong CYP3A inhibitor requires venetoclax reduction during initiation and ramp-up to 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, and after the ramp-up phase give venetoclax 100 mg daily thereafter. In all patients, 2 to 3 days after discontinuation of a concurrent inhibitor, resume venetoclax dosage that was used prior .
Severity
Contraindicated
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of conivaptan (strong CYP3A inhibitor) with venetoclax (sensitive CYP3A substrate) is contraindicated at venetoclax initiation and during the ramp-up phase when treating chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL). A CYP3A substrate may be initiated no sooner than 1 week after completion of conivaptan therapy . For patients who have completed the CLL/SLL ramp-up phase, are on a steady venetoclax dosage, and require concurrent conivaptan, reduce venetoclax to 100 mg daily. For patients with acute myeloid leukemia (AML), coadministration with a strong CYP3A inhibitor 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 the ramp-up phase give venetoclax 100 mg daily thereafter. In all patients, 2 to 3 days after discontinuation of a concurrent strong CYP3A inhibitor, resume the venetoclax dosage that was used prior to initiating the inhibitor .
Mechanism Of Interaction
Inhibition of CYP3A-mediated venetoclax metabolism by conivaptan
Literature Reports
A) In a drug interaction study of 11 patients with previously-treated non-Hodgkin lymphoma, coadministration of venetoclax with ketoconazole 400 mg once daily for 7 days increased venetoclax Cmax by 2.3-fold and AUC by 6.4-fold .
B) The strong CYP3A inhibitor conivaptan 40 mg/day IV increased the AUC of midazolam, a CYP3A substrate, by approximately 100% with a 1-mg IV dose and by 200% with a 2-mg oral dose .
C) Conivaptan 30 mg/day IV tripled the AUC of simvastatin, a CYP3A substrate .
D) Conivaptan 40 mg orally twice daily doubled the AUC and half-life of amlodipine, a CYP3A substrate .
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.
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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.