Diltiazem with Tolvaptan Interaction Details

Brand Names Associated with Diltiazem

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Increased tolvaptan exposure

Interaction Summary

Coadministration of tolvaptan, a CYP3A substrate, with fluconazole, a moderate CYP3A inhibitor, resulted in a 200% increase in tolvaptan AUC resulting in significant increase in adverse reactions associated with tolvaptan, particularly significant diuresis, dehydration, and acute renal failure. If tolvaptan and fluconazole are concomitantly administered, the tolvaptan dose should be reduced and the patient should be frequently monitored for any adverse reactions associated with tolvaptan . Avoid concomitant use of tolvaptan with moderate CYP3A inhibitors when tolvaptan is being used to treat hyponatremia . When tolvaptan is being used to slow the decline in kidney function in patients with autosomal dominant polycystic kidney disease, reduce dose of tolvaptan if used concomitantly with moderate CYP3A inhibitors. For patients taking tolvaptan 90 mg in the morning and 30 mg in the afternoon, reduce dose to 45 mg and 15 mg, respectively. For those taking 60 mg in the morning and 30 mg in the afternoon, reduce dose to 30 mg and 15 mg. For those taking 45 mg in the morning and 15 mg in the afternoon, reduce to 15 mg for both doses. If the initial dose reduction is not tolerated, consider reducing the dose further. If reduced doses are not available, consider temporary interruption of tolvaptan for short-term therapy with a moderate CYP3A inhibitor .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Avoid concomitant use of tolvaptan with moderate CYP3A inhibitors when tolvaptan is being used to treat hyponatremia resulting in significant increase in adverse reactions associated with tolvaptan, particularly significant diuresis, dehydration, and acute renal failure. If tolvaptan and fluconazole are concomitantly administered, the tolvaptan dose should be reduced and the patient should be frequently monitored for any adverse reactions associated with tolvaptan . When tolvaptan is being used to slow the decline in kidney function in patients with autosomal dominant polycystic kidney disease, reduce dose of tolvaptan if used concomitantly with moderate CYP3A inhibitors. For patients taking tolvaptan 90 mg in the morning and 30 mg in the afternoon, reduce dose to 45 mg and 15 mg, respectively. For those taking 60 mg in the morning and 30 mg in the afternoon, reduce dose to 30 mg and 15 mg. For those taking 45 mg in the morning and 15 mg in the afternoon, reduce to 15 mg for both doses. If the initial dose reduction is not tolerated, consider reducing the dose further. If reduced doses are not available, consider temporary interruption of tolvaptan for short-term therapy with a moderate CYP3A inhibitor .

Mechanism Of Interaction

Inhibition of CYP3A-mediated metabolism of tolvaptan

Literature Reports

A) Tolvaptan AUC and Cmax were increased by 200% and 80% when fluconazole 400 mg was given one day before tolvaptan followed by fluconazole 200 mg concomitantly with tolvaptan .

Diltiazem Overview

• Diltiazem is used to treat high blood pressure and to control angina (chest pain). Diltiazem is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart.

• High blood pressure is a common condition, and when not treated it can cause damage to the brain, heart, blood vessels, kidneys, and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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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.