Verapamil with Bosentan Interaction Details

Brand Names Associated with Verapamil

Brand Names Associated with Bosentan

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 03, 2023

Interaction Effect

Increased bosentan plasma concentrations

Interaction Summary

Bosentan is primarily metabolized in the liver by CYP2C9 and CYP3A4 enzymes. Although the interaction between bosentan and verapamil, a moderate CYP3A4 inhibitor, has not been studied, concomitant use of bosentan 125 mg twice daily and ketoconazole, a potent CYP3A4 inhibitor, resulted in a 2-fold increase in bosentan plasma concentrations in healthy volunteers. While no dose adjustment is necessary when bosentan and verapamil are used together, patients may need to be monitored for increased bosentan adverse effects (headache, hypotension, flushing, decreased hemoglobin). Additionally, CYP2C9 inhibitors, such as fluconazole and amiodarone, may also increase bosentan levels. Therefore, coadministration of combinations of CYP2C9 inhibitors and a CYP3A4 inhibitor, including verapamil, with bosentan is not recommended.

Severity

Moderate

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Monitor patients for increased bosentan adverse effects (headache, hypotension, flushing, decreased hemoglobin) when bosentan and verapamil, a moderate CYP3A4 inhibitor, are coadministered as increased bosentan plasma concentrations may occur. Concomitant use of bosentan and ketoconazole, a potent CYP3A4 inhibitor, resulted in a 2-fold increase in bosentan plasma concentrations. A dose adjustment is not necessary when verapamil and bosentan are coadministered. In addition, bosentan is also metabolized by CYP2C9 enzymes. Therefore, coadministration of verapamil and a CYP2C9 inhibitor, such as amiodarone or fluconazole, with bosentan is not recommended.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated bosentan metabolism by verapamil

Verapamil Overview

• Verapamil is used to treat high blood pressure and to control angina (chest pain). The immediate-release tablets are also used alone or with other medications to prevent and treat irregular heartbeats. Verapamil 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 and slows electrical activity in the heart to control the heart rate.

• High blood pressure is a common condition and when not treated, 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.

Bosentan Overview

• Bosentan is used to treat pulmonary arterial hypertension (PAH, high blood pressure in the vessels that carry blood to the lungs) in adults and children 3 years of age and older. Bosentan may improve the ability to exercise and slow the worsening of symptoms in patients with PAH. Bosentan is in a class of medications called endothelin receptor antagonists. It works by stopping the action of endothelin, a natural substance that causes blood vessels to narrow and prevents normal blood flow in people who have PAH.

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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.