Sildenafil with Bosentan Interaction Details
Brand Names Associated with Sildenafil
- Revatio®
- Sildenafil
- Viagra®
Brand Names Associated with Bosentan
- Bosentan
- Tracleer®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
Increased bosentan exposure and reduced sildenafil exposure
Interaction Summary
Concomitant administration of bosentan with sildenafil decreases sildenafil exposure. Dose up-titration of sildenafil may be needed when initiating treatment with bosentan. Reduce the dose of sildenafil to 20 mg three times a day when discontinuing treatment with bosentan. In a pharmacokinetic study, coadministration of bosentan and sildenafil increased bosentan plasma concentrations and decreased sildenafil plasma concentrations. No dosage adjustments to either drug are necessary when sildenafil is used for treating either pulmonary arterial hypertension or erectile dysfunction . Sildenafil 80 mg 3 times a day with bosentan 125 mg twice a day resulted in a 49.8% increase in bosentan AUC, a 42% increase in bosentan Cmax and a 62.6% decrease in sildenafil AUC and 55.4% decrease in sildenafil Cmax .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant administration of bosentan (a CYP3A4 inducer) with sildenafil (a CYP3A4 substrate) decreases sildenafil exposure. Dose up-titration of sildenafil may be needed when initiating treatment with bosentan. Reduce the dose of sildenafil to 20 mg three times a day when discontinuing treatment with bosentan. In a pharmacokinetic study, coadministration of bosentan and sildenafil increased bosentan plasma concentrations and decreased sildenafil plasma concentrations. No dosage adjustments to either drug are necessary when sildenafil is used for treating either pulmonary arterial hypertension or erectile dysfunction .
Mechanism Of Interaction
Alteration of CYP3A4-mediated metabolism of bosentan and induction of CYP3A-mediated metabolism of sildenafil
Literature Reports
A) In normal volunteers, coadministration of multiple doses of 125 mg twice daily bosentan and 80 mg three times daily sildenafil resulted in a reduction of sildenafil plasma concentrations by 63% and increased bosentan plasma concentrations by 50%. The changes in plasma concentrations were not considered clinically relevant .
B) Population pharmacokinetic analysis of data from patients in clinical trials indicated approximately 3-fold the sildenafil clearance when it was coadministered with mild CYP3A inducers .
C) In a randomized, double-blind, parallel-group, placebo-controlled study in healthy males (n=55), concomitant use of bosentan and sildenafil led to increased bosentan AUC and Cmax and decreased sildenafil AUC and Cmax. Study participants were randomized to receive either sildenafil, bosentan, or combination of the two drugs. Dosing regimens were sildenafil three times daily on days 1 to 6 and 11 to 16 (20 mg initially and then 80 mg after 3 days) and bosentan 125 mg twice daily on days 7 to 17. On day 16, mean pharmacokinetic parameters revealed bosentan Cmax and AUC were 42% (90% confidence interval (CI) 15.4-74.8%) and 49.8% (90% CI 28.7-74.5%) higher with concomitant administration of sildenafil verses placebo, (Cmax, 1547 nanogram/mL vs 912 nanogram/mL), and (AUC, 6925 nanogram-hr/mL vs 4355 nanogram-hr/mL). On day 16, mean pharmacokinetic parameters revealed sildenafil Cmax, and AUC were 55.4% (90% CI 40.3-66.6%) and 62.6% (90% CI 56.8-67.7%) lower with concomitant administration of bosentan verses placebo, (Cmax, 275 nanogram/mL vs 585 nanogram/mL), and (AUC, 634 nanogram-hr/mL vs 1847 nanogram-hr/mL). No serious adverse events occurred, and greater than 96% of reported events were mild. The most common adverse event with combination treatment was headache (43 reports). Other commonly reported events with combination treatment were nasal congestion, backache, and myalgia .
Sildenafil Overview
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Sildenafil (Viagra) is used to treat erectile dysfunction (impotence; inability to get or keep an erection) in men. Sildenafil (Revatio) is used to improve the ability to exercise in adults and children 1 year of age and older with pulmonary arterial hypertension (PAH; high blood pressure in the vessels carrying blood to the lungs, causing shortness of breath, dizziness, and tiredness). Sildenafil is in a class of medications called phosphodiesterase (PDE) inhibitors. Sildenafil treats erectile dysfunction by increasing blood flow to the penis during sexual stimulation. This increased blood flow can cause an erection. Sildenafil treats PAH by relaxing the blood vessels in the lungs to allow blood to flow easily.
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If you are taking sildenafil to treat erectile dysfunction, you should know that it does not cure erectile dysfunction or increase sexual desire. Sildenafil does not prevent pregnancy or the spread of sexually transmitted diseases such as human immunodeficiency virus (HIV).
Bosentan Overview
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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:
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.