Sildenafil with Ritonavir Interaction Details
Brand Names Associated with Sildenafil
- Revatio®
- Sildenafil
- Viagra®
Brand Names Associated with Ritonavir
- Norvir®
- Ritonavir
- RTV
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
An increased risk of sildenafil adverse effects (hypotension, syncope, visual changes, priapism)
Interaction Summary
Sildenafil is metabolized by CYP3A4 enzymes, and ritonavir is a known potent inhibitor of CYP3A4. A case report described fatal cardiovascular events following coadministration of sildenafil (for erectile dysfunction) and saquinavir/ritonavir in a 47-year-old male. Pharmacokinetic study revealed significant increases in sildenafil exposure and plasma concentrations following coadministration with ritonavir in healthy volunteers . Due to lack of a safe and effective dose recommendation, concurrent use of sildenafil (as Revatio(R)) and ritonavir is contraindicated in patients being treated for pulmonary arterial hypertension. For erectile dysfunction (ED), a maximum dose of sildenafil 25 mg every 48 hours should not be exceeded in patients also receiving ritonavir. Due to the significant increase in sildenafil plasma concentrations, ED patients should be monitored for an increase in sildenafil adverse effects .
Severity
Contraindicated
Onset
Rapid
Evidence
Established
How To Manage Interaction
Ritonavir may increase the bioavailability of sildenafil. Due to lack of a safe and effective dose recommendation, concurrent use of sildenafil (as Revatio(R)) and ritonavir is contraindicated in patients treated for pulmonary arterial hypertension (PAH). When prescribed for erectile dysfunction, a maximum sildenafil dose of 25 mg every 48 hours should not be exceeded in patients also receiving ritonavir . Monitor for increased incidence of sildenafil adverse effects, such as headache, flushing, visual disturbance, hypotension, syncope, and priapism.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated sildenafil metabolism
Literature Reports
A) A 47-year-old male receiving ritonavir 400 mg twice daily and saquinavir 400 mg twice daily was prescribed sildenafil 25 mg for erectile dysfunction. He had taken a dose of sildenafil eight times without adverse effects. One hour after taking sildenafil 25 mg, he experienced chest pain and an electrocardiogram showed an extensive anterolateral myocardial infarction. There was no history of hypertension, diabetes mellitus, ischemic heart disease, or nitrate use. He was treated with recombinant tissue plasminogen activator but became hypotensive 24 hours later, with signs of pulmonary edema. Inotropic support, diuretic therapy, and ventilatory support provided a brief improvement, but he again became hypotensive and hypoxemic. Cardiac arrest and death soon followed. The combination of sildenafil and protease inhibitor therapy may have precipitated the cardiovascular events .
B) An eight day, open, placebo-controlled study involving 28 volunteers investigated the effect of ritonavir on the pharmacokinetic properties and tolerability of sildenafil and also investigated the effect of sildenafil on the steady-state pharmacokinetics of ritonavir. Multiple dosing with ritonavir produced significant increases in sildenafil AUC and Cmax values (p less than 0.0001 for both). A significantly delayed Tmax (p equal to 0.0018) relative to placebo was also observed. The results indicated an 11-fold (95% CI, 9 to 12) increase in AUC and a 3.9-fold (95% CI, 3.2 to 4.9) increase in Cmax, while Tmax was delayed by 3.1 hr (95% CI, 1.3 to 4.9 hr) .
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).
Ritonavir Overview
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Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.
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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.