Sildenafil with Erythromycin Interaction Details

Brand Names Associated with Sildenafil

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 12, 2023

Interaction Effect

An increased risk of sildenafil adverse effects (hypotension, visual changes, priapism)

Interaction Summary

Sildenafil is metabolized by cytochrome P450 3A4 enzymes, and erythromycin is a known inhibitor of CYP3A4. The coadministration of erythromycin 500 mg twice daily for five days and a single oral dose of sildenafil 100 mg increased the area under the concentration-time curve (AUC) of sildenafil by 182%. Due to the significant increase in sildenafil plasma concentrations patients should be monitored for increased sildenafil adverse effects. For erectile dysfunction, a starting sildenafil dose of 25 mg should be considered in patients also receiving erythromycin.

Severity

Moderate

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Erythromycin may increase the bioavailability of sildenafil. Monitor for increased incidence of sildenafil adverse effects such as headache, flushing, visual disturbance, hypotension, and priapism. For erectile dysfunction, a starting sildenafil dose of 25 mg should be considered in patients also receiving erythromycin.

Mechanism Of Interaction

Inhibition of cytochrome P450 3A4-mediated sildenafil metabolism

Literature Reports

A) Erythromycin modifies the pharmacokinetics of sildenafil by inhibiting its cytochrome P450 3A4-mediated first pass metabolism. Twenty male subjects completed a placebo-controlled, parallel-group study that evaluated the effects of multiple doses of erythromycin on the pharmacokinetics, safety and tolerability of a single oral dose of sildenafil 100 mg. On day 1 all subjects received sildenafil 100 mg. Half of the patients received blinded erythromycin twice daily on days 2-6, and the other half had received placebo. Sildenafil 100 mg was administered on day 6 to all subjects. Administration of erythromycin significantly increased (P less than 0.0001) the AUC and Cmax of sildenafil by a factor of 2.83 and 1.37 respectively, compared with placebo. Erythromycin had no effect on sildenafil Tmax, elimination rate, or half-life. The increase in plasma concentrations of sildenafil was not associated with an increase in the incidence of adverse effects. The authors conclude that the extent of the interaction does not constitute a safety concern, however, clinicians prescribing sildenafil may consider a lower starting dose of sildenafil (25 mg) for patients receiving potent cytochrome P450 3A4 inhibitors, such as erythromycin concomitantly .

Sildenafil Overview

• 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.

• 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).

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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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.