Comparison of PDE-5 Inhibitors

Phosphodiesterase-5 inhibitors, or PDE-5 inhibitors, are often the first-line therapy for erectile dysfunction.  PDE-5 inhibitors do not produce an erection in the absence of stimulation – rather they enhance the effect of nitric oxide by inhibiting PDE-5-mediated hydrolysis of cGMP, which is present during stimulation. Below we provide a comparison of PDE-5 Inhibitors.

Each PDE-5 inhibitor has similar efficacy, however, there are some differences to consider.  The choice of PDE-5 inhibitor may depend on frequency and timing of intercourse, patient preference, patient tolerance, or concurrent diagnoses.  

Sildenafil (Viagra) is taken 1 hour before intercourse at a dose of 25-100 mg, and its duration of action is 4-8 hours.  Tadalafil (Cialis) can be taken one of two ways.  It can be taken at a dose of 5-20 mg prior to intercourse, or it can be taken at a dose of 2.5 mg at the same time every day regardless of intercourse.  Tadalafil begins its effect in 45 minutes and lasts up to 36 hours.  Vardenafil (Levitra) should be taken 1 hour prior to intercourse at a dose of 2.5-20 mg.  It begins acting in 30 minutes and lasts 4-8 hours, and it’s available as tablets or orally disintegrating tablets. Avanafil (Stendra) has the quickest onset – patients should take 50-200 mg 15-30 minutes before intercourse.

The most commonly reported adverse effect among all PDE-5 inhibitors is a headache.  Flushing, dyspepsia, and rhinitis also occur frequently.  Patients may also experience nasal congestion, back pain, dizziness, or color visual disturbances, though these adverse effects are much less common.  

The combination of nitrates and PDE-5 inhibitors is contraindicated due to the risk of severe hypotension.  Generally, patients who take a daily nitrate, such as isosorbide dinitrate, should not be prescribed a PDE-5 inhibitor.  Patients who experience chest pain must wait before taking nitroglycerin tablets – the suggested time period before it is considered safe is different for each PDE-5 inhibitor.  Avanafil is the shortest at 12 hours, sildenafil and vardenafil both require 24 hours between, and tadalafil requires 48 hours.

PDE-5 inhibitors are extensively metabolized by CYP enzymes, which may lead to drug interactions or drive the selection of one of PDE-5 inhibitor over another.  Each PDE-5 inhibitor is metabolized by CYP3A4; some drugs have additional metabolic enzymes. Sildenafil is also metabolized by CYP2C9, vardenafil is also metabolized by CYP3A5 and CYP2C, and avanafil is also metabolized by CYP2C.

In practice, the most commonly used PDE-5 inhibitors are sildenafil and tadalafil.  Although all PDE-5 inhibitors have shown similar efficacy, they have different clinical and practical advantages.  Practitioners should consider a patient’s concurrent medications and conditions before selecting a medication.  The patient’s preferences should also be weighed.  Consider the onset and duration of action of each medication, as well as the once-daily dosing option of tadalafil to see what works best for each patient. Hopefully, this comparison of PDE-5 inhibitors helps you select the right medication for your patients!

This article was written by Sarah Jackson, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP.

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Written By Eric Christianson

July 21, 2021

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