Clinical Indications for Sildenafil Citrate Beyond Erectile Dysfunction

Sildenafil is predominantly metabolized by hepatic cytochrome P450 (CYP) enzymes.

7. Interactions

Telotristat Ethyl: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with telotristat is necessary as concurrent use may decrease sildenafil exposure. Terazosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of sildenafil. Tezacaftor; Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil. Tipranavir: (Major) Sildenafil is contraindicated for use with tipranavir when used for pulmonary arterial hypertension (PAH). Sildenafil is a sensitive CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor.

Alcohol interaction warning

Trandolapril; Verapamil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with verapamil is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Tranylcypromine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with sildenafil. Tucatinib: (Major) Coadministration with tucatinib is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving tucatinib. Vemurafenib: (Moderate) Concomitant use of vemurafenib with sildenafil may increase sildenafil exposure. One active metabolite with properties similar to the parent drug has been identified and is formed by N-desmethylation of sildenafil.

This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% of the parent drug.

What special precautions should I follow?

PDE5 is responsible for degradation of cGMP in the corpus cavernosum. Sildenafil enhances the effect of NO by inhibiting PDE5 thereby raising concentrations of cGMP in the corpus cavernosum. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum and, at recommended doses, has no effect in the absence of sexual stimulation. As reported by the manufacturer, the pharmacodynamic response to sildenafil was assessed in eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction. In these studies sexual stimulation resulted in improved erections, as assessed by penile plethysmography, after sildenafil administration compared with placebo.

Jet lag research

Most studies evaluated the efficacy of sildenafil approximately 60 minutes post dose. The erectile response, as determined by penile plethysmography, generally increased with sildenafil citrate 100 mg increasing sildenafil dose and plasma concentration. The time course of effect was examined in one study. The effects of sildenafil were evident for up to 4 hours, but the response was diminished compared to 2 hours.In vitro studies show that sildenafil is selective for PDE5 and its effect is more potent on PDE5 than on other known phosphodiesterases. The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil and accounts for about 20% of the pharmacologic effects of sildenafil.

3. Downsides

Sildenafil is cleared predominantly by CYP3A (major route) and CYP2C9 (minor route). Use caution and monitor patients for potential sildenafil-related side effects. Verapamil: (Moderate) sildenafil pink pill Monitor for an increase in sildenafil-related adverse reactions if coadministration with verapamil is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. PDE5 inhibitors, including sildenafil, may potentiate the hypotensive effects of vericiguat. Vigabatrin: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.

Sildenafil Tablets for ED

Vonoprazan; Amoxicillin; Clarithromycin: (Major) Coadministration of clarithromycin is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). Voriconazole: (Major) Coadministration of voriconazole is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving voriconazole. Voxelotor: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with voxelotor is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Zafirlukast: (Moderate) Concomitant use of zafirlukast with sildenafil may increase sildenafil exposure. However, the ratio of the metabolite to sildenafil is higher in patients with pulmonary arterial hypertension (PAH).

The History of Sildenafil Citrate, AKA Viagra

In vitro studies suggest zafirlukast inhibits CYP3A (weak) and CYP2C9 (moderate top potent). LiQrev Oral Susp: 1mL, 10mgRevatio/Sildenafil/Sildenafil Citrate Intravenous Inj Sol: 0.8mg, 1mLRevatio/Sildenafil/Sildenafil Citrate Oral Pwd F/Recon: 1mL, 10mgRevatio/Sildenafil/Sildenafil Citrate/Viagra Oral Tab: 20mg, 25mg, 50mg, 100mg 100 mg/day PO for erectile dysfunction; 240 mg/day PO or 30 mg/day IV for pulmonary arterial hypertension. 100 mg/day PO for erectile dysfunction; 240 mg/day PO or 30 mg/day IV for pulmonary arterial hypertension. Weight 45 kg or more: 40 mg PO 3 times daily.Weight 21 to 44 kg: 20 mg PO 3 times daily. Weight 45 kg or more: 40 mg PO 3 times daily.Weight 21 to 44 kg: 20 mg PO 3 times daily.Weight 20 kg or less: 10 mg PO 3 times daily.

Pregnancy Categories

Guidelines recommend 1 mg/kg/dose PO every 8 hours. Guidelines recommend 1 mg/kg/dose PO every 8 hours and 0.4 mg/kg IV as a loading dose followed by a continuous infusion of 0.067 mg/kg/hour. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cGMP. Cyclic guanosine monophosphate causes smooth muscle relaxation in the corpus cavernosum thereby allowing inflow of blood; the exact mechanism by which cGMP stimulates relaxation of smooth muscles has not been determined. The metabolite is further metabolized to inactive compounds.

• Sildenafil may interact with other medications, increasing risks.
• Significant interactions include nitrates and alpha-blockers.
• Patients should disclose all medications to their doctor.
• Combining with certain drugs can cause dangerous drops in blood pressure.
• Regular liver function monitoring may be necessary.
• Some herbal supplements also have interaction potential.
• Avoiding certain foods and medications reduces risks.
• Proper management improves treatment efficacy.

Sildenafil is excreted as metabolites primarily in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Both sildenafil and its active metabolite have terminal half-lives of about 4 hours.

• Sildenafil citrate can be combined with lifestyle changes.
• Exercise and weight management improve erectile function.
• Quitting smoking enhances medication effectiveness.
• Reducing alcohol intake minimizes side effects.
• Psychological therapy may support ED treatment.
• Counseling can address underlying emotional issues.
• Regular medical check-ups are recommended.
• Patient education improves safe and effective use.

Sildenafil concentrations at 24 hours post a single 100 mg oral dose average 2 ng/mL (compared to peak plasma concentrations of approximately 440 ng/mL).

While similar pharmacokinetic parameters were observed in healthy volunteers and patients with erectile dysfunction, the average steady-state

Side Effects

Sildenafil is one-tenth as potent for PDE6, an enzyme found in the retina, as it is for PDE5; this lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma concentrations of the drug. The mean steady state volume of distribution (Vss) is 105 L, indicating widespread tissue distribution. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations. Based upon measurements of sildenafil in semen of healthy volunteers 90 minutes after dosing, less than 0.001% of the administered dose may appear in the semen of patients. concentrations were 20% to 50% higher and Cmin levels doubled in patients with PAH compared to healthy volunteers.

Notes et références

Coadministration may alter plasma concentrations of sildenafil resulting in an increased risk of adverse reactions and/or decreased efficacy. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. Tacrolimus: (Moderate) Consider initiating sildenafil at a low dose (25 mg) in kidney transplant recipients receiving tacrolimus. In a study of renal transplant patients, coadministration of tacrolimus with a single 50 mg dose of sildenafil resulted in an increase in the AUC, Cmax, and half-life of sildenafil. Decreases in blood pressure were also observed.

Hazard Classifications

No significant effect on the pharmacokinetic parameters of tacrolimus were observed. Tamsulosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on tamsulosin therapy before initiating therapy with the lowest dose of sildenafil. Tazemetostat: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with tazemetostat is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Telmisartan; Amlodipine: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Affected cytochrome P450 isoenzymes: CYP3A4 and CYP2C9Sildenafil is metabolized principally by the hepatic cytochrome P450 (CYP) 3A4; CYP2C9 is also involved to a lesser degree.

Society and culture

Sildenafil can also inhibit PDE5 present in esophageal smooth muscle, lung tissue, and brain tissue. Inhibition of PDE5 in lung tissue results in relaxation of pulmonary vascular smooth muscle and subsequently pulmonary vasodilation, thereby making sildenafil an effective agent in treating pulmonary hypertension. Inhibition of PDE5 present in esophageal smooth muscle can cause a marked inhibition of esophageal motility as well as a reduction in lower esophageal sphincter (LES) tone. These effects may be beneficial in certain motor disorders involving the esophagus such as diffuse spasm, nutcracker esophagus, and hypertensive LES. However, the reduction in LES tone can worsen the symptoms of gastroesophageal reflux disease (GERD).