Sildenafil citrate is a potent, selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). It is the first oral therapy approved for the treatment of erectile dysfunction (ED) and is also a cornerstone treatment for pulmonary arterial hypertension (PAH) under the brand name Revatio. The 25mg strength is a lower dose, often used for initiation of therapy, in elderly patients, or in those with significant comorbidities or concomitant medications that increase sildenafil exposure.
Adult: For ED: The recommended dose is 50mg taken as needed, approximately 1 hour before sexual activity. Based on efficacy and tolerability, the dose may be increased to 100mg or decreased to 25mg. The 25mg dose is recommended as a starting dose for elderly patients (>65 years), patients with hepatic impairment (e.g., cirrhosis), severe renal impairment (CrCl <30 mL/min), and those on potent CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin).
Note: Take orally with or without food. A high-fat meal may delay onset of action. Tablet can be taken with a glass of water. Sexual stimulation is required for effect. Do not take more than once in 24 hours.
During sexual stimulation, nitric oxide (NO) is released in the corpus cavernosum. NO activates guanylate cyclase, leading to increased levels of cyclic guanosine monophosphate (cGMP). cGMP causes smooth muscle relaxation in the corpus cavernosum, allowing inflow of blood and erection. Sildenafil enhances this process by selectively inhibiting phosphodiesterase type 5 (PDE5), the enzyme responsible for degradation of cGMP in the corpus cavernosum. This results in increased intracellular cGMP levels, potentiating the smooth muscle relaxant effect of NO.
Pregnancy: Category B: Not indicated for use in women. Animal studies show no direct harm to fetus, but no adequate and well-controlled studies in pregnant women. Use in PAH (Revatio) during pregnancy only if potential benefit justifies potential risk to fetus.
Driving: May cause dizziness, visual disturbances, or hypotension. Patients should be cautioned about driving or operating machinery until they know how sildenafil affects them.
| Nitrates (Nitroglycerin, Isosorbide) | Profound, potentially fatal hypotension. | Contraindicated |
| Alpha-blockers (Doxazosin, Tamsulosin, Prazosin) | Additive hypotensive effect, risk of symptomatic hypotension (dizziness, lightheadedness, fainting). | Major |
| Potent CYP3A4 Inhibitors (Ketoconazole, Itraconazole, Ritonavir, Clarithromycin, Erythromycin) | Markedly increases sildenafil plasma levels. Dose adjustment required (max 25mg in 48h with ritonavir). | Major |
| Moderate CYP3A4 Inhibitors (Erythromycin, Saquinavir, Amlodipine) | Moderate increase in sildenafil levels. Consider starting dose of 25mg. | Moderate |
| CYP3A4 Inducers (Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Decreases sildenafil plasma levels, potentially reducing efficacy. | Moderate |
| Antihypertensives | Additive blood pressure lowering effect. | Moderate |
| Riociguat | Profound hypotension. | Contraindicated |