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 used for pulmonary arterial hypertension (PAH). It works by enhancing the effects of nitric oxide (NO) in the corpus cavernosum, facilitating penile erection upon sexual stimulation. In the Indian context, it is widely prescribed and available under numerous brand names, but its non-prescription sale is illegal and dangerous.
Adult: For ED: Recommended starting dose is 50 mg, taken orally approximately 1 hour before sexual activity. Dose may be increased to 100 mg or decreased to 25 mg based on efficacy and tolerability. Maximum dosing frequency is once per day. For PAH: 20 mg three times daily (specific PAH formulation).
Note: Take tablet with or without food. High-fat meals may delay onset of action. Swallow whole with a glass of water. Sexual stimulation is necessary for the drug to work for ED. Do not take more than one dose in 24 hours.
During sexual stimulation, nitric oxide (NO) is released from nerve endings and endothelial cells in the corpus cavernosum. NO activates guanylyl cyclase, which increases intracellular levels of cyclic guanosine monophosphate (cGMP). cGMP causes smooth muscle relaxation in the corpus cavernosum, allowing increased blood flow and erection. Sildenafil selectively inhibits phosphodiesterase type 5 (PDE5), the enzyme responsible for degrading cGMP in the corpus cavernosum. By inhibiting PDE5, sildenafil increases and sustains cGMP levels, thereby enhancing the natural erectile response to sexual stimulation.
Pregnancy: Category B: Not indicated for use in women. No adequate and well-controlled studies in pregnant women. Use only if clearly needed (e.g., for PAH) and benefit justifies potential risk.
Driving: May cause dizziness, visual disturbances, or hypotension. Patients should not drive or operate machinery until they know how sildenafil affects them, especially after the first dose.
| Nitrates (e.g., Nitroglycerin, Isosorbide) | Profound, life-threatening hypotension | Contraindicated |
| Alpha-blockers (e.g., Tamsulosin, Doxazosin) | Additive hypotensive effect, symptomatic postural hypotension | Major - Use with extreme caution; start with lowest sildenafil dose (25mg); separate administration times. |
| CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Ritonavir, Erythromycin, Clarithromycin, Grapefruit juice) | Increased sildenafil plasma levels, increased risk of adverse effects | Major - Dose adjustment required (max 25 mg in 48h with strong inhibitors). |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Decreased sildenafil plasma levels, reduced efficacy | Moderate - May require higher sildenafil dose. |
| Antihypertensives | Additive blood pressure lowering effect | Moderate - Monitor blood pressure. |
| Alcohol | Additive vasodilation and hypotensive effects; may increase risk of orthostatic hypotension, dizziness | Moderate - Avoid excessive consumption. |