1. Clinical Overview
Sildenafil citrate is a potent, selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). It is the first-line oral therapy for erectile dysfunction (ED) and is also approved for pulmonary arterial hypertension (PAH) at a different dose. In the context of the 100mg tablet, it is primarily indicated for the treatment of ED. It works by enhancing the effects of nitric oxide (NO) in the corpus cavernosum, leading to smooth muscle relaxation and increased blood flow, which facilitates an erection in response to sexual stimulation.
| Onset | Duration | Bioavailability |
|---|---|---|
| 30 to 60 minutes | Up to 4-5 hours (therapeutic window for erection) | Approximately 40% (oral) |
2. Mechanism of Action
During sexual stimulation, nitric oxide (NO) is released from nerve endings and endothelial cells in the corpus cavernosum. NO activates guanylate cyclase, which increases intracellular levels of cyclic guanosine monophosphate (cGMP). cGMP causes smooth muscle relaxation in the corpus cavernosum, allowing inflow of blood and erection. Sildenafil selectively inhibits phosphodiesterase type 5 (PDE5), the enzyme responsible for degradation of cGMP in the corpus cavernosum. By inhibiting PDE5, sildenafil increases cGMP levels, thereby enhancing and prolonging the smooth muscle relaxant effects of NO, leading to improved erectile function.
3. Indications & Uses
- Erectile Dysfunction (ED) of organic, psychogenic, or mixed etiology
4. Dosage & Administration
Adult Dosage: For ED: Recommended starting dose is 50mg taken approximately 1 hour before sexual activity. Based on efficacy and tolerability, the dose may be increased to 100mg (maximum recommended dose) or decreased to 25mg. Dosing frequency should not exceed once daily.
Administration: Take orally with or without food. A high-fat meal may delay the onset of action. Tablet should be swallowed whole with a glass of water. Sexual stimulation is required for the drug to be effective.
5. Side Effects
Common side effects may include:
- Headache
- Flushing
- Dyspepsia (indigestion)
- Nasal congestion
- Dizziness
- Visual disturbances (mild, transient blue-tinged vision, increased light sensitivity)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Nitrates (e.g., Nitroglycerin, Isosorbide) | Profound, life-threatening hypotension | Contraindicated |
| Alpha-blockers (e.g., Tamsulosin, Doxazosin) | Additive hypotensive effect, symptomatic postural hypotension | Major |
| Riociguat | Hypotensive crisis | Contraindicated |
| CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Ritonavir, Erythromycin, Clarithromycin, Grapefruit juice) | Markedly increased sildenafil plasma levels, increased risk of adverse effects | Major |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Reduced sildenafil plasma levels, potential therapeutic failure | Moderate |
| Antihypertensives | Additive blood pressure lowering effect | Moderate |
| Alcohol | Potential additive vasodilation and hypotension, increased risk of dizziness | Moderate |
7. Patient Counselling
- DO take the tablet approximately 30-60 minutes before planned sexual activity.
- DO understand that sexual stimulation is required for the medicine to work.
- DO inform your doctor about all other medicines you are taking, especially heart medicines (nitrates).
- DO seek immediate medical attention if an erection lasts more than 4 hours.
- DO NOT take more than one tablet (100mg) in a 24-hour period.
- DO NOT take sildenafil if you are taking any medicine containing nitrates (for chest pain).
- DO NOT take sildenafil with grapefruit or grapefruit juice.
- DO NOT share your medicine with others.
8. Toxicology & Storage
Overdose: Expected to be an extension of the drug's adverse effects: severe headache, flushing, dizziness, visual disturbances, hypotension, syncope, and potentially prolonged erection. In cases of massive overdose, cardiovascular collapse may occur.
Storage: Store below 30°C. Protect from light and moisture. Keep out of reach of children. Do not use after the expiry date printed on the pack.