Sildenafil (Viagra) for Erectile Dysfunction — Libido & Sex
Original PDE5 inhibitor FDA-approved for ED and pulmonary arterial hypertension, with the most extensive clinical evidence base.
Overview
Sildenafil was the first PDE5 inhibitor approved for erectile dysfunction (1998) and remains one of the most prescribed medications worldwide. Originally developed as an anti-anginal agent, sildenafil's erection-enhancing properties were discovered serendipitously during Phase 1 clinical trials. It selectively inhibits PDE5, the predominant phosphodiesterase in penile cavernosal tissue, increasing cGMP levels and promoting smooth muscle relaxation upon sexual stimulation. Sildenafil has a half-life of 4-5 hours and onset of action within 30-60 minutes when taken on an empty stomach (high-fat meals delay absorption by up to 1 hour). At the standard 50-100 mg dose, sildenafil improves erections in approximately 70-80% of men with ED across diverse etiologies including diabetes, post-prostatectomy, and psychogenic ED. Sildenafil also inhibits PDE6 (retinal), which accounts for its characteristic blue-tinged vision (cyanopsia) at higher doses. A separate formulation (Revatio, 20 mg TID) is FDA-approved for pulmonary arterial hypertension. Sildenafil has robust data for safety and efficacy from over 25 years of clinical experience and >30,000 participants in clinical trials.
Indications
- FDA-approved: Erectile dysfunction (Viagra)
- FDA-approved: Pulmonary arterial hypertension (Revatio)
- Off-label: Raynaud's phenomenon
- Off-label: Secondary pulmonary hypertension
- Off-label: High-altitude pulmonary edema prophylaxis
Mechanism of Action
Nitric oxide (NO) is released from parasympathetic nerve endings and endothelium in the corpus cavernosum during sexual arousal
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Sildenafil | 50 mg | As needed, 30-60 min before activity | Standard starting dose; effective for most patients |
| Sildenafil | 25 mg | As needed | For patients >65 years, hepatic impairment, or CYP3A4 inhibitor use |
| Sildenafil | 100 mg | As needed | Maximum dose; use if 50 mg insufficient |
| Sildenafil | 20 mg | Three times daily | Pulmonary arterial hypertension dosing (Revatio) |
Evidence Grade
GRADE A
Safety & Contraindications
- Absolute contraindication with nitrates — life-threatening hypotension
- Contraindicated with riociguat
- Headache (16%), flushing (10%), dyspepsia (7%), nasal congestion (4%)
- Blue-tinged vision (cyanopsia) due to PDE6 cross-reactivity — dose-dependent
- Priapism (rare) — medical emergency if erection lasts >4 hours
- Sudden sensorineural hearing loss (rare, FDA warning)
- NAION (non-arteritic anterior ischemic optic neuropathy) — rare
- High-fat meals significantly delay absorption and reduce peak levels