Sildenafil

• Erectile Dysfunction
• Pulmonary Arterial Hypertension
• Sexual Dysfunction

Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor with two distinct medical uses: treatment of erectile dysfunction (Viagra) and pulmonary arterial hypertension (Revatio). It works by enhancing the effects of nitric oxide to produce smooth muscle relaxation and vasodilation.

Mechanism of Action

Sildenafil inhibits PDE5, affecting the nitric oxide pathway:

• PDE5 inhibition: Blocks the enzyme that degrades cyclic GMP (cGMP)
• Increased cGMP: Prolongs the vasodilatory effects of nitric oxide
• Smooth muscle relaxation: In erectile dysfunction, enhances penile blood flow; in PAH, reduces pulmonary vascular resistance
• Erectile response: Requires sexual stimulation to initiate nitric oxide release
• Pulmonary effects: Reduces mean pulmonary arterial pressure and pulmonary vascular resistance

Available Formulations

Erectile Dysfunction (Viagra):

• Tablets: 25 mg, 50 mg, 100 mg

Pulmonary Arterial Hypertension (Revatio):

• Tablets: 20 mg
• Oral suspension: 10 mg/mL
• IV injection: 10 mg/12.5 mL

Medical Uses

FDA-Approved Indications:

• Erectile dysfunction (ED) in adult men
• Pulmonary arterial hypertension (PAH) - WHO Group I

The formulations are NOT interchangeable between indications.

Dosing Guidelines

Erectile Dysfunction:

• Starting dose: 50 mg approximately 1 hour before sexual activity
• Range: 25-100 mg
• Maximum: 100 mg once per day
• Effective for 4-5 hours after dosing

Pulmonary Arterial Hypertension:

• Oral: 20 mg three times daily, approximately 4-6 hours apart
• IV (when oral not feasible): 10 mg (2.5 mg or 10 mg) three times daily

Important Safety Information

Contraindications:

• Concomitant use with nitrates (any form)
• Concomitant use with riociguat (Adempas)
• Known hypersensitivity to sildenafil

Warnings and Precautions:

• Cardiovascular effects: Assess cardiovascular status before prescribing for ED
• Hypotension: Especially with alpha-blockers or antihypertensives
• Priapism: Prolonged erection >4 hours requires emergency treatment
• Vision changes: NAION (non-arteritic anterior ischemic optic neuropathy) reported
• Hearing loss: Sudden decrease or loss of hearing reported
• Pulmonary veno-occlusive disease (PAH indication): May worsen condition

Drug Interactions

• Nitrates: Contraindicated (profound hypotension)
• Riociguat: Contraindicated
• Alpha-blockers: Start sildenafil at 25 mg; use with caution
• Strong CYP3A4 inhibitors (ketoconazole, ritonavir): Maximum 25 mg in 48 hours for ED
• CYP3A4 inducers: May reduce efficacy
• Other PDE5 inhibitors: Do not use combination

Special Populations

• Hepatic Impairment: Start 25 mg for ED; no adjustment for PAH (use with caution)
• Renal Impairment: Start 25 mg for ED; no adjustment for PAH with mild-moderate impairment
• Elderly (>65): Consider 25 mg starting dose for ED
• Women: Not indicated for ED; PAH approved for women
• Pediatric: Not recommended for PAH (increased mortality in pediatric trial)