Sildenafil
Sildenafil
Generic Name
Sildenafil
Brand Names
Viagra®, Revatio®) is a selective phosphodiesterase‑5 (PDE5) inhibitor widely used for erectile dysfunction (ED) and pulmonary arterial hypertension (PAH).
Mechanism
- Selective inhibition of PDE5 in smooth‑muscle tissues, preventing cGMP breakdown.
- Elevation of intracellular cGMP enhances nitric‑oxide (NO) mediated vasodilation.
- In the corpus cavernosum, this relaxes smooth muscle → increased arterial inflow → erection.
- In pulmonary vasculature, PDE5 blockade causes vasodilation → lowered pulmonary arterial pressure.
- The drug has no effect on PDE4, PDE6, or other PDE isoforms, conferring favorable tolerability.
Pharmacokinetics
| Parameter | Details | |
| Absorption | Rapid; Cmax ~ 30 min post‑oral dose. | |
| Bioavailability | ~ 40% (first‑pass CYP3A4/1A2 metabolism). | |
| Elimination half‑life | 3–5 h (clinical effects up to 12 h). | |
| Metabolism | Primarily hepatic via CYP3A4 (≈ 74%) and CYP1A2 (≈ 14%). | |
| Drug interactions | Strong CYP3A4 inhibitors (ketoconazole, ritonavir) ↑ Cmax ~5‑fold; grapefruit juice ↓ metabolism (↑ exposure). Acid‑lowering agents may delay absorption. | |
| Renal/hepatic | Renal excretion minimal; hepatic function influences clearance. | |
| Drug formulations | Immediate‑release tablets (10‑100 mg); a 14‑mg/7‑day patch (Revatio®) for PAH. |
Indications
- Erectile dysfunction (low‑dose, on‑demand therapy).
- Pulmonary arterial hypertension (lowest‑effective dose thrice daily).
- Secondary use: lower‑leg ischemia, Raynaud’s phenomenon, and acute pulmonary embolism (off‑label; to be used only under specialist supervision).
Contraindications
- Concurrent nitrate or organic nitrate use – risk of profound hypotension.
- Severe hypotension or unstable angina – avoid.
- Advanced hepatic impairment (Child‑Pugh C) – contraindicated.
- Severe renal insufficiency (CrCl < 30 mL/min) – dose adjustment or avoid.
- Use with alpha‑blockers – may potentiate hypotension; start at lowest dose.
- Recent stroke or myocardial infarction – caution.
- Known hypersensitivity to sildenafil or excipients.
- Elderly or patients on multiple CYP3A4 inhibitors should start low.
Dosing
| Indication | Typical dose | Administration notes |
| Erectile dysfunction | *Start 50 mg* at least 30 min before sexual activity; may be increased to 100 mg if efficacy inadequate or decreased to 25 mg if adverse effects occur. | ≤ once daily. Avoid taking > 4 h after a fatty meal to reduce absorption time. |
| Pulmonary arterial hypertension | 20 mg orally *three times daily* (every 6–8 h). | Commence with 10 mg PO PO; titrate up to 20 mg PO PO PO as tolerated. |
| Patients ≥ 80 yr/renal/hepatic impairment | Start at 25 mg (ED) or 10 mg (PAH) PO PO; titrate slowly. | Monitor renal/liver function monthly. |
Special instructions
• Do not mix with grapefruit juice for the first 3–4 days of therapy.
• If dosing is missed, skip the forgotten dose; do not double dose.
• For PAH, keep the medication in a cool place; do not use pasteurised ketchup or other high‑fat sauces in the encapsulated form.
Adverse Effects
| Class | Common | Serious |
| Cardiovascular | Flushing, low‑grade hypotension, dizziness, headache. | Severe hypotension, syncope, priapism (> 4 h). |
| Ophthalmologic | Transient visual distortion (blue‑tinted vision), blurred vision, photopsia. | Vision loss (rare, possibly due to vasodilation). |
| Gastrointestinal | Nausea, dyspepsia, abdominal pain. | Severe GI upset, aspiration risk in > 75 yr. |
| Skin | Rash, pruritus, angioedema. | Anaphylaxis (rare). |
| Neurologic | Abnormal hearing (rare). | Sudden sensorineural hearing loss (rare). |
Monitoring
- Blood pressure & heart rate (before and after dose, especially in PAH).
- Liver function tests (ALT, AST, bilirubin) – baseline and quarterly.
- Renal function – CrCl or eGFR monthly.
- Ophthalmologic exam – baseline prior to therapy in PAH; report visual changes immediately.
- Sexual function – track efficacy and side‑effect profile in ED patients.
- Medication/interaction review – particularly nitrates, MAO‑I, and CYP3A4 inhibitors.
Clinical Pearls
- Primer for “blue‑tint” vision: The drug’s affinity for PDE6 in the retina produces a transient blue‑shift; it resolves within 2 h and is harmless.
- Nitric oxide synergy warning: Co‑administration with NO donors (nitroglycerin, isosorbide) precipitates life‑threatening hypotension; inform patients to avoid such drugs.
- “First‑dose headache”: Anticipate a transient headache in 20–30 % of users; if severe, break the dose in half or use non‑steroidal prophylaxis.
- Delayed absorption: If a patient has a high‑fat meal, consider delaying dose by 1‑2 h to avoid sub‑therapeutic effect.
- Grapefruit synergy: Grapefruit juice profoundly increases plasma levels; advise patients to avoid it for at least 3–4 days after initiating therapy and thereafter to take the medication with a bland diet.
- Priapism management: If erection > 4 h, seek emergency care; alpha‑adrenergic agonists and intracavernosal injection of phenylephrine are first‑line.
- Elderly caution: In patients > 75 yr, shift to lower doses first (25‑50 mg) to mitigate hypotension and visual side‑effects.
- Dental anesthesia: Avoid using nitrous oxide or high‑dose local anesthetics with nitroglycerinoma in patients on sildenafil.
*This drug card synthesizes the latest evidence for educational and clinical reference.*