Silagra

Approved Indications:

• Erectile Dysfunction (ED): Treatment of adult males with erectile dysfunction of psychogenic, organic, or mixed etiology.
• Pulmonary Arterial Hypertension (PAH): Approved for the treatment of WHO Group I PAH (idiopathic, heritable, or associated with connective tissue disease) to improve exercise capacity and delay clinical worsening in adults.
• Persistent Pulmonary Hypertension of the Newborn (PPHN): Not FDA-approved, but supported by off-label use in some countries when standard therapies fail.

Important Off-Label Uses:

• Raynaud’s Phenomenon: Occasionally prescribed in severe, refractory cases to improve peripheral blood flow.
• Altitude-Induced Pulmonary Edema (HAPE): Investigational or off-label use for prevention and treatment of high-altitude pulmonary edema.
• Female Sexual Arousal Disorder: Limited evidence supports cautious off-label use in select cases, though not widely recommended.

Erectile Dysfunction (Adults)

• Usual Starting Dose: 50 mg orally as needed, taken ~1 hour before sexual activity (range: 30 minutes to 4 hours).
• Adjustment: Increase to 100 mg or decrease to 25 mg based on efficacy and tolerability.
• Max Frequency: Once daily; do not exceed recommended dose.

Pulmonary Arterial Hypertension (Adults)

• Oral: 20 mg three times daily (6–8 hours apart).
• IV (when oral not feasible): 10 mg IV bolus three times daily, administered over ~10 minutes.

Pediatric PAH or PPHN (off-label in many regions)

• Dosing must be individualized by a specialist.
• Typical range: 0.5–2 mg/kg per dose every 6–8 hours; titration depends on clinical response and tolerability.

Elderly Patients

• Start at lower end of dosing range (e.g., 25 mg for ED) due to age-related changes in clearance.

Renal Impairment

• Mild–Moderate: No significant adjustment needed.
• Severe (CrCl <30 mL/min): Start at lowest dose (e.g., 25 mg for ED).

Hepatic Impairment

• Mild–Moderate: Start at reduced dose (e.g., 25 mg for ED).
• Severe: Use with caution; limited data available.

Administration:

• Take with or without food; high-fat meals may delay onset.
• For PAH, ensure consistent dosing intervals.
• Swallow whole with water; do not crush or split unless advised.

Sildenafil Citrate is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), an enzyme that degrades cyclic guanosine monophosphate (cGMP) in the smooth muscle of the corpus cavernosum and pulmonary vasculature. By inhibiting PDE5, Sildenafil enhances the effects of nitric oxide (NO) released during sexual stimulation or endogenous NO production in pulmonary vessels. The resultant increase in cGMP levels causes smooth muscle relaxation, vasodilation, and increased blood flow — enabling penile erection in ED and reducing pulmonary vascular resistance in PAH.

Absorption:

• Rapidly absorbed after oral administration.
• Peak plasma levels reached within 30–120 minutes (median ~60 minutes).
• Oral bioavailability ~40%.
• High-fat meals delay Tmax by ~60 minutes and reduce peak concentration by ~30%.

Distribution:

• Volume of distribution ~105 L, indicating wide tissue distribution.
• Highly protein-bound (~96%), mainly to plasma albumin.

Metabolism:

• Extensively metabolized in the liver, primarily via CYP3A4 (major pathway) and CYP2C9 (minor).
• Major circulating metabolite: N-desmethyl sildenafil (~50% activity of parent compound).

Excretion:

• Primarily excreted in feces (~80% of administered oral dose).
• About 13% excreted in urine as metabolites.
• Terminal half-life: ~3–5 hours.

Pregnancy:

• FDA Category: Previously Pregnancy Category B (no adequate well-controlled studies in pregnant women; animal studies did not show fetal harm at therapeutic doses).
• Use: Not indicated for use in pregnancy for ED; use in PAH only if the benefit outweighs potential risk.

Lactation:

• Unknown if Sildenafil is excreted in human milk.
• Due to potential for serious adverse effects in the nursing infant, caution is advised; weigh risks and benefits.

• Class: Phosphodiesterase Type 5 (PDE5) Inhibitor
• Subclass: Selective PDE5 Inhibitor

• Concurrent use with organic nitrates in any form (risk of severe, potentially life-threatening hypotension)
• Concomitant use with guanylate cyclase stimulators like riociguat
• Known hypersensitivity to Sildenafil or any excipients in the formulation
• Severe cardiovascular disorders that make sexual activity inadvisable (e.g., unstable angina, recent MI or stroke)

• Cardiac Risk: Evaluate cardiovascular status before prescribing for ED; sexual activity carries inherent cardiac risk.
• Hypotension: Risk increases with nitrates or alpha-blockers — monitor closely.
• Priapism: Risk of prolonged erection >4 hours; requires immediate medical intervention to prevent penile damage.
• Ocular Events: Rare risk of sudden vision loss due to non-arteritic anterior ischemic optic neuropathy (NAION).
• Hearing Impairment: Sudden hearing decrease/loss has been reported.
• PAH Use: Should only be used for PAH under specialist care; different PDE5 inhibitors are not interchangeable for PAH treatment.
• Hepatic/Renal Impairment: Use cautiously with dose adjustments as needed.

Common Side Effects (by system):

• Neurological: Headache, dizziness.
• Cardiovascular: Flushing, mild hypotension.
• Gastrointestinal: Dyspepsia, nausea.
• ENT: Nasal congestion.
• Ophthalmic: Visual disturbances (blue tinge, blurred vision, increased light sensitivity).

Serious/Rare Side Effects:

• Priapism (prolonged painful erection)
• Sudden vision loss (NAION)
• Sudden hearing loss
• Severe hypotension
• Myocardial infarction or cerebrovascular events (rare)

Onset: Side effects usually occur within hours of dosing; severity and frequency may increase at higher doses.

Major Drug-Drug Interactions:

• Organic nitrates (e.g., nitroglycerin): Absolute contraindication due to risk of severe hypotension.
• Alpha-blockers (e.g., tamsulosin, doxazosin): May cause symptomatic hypotension; co-administer with caution.
• Strong CYP3A4 inhibitors (e.g., ritonavir, ketoconazole): Increase plasma Sildenafil levels — consider dose reduction.
• CYP3A4 inducers (e.g., rifampin): May reduce effectiveness by increasing metabolism.
• Alcohol: May enhance hypotensive effect; limit intake.

Enzyme System: Primarily CYP3A4; CYP2C9 minor role.

• No major new indications or dosing changes in recent FDA or EMA updates.
• PAH guidelines (NICE, ESC/ERS) continue to support Sildenafil as a viable option for WHO Group I PAH.
• Ongoing surveillance for rare ocular and hearing side effects; patients advised to discontinue and seek care if sudden loss occurs.

• Store at controlled room temperature: 20°C to 30°C (68°F–86°F).
• Protect from excessive humidity and light.
• Keep in original blister until use.
• Do not freeze.
• No reconstitution required; no refrigeration needed.