Important Safety Information — Sildenafil

Indications

Sildenafil citrate is a phosphodiesterase type 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED). Sildenafil enhances the effect of nitric oxide by inhibiting PDE5, which is responsible for the degradation of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and increased blood flow.

Contraindications

• Nitrates: Concomitant use with organic nitrates in any form (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, amyl nitrite/poppers) is absolutely contraindicated. The combination can cause a severe, potentially fatal drop in blood pressure.
• Guanylate cyclase (GC) stimulators: Do not use with riociguat or other GC stimulators, as PDE5 inhibitors may potentiate the hypotensive effects.
• Known hypersensitivity to sildenafil or any component of the tablet

Warnings and Precautions

• Cardiovascular risk: There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Physicians should consider whether their patients with underlying cardiovascular disease could be adversely affected by the vasodilatory effects of sildenafil.
• Hypotension: Sildenafil has vasodilatory properties and can cause transient decreases in blood pressure. Caution in patients on antihypertensive medications or alpha-blockers.
• Priapism: Prolonged erections greater than 4 hours and priapism (painful erections lasting more than 6 hours) have been reported. Seek immediate medical attention if an erection lasts longer than 4 hours, as permanent damage to the penis can occur.
• Vision loss (NAION): Non-arteritic anterior ischemic optic neuropathy (NAION) has been reported rarely post-marketing in temporal association with PDE5 inhibitor use. Advise patients to stop sildenafil and seek medical attention if sudden loss of vision in one or both eyes occurs.
• Sudden hearing loss: Cases of sudden decrease or loss of hearing, sometimes with tinnitus and dizziness, have been reported with PDE5 inhibitor use. Advise patients to stop and seek medical attention if sudden hearing loss occurs.
• Alpha-blockers: Concomitant use may lead to symptomatic hypotension in some patients. Use with caution and consider lower starting doses.
• Hepatic impairment: Patients with hepatic impairment may have increased plasma levels. A starting dose of 25 mg should be considered.
• Renal impairment: Patients with severe renal impairment may have increased plasma levels. A starting dose of 25 mg should be considered.

Common Side Effects

• Headache (up to 28%)
• Flushing (up to 19%)
• Dyspepsia / indigestion (up to 17%)
• Abnormal vision, including color tinge and increased light sensitivity (up to 11%)
• Nasal congestion
• Back pain
• Myalgia (muscle pain)
• Nausea
• Dizziness
• Rash

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

• An erection lasting longer than 4 hours (priapism)
• Sudden loss of vision in one or both eyes
• Sudden decrease or loss of hearing
• Chest pain, dizziness, or nausea during sexual activity
• Severe hypotension (lightheadedness, fainting)
• Seizures
• Signs of a serious allergic reaction (rash, hives, swelling, difficulty breathing)

Drug Interactions

• Nitrates: Absolutely contraindicated. The combination can cause severe, life-threatening hypotension.
• GC stimulators (riociguat): Contraindicated due to risk of hypotension.
• Alpha-blockers (e.g., doxazosin, tamsulosin): Additive blood pressure lowering effects. Use with caution; initiate sildenafil at the lowest dose.
• CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, ritonavir): May increase sildenafil plasma levels. For patients on ritonavir, do not exceed 25 mg within 48 hours.
• CYP3A4 inducers (e.g., rifampin): May decrease sildenafil plasma levels.
• Other PDE5 inhibitors: Do not use with tadalafil, vardenafil, or avanafil.
• Alcohol: May increase the risk of hypotension, dizziness, and headache.
• Grapefruit juice: May increase sildenafil levels via CYP3A4 inhibition.
• Amlodipine: Additional reduction in blood pressure may occur.

Use in Specific Populations

• Pregnancy: Sildenafil for ED is not indicated for use in women.
• Pediatric use: Not indicated for use in pediatric patients.
• Geriatric use: A starting dose of 25 mg should be considered in patients over 65 years of age due to higher plasma levels observed in healthy elderly volunteers.
• Hepatic impairment: Starting dose of 25 mg recommended.
• Renal impairment: Starting dose of 25 mg recommended for severe impairment (creatinine clearance less than 30 mL/min).