Sildenafil

# Sildenafil ## Overview - **Classification**: Phosphodiesterase-5 (PDE5) Inhibitor - **Mechanism**: Inhibits PDE5, increasing cyclic guanosine monophosphate (cGMP) in corpus cavernosum (ED) and pulmonary vasculature (PAH), leading to smooth muscle relaxation and vasodilation. ## Primary Indications 1. **Erectile Dysfunction (ED)** - Management of male impotence. 2. **Pulmonary Arterial Hypertension (PAH)** - Improvement of exercise capacity and delay of clinical worsening. ## Adult Dosing ### Standard Dosing **Erectile Dysfunction (ED)** - **Dose**: **50 mg** (initial), range **25-100 mg** - **Frequency**: As needed, approx. 1 hour prior to sexual activity - **Route**: Oral - **Maximum**: **100 mg** per day **Pulmonary Arterial Hypertension (PAH)** - **Dose**: **20 mg** - **Frequency**: Three times daily (**TID**) - **Route**: Oral or Intravenous (IV) - **Maximum**: **60 mg** per day (oral), **10 mg TID** (IV equivalent) ### Dose Adjustments - **Renal Impairment**: - CrCl <30 mL/min: ED - initial **25 mg**; PAH - initial **20 mg BID**. - **Hepatic Impairment**: - Moderate to severe (Child-Pugh B or C): ED - initial **25 mg**; PAH - initial **20 mg BID**. - **Elderly Patients**: - For ED, consider starting at **25 mg** if >65 years due to increased plasma levels. ## Pediatric Dosing (PAH only; ED not indicated) ### Neonates (0-28 days) - Sildenafil **not recommended** for persistent pulmonary hypertension of the newborn (PPHN) due to lack of efficacy/safety data and potential adverse effects. - **Special Notes**: Use only in extreme critical situations under expert guidance with close monitoring. ### Infants (1-12 months) - **PAH**: **0.5-1 mg/kg/dose** - **Frequency**: Three times daily (**TID**) - **Maximum**: **20 mg/dose** or **2.5 mg/kg/day**. ### Children (1-12 years) - **PAH**: **0.5-1 mg/kg/dose** - **Frequency**: Three times daily (**TID**) - **Maximum**: **20 mg/dose** or **2.5 mg/kg/day**. ### Adolescents (13-18 years) - **PAH**: Follow adult dosing: **20 mg TID**. - **Maximum**: **20 mg/dose**. ## Safety Information ### Contraindications - **Absolute**: Concomitant use with **nitrates** (any form, e.g., nitroglycerin, isosorbide). - **Absolute**: Concomitant use with **riociguat** (guanylate cyclase stimulator). - **Relative**: Known hypersensitivity to sildenafil. - **Relative**: Recent myocardial infarction or stroke, severe cardiac conditions. ### Common Adverse Effects - **Very Common (>10%)**: Headache, flushing, dyspepsia, abnormal vision (e.g., color tinge, blurred vision). - **Common (1-10%)**: Nasal congestion, dizziness, back pain, muscle pain, nausea, rash. - **Serious but Rare**: Priapism (erection >4 hours), sudden vision loss (NAION), sudden hearing loss, severe hypotension, cardiovascular events. ### Key Drug Interactions - **Nitrates**: Potentiation of hypotensive effects leading to profound and life-threatening drops in blood pressure. **ABSOLUTE CONTRAINDICATION**. - **Alpha-blockers (e.g., doxazosin, tamsulosin)**: Increased risk of symptomatic hypotension. Start sildenafil at **25 mg** for ED, caution with PAH. - **Strong CYP3A4 Inhibitors (e.g., ritonavir, ketoconazole, clarithromycin)**: Significantly increase sildenafil plasma levels. Reduce sildenafil dose (e.g., **25 mg** initial for ED; **10 mg BID** for PAH). - **CYP3A4 Inducers (e.g., rifampin, phenytoin)**: May decrease sildenafil levels, reducing efficacy. ## Monitoring & Follow-up - **Before Treatment**: Baseline blood pressure, cardiovascular assessment. For PAH, evaluate pulmonary hemodynamics. - **During Treatment**: Monitor blood pressure, especially when co-administered with alpha-blockers. - **Clinical Signs**: Watch for signs of priapism (prolonged erection), sudden vision changes, sudden hearing loss, or severe dizziness/fainting. ## Clinical Pearls - 💡 **Tip 1**: For ED, take **1 hour before** sexual activity, but effective range is 30 minutes to 4 hours. - 💡 **Tip 2**: A **high-fat meal** can delay onset of action for ED. - 💡 **Tip 3**: Counsel patients on the risk of **priapism**; seek immediate medical attention if an erection lasts >4 hours. - 💡 **Tip 4**: Visual disturbances (e.g., blue tinge to vision) are common but usually transient. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.