SILDENAFIL CITRATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Sildenafil citrate inhibits phosphodiesterase type 5 (PDE5) in the corpus cavernosum, increasing cGMP levels and enhancing nitric oxide-mediated smooth muscle relaxation, leading to penile erection. It also inhibits PDE5 in pulmonary vasculature, causing vasodilation and reducing pulmonary artery pressure.
| Metabolism | Primarily hepatic via CYP3A4 (major) and CYP2C9 (minor) isoenzymes; metabolized to N-desmethyl sildenafil (active metabolite) with half-life ~4 hours. |
| Excretion | Approximately 80% fecal, 13% renal as metabolites; <1% unchanged in urine. |
| Half-life | Terminal elimination half-life 3-5 hours; clinical effect duration shorter due to distribution. |
| Protein binding | 96% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 1 L/kg (range 0.5-1.5); indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability 40% due to first-pass metabolism; increased by high-fat meal (delayed absorption). |
| Onset of Action | Oral: 30-60 minutes; peak effect 1 hour. |
| Duration of Action | 4-6 hours; may persist up to 12 hours with high-fat meal or mild erectile dysfunction. |
50 mg orally as needed approximately 1 hour before sexual activity; range 25-100 mg based on efficacy and tolerability; maximum dosing frequency once per day.
| Dosage form | TABLET |
| Renal impairment | For GFR < 30 mL/min: consider starting dose of 25 mg due to reduced clearance; no adjustment needed for GFR >= 30 mL/min. |
| Liver impairment | For Child-Pugh class A and B: consider starting dose of 25 mg due to reduced clearance; for Child-Pugh class C: not recommended. |
| Pediatric use | Not FDA-approved for pediatric use; however, for pulmonary arterial hypertension in children: weight-based dosing of 0.3-1 mg/kg/dose every 4-8 hours, max 20 mg/dose, titrated based on response. |
| Geriatric use | Plasma concentrations of sildenafil are increased in elderly (>=65 years); consider starting dose of 25 mg due to reduced clearance; adjust based on tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Nitrates can cause severe hypotension Can cause priapism and sudden hearing loss.
| Breastfeeding | Excreted into breast milk in small amounts. M/P ratio unknown. No adverse effects reported in nursing infants. Consider risk-benefit; caution in preterm infants or those with renal impairment. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies showed no evidence of teratogenicity or embryotoxicity. No adequate human studies in first trimester; use only if clearly needed. In second and third trimesters, increased risk of fetal hypotension and uterine hyperstimulation has been reported, especially when used for fetal growth restriction. Avoid in preeclampsia due to vasodilatory effects. |
■ FDA Black Box Warning
None
| Common Effects | PAH |
| Serious Effects |
["Concurrent use with any nitrate (organic nitrates, nitrites) or nitric oxide donors","Concurrent use with riociguat (a soluble guanylate cyclase stimulator)","Severe hepatic impairment (Child-Pugh C)","Severe renal impairment (CrCl <30 mL/min) for PAH indication","Known hypersensitivity to sildenafil or any component"]
| Precautions | ["Risk of hypotension when used with nitrates or alpha-blockers","Contraindicated in patients with severe hepatic impairment (Child-Pugh C) or severe renal impairment (CrCl <30 mL/min)","Use caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, Peyronie's disease) or conditions predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia)","Avoid use in patients with cardiovascular disease where sexual activity is inadvisable (e.g., unstable angina, recent MI, uncontrolled hypertension)","Risk of non-arteritic anterior ischemic optic neuropathy (NAION) and sudden hearing loss","Concurrent use with ritonavir or other potent CYP3A4 inhibitors increases sildenafil exposure"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate, fetal heart rate via ultrasound, and uterine activity. Assess for signs of priapism, hypotension, and vision/hearing loss. In pregnancy, monitor fetal growth and amniotic fluid index. |
| Fertility Effects | No adverse effects on fertility in animal studies. May slightly improve sperm motility/morphology in men with erectile dysfunction. No known impact on female fertility. |