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. |
| Molecular Weight | 666.7 |
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 | Limited data; no teratogenicity in animal studies, but avoid unless clearly needed. |
| 2nd trimester | Use only if potential benefit justifies risk; monitor for maternal hypotension. |
| 3rd trimester | Avoid due to risk of fetal acidosis, neonatal respiratory distress, and maternal hemodynamic instability. |
Clinical note
Nitrates can cause severe hypotension Can cause priapism and sudden hearing loss.
| Placental transfer | Minimal placental transfer; limited human data show low levels in fetal circulation. |
| Breastfeeding | Potentially excreted in breast milk; limited data suggest minimal risk, but caution advised due to unknown effects on infant. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Common Effects | PAH |
| Serious Effects |
Concurrent use of nitratesHypersensitivity to sildenafilSevere hepatic impairment (Child-Pugh C)Severe hypotension (sBP <90 mmHg)Recent stroke or myocardial infarctionRetinitis pigmentosa
| 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 |
Loading safety data…
| L3 (Moderately safe) |
| 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. |
| 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. |
| Food/Dietary | Avoid high-fat meals (e.g., cheeseburgers, fried foods) as they delay absorption and reduce peak concentration. Grapefruit juice may increase sildenafil levels and should be avoided. Alcohol can potentiate vasodilation and orthostatic hypotension. |
| Clinical Pearls | Use with caution in patients with cardiovascular disease; contraindicated with nitrates. May cause non-arteritic anterior ischemic optic neuropathy (NAION). Onset is 30-60 minutes, duration ~4 hours. Dose adjustment needed for hepatic impairment (Child-Pugh class B and C) and severe renal impairment (CrCl <30 mL/min). |
| Patient Advice | Do not take with nitrates (e.g., nitroglycerin) as it can cause a dangerous drop in blood pressure. · Take approximately 1 hour before sexual activity. Do not take more than once daily. · Common side effects include headache, flushing, dyspepsia, and nasal congestion. · Seek immediate medical attention if you experience sudden vision loss or an erection lasting more than 4 hours. · Avoid consuming alcohol in large amounts as it may reduce the effectiveness and increase side effects. · Inform your doctor about all medications you are taking, especially alpha-blockers, antihypertensives, and other ED treatments. |