SILDAFLO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SILDAFLO (SILDAFLO).
Selective inhibitor of phosphodiesterase type 5 (PDE5), enhancing nitric oxide-mediated vasodilation by increasing cyclic guanosine monophosphate (cGMP) levels in vascular smooth muscle.
| Metabolism | Primarily hepatic via CYP3A4 (major) and CYP2C9 (minor) isoforms. |
| Excretion | Primarily hepatic metabolism (>80%) with metabolites excreted in feces (approximately 70-80% of dose) and urine (approximately 20-30% as metabolites); less than 1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 4-5 hours in healthy adults; may be prolonged in elderly patients and those with hepatic impairment. |
| Protein binding | Approximately 96% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Volume of distribution is approximately 105 L (1.5 L/kg based on 70 kg); indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 40% (range 25-63%) due to first-pass metabolism; enhanced by high-fat meal (delays absorption but may increase AUC). |
| Onset of Action | Oral: Onset of clinical effect (erection sufficient for intercourse) occurs within 30-60 minutes; maximal effect at 1-2 hours. |
| Duration of Action | Duration of effect up to 4-6 hours; clinical responsiveness may persist up to 12 hours in some patients. |
50 mg orally once daily, approximately 1 hour before sexual activity; or 100 mg orally once daily maximum dose. Alternatively, 25 mg orally once daily for elderly or patients with renal impairment. Dose may be increased to 100 mg or decreased to 25 mg based on efficacy and tolerability.
| Dosage form | DRESSING |
| Renal impairment | For CrCl 30-50 mL/min: starting dose 25 mg once daily; maximum 50 mg per dose. For CrCl <30 mL/min: contraindicated (dialysis studies not available). |
| Liver impairment | For Child-Pugh class A and B: starting dose 25 mg once daily; maximum 50 mg per dose. For Child-Pugh class C: contraindicated (no studies). |
| Pediatric use | Not recommended for use in pediatric patients (<18 years) as safety and efficacy not established. |
| Geriatric use | Patients ≥65 years: starting dose 25 mg once daily; maximum 50 mg per dose due to increased plasma concentrations and reduced clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SILDAFLO (SILDAFLO).
| Breastfeeding | Sildenafil is excreted in breast milk in low amounts. Milk-to-plasma ratio (M/P) unknown. Relative infant dose estimated <0.5% of maternal weight-adjusted dose. No adverse effects reported in breastfed infants. Use with caution, consider infant risk of adverse effects (e.g., hypotension). |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies with sildenafil at doses up to 32 times the MRHD revealed no evidence of teratogenicity or embryotoxicity. No adequate human studies in pregnant women. Risk cannot be ruled out; use only if clearly needed. First trimester: limited data; no increased risk of major malformations reported. Second/third trimester: avoid in women with pulmonary hypertension due to increased maternal mortality; no fetal harm reported in limited cases. |
■ FDA Black Box Warning
Not approved for use in pediatric patients; increased mortality risk in children with pulmonary hypertension.
| Serious Effects |
["Concomitant use of nitrates","Concomitant use of guanylate cyclase stimulators (e.g., riociguat)","Known hypersensitivity to sildenafil"]
| Precautions | ["Risk of hypotension when co-administered with nitrates","Priapism risk","Vision or hearing loss","Avoid in severe hepatic impairment","Avoid in patients with retinitis pigmentosa"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate due to vasodilatory effects. Assess fetal heart rate patterns if used near term for potential effects on uteroplacental perfusion. In pulmonary hypertension: continuous maternal hemodynamic monitoring and fetal monitoring via ultrasound and non-stress test. |
| Fertility Effects | In males: no effect on spermatogenesis or sperm motility demonstrated; may improve erectile function in men with infertility due to ejaculatory dysfunction. In females: no human data; animal studies show no impairment of fertility at doses up to 60 mg/kg/day. Sildenafil may enhance uterine blood flow and endometrial receptivity, theoretical benefit in assisted reproduction but not established. |