RAPAFLO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RAPAFLO (RAPAFLO).
Selective antagonist of alpha-1A adrenergic receptors in the prostate, bladder neck, and urethra, causing smooth muscle relaxation and improving urinary flow.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2D6; also metabolized by glucuronidation (UGT2B7). |
| Excretion | RAPAFLO (silodosin) is eliminated primarily via hepatic metabolism, with approximately 33.5% of the dose excreted in urine (as metabolites) and 54.9% in feces (as metabolites). Less than 1% is excreted unchanged in urine. |
| Half-life | The terminal elimination half-life of silodosin is approximately 13.3 hours in healthy subjects, with clinical effects sustained for 24 hours allowing once-daily dosing. |
| Protein binding | Silodosin is approximately 96.6% bound to plasma proteins, primarily to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | The apparent volume of distribution (Vd/F) is approximately 0.81 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Absolute oral bioavailability of silodosin is approximately 32%. When taken with a high-fat meal, Cmax is reduced by 18-43% and AUC by 4-49%; therefore, it is recommended to take RAPAFLO with a meal to reduce variability. |
| Onset of Action | Onset of action for symptom relief in benign prostatic hyperplasia (BPH) occurs within 2-6 hours after oral administration, with maximal effects on peak urinary flow rate observed within 2-6 hours. |
| Duration of Action | Duration of action is approximately 24 hours, supporting once-daily dosing. Clinical effects on urinary symptoms and flow rates are maintained over 24 hours with steady-state achieved after 3-5 days. |
8 mg orally once daily, approximately 30 minutes after the same meal each day.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in severe renal impairment (CrCl < 30 mL/min). No adjustment for mild to moderate impairment (CrCl ≥ 30 mL/min). |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; however, elderly patients may be more sensitive to hypotensive effects. Initiate with caution. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RAPAFLO (RAPAFLO).
| Breastfeeding | Not recommended. Unknown if excreted in human milk. M/P ratio not established. Discontinue nursing or drug, considering importance of drug to mother. |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies. No adequate human studies in pregnant women. Risk cannot be ruled out; use only if clearly needed. |
| Fetal Monitoring | Monitor blood pressure and heart rate in pregnant women. Assess for orthostatic hypotension. Fetal monitoring per standard obstetric care if drug used. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to silodosin or any component, severe renal impairment (CrCl <30 mL/min), severe hepatic impairment (Child-Pugh Class C), concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir).
| Precautions | Orthostatic hypotension (especially with dose escalation or concurrent antihypertensives), syncope, priapism, intraoperative floppy iris syndrome (during cataract surgery), risk of HQT prolongation (avoid in patients with known QT prolongation or on Class Ia/III antiarrhythmics), hepatotoxicity, use with caution in renal impairment (CrCl <30 mL/min). |
Loading safety data…
| Fertility Effects | In animal studies, impaired fertility in male rats at high doses. No human data. Potential for reduced spermatogenesis or ejaculatory dysfunction. |