NORMIFLO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORMIFLO (NORMIFLO).
NORMIFLO is a selective alpha-1 adrenergic receptor antagonist that inhibits the binding of norepinephrine to alpha-1 receptors in the smooth muscle of the prostate and bladder neck, leading to relaxation of these muscles and improved urine flow.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2D6 isoenzymes; undergoes extensive first-pass metabolism. |
| Excretion | Renal excretion of unchanged drug accounts for 65-75% of elimination; biliary/fecal excretion accounts for 20-30%, with the remainder as metabolites. |
| Half-life | Terminal elimination half-life is 8-12 hours in adults with normal renal function; prolonged to 20-30 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 90-95% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.5-0.8 L/kg, indicating moderate tissue distribution. |
| Bioavailability | Oral bioavailability is 80-90% with moderate interindividual variability. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 2-5 minutes. |
| Duration of Action | Oral: 6-8 hours; Intravenous: 4-6 hours; duration is dose-dependent and may be extended in hepatic impairment. |
Adults: 75 mg orally once daily.
| Dosage form | INJECTABLE |
| Renal impairment | GFR ≥30 mL/min: No adjustment. GFR 15-29 mL/min: 50 mg once daily. GFR <15 mL/min: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 50 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Children ≥6 years: 2 mg/kg orally once daily; maximum 75 mg. |
| Geriatric use | Adults ≥65 years: 50 mg once daily; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORMIFLO (NORMIFLO).
| Breastfeeding | No data on excretion in human milk; M/P ratio unknown. Due to potential for anti-androgenic effects in nursing infants, recommend avoiding breastfeeding during therapy and for at least 5 half-lives after last dose. |
| Teratogenic Risk | First trimester: Limited data, but based on animal studies and class effect (anti-androgen), risk of ambiguous genitalia in male fetuses (hypospadias) cannot be excluded. Second and third trimesters: Continued exposure may cause feminization of male fetuses due to androgen receptor blockade; also risk of preterm labor and fetal growth restriction. Avoid use in pregnancy unless no alternative. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to NORMIFLO or any component of the formulation","Use of strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) due to increased risk of hypotension","Severe hepatic impairment","History of orthostatic hypotension or syncope"]
| Precautions | ["Orthostatic hypotension, especially at initiation of therapy or dose increase; advise patients to avoid sudden postural changes.","Intraoperative floppy iris syndrome (IFIS) during cataract surgery.","Caution in patients with severe hepatic impairment.","Dizziness, syncope, and somnolence; avoid driving or hazardous activities until response is known."] |
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| Fetal Monitoring | Monitor maternal liver function tests, serum electrolytes, and blood pressure. In pregnant patients, perform fetal ultrasound for growth and anatomy, and assess amniotic fluid volume. Monitor for signs of preterm labor. |
| Fertility Effects | In males: may cause reversible oligospermia, decreased libido, and erectile dysfunction. In females: may disrupt menstrual cycle and inhibit ovulation. Fertility effects reverse after discontinuation. |