NUMBRINO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NUMBRINO (NUMBRINO).
Selective serotonin reuptake inhibitor (SSRI); increases synaptic serotonin by inhibiting SERT.
| Metabolism | Hepatic via CYP2D6, CYP3A4, and CYP2C19; active metabolite norfluoxetine. |
| Excretion | Renal: 70% unchanged; hepatic metabolism: 20%; fecal: 10% |
| Half-life | Terminal half-life 12-15 hours; prolonged in renal impairment (up to 30 hours in CrCl <30 mL/min) |
| Protein binding | 95% bound to albumin |
| Volume of Distribution | 0.3-0.5 L/kg; indicates moderate tissue distribution |
| Bioavailability | Oral: 80% (due to first-pass metabolism) |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes |
| Duration of Action | 6-8 hours; extended in hepatic impairment |
2 mg/kg intravenously every 8 hours, max 150 mg per dose.
| Dosage form | SOLUTION |
| Renal impairment | GFR >60 mL/min: no adjustment; GFR 30-60: 50% dose reduction; GFR <30: avoid use or administer 25% dose with extended interval. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: 50% dose reduction; Child-Pugh class C: contraindicated. |
| Pediatric use | 3 mg/kg intravenously every 12 hours for children 1 month to 12 years; for infants <1 month: 4 mg/kg every 24 hours. |
| Geriatric use | Reduce dose by 25% from standard; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NUMBRINO (NUMBRINO).
| Breastfeeding | Excreted in breast milk; M/P ratio 1.2 (estimated). Avoid breastfeeding due to potential adverse effects on infant renal function and growth. If exposure unavoidable, monitor infant for oliguria, hyperkalemia, and weight loss. |
| Teratogenic Risk | First trimester: Probable major malformations (neural tube defects, cardiac anomalies) based on animal studies and limited human data; avoid use. Second trimester: Increased risk of intrauterine growth restriction (IUGR) and oligohydramnios. Third trimester: Risk of premature closure of ductus arteriosus, neonatal pulmonary hypertension, and renal impairment. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
Concurrent MAOIs, linezolid, methylene blue; known hypersensitivity; concurrent pimozide or thioridazine; use in patients with uncontrolled angle-closure glaucoma.
| Precautions | Serotonin syndrome, MAOI interaction, bleeding risk, hyponatremia, activation of mania/hypomania, seizure threshold lowering, angle-closure glaucoma, sexual dysfunction, QT prolongation at high doses. |
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| Fetal Monitoring | Maternal: Serum creatinine, BUN, liver enzymes, and blood pressure weekly. Fetal: Ultrasound for growth, amniotic fluid index, and Doppler studies every 2-4 weeks. In third trimester, fetal echocardiography for ductus arteriosus patency. |
| Fertility Effects | Reversible impairment of spermatogenesis in males (reduced sperm count and motility) due to direct testicular toxicity. In females, may cause anovulation and menstrual irregularities via hormonal disruption. Effects are dose-dependent and typically resolve within 3-6 months of discontinuation. |