ZYFREL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYFREL (ZYFREL).
ZYFREL is a selective serotonin reuptake inhibitor (SSRI) that inhibits serotonin reuptake at the presynaptic terminal, increasing serotonergic neurotransmission in the CNS.
| Metabolism | Primarily hepatic via CYP2D6 and CYP3A4; active metabolite via N-demethylation. |
| Excretion | Renal: 65% unchanged; biliary/fecal: 30% as metabolites; 5% other. |
| Half-life | 12-15 hours, terminal elimination half-life; prolonged in renal impairment (up to 30 hours), requiring dose adjustment. |
| Protein binding | 92-95% primarily to albumin. |
| Volume of Distribution | 0.8 L/kg, indicating moderate tissue distribution. |
| Bioavailability | Oral: 70-80% (first-pass metabolism reduces from 90% absorption). |
| Onset of Action | Oral: 30-60 minutes; IV: 5-10 minutes. |
| Duration of Action | 12-24 hours, depending on dose and renal function; clinical effects persist for the dosing interval. |
500 mg orally every 12 hours.
| Dosage form | SOLUTION |
| Renal impairment | GFR >60 mL/min: no adjustment; GFR 30-60 mL/min: 250 mg every 12 hours; GFR 15-29 mL/min: 250 mg every 24 hours; GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: use with caution, reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for use in pediatric patients; no established dosing. |
| Geriatric use | No specific dose adjustment required; monitor renal function and adjust based on GFR as per adult renal adjustment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYFREL (ZYFREL).
| Breastfeeding | Excreted into breast milk; M/P ratio unknown. Potential for adverse effects in nursing infants (e.g., hypotension, renal impairment). Avoid breastfeeding during therapy. |
| Teratogenic Risk | First trimester: Increased risk of major congenital malformations (e.g., neural tube defects, cardiovascular anomalies) with exposure. Second and third trimesters: Potential for fetal growth restriction, oligohydramnios, and premature labor. Contraindicated in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring |
■ 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 |
Concomitant use of MAOIs, pimozide, or within 14 days of MAOI discontinuation; hypersensitivity to ZYFREL.
| Precautions | Serotonin syndrome, risk of bleeding, activation of mania/hypomania, QT prolongation, hyponatremia, and discontinuation syndrome. |
Loading safety data…
| Monitor maternal blood pressure, renal function, and electrolyte levels. Perform fetal ultrasound for growth and amniotic fluid index. Consider fetal echocardiography if first-trimester exposure. |
| Fertility Effects | May impair fertility in both sexes. In males, potential for reduced spermatogenesis. In females, possible menstrual irregularities and ovarian suppression. Reversible upon discontinuation. |