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. |
| Molecular Weight | 345.42 |
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 | Avoid unless absolutely necessary. Limited human data; animal studies suggest risk. |
| 2nd trimester | Avoid unless benefit outweighs risk. May cause fetal harm. |
| 3rd trimester | Avoid in third trimester; may cause adverse effects in neonate. |
Clinical note
Comprehensive clinical and safety monograph for ZYFREL (ZYFREL).
| Placental transfer | Crosses placenta in animals; unknown degree in humans. Likely due to low molecular weight and lipophilicity. |
| Breastfeeding | Not recommended. Unknown if excreted in human milk; potential for serious adverse reactions in nursing infants. |
| Lactation Rating |
■ 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 |
History of hypersensitivity to ZYFRELSevere hepatic impairmentConcurrent use with strong CYP3A4 inducers
| Precautions | Serotonin syndrome, risk of bleeding, activation of mania/hypomania, QT prolongation, hyponatremia, and discontinuation syndrome. |
| Food/Dietary | Take with or without food. Grapefruit juice may increase tramadol plasma concentrations; avoid concurrent use. Avoid excessive caffeine intake as it may increase the risk of seizures. |
| Clinical Pearls |
Loading safety data…
| L5 - Contraindicated |
| 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 | 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. |
| ZYFREL (tramadol hydrochloride) is a centrally acting analgesic with mu-opioid receptor agonism and serotonin/norepinephrine reuptake inhibition. Monitor for serotonin syndrome when used with SSRIs, SNRIs, MAOIs, or triptans. Avoid in patients with a history of seizures or those taking medications that lower seizure threshold. Renal dose adjustment required: for CrCl <30 mL/min, extend dosing interval to q12h. Do not exceed 400 mg/day (300 mg in patients >75 years). Onset of action ~1 hour; peak effect at 2-3 hours. Risks of opioid withdrawal with abrupt discontinuation after prolonged use. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not crush, chew, or break extended-release tablets; swallow whole. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they increase risk of respiratory depression and sedation. · May cause dizziness or drowsiness; do not drive until you know how this medication affects you. · Inform your doctor if you have a history of seizures, head injury, liver or kidney disease, or if you are pregnant or breastfeeding. · Do not stop suddenly; your doctor will taper the dose to prevent withdrawal symptoms. · Keep out of reach of children and store in a secure place to prevent accidental overdose. · Do not share this medication with others as it may cause serious harm or death. |