REDEMPLO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REDEMPLO (REDEMPLO).
REDEMPLO is a synthetic tricyclic analog that acts as a selective serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It binds to the presynaptic transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT), inhibiting their reuptake and increasing synaptic concentrations of these monoamines. Additionally, it has weak antagonistic properties at the 5-HT2A and alpha-2 adrenergic receptors, contributing to its antidepressant and anxiolytic effects.
| Metabolism | REDEMPLO undergoes extensive hepatic metabolism primarily via cytochrome P450 (CYP) 2D6 and, to a lesser extent, CYP3A4 and CYP2C9. The major active metabolite, N-desmethylredemplo, is formed by N-demethylation via CYP2D6 and contributes to the therapeutic effect. Approximately 30% of the dose is excreted unchanged in urine, with the remainder as metabolites. |
| Excretion | Primarily hepatic metabolism with 70% renal excretion of metabolites and 30% fecal elimination; less than 5% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is 12-15 hours in healthy adults; prolonged in hepatic impairment (up to 30 hours) and end-stage renal disease (up to 40 hours). |
| Protein binding | 92-96% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.6-0.8 L/kg, indicating moderate tissue distribution; increased in cardiac failure or hypoalbuminemia. |
| Bioavailability | Oral: 75% (range 60-90%) with high interindividual variability; intramuscular: 80-90%; subcutaneous: similar to intramuscular. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes; Intramuscular: 15-30 minutes. |
| Duration of Action | Oral and intramuscular: 6-8 hours; Intravenous: 4-6 hours; duration is dose-dependent and increased in hepatic impairment. |
100 mg orally once daily, with or without food.
| Dosage form | SOLUTION |
| Renal impairment | GFR ≥60 mL/min: no adjustment; GFR 30-59 mL/min: 50 mg once daily; GFR 15-29 mL/min: 25 mg once daily; GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 50 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Weight <40 kg: 2.5 mg/kg orally once daily (max 100 mg); Weight ≥40 kg: 100 mg once daily. |
| Geriatric use | No specific dose adjustment recommended, but monitor renal function and consider starting at lower end of dosing range due to age-related decline in renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REDEMPLO (REDEMPLO).
| Breastfeeding | REDEMPLO is excreted in human milk; the milk-to-plasma ratio is 0.8. Potential for serious adverse reactions in breastfeeding infants; therefore, women should not breastfeed during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | REDEMPLO is contraindicated in pregnancy. First trimester exposure is associated with major congenital malformations including neural tube defects and cardiac anomalies. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and neonatal renal impairment. |
■ FDA Black Box Warning
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS REDEMPLO increased the risk of suicidal thinking and behavior in short-term studies in children, adolescents, and young adults with major depressive disorder (MDD) and other psychiatric disorders. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with MDD and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.
| Serious Effects |
Hypersensitivity to REDEMPLO or any excipients, concurrent use of MAOIs (or within 14 days of MAOI discontinuation), concurrent use of linezolid or methylene blue IV, uncontrolled narrow-angle glaucoma, severe hepatic impairment (Child-Pugh class C), and concomitant use with drugs known to cause QT prolongation (e.g., class IA/III antiarrhythmics, certain antipsychotics).
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| Fetal Monitoring |
| Monitor maternal renal function, hepatic function, and complete blood count monthly. Perform fetal ultrasound for anatomy and growth every 4 weeks. Assess amniotic fluid volume every trimester. Monitor neonatal renal function for 48 hours post-delivery. |
| Fertility Effects | REDEMPLO may impair fertility in females based on animal studies showing ovarian follicular atresia. In males, reversible reduction in spermatogenesis has been observed. Relevance to human fertility is unknown. |
| Precautions | Serotonin syndrome (risk with concurrent serotonergic drugs), increased risk of bleeding (especially with NSAIDs or anticoagulants), activation of mania/hypomania in bipolar disorder, angle-closure glaucoma (caution in patients with narrow angles), hyponatremia (SIADH, especially in elderly or volume-depleted patients), QT prolongation (caution in patients with cardiac disease or electrolyte abnormalities), sexual dysfunction, weight gain, and withdrawal symptoms upon abrupt discontinuation. |