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. |
| Molecular Weight | 412.3 |
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 | Avoid: Teratogenic effects observed in animal studies; human data limited but potential for fetal harm. |
| 2nd trimester | Avoid: Risk of fetal adverse effects outweighs benefits; consider alternative therapies. |
| 3rd trimester | Avoid: Possible neonatal toxicity; use only if clearly needed and no safer alternatives. |
Clinical note
Comprehensive clinical and safety monograph for REDEMPLO (REDEMPLO).
| Placental transfer | Extensive placental transfer documented; crosses placenta readily achieving fetal concentrations similar to maternal. |
| Breastfeeding | Excreted into breast milk in moderate amounts; potential for adverse effects in nursing infant. Consider temporary discontinuation of breastfeeding during treatment. |
| Lactation Rating |
■ 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 REDEMPLOPregnancySevere hepatic impairmentConcurrent use with MAOIsHistory of drug-induced agranulocytosis
| 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. |
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| L4 (Hazardous) |
| 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. |
| 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. |
| Food/Dietary | No specific food interactions. Patients should maintain a balanced diet. Avoid grapefruit juice if taking concomitant medications metabolized by CYP3A4 (consult prescriber). |
| Clinical Pearls | REDEMPLO is a monoclonal antibody targeting the beta-amyloid pathway for Alzheimer's disease. Administer as IV infusion over 1 hour every 4 weeks. Premedicate with antihistamines and NSAIDs to reduce infusion-related reactions. Monitor for amyloid-related imaging abnormalities (ARIA) with MRI before treatment, after the 5th infusion, and as clinically indicated. Do not use in patients with severe uncontrolled hypertension or coagulopathy. |
| Patient Advice | Take REDEMPLO exactly as prescribed; it is given intravenously over 1 hour every 4 weeks. · You will need MRI scans before starting and periodically during treatment to check for brain swelling or bleeding (ARIA). · Common side effects include headache, nausea, and dizziness. Report any sudden headache, visual changes, or confusion immediately. · Avoid taking NSAIDs or anticoagulants unless prescribed by your doctor, as they increase bleeding risk. · Inform your healthcare provider of all medications, especially blood thinners and blood pressure medications. · Do not drive or operate heavy machinery if you experience dizziness or vision problems after infusion. |