TRIALODINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIALODINE (TRIALODINE).
TRIALODINE is a selective serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that potentiates the effects of serotonin, norepinephrine, and dopamine by blocking their reuptake at presynaptic neurons.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2D6 isoenzymes; active metabolite TRIALODINE-M1 contributes to therapeutic effect. |
| Excretion | Renal excretion accounts for 70-80% of clearance, primarily as unchanged drug. Biliary/fecal elimination constitutes 15-20%, with the remainder as minor metabolites. |
| Half-life | Terminal elimination half-life is 6-8 hours in healthy adults; prolongs to 12-15 hours in moderate renal impairment (CrCl 30-50 mL/min). |
| Protein binding | 92-95% bound, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 1.5-2.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 60-70% due to first-pass metabolism; rectal: 80-90%; intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; intravenous: 2-5 minutes. |
| Duration of Action | Analgesic effect lasts 4-6 hours; respiratory depression may persist up to 8 hours after high doses. |
50–100 mg orally twice daily; maximum 200 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR ≥60 mL/min: no adjustment. GFR 30–59: 50 mg once daily. GFR 15–29: 25 mg once daily. GFR <15: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 50 mg once daily. Child-Pugh C: contraindicated. |
| Pediatric use | 1–2 mg/kg/dose orally twice daily; maximum 4 mg/kg/day (up to 200 mg/day). |
| Geriatric use | Initiate at 25 mg once daily; titrate slowly to a maximum of 100 mg/day. Monitor renal function and serum drug levels. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIALODINE (TRIALODINE).
| Breastfeeding | Excreted in human milk (M/P ratio 1.2). Peak milk concentration 2 hours post-dose. Relative infant dose 8% of maternal weight-adjusted dose. Avoid breastfeeding due to potential for infant hypotension and renal impairment. |
| Teratogenic Risk | First trimester: Limited human data; animal studies at 10x MRHD show skeletal anomalies (rib fusion, vertebral malformations). Second trimester: No specific pattern identified but risk of fetal growth restriction. Third trimester: May cause premature closure of ductus arteriosus (risk of persistent pulmonary hypertension) and oligohydramnios due to fetal renal effects. |
■ 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 with MAOIs or within 14 days of MAOI therapy.","Uncontrolled narrow-angle glaucoma.","Hypersensitivity to TRIALODINE or any excipients."]
| Precautions | ["May cause serotonin syndrome when used with other serotonergic drugs.","Monitor for increases in blood pressure and heart rate.","Avoid abrupt discontinuation; taper dose to reduce withdrawal symptoms.","Potential for activation of mania/hypomania in patients with bipolar disorder."] |
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| Fetal Monitoring | Baseline fetal ultrasound for anatomy and growth. Serial ultrasounds for fetal growth restriction (every 4 weeks). Fetal echocardiography at 20-24 weeks GA. Non-stress test or biophysical profile weekly from 32 weeks GA. Maternal blood pressure and renal function monitoring monthly. |
| Fertility Effects | Animal studies show reversible decreases in fertility at doses ≥5x MRHD. Human data limited: may impair ovulation in women (anti-angiogenic properties) but no evidence of permanent infertility. |