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. |
| Molecular Weight | 322.4 |
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 | Avoid. Teratogenic in animal studies; insufficient human data. |
| 2nd trimester | Avoid except if benefit outweighs risk. |
| 3rd trimester | Avoid; may cause neonatal adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for TRIALODINE (TRIALODINE).
| Placental transfer | Crosses placenta (molecular weight <500 Da). |
| Breastfeeding | Excreted in breast milk; potential for sedation and respiratory depression in infant. Use only if clearly needed and monitor infant. |
| Lactation Rating | L4 - Possibly Hazardous |
■ 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 |
Hypersensitivity to trialodine or any componentAcute narrow-angle glaucomaUrinary retentionSevere respiratory insufficiencyConcurrent MAOI therapy
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase TRIALODINE levels by inhibiting CYP3A4. High-fat meals may delay absorption; take consistently with or without food. Avoid alcohol. |
Loading safety data…
| 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. |
| 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. |
| Clinical Pearls | TRIALODINE is a synthetic opioid analgesic; monitor for respiratory depression especially in opioid-naïve patients and those with COPD. Due to its long half-life (24-48 hours), dose titration should be gradual. Avoid in patients with paralytic ileus or suspected surgical abdomen. Contraindicated in patients with known hypersensitivity to triazoline opioids. In renal impairment (CrCl <30 mL/min), reduce dose by 50%. |
| Patient Advice | Do not crush or chew extended-release tablets; swallow whole. · Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines) due to risk of severe sedation and respiratory depression. · Do not stop abruptly; withdrawal symptoms (e.g., anxiety, sweating, diarrhea) may occur. · Store in a secure place out of reach of children; do not share medication. · May cause constipation; increase fluid and fiber intake, and consider stool softeners if needed. · Report dizziness, slow heart rate, or difficulty breathing immediately. · Do not drive or operate machinery until you know how TRIALODINE affects you. |