TRIDIONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIDIONE (TRIDIONE).
Increases seizure threshold by modulating voltage-gated sodium channels and enhancing GABA-ergic inhibition.
| Metabolism | Primarily hepatic via CYP450 enzymes; active metabolite dimethadione. |
| Excretion | Renal: ~70% as unchanged drug and metabolites (including dimethadione); biliary/fecal: minimal (<10%). |
| Half-life | 16-24 hours (trimethadione); dimethadione (active metabolite) has a half-life of ~6-12 days, leading to drug accumulation. |
| Protein binding | <10% bound to plasma proteins. |
| Volume of Distribution | 0.5-0.7 L/kg, indicating distribution into total body water. |
| Bioavailability | PO: ~100%. |
| Onset of Action | PO: 2-4 hours (anticonvulsant effect). |
| Duration of Action | 6-8 hours (single dose); chronic use: sustained due to long-lived metabolite. |
300-600 mg orally three times daily; titrate to seizure control.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in severe renal impairment (GFR <30 mL/min). For GFR 30-60 mL/min, reduce dose by 50%. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). For Child-Pugh B, reduce dose by 50%. |
| Pediatric use | Initial 25-50 mg/kg/day in 3-4 divided doses; maintenance 100-200 mg/kg/day. |
| Geriatric use | Start at lowest effective dose; monitor for renal function and CNS side effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIDIONE (TRIDIONE).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Contraindicated due to risk of neonatal hepatic toxicity and adverse effects. Discontinue nursing or avoid drug. |
| Teratogenic Risk | First trimester: High risk of major congenital malformations including neural tube defects, cleft lip/palate, and congenital heart defects. Second/third trimester: Risk of intrauterine growth restriction, microcephaly, and neurodevelopmental delay. Avoid in pregnancy unless benefit outweighs teratogenic risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
May cause fatal hepatotoxicity and blood dyscrasias (aplastic anemia, agranulocytosis).
| Serious Effects |
["Hypersensitivity to trimethadione or components","Severe hepatic disease","Severe renal disease","Blood dyscrasias"]
| Precautions | ["Hepatotoxicity risk","Bone marrow suppression","Teratogenicity","SLE-like syndrome","Visual disturbances (glare phenomenon)","Renal impairment"] |
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| Maternal: CBC, liver function tests, renal function, and urinalysis at baseline and periodically. Fetal: Ultrasound for malformations, fetal growth monitoring, and consider fetal echocardiography. Monitor for neonatal bleeding if used near term. |
| Fertility Effects | May impair female fertility due to inhibition of ovulation; reversible upon discontinuation. Male fertility: No well-documented effects, but potential for decreased spermatogenesis based on animal data. |