EpilepsyRx

Trimethadione

Tridione · Discontinued

Historical antiseizure indications · Discontinued

Indication / use

Label / evidence summary
Discontinued. Historical Tridione indication: absence seizures refractory to other drugs.
Role
Historical maintenance use · Discontinued
Class
Oxazolidinedione antiseizure medication

Historical reference only. The linked FDA PDF is an archived label, not a current DailyMed product label. Discontinued marketing status does not by itself establish the reason for discontinuation or withdrawal of approval.

Formulations & strengths

Archived U.S. label; historical strengths, not current availability.

Brand & formulation labels

Each link names the product and formulation it covers. Archived labels do not establish current availability.

Dosing & administration

Adult / product-specific schedule
Historical label: start 900 mg/day; increase by 300 mg/day at weekly intervals. Usual total 900–2,400 mg/day in 3–4 equal doses; use the lowest effective maintenance dose.
Pediatric
Historical label: usually 300–900 mg/day in 3–4 equal doses. No numeric minimum age is stated.
Titration / repeat dosing
Historical information only. The archived warning restricts use to refractory absence seizures after less toxic drugs fail; strict supervision and toxicity monitoring were required.
Dose basis
Historical archived-label dosing for a discontinued drug; included for reference, not current prescribing.

Practical administration

Product instructions
Historical chewable oral tablet; archived label specified refrigerated storage.

Dose adjustment & concentrations

Renal impairment
Use extreme caution in renal dysfunction; active dimethadione is slowly cleared by the kidney.
Hepatic impairment
Use extreme caution in hepatic dysfunction; archived label requires monitoring for liver injury.
Serum reference information
No established therapeutic serum range is supplied in the cited label.

Safety

Boxed warning
Prominent archived warning: fetal malformations and serious adverse effects; use was restricted to absence seizures unresponsive to less toxic medicines.
Contraindications
Known hypersensitivity to trimethadione.
Serious precautions & monitoring
Severe blood dyscrasias, nephrosis, liver injury, exfoliative dermatitis, visual disturbance and lupus-like or myasthenia-like syndromes. Archived label calls for close supervision and baseline / monthly blood counts, with renal and liver monitoring.

Common / selected adverse effects

  • Drowsiness / ataxia
  • Visual disturbance in bright light
  • Nausea / gastrointestinal symptoms
  • Rash

Selected label-reported effects; frequencies cannot be compared across drugs.

Drug interactions: toxicity & clinical action

Partner / combinationClinical effectClinical action
Other sedating medicines / alcoholPotential additive CNS impairment.Review the full regimen; the archived label warns about impaired alertness.

Selected interactions; consult the full label and complete medication list.

Pregnancy & contraception

Fetal / neonatal risk
Well-recognized fetal malformation risk; the archived label strongly warns against pregnancy exposure. Fetal trimethadione syndrome and pregnancy loss have been described.

Clinical evidence

Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.

Product-label evidence

Trial summary

Study design / duration
No modern pivotal randomized trial is summarized in the cited label.
Primary endpoint
No quantified pivotal endpoint supplied in the cited label.

This profile uses product-label evidence; no pivotal journal publication is asserted.

Comparative evidence

Findings
No head-to-head efficacy comparison is summarized.

Mechanism of action

  • Proposed target: low-voltage-activated T-type calcium channels in thalamic neurons. Electrophysiology studies found that dimethadione, the active metabolite of trimethadione, reduced the low-threshold calcium current at clinically relevant concentrations.
  • Hepatic demethylation produces dimethadione. In rodent thalamocortical slices, dimethadione was substantially more effective than the parent drug at suppressing absence-like discharges, paralleling their relative effects on T-type current.
  • These cellular and animal findings support a proposed mechanism; the historical product label does not assign a precise molecular target.

Pharmacology

Adult values unless specified. Vd/F denotes apparent oral distribution volume.

Pharmacokinetics

Bioavailability
Rapidly absorbed from the gastrointestinal tract; absolute bioavailability not quantified in the archived label.
Elimination half-life
A small single-dose study in 11 young and 11 elderly men reported mean parent half-lives of 11.8 and 23.5 hours, respectively. These are study-specific estimates, not a universal clinical range.
Volume of distribution
Not quantified in the cited product label.
Active metabolite(s)
Dimethadione (active).
Active-metabolite half-life
Not quantified in the cited label or the parent-drug study summarized here; do not substitute the parent half-life.
Protein binding
Not quantified in the cited product label.
Metabolism / elimination
Hepatic demethylation to dimethadione. Most of the dose is slowly excreted renally as dimethadione; about 3% is excreted unchanged.

Values reflect the cited product and study population; they are not interchangeable across formulations.

Molecular structure

Molecular structure of Trimethadione
Principal compound; salt and product forms may differ.
NIH PubChem structure and record ↗

Product history

Initial U.S. approval
January 25, 1946 — Tridione (NDA 005856)
Market / formulation history
FDA application lists Tridione products as Discontinued; this entry describes the 150 mg tablet in the archived 2012 label.
Brands
Tridione · Discontinued
Manufacturer / marketer
Abbott in the archived label
Generic availability
No currently marketed U.S. product is identified in the cited FDA application.
Related drugs
Paramethadione is another historical oxazolidinedione.

Sources & review status

Archived FDA label and product marketing status checked: 2026-09-27. Other profile sources reviewed: 2026-09-27 · label revision noted at that review: Archived FDA Tridione label: 2012.. This is a draft reference; final review is pending.