Paramethadione

157.16714

157.17

204-098-8

760129

DTXSID8023420

CLEAR, COLORLESS LIQUID|Liquid

N - Nervous system

2934999090

46.61000

0.70160

Liquid

d425 1.1180-1.1240

31-32 °C

101-102 °C @ Press: 11.3 Torr

nD25 1.449

1.35e+02 g/L

Store below 40 deg C (104 deg F), preferably between 15 and 25 deg C (59 and 77 deg F), unless otherwise specified by manufacturer. Store in a tight container. /Paramethadione Capsules/

FRUITY, ESTERLIKE ODOR

ABOUT 6 (1 IN 40 SOLN)

NONH for all modes of transport

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Graca LM, Machado MH; Acta Med Port 8 (7-8): 441-9 (1995). Teratogenic effects of exogenous agents.|Brent RL, Beckman DA; Clin Obstet Gynecol 37 (3): 646-70 (1994). The contribution of environmental teratogens to embryonic and fetal loss.|Stevenson RE; Human Malformations and Related Anomalies (Oxford Monographs on Medical Genetics 27: 137-68 (1993). The environmental basis of human anomalies.|Schardein JL; Chemically Induced Birth Defects 2: 157-207 (1993). /A review of the/ anticonvulsants.|For more Special Reports (Complete) data for PARAMETHADIONE (7 total), please visit the HSDB record page.

Symptoms of overdose include clumsiness or unsteadiness, coma, severe dizziness, severe drowsiness, severe nausea, and problems with vision.

Concurrent use of alcohol or CNS depression-producing medications with dione anticonvulsants may enhance CNS depression. /Dione anticonvulsants/|Concurrent use of tricyclic antidepressants; haloperidol; loxapine; maprotiline; molindone; monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and >10 mg/day selegiline; phenothiazines; pimozide; or thioxanthenes with dione anticonvulsants may lower the convulsive threshold, enhance CNS depression, and decrease the effects of the anticonvulsant medication. dosage adjustments may be necessary. /Dione anticonvulsants/|Concurrent use of phenacemide with dione anticonvulsants may result in additive toxicity. /Dione anticonvulsants/

Not significant

Used for the control of absence (petit mal) seizures that are refractory to treatment with other medications.

Anticonvulsants|/PARAMETHADIONE & TRIMETHADIONE/...WERE MAJOR AGENTS FOR TREATMENT OF PETIT MAL EPILEPSY & ATYPICAL SPIKE-AND-WAVE ABSENCE ATTACKS BEFORE INTRODUCTION OF ETHOSUXIMIDE. THOUGH EFFECTIVE, THEIR SIDE EFFECTS MAKE THEM DRUGS OF SECOND CHOICE.|MEDICATION (VET): ANTICONVULSANT. USE: NOW RARE, TO CONTROL CONVULSIONS IN ANIMALS.|Paramethadione and trimethadione are indicated in the control of absence (petit mal) seizures that are refractory to treatment with other medications. /Included in US product labeling./|... Its pharmacological properties, therapeutic uses, dosage, and toxicity are similar to those of trimethadione.

ALTHOUGH IT IS SLIGHTLY LESS POTENT, DOES NOT INDUCE MYASTHENIA GRAVIS-LIKE SYNDROME, & INDUCES PHOTOPHOBIA & SKIN RASHES IN SOMEWHAT FEWER PATIENTS, IT HAS SAME LIMITATIONS & EXHIBITS SAME SIDE REACTIONS AS.../TRIMETHADIONE/.|AS WITH TRIMETHADIONE, THERE IS SUGGESTIVE EVIDENCE THAT USE OF PARAMETHADIONE DURING PREGNANCY IS ASSOCIATED WITH INCR IN INCIDENCE OF CONGENITAL ABNORMALITIES. ACCORDINGLY, PARAMETHADIONE SHOULD BE AVOIDED IN PREGNANT WOMEN IF POSSIBLE.|NEPHROPATHIES HAVE DEVELOPED...ESP IN PATIENTS RECEIVING...PARAMETHADIONE. THESE REACTIONS MAY DEVELOP INSIDIOUSLY, & URINALYSES SHOULD BE MADE BEFORE & PERIODICALLY DURING TREATMENT. DEVELOPMENT OF ANY SIGNIFICANT RENAL ABNORMALITY IS INDICATION FOR DISCONTINUING THE DRUG.|SINCE EARLY RECOGNITION OF /BLOOD/ DYSCRASIA & DISCONTINUANCE OF...DRUG ARE ESSENTIAL, PT SHOULD BE ADVISED TO REPORT PROMPTLY SUCH SYMPTOMS AS SORE THROAT, FEVER, EASY BRUISING, PETECHIAE, EPISTAXIS, OR OTHER SIGNS OF INFECTION OR BLEEDING TENDENCY. /ANTICONVULSANTS /|For more Drug Warnings (Complete) data for PARAMETHADIONE (15 total), please visit the HSDB record page.

Paramethadione is an oxazolidinedione anticonvulsant similar to trimethadione that acts on the central nervous system (CNS) to reduce the number of absence seizures (often seen in epileptics). Absence seizures involve an interruption to consciousness where the person experiencing the seizure seems to become vacant and unresponsive for a short period of time (usually up to 30 seconds). Paramethadione acts on thalamic neurons in the thalamic reticular nucleus (which studies have shown to be associated with absence seizures, von Krosigk et al., 1993).

Rapid via the digestive tract.|PARAMETHADIONE IS COMPLETELY N-DEMETHYLATED TO 5-ETHYL-5-METHYL-OXAZOLIDINE-2,4-DIONE AND SLOWLY EXCRETED BY KIDNEYS.

Primarily hepatic (mainly via cytochrome P450 isozyme 2C9), paramethadione is completely demethylated to 5-ethyl-5-methyl-2,4-oxazolidinedione, the active metabolite.|PARAMETHADIONE IS COMPLETELY N-DEMETHYLATED TO 5-ETHYL-5-METHYL-OXAZOLIDINE-2,4-DIONE...|PARAMETHADIONE IS N-DEMETHYLATED BY HEPATIC MICROSOMAL ENZYMES TO ACTIVE METABOLITE THAT IS SLOWLY EXCRETED IN URINE...|PARAMETHADIONE IS N-DEMETHYLATED BY HEPATIC MICROSOMAL ENZYMES TO ACTIVE METABOLITE... METABOLITE ACCUMULATES DURING CHRONIC MEDICATION & IS PROBABLY RESPONSIBLE FOR MOST OF ANTICONVULSANT ACTIVITY OF PARENT DRUG...

12 to 24 hours (however the half-life for the active metabolite is not known)|Paramethadion - 12 to 24 hours; active metabolite - unknown.

Dione anticonvulsants such as paramethadione reduce T-type calcium currents in thalamic neurons (including thalamic relay neurons). This inhibits corticothalamic transmission and raises the threshold for repetitive activity in the thalamus. This results in a dampening of the abnormal thalamocortical rhythmicity proposed to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) during absence seizures.|Dione anticonvulsants reduce T-type calcium currents in thalamic neurons, including thalamic relay neurons. this raises the threshold for repetitive activity in the thalamus, and inhibits corticothalamic transmission. Thus, the abnormal thalamocortical rhythmicity, which is thought to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) with absence seizures, is dampened. The maximal seizure pattern in patients undergoing electroconvulsive therapy is not modified. /Dione anticonvulsants/

Treatment of overdose: To decrease absorption - immediate evacuation of stomach by induction of emesis, lavage, or both is recommended. To enhance elimination - alkalinization of urine is reported to enhance elimination of active metabolites. Monitoring - frequent monitoring of vital signs and close patient observation are required. Following recovery, a complete blood count and a careful evaluation of hepatic and renal function should be done. Supportive care - general supportive care is necessary in dione anticonvulsant overdose treatment. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation. /Dione anticonvulsants/

SEDATION MAY OCCUR WITH HIGH DOSES. UNCOMFORTABLE VISUAL ALTERATIONS, PARTICULARLY UNPLEASANT GLARE WHEN EMERGING INTO SUNLIGHT OR WELL-LIT ROOM... EDEMA & SEVERE PROTEIN-LOSING NEPHROPATHY MAY OCCUR... NEUTROPENIA OCCURS IN ABOUT 20% OF RECIPIENTS & OCCASIONALLY PANCYTOPENIA & FATAL APLASTIC ANEMIA HAVE BEEN REPORTED.|OTHER ADVERSE EFFECTS INCL HEPATITIS, SKIN REACTIONS (GENERALIZED ERYTHEMA, MACULOPAPULAR ERUPTIONS & EXFOLIATIVE DERMATITIS) &, RARELY, MILD GI DISTURBANCES.|Acute effects of overdose include ataxia (clumsiness or unsteadiness); coma - following massive overdose; severe dizziness; severe drowsiness; severe nausea; and visual disturbances.|The neuroactive drugs taken by pregnant women have two principal side effects: a teratogenic effect and a postnatal withdrawal effect. /The following characteristic syndromes are noted/: hydantoin-barbiturate syndrome, the trimethadione-paramethadione syndrome.

5-ethyl-3,5-dimethyloxazolinedione

PARADIONE (ABBOTT). ORAL: CAPSULES 150 & 300 MG; SOLN 1.5 G/5 ML.

A GAS-LIQUID CHROMATOGRAPHIC METHOD FOR QUANTITATING PARAMETHADIONE & ITS MAJOR METABOLITE, 5-ETHYL-5-METHYL-2,4-OXAZOLIDINEDIONE IN SERUM.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients