Rufinamide

238.1935264

238.19

200-659-6

WFW942PR79

DTXSID1046506

N03AF03|N - Nervous system

29339900

73.8

0.7

white

1.52±0.1 g/cm3(Predicted)

236-237 °C @ Solvent: Methanol

473.8±55.0 °C(Predicted)

2℃

1.635

H2O: Insoluble ;DMSO: soluble 9mg/mL

−20°C

3.81E-09mmHg at 25°C

148.6 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

UN 1648 3 / PGII

3

11-23/24/25-39/23/24/25-48-41-38-28

7-16-36/37-45-36/37/39-28-26-24/25

F,T

|Warning|H336 (100%): May cause drowsiness or dizziness [Warning Specific target organ toxicity, single exposure; Narcotic effects]|P261, P271, P304+P340, P312, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

The most commonly observed adverse reactions (≥10% and greater than placebo) were headache, dizziness, fatigue, somnolence, and nausea.

In prelicensure clinical trials, addition of rufinamide to standard anticonvulsant therapy was reported to be associated with only rare elevations in ALT above 3 times the upper limit of normal (ULN). Rufinamide was not linked to instances of clinically apparent liver injury, but a pooled analysis of more than 200 children mentioned that two patients needed to discontinue therapy early because of liver related adverse events, one of which was described as “toxic hepatitis”. Since approval, there have been no reports of clinically apparent liver injury associated with rufinamide use, but it has had limited use in epilepsy. Rufinamide has been linked to instances of severe cutaneous reactions, including Stevens Johnson syndrome which often has some degree of associated liver injury. Thus, rufinamide may cause liver injury, but it is rare.

26.3% - 34.8% with 90% binding to albumin (27%).

Adjunct therapy for treatment of seizures associated with Lennox-Gastaut syndrome.|FDA Label|Inovelon is indicated as adjunctive therapy in the treatment of seizures associated with Lennox Gastaut syndrome in patients 4 years of age and older.|Treatment of Lennox-Gastaut syndrome

Rufinamide is a unique anticonvulsant that is used in combination with other agents as therapy of severe forms of seizure disorders. Rufinamide therapy is associated with a low rate of transient serum enzyme elevations and with rare instances of clinically apparent liver injury.

Anticonvulsants

At high concentrations will inhibit action of mGluR5 subtype receptors thus preventing the production of glutamate.

A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)|Drugs used to prevent SEIZURES or reduce their severity. (See all compounds classified as Anticonvulsants.)

The oral suspension and tablet are bioequivalent on a mg per mg basis. Rufinamide is well absorbed but the rate is slow and the extent of absorption decreases as dose is increases. Based on urinary excretion, the extent of absorption was at least 85% following oral administration of a single dose of 600 mg rufinamide tablet under fed conditions. Bioavailability= 70%-85% (decreases with increasing doses); Tmax, fed and fasted states= 4-6 hours; Cmax, 10 mg/kg/day= 4.01 µL/mL; Cmax, 30mg/kg/day= 8.68 µL/mL; AUC (0h-12h), 10mg/kg/day= 37.8±47 µg·h/mL; AUC (0h-12h), 30mg/kg/day= 89.3±59 µg·h/mL.|Renally (91%; 66% as CGP 47292, 2% as unchanged drug) and fecally (9%) eliminated.|Rufinamide was evenly distributed between erythrocytes and plasma. The apparent volume of distribution is dependent upon dose and varies with body surface area. The apparent volume of distribution was about 50 L at 3200 mg/day. Volume of distribution is similar between adults and children and is non-linear.

Rufinamide is extensively metabolized but has no active metabolites. Metabolism by carboxyesterases into inactive metabolite CGP 47292, a carboxylic acid derivative, via hydrolysis is the primary biotransformation pathway. A few minor additional metabolites were detected in urine, which appeared to be acyl-glucuronides of CGP 47292. The cytochrome P450 enzyme system or glutathiones are not involved with the metabolism of rufinamide. Rufinamide is a weak inhibitor of CYP 2E1. Rufinamide is a weak inducer of CYP 3A4 enzymes.

Elimination half-life, healthy subjects and patients with epilepsy = 6-10 hours.

Rufinamide is a triazole derivative antiepileptic that prolongs the inactive state of voltage gated sodium channels thus stabilizing membranes, ultimately blocking the spread of partial seizure activity.

1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide

Human drugs -> Inovelon -> EMA Drug Category|Antiepileptics -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients