| Identification | Back Directory | [Name]
Rufinamide | [CAS]
106308-44-5 | [Synonyms]
E 2080
RUF 331
CS-1133
Inovelon
CGP 33101
Rufinamide
Rufinamide>
Rufinamide(E 2080
Rufinamide, >=99%
RufinaMide(Banzel)
Rufinamide (200 mg)
Rufinamide solution
Rufinamide USP/EP/BP
Rufinamide, 98%, a sodium channel blocker
CGP 33101; E 2080; INOVELON; RUF 331; BANZEL;E2080
1-[(2,6-difluorophenyl)methyl]-4-triazolecarboxamide
1-(2,6-Difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide
1H-1,2,3-TRIAZOLE-4-CARBOXAMIDE, 1-[(2,6-DIFLUOROPHENYL)METHYL]- | [EINECS(EC#)]
200-659-6 | [Molecular Formula]
C10H8F2N4O | [MDL Number]
MFCD00865314 | [MOL File]
106308-44-5.mol | [Molecular Weight]
238.194 |
| Chemical Properties | Back Directory | [Melting point ]
232-234?C | [Boiling point ]
473.8±55.0 °C(Predicted) | [density ]
1.52±0.1 g/cm3(Predicted) | [Fp ]
2℃ | [storage temp. ]
−20°C | [solubility ]
DMSO: soluble9mg/mL | [form ]
powder | [pka]
14.37±0.50(Predicted) | [color ]
white | [Merck ]
14,8293 | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. |
| Hazard Information | Back Directory | [Chemical Properties]
White Solid | [Uses]
Labelled Rufinamide (R701552). Antiepileptic triazole derivative which decreases firing by neurons at sodium channels. Anticonvulsant. | [Uses]
Rufinamide, a triazole derivative, is an anticonvulsant medication. It is used in combination with other medication and therapy to treat Lennox–Gastaut syndrome and various other seizure disorders. Rufinamide is presumed to involve stabilization of the so | [Biological Activity]
Board spectrum anticonvulsant. Prolongs the inactivation of sodium channels and limits the frequency of action potential firing in cultured and acutely isolated neurons. Displays anticonvulsive activity in a range of animal seizure models. | [Originator]
Novartis (US) | [Definition]
ChEBI: Rufinamide is a heteroarene and an aromatic amide. | [Brand name]
Inovelon | [General Description]
An antiepileptic drug and anticonvulsant, Rufinamide is approved for the treatment of partial seizures associated with Lennox-Gastaut syndrome in adults and children 4 years and older. Rufinamide is marketed as Banzel® in the US and Inovelon® in the EU. | [Biochem/physiol Actions]
Broad-spectrum anticonvulsant. | [Clinical Use]
Adjunctive treatment of seizures in Lennox-Gastaut
syndrome | [Side effects]
Rufinamide was well tolerated with the most common adverse events including fatigue, somnolence, tremors, mild-to-moderate dizziness, nausea, headache, and diplopia. Since rufinamide is not metabolized by the CYP450 system, it is anticipated to have a low potential for interaction with drugs metabolized by the CYP isozymes. Rufinamide, however, does exhibit clinically relevant interactions with other antiepileptic drugs; concomitant treatment with valproate results in a reduction in rufinamide clearance while concomitant treatment with phenytoin, primidone, phenobarbital, carbamazepine, or vigabatrin causes an increase in rufinamide clearance. In these situations, rufinamide dosage adjustment may be required. | [Synthesis]
While rufinamide may be prepared by several related routes, the preferred starting material is 2,6-difluorobenzyl azide. Reaction with either 2-propynoic acid or 2-chloroacrylonitrile affords 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid or 1-(2,6-difluorobenzyl)- 1H-1,2,3-triazole-4-carbonitrile, respectively. For the carboxylic acid Shridhar Hegde and Michelle Schmidt intermediate, treatment with thionyl chloride followed by concentrated aqueous ammonium hydroxide or conversion to its methyl ester (methanol/sulfuric acid) with subsequent ammonolyis provides rufinamide. | [Drug interactions]
Potentially hazardous interactions with other drugs
Antidepressants: antagonism of anticonvulsant effect
(convulsive threshold lowered); avoid with St John’s
wort.
Antimalarials: mefloquine antagonises
anticonvulsant effect.
Antipsychotics: antagonism of anticonvulsant effect
(convulsive threshold lowered).
Oestrogens and progestogens: metabolism
accelerated by rufinamide - reduced contraceptive
effect.
Orlistat: possibly increased risk of convulsions with
orlistat.
Ulipristal: possibly reduces contraceptive effect. | [Metabolism]
Almost exclusively eliminated by metabolism
via hydrolysis of the carboxylamide group to the
pharmacologically inactive acid derivative CGP 47292.
Cytochrome P450-mediated metabolism is very minor.
The formation of small amounts of glutathione conjugates
cannot be completely excluded. 84.7% was excreted by the
renal route. | [storage]
room temperature (desiccate) | [References]
1) Hakimian et al. (2007), Rufinamide: a new anti-epileptic medication; Expert Opin. Pharmacother. 8 1931
2) Gilchrist et al. (2014), Nav1.1 Modulation by a Novel Triazole Compound Attenuates Epileptic Seizures in Rodents; ACS Chem. Biol. 9 1204
3) Chen et al. (2018), Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB; Chem. Biol. Interact. 286 71 |
| Questions And Answer | Back Directory | [Description]
Rufinamide (licensed in 2007) is a third- generation AED known with the proprietary
brand name of Invelon®(Eisai, Hatfield) in the UK and USA.
| [Generic formulation]
MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):
- The need for continued supply of a particular manufacturer’s product should be based on clinical judgment and consultation with the patient and/ or carer taking into account factors such as seizure frequency and treatment history.
| [Indications]
Epilepsy: Adjunctive treatment of Lennox– Gastaut syndrome; refractory tonic/ atonic seizures (unlicensed).
| [Dose titration]
- Epilepsy— adjunctive therapy (adults with body weight 30– 50 kg): 200 mg bd for at least 2 days, then increased by 200 mg bd every 2 or more days (max. 900 mg bd).
- Epilepsy— adjunctive therapy (adults with body weight 50– 70 kg): 200 mg bd for at least 2 days, then increased by 200 mg bd every 2 or more days (max. 1200 mg bd).
- Epilepsy— adjunctive therapy (adults with body weight above 70 kg): 200 mg bd for at least 2 days, then increased by 200 mg bd every 2 or more days (max. 1600 mg bd).
| [Interactions]
With AEDs
Significant increases in rufinamide plasma concentrations may occur with coadministration of valproate.
With other drugs
- Women of child- bearing age using hormonal contraceptives are advised to use an additional safe and effective contraceptive method as co- administration of rufinamide has been shown to decrease exposure to a combined oral contraceptives.
- Rufinamide has been shown to induce the cytochrome P450 enzyme CYP3A4 and may, therefore, reduce the plasma concentrations of substances, which are metabolized by this enzyme (modest- to- moderate effect). It is therefore recommended that patients treated with substances that are metabolized by the CYP3A4 enzyme system are to be carefully monitored for 2 weeks at the start of or after the end of treatment with rufinamide, or after any marked change in the dose (a dose adjustment of the concomitantly administered medicinal product may need to be considered). These recommendations should also be considered when rufinamide is used concomitantly with substances with a narrow therapeutic window, such as warfarin and digoxin.
With alcohol/food
- No data on the interaction of rufinamide with alcohol are available • As a food effect was observed, rufinamide should be administered with food
| [Special populations]
Hepatic impairment
- Caution and careful dose titration in mild- to- moderate impairment
- Avoid in severe impairment
Renal impairment
The pharmacokinetics of rufinamide does not appear to be altered in subjects with chronic and severe renal failure compared to healthy volunteers
Pregnancy
- No clinical data are available on pregnancies exposed to rufinamide. Therefore, rufinamide should not be used during pregnancy or in women of childbearing age who are not using contraceptive measures, unless clearly necessary. Women of childbearing age must use contraceptive measures during treatment with rufinamide.
- If women treated with rufinamide plan to become pregnant, the continued use of this product should be carefully weighed. In case of treatment with rufinamide, the dose should be monitored carefully during pregnancy and after birth, and adjustments made on a clinical basis.
- It is not known if rufinamide is excreted in human breastmilk. Due to the potential harmful effects for the breastfed infant, breastfeeding should be avoided during maternal treatment with rufinamide.
| [Behavioural and cognitive effects in patients with epilepsy]
For this third- generation agent, clinical experience is still limited, and little is known
about its positive and negative psychotropic properties, and their implications for
the management of behavioural symptoms in patients with epilepsy. There are
initial reports of anxiety, depression, irritability, and agitation. Reports of cognitive
effects are rare. | [Psychiatric use]
Rufinamide has no indications for the treatment of psychiatric disorders. There
is insufficient experience with rufinamide to draw any conclusion regarding its
psychotropic profile. |
|
|