| Revision as of 12:09, 17 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 447435911 of page Felbamate for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 17:51, 27 April 2024 edit C.Fred (talk | contribs)Autopatrolled, Administrators277,596 editsm Reverted edit by Joeseppiman (talk) to last version by InternetArchiveBotTag: Rollback |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Infobox drug |
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{{Drugbox |
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| verifiedrevid = 443752184 |
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| verifiedrevid = 461099211 |
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| IUPAC_name = ''(3-carbamoyloxy-2-phenylpropyl) carbamate'' |
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| IUPAC_name = (3-carbamoyloxy-2-phenylpropyl) carbamate |
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| image = Felbamate.svg |
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| image = Felbamate.svg |
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| width = 150px |
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| width = 225 |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| Drugs.com = {{drugs.com|monograph|felbamate}} |
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| Drugs.com = {{drugs.com|monograph|felbamate}} |
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| MedlinePlus = a606011 |
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| MedlinePlus = a606011 |
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| pregnancy_US = C |
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| pregnancy_category = C (]) |
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| legal_status = Unscheduled |
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| legal_status = Rx-only |
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| routes_of_administration = Oral |
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| routes_of_administration = ] (], oral ]) |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| bioavailability = > 90% |
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| bioavailability = >90% |
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| metabolism = ] |
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| metabolism = ] |
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| elimination_half-life = 20-23 hours |
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| elimination_half-life = 20–23 hours |
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| excretion = ? |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| IUPHAR_ligand = 5473 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 25451-15-4 |
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| CAS_number = 25451-15-4 |
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| ATC_prefix = N03 |
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| ATC_prefix = N03 |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=11 | H=14 | N=2 | O=4 |
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| C=11 | H=14 | N=2 | O=4 |
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⚫ |
| smiles = O=C(N)OCC(c1ccccc1)COC(N)=O |
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| molecular_weight = 238.24 |
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| smiles = O=C(OCC(c1ccccc1)COC(=O)N)N |
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| InChI = 1/C11H14N2O4/c12-10(14)16-6-9(7-17-11(13)15)8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H2,12,14)(H2,13,15) |
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| InChIKey = WKGXYQFOCVYPAC-UHFFFAOYAJ |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C11H14N2O4/c12-10(14)16-6-9(7-17-11(13)15)8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H2,12,14)(H2,13,15) |
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| StdInChI = 1S/C11H14N2O4/c12-10(14)16-6-9(7-17-11(13)15)8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H2,12,14)(H2,13,15) |
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| StdInChIKey = WKGXYQFOCVYPAC-UHFFFAOYSA-N |
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| StdInChIKey = WKGXYQFOCVYPAC-UHFFFAOYSA-N |
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}} |
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}} |
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'''Felbamate''' (marketed under the brand name '''Felbatol''' by ]) is an ]<ref name="pmid9067327">{{cite journal |vauthors=Rho JM, Donevan SD, Rogawski MA |title=Barbiturate-Like Actions of the Propanediol Dicarbamates Felbamate and Meprobamate |journal=J. Pharmacol. Exp. Ther. |volume=280 |issue=3 |pages=1383–91 |date=March 1997 |pmid=9067327 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9067327}}</ref> used in the treatment of ]. It is used to treat ]s<ref name="pmid1944909">{{cite journal |vauthors=Leppik IE, Dreifuss FE, Pledger GW |title=Felbamate for Partial Seizures: Results of a Controlled Clinical Trial |journal=Neurology |volume=41 |issue=11 |pages=1785–9 |date=November 1991 |pmid=1944909 |doi= 10.1212/wnl.41.11.1785|s2cid=25245002 |display-authors=etal}}</ref><ref name="pmid7796796">{{cite journal |vauthors=Devinsky O, Faught RE, Wilder BJ |title=Efficacy of Felbamate Monotherapy in Patients Undergoing Presurgical Evaluation of Partial Seizures |journal=Epilepsy Res. |volume=20 |issue=3 |pages=241–6 |date=March 1995 |pmid=7796796 |doi= 10.1016/0920-1211(94)00084-A|s2cid=21915205 |display-authors=etal|doi-access=free }}</ref> (with and without generalization) in adults and partial and generalized seizures associated with ] in children. However, an increased risk of potentially fatal ] and/or ] limit the drug's usage to severe refractory epilepsy. |
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==Mechanism of action== |
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Felbamate has been proposed to have a unique dual mechanism of action as a positive modulator of ]<ref name="pmid8109904">{{cite journal |vauthors=Rho JM, Donevan SD, Rogawski MA | title= Mechanism of Action of the Anticonvulsant Felbamate: Opposing Effects on ''N''-Methyl-<small>D</small>-aspartate and Gamma-Aminobutyric Acid A Receptors |journal= Annals of Neurology |date=Feb 1994| volume=35 | issue=2 | pages=229–34 | pmid=8109904 | doi=10.1002/ana.410350216| s2cid= 33913077 }}</ref><ref name="pmid8667250">{{cite journal |vauthors=Kume A, Greenfield LJ, Macdonald RL, Albin RL |title=Felbamate Inhibits ''t''-Butylbicycloorthobenzoate (TBOB) Binding and Enhances Cl<sup>–</sup> Current at the Gamma-Aminobutyric Acid A (GABAA) Receptor |journal=J. Pharmacol. Exp. Ther. |volume=277 |issue=3 |pages=1784–92 |date=June 1996 |pmid=8667250 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8667250}}</ref> and as a blocker of ]s, particularly isoforms containing the ] subunit.<ref>{{Cite journal |vauthors=Subramaniam S, Rho JM, Penix L, Donevan SD, Fielding RP, Rogawski MA | title = Felbamate Block of the ''N''-Methyl-<small>D</small>-aspartate Receptor | journal = ] | volume = 273 | issue = 2 | pages = 878–86 | date=May 1995 | pmid = 7752093}}</ref><ref>{{Cite journal |vauthors=Kleckner NW, Glazewski JC, Chen CC, Moscrip TD | title = Subtype-Selective Antagonism of ''N''-Methyl-<small>D</small>-aspartate Receptors by Felbamate: Insights into the Mechanism of Action | journal = ] | volume = 289 | issue = 2 | pages = 886–894 | date=May 1999 | pmid = 10215667}}</ref><ref>{{Cite journal |
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|vauthors=Harty TP, Rogawski MA | title = Felbamate Block of Recombinant ''N''-Methyl-<small>D</small>-aspartate Receptors: Selectivity for the NR2B Subunit | journal = ] | volume = 39 | issue = 1 | pages = 47–55 | date=March 2000 | pmid = 10690753 | doi=10.1016/s0920-1211(99)00108-4| s2cid = 25467576 | url = https://zenodo.org/record/1260129 }}</ref><ref>{{Cite journal |vauthors=Chang HR, ((Chung-Chin Kuo CC)) | title = Molecular determinants of the anticonvulsant felbamate binding site in the N-methyl-D-aspartate receptor | journal = ] | volume = 51 | issue = 6| pages = 1534–45 | date=March 2008 | doi = 10.1021/jm0706618 | pmid = 18311896}}</ref> Although it is clear that felbamate does cause pharmacological inhibition of NMDA receptors, the relevance of NMDA receptor blockade as a strategy for the treatment of human epilepsy has been questioned.<ref>{{Cite journal | author = Rogawski MA | title = Revisiting AMPA Receptors as an Antiepileptic Drug Target | journal = ] | volume = 11 | issue = 2 | pages = 56–63 | date=March 2011 | doi = 10.5698/1535-7511-11.2.56 | pmid = 21686307 | pmc=3117497}}</ref> Therefore, the importance of the effects of felbamate on NMDA receptors to its therapeutic action in epilepsy is uncertain. |
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==Approval history== |
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===United States=== |
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* '''August 1993'''. Felbamate was approved for partial seizures with and without secondary generalization in adults and for Lennox–Gastaut Syndrome, a serious form of childhood epilepsy. Over the following year 150,000 people were started on felbamate therapy and a third of these became established. |
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* '''August 1, 1994'''. It was urgently withdrawn after 10 cases of aplastic anemia.<ref name="urlwww.fda.gov">{{cite web|url=https://www.fda.gov/bbs/topics/NEWS/NEW00488.html |title=www.fda.gov |website=] |access-date=2008-11-15 |url-status=dead |archive-url=https://web.archive.org/web/20081102231156/https://www.fda.gov/bbs/topics/NEWS/NEW00488.html |archive-date=November 2, 2008 }}</ref> A "Dear Doctor" letter was sent to 240,000 physicians. |
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* '''September 27, 1994'''. Felbamate had a limited redemption in another "Dear Doctor" letter sent to 260,000 physicians. It was recommended that the drug remain available only for patients with severe epilepsy for whom the benefits outweigh the risks, and that changes be made to the product's labelling to reflect the newly recognized risk.<ref name="urlwww.fda.gov2">{{cite web|url=https://www.fda.gov/bbs/topics/ANSWERS/ANS00605.html |title=www.fda.gov |website=] |access-date=2008-11-15 |url-status=dead |archive-url=https://web.archive.org/web/20070929141432/https://www.fda.gov/bbs/topics/ANSWERS/ANS00605.html |archive-date=September 29, 2007 }}</ref> This redemption came with an additional warning since there had been 10 cases acute liver failure (4 of which were fatal). At this point, 10,000 to 12,000 people remained on the drug. |
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===United Kingdom=== |
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* The drug is only available on a limited named-patient basis. |
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==Indications and usage== |
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* Adults: Monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization. |
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* Children: Adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome. |
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==Dosing== |
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Felbamate is available in tablets (400 mg and 600 mg) and as a peach-coloured oral suspension (600 mg/5 mL). |
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* Adults (≥ 14 years): begin with 1,200 mg daily given every 6 to 8 hours |
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* Children (2–14 years): 15 to 45 mg per kg per day given every 6 to 8 hours |
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==Side effects== |
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Adverse reactions include decreased appetite, vomiting, ], nausea, dizziness, somnolence, and headache. Many patients report increased alertness with the drug. |
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Two rare but very serious effects include ] and serious liver damage. The risk of aplastic anemia is between 1:3,600 and 1:5,000, of which 30% of cases are fatal. The risk of liver damage is between 1:24,000 to 1:34,000, of which 40% of cases are fatal. {{Citation needed|date=December 2018}} |
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==Drug interactions== |
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Felbamate is an ] of ] - an enzyme involved in the ] of several commonly used medications.<ref name=Flockhart>{{cite web |author=Flockhart DA |title=Drug Interactions: Cytochrome P450 Drug Interaction Table |publisher=] |year=2007 |url=http://medicine.iupui.edu/flockhart/table.htm}} Retrieved on December 25, 2008.</ref> Felbamate interacts with several other AEDs, including ], ], and ]; dosage adjustments may be necessary to avoid adverse effects. Concomitant administration of felbamate and carbamazepine decreases blood levels of both drugs, while increasing the level of ''carbamazepine-10,11 epoxide'', the active ] of carbamazepine.<ref name=Curry>{{cite journal |vauthors=Curry WJ, Kulling DL |title=Newer Antiepileptic Drugs: Gabapentin, Lamotrigine, Felbamate, Topiramate and Fosphenytoin |journal=] |volume=57 |issue=3 |pages=513–20 |date=February 1998 |pmid=9475899 |url=http://www.aafp.org/afp/980201ap/curry.html |access-date=2005-12-06 |archive-date=2011-09-27 |archive-url=https://web.archive.org/web/20110927000712/http://www.aafp.org/afp/980201ap/curry.html |url-status=dead }}</ref> |
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== History == |
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Felbamate was discovered by ] at ].<ref>{{Cite news|url=https://www.telegraph.co.uk/news/obituaries/1584273/Frank-Berger.html|title=Frank Berger|journal=Daily Telegraph|date=2008-04-07|access-date=2018-09-22|language=en-GB|issn=0307-1235}}</ref> |
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==References== |
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{{Reflist|2}} |
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==External links== |
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* |
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* contains extensive information including the patient warning and a sample consent form. |
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* |
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* {{Webarchive|url=https://web.archive.org/web/20110927000712/http://www.aafp.org/afp/980201ap/curry.html |date=2011-09-27 }} |
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* |
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{{Anticonvulsants}} |
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{{GABAA receptor positive modulators}} |
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{{Ionotropic glutamate receptor modulators}} |
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] |
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] |
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] |
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] |
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] |
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] |