| Revision as of 12:09, 17 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,074 edits Saving copy of the {{drugbox}} taken from revid 447131021 of page Felodipine for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 16:07, 12 January 2025 edit Arthurfragoso (talk | contribs)Extended confirmed users, Template editors4,591 edits dark mode fix |
| Line 1: |
Line 1: |
|
|
{{short description|Medication of the calcium channel blocker type}} |
|
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
|
|
|
{{cs1 config|name-list-style=vanc}} |
|
|
{{Use dmy dates|date=February 2015}} |
|
{{Drugbox |
|
{{Drugbox |
|
|
| Watchedfields = changed |
|
| verifiedrevid = 411546831 |
|
|
|
| verifiedrevid = 461099283 |
|
| IUPAC_name = 3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate |
|
|
|
| IUPAC_name = (''RS'')-3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate |
|
| image = Felodipine.png |
|
|
|
| image = Felodipine structure.svg |
|
|
| image_class = skin-invert-image |
|
| image2 = Felodipine-from-xtal-1989-3D-balls.png |
|
| image2 = Felodipine-from-xtal-1989-3D-balls.png |
|
|
|
|
<!--Clinical data--> |
|
<!--Clinical data--> |
|
| tradename = Plendil |
|
| tradename = Plendil |
| Line 13: |
Line 16: |
|
| legal_status = Rx-only |
|
| legal_status = Rx-only |
|
| routes_of_administration = ] |
|
| routes_of_administration = ] |
|
|
|
|
<!--Pharmacokinetic data--> |
|
<!--Pharmacokinetic data--> |
|
| bioavailability = 15% <ref>AstraZeneca MI Department, 16th April 2010</ref> |
|
| bioavailability = 15% |
|
|
<!-- | pKa = 5.07 <ref>Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 115, 2013, pp. 887-890</ref> --> |
|
| metabolism = ] |
|
| metabolism = ] |
|
|
| onset = 2.5–5 hours |
|
| elimination_half-life = ?? |
|
|
|
| elimination_half-life = 25 hours<ref name=UKlabel2015>{{cite web|title=Felopidine UK label|url=https://www.medicines.org.uk/emc/medicine/191/SPC/Plendil+2.5mg,+Plendil+5mg+and+Plendil+10mg/|publisher=UK Electronic Medicines Compendium|date=15 September 2015|access-date=19 February 2015|archive-date=16 August 2019|archive-url=https://web.archive.org/web/20190816034416/https://www.medicines.org.uk/emc/medicine/191/SPC/Plendil%2B2.5mg,%2BPlendil%2B5mg%2Band%2BPlendil%2B10mg/|url-status=dead}}</ref> |
|
| excretion = ] |
|
| excretion = ] |
|
|
|
|
<!--Identifiers--> |
|
<!--Identifiers--> |
|
| CASNo_Ref = {{cascite|correct|CAS}} |
|
| CAS_number_Ref = {{cascite|correct|??}} |
|
| CAS_number = 72509-76-3 |
|
| CAS_number = 72509-76-3 |
|
| ATC_prefix = C08 |
|
| ATC_prefix = C08 |
|
| ATC_suffix = CA02 |
|
| ATC_suffix = CA02 |
|
| PubChem = 3333 |
|
| PubChem = 3333 |
|
|
| IUPHAR_ligand = 4190 |
|
|
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
|
| DrugBank = DB01023 |
|
| DrugBank = DB01023 |
|
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
|
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
| Line 33: |
Line 38: |
|
| KEGG_Ref = {{keggcite|correct|kegg}} |
|
| KEGG_Ref = {{keggcite|correct|kegg}} |
|
| KEGG = D00319 |
|
| KEGG = D00319 |
|
|
| ChEBI_Ref = {{ebicite|correct|EBI}} |
|
| ChEBI = 585948 |
|
| ChEBI = 585948 |
|
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
|
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
|
| ChEMBL = 1480 |
|
| ChEMBL = 1480 |
|
|
|
|
<!--Chemical data--> |
|
<!--Chemical data--> |
|
| C=18 | H=19 | Cl=2 | N=1 | O=4 |
|
| C=18 | H=19 | Cl=2 | N=1 | O=4 |
|
| molecular_weight = 384.259 g/mol |
|
|
| smiles = O=C(OCC)\C1=C(\N/C(=C(/C(=O)OC)C1c2cccc(Cl)c2Cl)C)C |
|
| smiles = O=C(OCC)\C1=C(\N/C(=C(/C(=O)OC)C1c2cccc(Cl)c2Cl)C)C |
|
| InChI = 1/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3 |
|
|
| InChIKey = RZTAMFZIAATZDJ-UHFFFAOYAS |
|
|
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChI = 1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3 |
|
| StdInChI = 1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3 |
| Line 48: |
Line 50: |
|
| StdInChIKey = RZTAMFZIAATZDJ-UHFFFAOYSA-N |
|
| StdInChIKey = RZTAMFZIAATZDJ-UHFFFAOYSA-N |
|
}} |
|
}} |
|
|
<!-- Definition and medical uses --> |
|
|
'''Felodipine''' is a medication of the ] type that is used to treat ]. |
|
|
|
|
|
<!-- Society and culture --> |
|
|
It was patented in 1978, and approved for medical use in 1988.<ref>{{cite book | vauthors = Fischer J, Ganellin CR |title= Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=465 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA465 |language=en}}</ref> |
|
|
|
|
|
==Medical uses== |
|
|
Felodipine is used to treat ] and stable ].<ref name=UKlabel2015/><ref name=USlabel2012>{{cite web|title=Felodipine US label|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019834s025lbl.pdf|publisher=FDA|date=October 2012}}</ref> |
|
|
|
|
|
It should not be used for people who are pregnant, have ], are having a ], have an ], or have obstructions that block ].<ref name=UKlabel2015/> |
|
|
|
|
|
For people with ] the dose needs to be lowered, because felodipine is cleared by the liver.<ref name=UKlabel2015/> |
|
|
|
|
|
==Adverse effects== |
|
|
The only very common side effect, occurring in more than 1/10 people, is ] in the arms and legs.<ref name=UKlabel2015/> |
|
|
|
|
|
Common side effects, occurring in between 1% and 10% of people, include flushing, headache, ]s, dizziness and fatigue.<ref name=UKlabel2015/> |
|
|
|
|
|
Felodipine can exacerbate ].<ref name=UKlabel2015/> |
|
|
|
|
|
== Interactions == |
|
|
|
|
|
Felodipine is metabolized by ], so substances that inhibit or activate CYP3A4 can strongly effect how much felodipine is present.<ref name=UKlabel2015/> |
|
|
|
|
|
CYP3A4 inhibitors, which increase the amount of felodipine available per dose, include ], ], ], ], ], and ].<ref name=UKlabel2015/><ref>{{cite journal | vauthors = Kiani J, Imam SZ | title = Medicinal importance of grapefruit juice and its interaction with various drugs | journal = Nutrition Journal | volume = 6 | issue = 33 | pages = 33 | date = October 2007 | pmid = 17971226 | pmc = 2147024 | doi = 10.1186/1475-2891-6-33 | doi-access = free }}.</ref> |
|
|
|
|
|
CYP3A4 activators, which decrease the amount of felodipine available per dose, include ], ], ], ], ], ], and ].<ref name=UKlabel2015/> |
|
|
|
|
|
==Mechanism of action== |
|
|
Felodipine is a ].<ref name=UKlabel2015/> Felodipine has additionally been found to act as an ] of the ], or as an ].<ref name="Luther2014">{{cite journal | vauthors = Luther JM | title = Is there a new dawn for selective mineralocorticoid receptor antagonism? | journal = Current Opinion in Nephrology and Hypertension | volume = 23 | issue = 5 | pages = 456–461 | date = September 2014 | pmid = 24992570 | pmc = 4248353 | doi = 10.1097/MNH.0000000000000051 }}</ref> |
|
|
|
|
|
Different calcium channels are present in vascular tissue and cardiac tissue; an ''in vitro'' study on human vascular and cardiac tissues comparing how selective various calcium channel blockers are for vascular compared to cardiac tissue found the following vascular/cardiac tissue ratios: ] 41, felodipine 12; ] 7, ] 5, and ] 0.2.<ref name=Burger/>{{rp|172}} |
|
|
|
|
|
==Chemistry== |
|
|
Felodipine is a member of the 1,4-] class of calcium channel blockers.<ref name=Burger>{{cite book| vauthors = Joshi GS, Burnett JC, Abraham DJ | veditors = Abraham DJ |title=Burger's medicinal chemistry and drug discovery. Volume 3: Cardiovascular Agents and Endocrines |date=2003 |publisher=Wiley |location=Hoboken, N.J. |isbn=9780471270904|edition=6th|chapter=Cardiac Drugs: Antianginal, Vasodilators, Antiarrhythmic}}</ref>{{rp|20–21}} It is a racemic mixture, and is insoluble in water but is soluble in dichloromethane and ethanol.<ref name=Burger/>{{rp|25}} |
|
|
|
|
|
==History== |
|
|
The Swedish company Hässle, a division of ], ] felodipine;<ref name=PinkSheet1991/> it filed a patent application in 1979 claiming felodipine as an antihypertensive drug.<ref name=court>{{cite court |litigants=Astrazeneca AB v. Mutual Pharmaceutical Co. |vol= |reporter= |opinion= |pinpoint= |court=United States Court of Appeals for the Federal Circuit |date=2004 |url=http://www.finnegan.com/files/Publication/accd1584-eb7c-4960-802d-575bd78b6477/Presentation/PublicationAttachment/19322ddc-88ee-42cb-8063-61f950956040/04-1100%209-30-04.pdf |access-date=2016-11-10 |quote=}}</ref><ref name=Patent611>{{cite patent| country = US| number = 4,264,611| status = patent| title = 2,6-Dimethyl-4-2,3-Disubstituted Phenyl-1,4-Dihydro-Pyridine-3,5 Dicarboxylic Acid-3,5-Asymmetric Diesters having Hypotensive Properties, as well as Method for Treating Hypertensive Conditions and Pharmaceutical Preparations Containing Same| gdate = 28 April 1981| fdate = 19 June 1979-06-19 | inventor = Berntsson P, Carlsson S, Gaarder J, Ljung B | assign1 = Aktiebolaget Hassle| url = https://patents.google.com/patent/US4264611A/en}}</ref> Astra partnered this drug and others with ] in the US under a 1982 agreement between the companies.<ref name=PinkSheet1991>{{cite news|title=Merck's Plendil (Felodipine) Approved with "1C" Rating|url=https://pink.pharmamedtechbi.com/PS019532/MERCKs-PLENDIL-FELODIPINE-APPROVED-WITH-1C-RATING|work=Pink Sheet|date=5 August 1991}}</ref> The drug was approved by the FDA in 1991 after a three-and-a-half-year review; the drug entered a very crowded market to included the other calcium channel blockers ], ], ], and ].<ref name=PinkSheet1991/> The FDA gave the drug a 1C rating, meaning that it found little difference between felodipine and the drugs already approved for the same use.<ref name=PinkSheet1991/> |
|
|
|
|
|
In 1994 Astra AB and Merck changed their partnership to a ] called Astra Merck,<ref name=biz>{{cite news | vauthors = George J |date=1997-07-28 |title=Secret of Astra Merck |url=http://www.bizjournals.com/philadelphia/stories/1997/07/28/story3.html |newspaper=Philadelphia Business Journal |location=Philadelphia |access-date=2016-11-07 }}</ref> and in 1998 Astra (by that time, ]) bought out Merck's rights in the joint venture.<ref name=cnnmoney>{{cite news |author=<!--Staff writer(s); no by-line.--> |title=Astra, Merck restructure |url=https://money.cnn.com/1998/06/19/deals/merck/ |newspaper=CNNMoney |date=1998-06-19 |access-date=2016-11-07}}</ref> |
|
|
|
|
|
The first generics became available in Sweden in 2003<ref>{{cite book| vauthors = Jönsson B | veditors = Rapoport J, Jacobs P, Jonsson E |title=Cost Containment and Efficiency in National Health Systems a Global Comparison.|date=2008|publisher=Wiley-VCH|location=Weinheim|isbn=9783527622955|page=218|chapter-url=https://books.google.com/books?id=XdMez8MdN0sC&pg=PA218|chapter=Sweden}}</ref> and in the US in 2004.<ref>{{cite book|title=Approved Drug Products with Therapeutic Equivalence Evaluations |date=2014 |publisher=FDA |edition=36th |url=http://www.nber.org/fda/orange-book/pdf/UCM071436.pdf}}</ref>{{rp|155}} |
|
|
|
|
|
In April 2016, AstraZeneca announced that they were selling the right to market felodipine in China to China Medical System Holdings for $310 million; AZ would continue to manufacture the drug.<ref name=AZrelease>{{cite press release |author=<!--Staff writer(s); no by-line.--> |title=AstraZeneca enters licensing agreement with China Medical System Holdings for hypertension medicine |url=https://www.astrazeneca.com/media-centre/press-releases/2016/AstraZeneca-enters-licensing-agreement-with-China-Medical-System-Holdings-for-hypertension-medicine-29022016.html |publisher=AstraZeneca |date=29 February 2016 |access-date=2016-11-07}}</ref> |
|
|
|
|
|
==Society and culture== |
|
|
As of 2016, felodipine was marketed under many brand names worldwide: Auronal, Cardioplen, Catrazil, Dewei, Dilahex, Enfelo, Erding, Fedil, Fedisyn, Feldil, Felicipin, Felo, Felocard, Felocor, Feloday, Felodil, Felodin, Felodip, Felodipin, Felodipina, Felodipine, Felodipino, Felodistad, Felogard, Felohexal, Felop, Felopine, Felostad, Feloten, Felotens, Felpin, Flodicar, Flodil, Keliping, Keydipin, Lodistad, Modip, Munobal, Nirmadil, Parmid, Penedil, Perfudal, Phelop, Phenodical, Plendil, Plentopine, Polo, Presid, Preslow, Prevex, Renedil, Sistar, Splendil, Stapin, Topidil, Vascalpha, Versant, and XiaoDing.<ref name=brands2016>{{cite web|title=International brand names: Felodipine|url=https://www.drugs.com/international/felodipine.html|publisher=Drugs.com|access-date=15 November 2016}}</ref> |
|
|
|
|
|
The combination of felodipine and ] was marketed as Atacand.<ref name=brands2016/> |
|
|
|
|
|
The combination of felodipine and ] was marketed as Delmuno, Tazko, Triacor, Triapin, Triasyn, Tri-Plen, Unimax, and Unitens.<ref name=brands2016/> |
|
|
|
|
|
The combination of felodipine and ] was marketed as Lexxel.<ref name=brands2016/> |
|
|
|
|
|
The combination of felodipine and ] was marketed as Logimat, Logimax, and Mobloc.<ref name=brands2016/> |
|
|
|
|
|
== References == |
|
|
{{Reflist}} |
|
|
|
|
|
{{Navboxes |
|
|
| title = ] |
|
|
| titlestyle = background:#ccccff |
|
|
| list1 = |
|
|
{{Ion channel modulators}} |
|
|
{{Mineralocorticoid receptor modulators}} |
|
|
{{Xenobiotic-sensing receptor modulators}} |
|
|
}} |
|
|
|
|
|
] |
|
|
] |
|
|
] |
|
|
] |
|
|
] |
|
|
] |
|
|
] |