Felodipine

Felodipine is used to treat high blood pressure and stable angina.{{cite web|title=Felodipine US label|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019834s025lbl.pdf|archive-url=https://web.archive.org/web/20161115141024/http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019834s025lbl.pdf|url-status=dead|archive-date=15 November 2016|publisher=FDA|date=October 2012}}

It should not be used for people who are pregnant, have acute heart failure, are having a heart attack, have an obstructed heart valve, or have obstructions that block bloodflow out of the heart.

For people with liver failure the dose needs to be lowered, because felodipine is cleared by the liver.

The only very common side effect, occurring in more than 1/10 people, is pain and swelling in the arms and legs.

Common side effects, occurring in between 1% and 10% of people, include flushing, headache, heart palpitations, dizziness and fatigue.

Felodipine can exacerbate gingivitis.

Felodipine is metabolized by cytochrome P450 3A4, so substances that inhibit or activate CYP3A4 can strongly effect how much felodipine is present.

CYP3A4 inhibitors, which increase the amount of felodipine available per dose, include cimetidine, erythromycin, itraconazole, ketoconazole, HIV protease inhibitors, and grapefruit juice.{{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 }}.

CYP3A4 activators, which decrease the amount of felodipine available per dose, include phenytoin, carbamazepine, rifampicin, barbiturates, efavirenz, nevirapine, and Saint John's wort.

Felodipine is a calcium channel blocker. Felodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.{{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 }}

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: mibefradil 41, felodipine 12; nifedipine 7, amlodipine 5, and verapamil 0.2.{{rp|172}}

Felodipine is a member of the 1,4-dihydropyridine class of calcium channel blockers.{{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}}{{rp|20–21}} It is a racemic mixture, and is insoluble in water but is soluble in dichloromethane and ethanol.{{rp|25}}

The Swedish company Hässle, a division of Astra AB, discovered felodipine; it filed a patent application in 1979 claiming felodipine as an antihypertensive drug.{{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=}}{{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}} Astra partnered this drug and others with Merck & Co. in the US under a 1982 agreement between the companies.{{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}} 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 nifedipine, verapamil, nicardipine, and isradipine. 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.

In 1994 Astra AB and Merck changed their partnership to a joint venture called Astra Merck,{{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 }} and in 1998 Astra (by that time, AstraZeneca) bought out Merck's rights in the joint venture.{{cite news |author= |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}}

The first generics became available in Sweden in 2003{{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}} and in the US in 2004.{{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}}{{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.{{cite press release |author= |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}}

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.{{cite web|title=International brand names: Felodipine|url=https://www.drugs.com/international/felodipine.html|publisher=Drugs.com|access-date=15 November 2016}}

The combination of felodipine and candesartan was marketed as Atacand.

The combination of felodipine and ramipril was marketed as Delmuno, Tazko, Triacor, Triapin, Triasyn, Tri-Plen, Unimax, and Unitens.

The combination of felodipine and enalapril was marketed as Lexxel.

The combination of felodipine and metoprolol was marketed as Logimat, Logimax, and Mobloc.

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Category:Antimineralocorticoids

Category:Calcium channel blockers

Category:CYP2D6 inhibitors

Category:Dihydropyridines

Category:Drugs developed by AstraZeneca

Category:Carboxylate esters

Category:Chloroarenes