Felodipine

Felodipine
Clinical data
Trade names Plendil
AHFS/Drugs.com Monograph
MedlinePlus a692016
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		 Oral
ATC code C08CA02 (WHO)
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 15%
Metabolism Hepatic
Onset of action 2.5–5 hours
Biological half-life 25 hours[1]
Excretion Renal
Identifiers
CAS Number 72509-76-3 YesY
PubChem (CID) 3333
IUPHAR/BPS 4190
DrugBank DB01023 YesY
ChemSpider 3216 YesY
UNII OL961R6O2C YesY
KEGG D00319 YesY
ChEBI CHEBI:585948 YesY
ChEMBL CHEMBL1480 YesY
ECHA InfoCard 100.149.305
Chemical and physical data
Formula C18H19Cl2NO4
Molar mass 384.259 g/mol
3D model (Jmol) Interactive image
  (verify)

Felodipine is a medication of the calcium channel blocker type which is used to treat high blood pressure.

Medical use

Felodipine is used to treat high blood pressure and stable angina.[1][2]

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.[1]

For people with liver failure the dose needs to be lowered, because felodipine is cleared by the liver.[1]

Interactions

Felodipine is metabolized by cytochrome P450 3A4, so substances that inhibit or activate CYP3A4 can strongly effect how much felodipine is present.[1]

CYP3A4 inhibitors, which increase the amount of felodipine available per dose, include cimetidine, erythromycin, itraconazole, ketoconazole, HIV protease inhibitors, and grapefruit juice.[1][3]

CYP3A4 activators, which decrease the amount of felodipine available per dose, include phenytoin, carbamazepine, rifampicin, barbiturates, efavirenz, nevirapine, and Saint John's wort.[1]

Adverse effects

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

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

Felodipine can exacerbate gingivitis.[1]

Mechanism

Felodipine is a calcium channel blocker.[1] Felodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.[4]

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.[5]:172

Chemistry

Felodipine is a member of the 1,4-dihydropyridine class of calcium channel blockers.[5]:20-21 It is a racemic mixture, and is insoluble in water but is soluble in dichloromethane and ethanol.[5]:25

History

The Swedish company Hässle, a division of Astra AB, discovered felodipine;[6] it filed a patent application in 1979 claiming felodipine as an antihypertensive drug.[7][8] Astra partnered this drug and others with Merck & Co. in the US under a 1982 agreement between the companies.[6] The drug was approved by the FDA in 1991 after a three and a half year review; the drug entered a very crowded market the included the other calcium channel blockers nifedipine, verapamil, nicardipine, and isradipine.[6] 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.[6]

In 1994 Astra AB and Merck changed their partnership to a joint venture called Astra Merck,[9] and in 1998 Astra (by that time, AstraZeneca) bought out Merck's rights in the joint venture.[10]

The first generics became available in Sweden in 2003[11] and in the US in 2004.[12]: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.[13]

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.[14]

The combination of felodipine and candesartan was marketed as Atacand.[14]

The combination of felodipine and ramipril was marketed as Delmuno, Tazko, Triacor, Triapin, Triasyn, Tri-Plen, Unimax, and Unitens.[14]

The combination of felodipine and enalapril was marketed as Lexxel.[14]

The combination of felodipine and metoprolol was marketed as Logimat, Logimax, and Mobloc.[14]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Felopidine UK label". UK Electronic Medicines Compendium. 15 September 2015.
  2. ↑ "Felodipine US label" (PDF). FDA. October 2012.
  3. ↑ Jawad Kiani, Sardar Z Imam (October 30, 2007). "Medicinal importance of grapefruit juice and its interaction with various drugs". Nutr J. 6 (33): 33. doi:10.1186/1475-2891-6-33. PMC 2147024Freely accessible. PMID 17971226. .
  4. ↑ Luther, James M. (2014). "Is there a new dawn for selective mineralocorticoid receptor antagonism?". Current Opinion in Nephrology and Hypertension. 23 (5): 456–461. doi:10.1097/MNH.0000000000000051. ISSN 1062-4821.
  5. 1 2 3 Joshi, Gajanan S.; Burnett, James C.; Abraham, Donald J. (2003). "Cardiac Drugs: Antianginal, Vasodilators, Antiarrhythmic". In Abraham, Donald J. Burger's medicinal chemistry and drug discovery. Volume 3: Cardiovascular Agents and Endocrines (6th ed.). Hoboken, N.J.: Wiley. ISBN 9780471270904.
  6. 1 2 3 4 "Merck's Plendil (Felodipine) Approved with "1C" Rating". Pink Sheet. 5 August 1991.
  7. ↑ Astrazeneca AB v. Mutual Pharmaceutical Co. (United States Court of Appeals for the Federal Circuit 2004). Text
  8. ↑ US patent 4,264,611, Berntsson, Peder; Carlsson, Stig & Gaarder, Jan et al., "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", issued April 28, 1981, assigned to Aktiebolaget Hassle
  9. ↑ George, John (1997-07-28). "Secret of Astra Merck". Philadelphia Business Journal. Philadelphia. Retrieved 2016-11-07.
  10. ↑ "Astra, Merck restructure". CNNMoney. 1998-06-19. Retrieved 2016-11-07.
  11. ↑ Jönsson, Bengt (2008). "Sweden". In Rapoport, John; Jacobs, Philip; Jonsson, Egon. Cost Containment and Efficiency in National Health Systems a Global Comparison. Weinheim: Wiley-VCH. p. 218. ISBN 9783527622955.
  12. ↑ Approved Drug Products with Therapeutic Equivalence Evaluations (PDF) (36th ed.). FDA. 2014.
  13. ↑ "AstraZeneca enters licensing agreement with China Medical System Holdings for hypertension medicine" (Press release). AstraZeneca. February 29, 2016. Retrieved 2016-11-07.
  14. 1 2 3 4 5 "International brand names: Felodipine". Drugs.com. Retrieved 15 November 2016.
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