Felodipine

Last updated

Felodipine
Felodipine structure.svg
Felodipine-from-xtal-1989-3D-balls.png
Clinical data
Trade names Plendil
AHFS/Drugs.com Monograph
MedlinePlus a692016
Routes of
administration 		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 15%
Metabolism Hepatic
Onset of action 2.5–5 hours
Elimination half-life 25 hours [1]
Excretion Renal
Identifiers
  • (RS)-3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.149.305 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H19Cl2NO4
Molar mass 384.25 g·mol−1
3D model (JSmol)
  • O=C(OCC)\C1=C(\N/C(=C(/C(=O)OC)C1c2cccc(Cl)c2Cl)C)C
  • InChI=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 Yes check.svgY
  • Key:RZTAMFZIAATZDJ-UHFFFAOYSA-N Yes check.svgY
   (verify)

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

Contents

It was patented in 1978, and approved for medical use in 1988. [2]

Medical uses

Felodipine is used to treat high blood pressure and stable angina. [1] [3]

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]

Adverse effects

The only very common side effect, occurring in more than 1/10 people, is pain and swelling 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]

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] [4]

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

Mechanism of action

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. [5]

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. [6] : 172 

Chemistry

Felodipine is a member of the 1,4-dihydropyridine class of calcium channel blockers. [6] : 20–21  It is a racemic mixture, and is insoluble in water but is soluble in dichloromethane and ethanol. [6] : 25 

History

The Swedish company Hässle, a division of Astra AB, discovered felodipine; [7] it filed a patent application in 1979 claiming felodipine as an antihypertensive drug. [8] [9] Astra partnered this drug and others with Merck & Co. in the US under a 1982 agreement between the companies. [7] 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. [7] 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. [7]

In 1994 Astra AB and Merck changed their partnership to a joint venture called Astra Merck, [10] and in 1998 Astra (by that time, AstraZeneca) bought out Merck's rights in the joint venture. [11]

The first generics became available in Sweden in 2003 [12] and in the US in 2004. [13] : 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. [14]

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. [15]

The combination of felodipine and candesartan was marketed as Atacand. [15]

The combination of felodipine and ramipril was marketed as Delmuno, Tazko, Triacor, Triapin, Triasyn, Tri-Plen, Unimax, and Unitens. [15]

The combination of felodipine and enalapril was marketed as Lexxel. [15]

The combination of felodipine and metoprolol was marketed as Logimat, Logimax, and Mobloc. [15]

Related Research Articles

Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate, to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Simvastatin</span> Lipid-lowering medication

Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart problems in those at high risk. It is taken by mouth.

<span class="mw-page-title-main">Rosuvastatin</span> Statin medication

Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, and weight loss. It is taken orally.

<span class="mw-page-title-main">Amlodipine</span> Medication against high blood pressure

Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure, coronary artery disease (CAD) and variant angina. It is taken orally.

<span class="mw-page-title-main">Amiodarone</span> Antiarrhythmic medication used for various types of irregular heartbeats

Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxysmal supraventricular tachycardia. Evidence in cardiac arrest, however, is poor. It can be given by mouth, intravenously, or intraosseously. When used by mouth, it can take a few weeks for effects to begin.

<span class="mw-page-title-main">Nifedipine</span> Calcium channel blocker medication

Nifedipine, sold under the brand name Procardia among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. It is one of the treatments of choice for Prinzmetal angina. It may be used to treat severe high blood pressure in pregnancy. Its use in preterm labor may allow more time for steroids to improve the baby's lung function and provide time for transfer of the mother to a well qualified medical facility before delivery. It is a calcium channel blocker of the dihydropyridine type. Nifedipine is taken by mouth and comes in fast- and slow-release formulations.

<span class="mw-page-title-main">CYP3A4</span> Enzyme that metabolizes substances by oxidation

Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by CYP3A4 gene. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme.

<span class="mw-page-title-main">Isosorbide mononitrate</span> Chemical compound

Isosorbide mononitrate, sold under many brand names, is a medication used for heart-related chest pain (angina), heart failure and esophageal spasms. It can be used both to treat and to prevent heart-related chest pain; however, it is generally less preferred than beta blockers or calcium channel blockers. It is taken by mouth.

<span class="mw-page-title-main">Lisinopril</span> Medication used to treat hypertension and heart failure

Lisinopril is a medication belonging to the drug class of angiotensin-converting enzyme (ACE) inhibitors and is used to treat hypertension, heart failure, and heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus. Lisinopril is taken orally. Full effect may take up to four weeks to occur.

Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage.

<span class="mw-page-title-main">Terfenadine</span> Chemical compound

Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel and was marketed under various brand names, including Seldane in the United States, Triludan in the United Kingdom, and Teldane in Australia. It was superseded by fexofenadine in the 1990s due to the risk of a particular type of disruption of the electrical rhythms of the heart and has been withdrawn from markets worldwide.

<span class="mw-page-title-main">Eplerenone</span> Chemical compound

Eplerenone, sold under the brand name Inspra, is an aldosterone antagonist type of potassium-sparing diuretic that is used to treat chronic heart failure and high blood pressure, particularly for people with resistant hypertension due to elevated aldosterone. It is a steroidal antimineralocorticoid of the spirolactone group and a selective aldosterone receptor antagonist (SARA).

<span class="mw-page-title-main">Nicardipine</span> Antihypertensive drug of the calcium channel blocker class

Nicardipine (Cardene) is a medication used to treat high blood pressure and angina. It belongs to the dihydropyridine class of calcium channel blockers (CCBs). It is also used for Raynaud's phenomenon. It is available in by mouth and intravenous formulations. It has been used in percutaneous coronary intervention.

<span class="mw-page-title-main">Lercanidipine</span> Antihypertensive drug of the calcium channel blocker class

Lercanidipine is an antihypertensive drug. It belongs to the dihydropyridine class of calcium channel blockers, which work by relaxing and opening the blood vessels allowing the blood to circulate more freely around the body. This lowers the blood pressure and allows the heart to work more efficiently.

<span class="mw-page-title-main">Nisoldipine</span> Antihypertensive drug of the calcium channel blocker class

Nisoldipine is a pharmaceutical drug used for the treatment of chronic angina pectoris and hypertension. It is a calcium channel blocker of the dihydropyridine class. It is sold in the United States under the proprietary name Sular. Nisoldipine has tropism for cardiac blood vessels.

<span class="mw-page-title-main">Vandetanib</span> Chemical compound

Vandetanib, sold under the brand name Caprelsa, is an anti-cancer medication that is used for the treatment of certain tumours of the thyroid gland. It acts as a kinase inhibitor of a number of cell receptors, mainly the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), and the RET-tyrosine kinase. The drug was developed by AstraZeneca who later sold the rights to Sanofi in 2015.

<span class="mw-page-title-main">Vernakalant</span> Medication for the treatment of atrial fibrillation

Vernakalant, sold under the brand name Brinavess, is a class III antiarrhythmic drug for the acute conversion of atrial fibrillation, a kind of irregular heartbeat, in form of an intravenous infusion. It has been approved for use in the European Union and the United Kingdom since 2010. The US Food and Drug Administration denied approval in 2008 and 2019.

<span class="mw-page-title-main">AH-1058</span> Chemical compound

AH-1058 is a lipophilic antiarrhythmic calcium channel blocker synthesized by the Pharmaceutical Research Laboratories of Ajinomoto Co., Inc in Kawasaki, Japan. It is derived from cyproheptadine, a compound with known antiserotonic, antihistaminic and calcium channel blocking properties. The IUPAC name of AH-1058 is: 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[E-3-(3-methoxy-2-nitro) phenyl-2-propenyl]piperidine hydrochloride.

<span class="mw-page-title-main">Sitagliptin/simvastatin</span> Combination drug

Sitagliptin/simvastatin, sold under the brand name Juvisync, is a fixed-dose combination anti-diabetic medication used to treat type 2 diabetes and hypercholesterolemia. It contains sitagliptin and simvastatin. Sitagliptin is a dipeptidyl peptidase-4 inhibitor and simvastatin is an HMG-CoA reductase inhibitor. These two disorders commonly occur in people at the same time, and have been typically treated with administration of these medications separately. The combination was approved in 2011, and sold under the brand name Juvisync by Merck. Juvisync was later removed from the market in 2013, due to business reasons.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Felopidine UK label". UK Electronic Medicines Compendium. 15 September 2015. Archived from the original on 16 August 2019. Retrieved 19 February 2015.
  2. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 465. ISBN   9783527607495.
  3. ↑ "Felodipine US label" (PDF). FDA. October 2012.
  4. ↑ Kiani J, Imam SZ (October 2007). "Medicinal importance of grapefruit juice and its interaction with various drugs". Nutrition Journal. 6 (33): 33. doi: 10.1186/1475-2891-6-33 . PMC   2147024 . PMID   17971226..
  5. ↑ Luther JM (September 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. PMC   4248353 . PMID   24992570.
  6. 1 2 3 Joshi GS, Burnett JC, Abraham DJ (2003). "Cardiac Drugs: Antianginal, Vasodilators, Antiarrhythmic". In Abraham DJ (ed.). Burger's medicinal chemistry and drug discovery. Volume 3: Cardiovascular Agents and Endocrines (6th ed.). Hoboken, N.J.: Wiley. ISBN   9780471270904.
  7. 1 2 3 4 "Merck's Plendil (Felodipine) Approved with "1C" Rating". Pink Sheet. 5 August 1991.
  8. ↑ Astrazeneca AB v. Mutual Pharmaceutical Co.(United States Court of Appeals for the Federal Circuit2004), Text .
  9. ↑ USpatent 4,264,611,Berntsson P, Carlsson S, Gaarder J, Ljung B,"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 28 April 1981, assigned to Aktiebolaget Hassle
  10. ↑ George J (28 July 1997). "Secret of Astra Merck". Philadelphia Business Journal. Philadelphia. Retrieved 7 November 2016.
  11. ↑ "Astra, Merck restructure". CNNMoney. 19 June 1998. Retrieved 7 November 2016.
  12. ↑ Jönsson B (2008). "Sweden". In Rapoport J, Jacobs P, Jonsson E (eds.). Cost Containment and Efficiency in National Health Systems a Global Comparison. Weinheim: Wiley-VCH. p. 218. ISBN   9783527622955.
  13. ↑ Approved Drug Products with Therapeutic Equivalence Evaluations (PDF) (36th ed.). FDA. 2014.
  14. ↑ "AstraZeneca enters licensing agreement with China Medical System Holdings for hypertension medicine" (Press release). AstraZeneca. 29 February 2016. Retrieved 7 November 2016.
  15. 1 2 3 4 5 "International brand names: Felodipine". Drugs.com. Retrieved 15 November 2016.
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