Felodipine
Medication of the calcium channel blocker type
From Wikipedia, the free encyclopedia
Felodipine is a medication of the calcium channel blocker type that is used to treat high blood pressure.
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| Trade names | Plendil |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a692016 |
| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Bioavailability | 15% |
| Metabolism | Hepatic |
| Onset of action | 2.5–5 hours |
| Elimination half-life | 25 hours[1] |
| Excretion | Renal |
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| ECHA InfoCard | 100.149.305 |
| Chemical and physical data | |
| Formula | C18H19Cl2NO4 |
| Molar mass | 384.25 g·mol−1 |
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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]