Felodipine

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Template:Short description Template:Cs1 config Template:Use dmy dates Template:Drugbox Felodipine is a medication of the calcium channel blocker type that is used to treat high blood pressure.

It was patented in 1978, and approved for medical use in 1988.[1]

Medical uses

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

For people with liver failure the dose needs to be lowered, because felodipine is cleared by the liver.[2]

Adverse effects

The only very common side effect, occurring in more than 1/10 people, is pain and swelling in the arms and legs.[2]

Common side effects, occurring in between 1% and 10% of people, include flushing, headache, heart palpitations, dizziness and fatigue.[2]

Felodipine can exacerbate gingivitis.[2]

Interactions

Felodipine is metabolized by cytochrome P450 3A4, so substances that inhibit or activate CYP3A4 can strongly effect how much felodipine is present.[2]

CYP3A4 inhibitors, which increase the amount of felodipine available per dose, include cimetidine, erythromycin, itraconazole, ketoconazole, HIV protease inhibitors, and grapefruit juice.[2][4]

CYP3A4 activators, which decrease the amount of felodipine available per dose, include phenytoin, carbamazepine, rifampicin, barbiturates, efavirenz, nevirapine, and Saint John's wort.[2]

Mechanism of action

Felodipine is a calcium channel blocker.[2] 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]Template:Rp

Chemistry

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

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]Template:Rp

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]

References

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