Felodipine

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.<ref>Template:Cite book</ref>

Medical uses

Felodipine is used to treat high blood pressure and stable angina.<ref name=UKlabel2015/><ref name=USlabel2012>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref name=UKlabel2015/>

For people with liver failure the dose needs to be lowered, because felodipine is cleared by the liver.<ref name=UKlabel2015/>

Adverse effects

The only very common side effect, occurring in more than 1/10 people, is pain and swelling in the arms and legs.<ref name=UKlabel2015/>

Common side effects, occurring in between 1% and 10% of people, include flushing, headache, heart palpitations, dizziness and fatigue.<ref name=UKlabel2015/>

Felodipine can exacerbate gingivitis.<ref name=UKlabel2015/>

Interactions

Felodipine is metabolized by cytochrome P450 3A4, so substances that inhibit or activate CYP3A4 can strongly effect how much felodipine is present.<ref name=UKlabel2015/>

CYP3A4 inhibitors, which increase the amount of felodipine available per dose, include cimetidine, erythromycin, itraconazole, ketoconazole, HIV protease inhibitors, and grapefruit juice.<ref name=UKlabel2015/><ref>Template:Cite journal.</ref>

CYP3A4 activators, which decrease the amount of felodipine available per dose, include phenytoin, carbamazepine, rifampicin, barbiturates, efavirenz, nevirapine, and Saint John's wort.<ref name=UKlabel2015/>

Mechanism of action

Felodipine is a calcium channel blocker.<ref name=UKlabel2015/> Felodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.<ref name="Luther2014">Template:Cite journal</ref>

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.<ref name=Burger/>Template:Rp

Chemistry

Felodipine is a member of the 1,4-dihydropyridine class of calcium channel blockers.<ref name=Burger>Template:Cite book</ref>Template:Rp It is a racemic mixture, and is insoluble in water but is soluble in dichloromethane and ethanol.<ref name=Burger/>Template:Rp

History

The Swedish company Hässle, a division of Astra AB, discovered felodipine;<ref name=PinkSheet1991/> it filed a patent application in 1979 claiming felodipine as an antihypertensive drug.<ref name=court>Template:Cite court</ref><ref name=Patent611>Template:Cite patent</ref> Astra partnered this drug and others with Merck & Co. in the US under a 1982 agreement between the companies.<ref name=PinkSheet1991>Template:Cite news</ref> 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.<ref name=PinkSheet1991/> 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.<ref name=PinkSheet1991/>

In 1994 Astra AB and Merck changed their partnership to a joint venture called Astra Merck,<ref name=biz>Template:Cite news</ref> and in 1998 Astra (by that time, AstraZeneca) bought out Merck's rights in the joint venture.<ref name=cnnmoney>Template:Cite news</ref>

The first generics became available in Sweden in 2003<ref>Template:Cite book</ref> and in the US in 2004.<ref>Template:Cite book</ref>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.<ref name=AZrelease>Template:Cite press release</ref>

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.<ref name=brands2016>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The combination of felodipine and candesartan was marketed as Atacand.<ref name=brands2016/>

The combination of felodipine and ramipril was marketed as Delmuno, Tazko, Triacor, Triapin, Triasyn, Tri-Plen, Unimax, and Unitens.<ref name=brands2016/>

The combination of felodipine and enalapril was marketed as Lexxel.<ref name=brands2016/>

The combination of felodipine and metoprolol was marketed as Logimat, Logimax, and Mobloc.<ref name=brands2016/>