Felodipine

FEXOFENADINE HCL · Plendil · Felodipin · Agon · modip · Hydac · Spendil · CGH-869

Identifikatoren & physikalische Daten

CAS No.	72509-76-3
Summenformel	C18H19Cl2NO4
Durchschnittliche Molmasse	384,2 g/mol
Monoisotopische Masse	383,0691135 g/mol
SMILES	CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1c1cccc(Cl)c1Cl
InChIKey	RZTAMFZIAATZDJ-UHFFFAOYSA-N
PubChem CID	3333
ChEMBL	CHEMBL1480
ChEBI	CHEBI:585948
EC No.	620-472-7
DTXSID	DTXSID4023042

Chemische & physikalische Eigenschaften

XLogP	3,9
Polarare Oberfläche (TPSA)	64,6
H-Brücken-Donoren	1
H-Brücken-Akzeptoren	5
Frei drehbare Bindungen	6
Schwere Atome	25
Formalladung	0
Komplexität	614
LogP (Verteilungskoeffizient)	3.86
Löslichkeit	19.77.15e-03 g/LDMSO: 28 mg/mLinsoluble
Schmelzpunkt	145145 °C142-145°C
Caco2 Permeability	-4.64
Physical Description	Solid
Kovats Retention Index	2718.22678
Siedepunkt	471.5±45.0 °C(Predicted)
Dichte	1.3506 (rough estimate)
Brechungsindex	1.6500 (estimate)
Lagerbedingungen	2-8°C
Aggregatzustand	solid
pKa (Säurekonstante)	2.73±0.70(Predicted)
Farbe	light yellow
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
Hauptanwendungen	pharmaceuticalpharmaceutical small molecule
InChI	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
InChIKey	RZTAMFZIAATZDJ-UHFFFAOYSA-N
SMILES	C1(C)NC(C)=C(C(OC)=O)C(C2=CC=CC(Cl)=C2Cl)C=1C(OCC)=O
CAS Datenbank	72509-76-3(CAS DataBase Reference)
NIST chemische Informationen	Felodipine(72509-76-3)

Sicherheit & Vorschriften

GHS-Einstufung	WarningH302 (93.2%): Harmful if swallowed [Warning Acute toxicity, oral]H361 (22%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]H373 (22%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]H410 (15.3%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]P203, P260, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 59 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.
Hazard Classes and Categories	Acute Tox. 4 (93.2%)Repr. 2 (22%)STOT RE 2 (22%)Aquatic Chronic 1 (15.3%)
Unerwünschte Wirkungen	The adverse effects of felodipine are classified as either dose-dependent or dose-independent.* The common dose-dependent adverse effects of felodipine include peripheral edema, flushing, palpitations, and headaches. The most common clinical side effect of Felodipine use is peripheral edema. The frequency of peripheral edema is higher in individuals taking a higher dose of felodipine and elderly individuals. The incidence of peripheral edema is about 30% in elderly patients taking 20 mg of felodipine daily. Felodipine selectively dilates the arterioles, which increases intra-capillary pressure, causing extravasation of fluid into the interstitial space and resulting in peripheral edema. ACE inhibitors or angiotensin receptor blockers can prevent peripheral edema. Flushing and headaches also occur because of the vasodilatory effects of felodipine. Palpitations may occur because of reflex tachycardia.* In older adults with hypertension, initiating CCBs like felodipine frequently triggers a prescribing cascade, resulting in the subsequent unnecessary prescription of diuretics. Evaluating whether the edema is attributed to an underlying medical condition or is a result of Felodipine use is a risk mitigation strategy.* The dose-independent adverse effects of felodipine include fatigue, nausea, and gingival hyperplasia. Gingival hyperplasia occurs in less than 1% of patients and is more common in individuals with poor dental hygiene. The mechanism of gingival hyperplasia is overexpression of growth factors due to high concentrations of calcium ions, leading to fibroblast proliferation and chronic inflammatory cell infiltration. Gingival hyperplasia is usually reversible on discontinuation of felodipine.Drug-Drug InteractionsCytochrome P450 3A4 metabolizes felodipine.* The plasma level of felodipine increases when used in conjunction with CYP 3A4 inhibitors such as azole antifungals (Itraconazole and Ketoconazole), macrolide antibiotics (Clarithromycin and Azithromycin), HIV protease inhibitors, immunosuppressants (Cyclosporine), Cimetidine, or grapefruit juice.* The plasma level and efficacy of felodipine decrease when co-administered with CYP3A4 inducers such as anticonvulsants (Phenytoin and Carbamazepine), St John’s wort, or rifampicin.* When Metoprolol is subsequently administered with a conventional Felodipine formulation to treat essential hypertension, the plasma concentration of Metoprolol increases while that of felodipine remains unchanged.* If felodipine is co-administered with Theophylline, it results in a decrease in the plasma concentration of Theophylline.* CCBs and statins are frequently prescribed in patients with cardiovascular risk factors. In a study, acute kidney injury, hyperkalemia, acute myocardial infarction, and acute ischemic stroke were increased due to interaction between CYP3A4-metabolized statins and CCBs that inhibit CYP3A4, like Felodipine.
Toxizitätsübersicht	A mild-to-moderate overdose of felodipine can result in hypotension secondary to peripheral vasodilation and reflex tachycardia. However, a severe overdose of felodipine can cause life-threatening profound hypotension and bradycardia. Case fatality due to profound, refractory circulatory collapse overdose has been reported in the literature. The risk of overdose increases in elderly individuals, patients with liver impairment, and concomitant administration of felodipine with beta blockers. Overdose symptoms can include lightheadedness, syncope, altered mental status, and shock secondary to profound hypotension. The insulin release from the pancreas depends on calcium influx through the L-type channels. Felodipine blocks these calcium channels and results in hyperglycemia because of decreased insulin release.The first step in managing Felodipine overdose is maintaining a patent airway. Patients who have consumed an excess of felodipine ER tablets but have not yet developed any symptoms should be started on gastrointestinal decontamination with whole bowel irrigation if they present within 6 to 8 hours of drug ingestion. Patients with hypotension should undergo resuscitation with IV fluids. However, caution is necessary for individuals with congestive heart failure and pulmonary edema. Vasopressor therapy with dopamine or norepinephrine is an as-needed option for hypotension. IV calcium gluconate or calcium chloride (given via central line) are also options in treating Felodipine overdose.In patients with severe overdose, atropine should be administered IV for bradycardia. The vital signs, serum electrolytes, especially potassium, blood glucose, urine output, and ECG, should be monitored regularly. Hyperinsulinemia-euglycemia therapy is also an established treatment for CCB overdose. This therapy helps mobilize glucose from the peripheral tissue to serve as an alternative energy source for the myocardium.
Drug Induced Liver Injury	Drug Induced Liver Injury Rank (DILIrank 2.0)FelodipinevLess-DILI-concern3Adverse reactionsDOI:10.1016/j.drudis.2016.02.015
Effects During Pregnancy and Lactation	◉ Summary of Use during LactationBecause no information is available on the use of felodipine during breastfeeding, an alternate drug may be preferred.◉ Effects in Breastfed InfantsRelevant published information was not found as of the revision date.◉ Effects on Lactation and Breastmilk
Wassergefährdungsklasse (WGK)	3
UN-Transportnummer	UN 3077 9 / PGIII
Zollcode	29333990
RTECS-Nr.	US7968700
R-Sätze (R)	22
Gefahrensymbole	Xn
Sicherheitshinweise (S)	36
Lagerklasse	11 - Combustible Solids
Gefahrenklasse	Acute Tox. 4 OralAquatic Acute 1Aquatic Chronic 1Repr. 2STOT RE 2 Inhalation

Anwendungen & Verwendung

Beschreibung

Felodipine is a vasodilatory calcium antagonist with a high degree of vascular selectivity. It is currently indicated for use only in hypertension, either as monotherapy or in conjunction with diuretics or beta blockers.

Verwenden

Felodipine is used as a dihydropyridine calcium channel blocker. It displays high vascular selectivity; lowers arterial blood pressure without altering cardiac contractility. Antihypertensive.