Agon - General Information
A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.
Pharmacology of Agon
Agon, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Agon is similar to other peripheral vasodilators. Agon inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes blocking the calcium channels. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Agon for patients
Information for the Patient
Patients should be instructed to take felodipine whole and not to crush or chew the
tablets. They should be told that mild gingival hyperplasia (gum swelling) has been
reported. Good dental hygiene decreases its incidence and severity.
Note: As with many other drugs, certain advice to patients being treated with felodipine
is warranted. This information is intended to aid in the safe and effective use of this
medication. It is not a disclosure of all possible adverse or intended effects.
CYP3A4 Inhibitors—Felodipine is metabolized by CYP3A4. Co-administration of CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, grapefruit juice, cimetidine) with felodipine may lead to several- fold increases in the plasma levels of felodipine, either due to an increase in bioavailability or due to a decrease in metabolism. These increases in concentration may lead to increased effects, (lower blood pressure and increased heart rate). These effects have been observed with co-administration of itraconazole (a potent CYP3A4 inhibitor). Caution should be used when CYP3A4 inhibitors are co-administered with felodipine. A conservative approach to dosing felodipine should be taken. The following specific interactions have been reported:
Itraconazole—Co-administration of another extended release formulation of felodipine with itraconazole resulted in approximately 8-fold increase in the AUC, more than 6- fold increase in the Cmax, and 2-fold prolongation in the half- life of felodipine.
Erythromycin—Co-administration of felodipine (PLENDIL) with erythromycin resulted in approximately 2.5- fold increase in the AUC and Cmax, and about 2- fold prolongation in the half- life of felodipine.
Grapefruit juice—Co-administration of felodipine with grapefruit juice resulted in more than 2-fold increase in the AUC and Cmax, but no prolongation in the half- life of felodipine.
Cimetidine—Co-administration of felodipine with cimetidine (a non-specific CYP-450 inhibitor) resulted in an increase of approximately 50% in the AUC and the Cmax, of felodipine.
Beta-Blocking Agents— A pharmacokinetic study of felodipine in conjunction with metoprolol demonstrated no significant effects on the pharmacokinetics of felodipine. The AUC and Cmax of metoprolol, however, were increased approximately 31 and 38%, respectively. In controlled clinical trials, however, beta blockers including metoprolol were concurrently administered with felodipine and were well tolerated.
Digoxin— When given concomitantly with PLENDIL the pharmacokinetics of digoxin in patients with heart failure were not significantly altered.
Anticonvulsants— In a pharmacokinetic study, maximum plasma concentrations of felodipine were considerably lower in epileptic patients on long-term anticonvulsant therapy (eg, phenytoin, carbamazepine, or phenobarbital) than in healthy volunteers. In such patients, the mean area under the felodipine plasma concentration-time curve was also reduced to approximately 6% of that observed in healthy volunteers. Since a clinically significant interaction may be anticipated, alternative antihypertensive therapy should be considered in these patients.
Tacrolimus— Felodipine may increase the blood concentration of tacrolimus. When given concomitantly with felodipine, the tacrolimus blood concentration should be followed and the tacrolimus dose may need to be adjusted.
Other Concomitant Therapy— In healthy subjects there were no clinically significant interactions when felodipine was given concomitantly with indomethacin or spironolactone.
Interaction with Food— See CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism.
PLENDIL is contraindicated in patients who are hypersensitive to this product.
Additional information about Agon
Agon Indication: For the treatment of hypertension and angina.
Mechanism Of Action: Agon is Ca++ channel blocker. It reversibly competes with nitrendipine and/or other calcium channel blockers for dihydropyridine binding sites, blocks voltage-dependent Ca++ currents in vascular smooth muscle and cultured rabbit atrial cells, and blocks potassium- induced contracture of the rat portal vein. By blocker the Ca++ channels, Agon inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes and results in a decrease of peripheral vascular resistance.
Drug Interactions: Amobarbital The barbiturate decreases the effect of felodipine
Aprobarbital The barbiturate decreases the effect of felodipine
Butabarbital The barbiturate decreases the effect of felodipine
Butalbital The barbiturate decreases the effect of felodipine
Butethal The barbiturate decreases the effect of felodipine
Carbamazepine Carbamazepine decreases the effect of felodipine
Dihydroquinidine barbiturate The barbiturate decreases the effect of felodipine
Heptabarbital The barbiturate decreases the effect of felodipine
Hexobarbital The barbiturate decreases the effect of felodipine
Methohexital The barbiturate decreases the effect of felodipine
Methylphenobarbital The barbiturate decreases the effect of felodipine
Pentobarbital The barbiturate decreases the effect of felodipine
Phenobarbital The barbiturate decreases the effect of felodipine
Primidone The barbiturate decreases the effect of felodipine
Quinidine barbiturate The barbiturate decreases the effect of felodipine
Secobarbital The barbiturate decreases the effect of felodipine
Talbutal The barbiturate decreases the effect of felodipine
Erythromycin Erythromycin increases the effect of felodipine
Josamycin Erythromycin increases the effect of felodipine
Ethotoin The hydantoin decreases the effect of felodipine
Fosphenytoin The hydantoin decreases the effect of felodipine
Mephenytoin The hydantoin decreases the effect of felodipine
Phenytoin The hydantoin decreases the effect of felodipine
Quinupristin This combination presents an increased risk of toxicity
Itraconazole Itraconazole increases effect/toxicity of felodipine
Nelfinavir Nelfinavir increases the effect and toxicity of felodipine
Oxcarbazepine Oxcarbazepine decreases the levels of felodipine
Tacrolimus Agon increases tacrolimus levels
Food Interactions: Take without regard to meals.
Grapefruit and grapefruit juice should be avoided throughout treatment as grapefruit can significantly increase serum levels of this product.
Generic Name: Felodipine
Synonyms: Felodipina [Inn-Spanish]; Felodipine [Usan-Ban-Inn]; Felodipinum [Inn-Latin]; Dl-Felodipine
Drug Category: Vasodilator Agents; Antihypertensive Agents; Antiarrhythmic Agents; Dihydropyridines
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Felodipine: AGON SR; Agon; Feloday; Felodur Er; Felogard; Flodil; Hydac; Lexxel; Modip; Munobal; Munobal Retard; Penedil; Perfudal; Plandil; Plendil; Plendil Depottab; Plendil Er; Plendil Retard; Preslow; Prevex; Renedil; Splendil;
Toxicity (Overdose): excessive peripheral vasodilation with marked hypotension and possibly bradycardia
Protein Binding: 99%
Half Life: 14.1 hours
Dosage Forms of Agon: Tablet, extended release Oral
Chemical IUPAC Name: O3-ethyl O5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Chemical Formula: C18H19Cl2NO4
Felodipine on Wikipedia: http://en.wikipedia.org/wiki/Felodipine
Organisms Affected: Humans and other mammals