Brands, Medical Use, Clinical Data
- Vasodilator Agents
- Antihypertensive Agents
- Antiarrhythmic Agents
Brands / Synonyms
Agon; AGON SR; Dl-Felodipine; Faropenem; Feloday; Felodipina [Inn-Spanish]; Felodipine [Usan:Ban:Inn]; Felodipinum [Inn-Latin]; Felodur Er; Felogard; FEXOFENADINE HCL; Fexofenadine Hydrochloride; Fexofinadine Hcl; Flodil; Hydac; Lexxel; Modip; Munobal; Munobal Retard; Penedil; Perfudal; Plandil; Plendil; Plendil Depottab; Plendil Er; Plendil Retard; Preslow; Prevex; Renedil; Splendil
For the treatment of hypertension
Felodipine, 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. Felodipine is similar to other peripheral vasodilators. Felodipine 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.
Mechanism of Action
Felodipine 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, Felodipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes and results in a decrease of peripheral vascular resistance.
excessive peripheral vasodilation with marked hypotension and possibly bradycardia
Biotrnasformation / Drug Metabolism
PLENDIL is contraindicated in patients who are hypersensitive to this product.
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
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
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.