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Plendil (Felodipine) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

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.

OVERDOSAGE

Oral doses of 240 mg/kg and 264 mg/kg in male and female mice, respectively, and 2390 mg/kg and 2250 mg/kg in male and female rats, respectively, caused significant lethality.

In a suicide attempt, one patient took 150 mg felodipine together with 15 tablets each of atenolol and spironolactone and 20 tablets of nitrazepam. The patient's blood pressure and heart rate were normal on admission to hospital; he subsequently recovered without significant sequelae.

Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly bradycardia.

If severe hypotension occurs, symptomatic treatment should be instituted. The patient should be placed supine with the legs elevated. The administration of intravenous fluids may be useful to treat hypotension due to overdosage with calcium antagonists. In case of accompanying bradycardia, atropine (0.5−1 mg) should be administered intravenously. Sympathomimetic drugs may also be given if the physician feels they are warranted.

It has not been established whether felodipine can be removed from the circulation by hemodialysis.

To obtain up-to-date information about the treatment of overdose, consult your Regional Poison-Control Center. Telephone numbers of certified poison-control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and unusual drug kinetics in your patient.

CONTRAINDICATIONS

PLENDIL is contraindicated in patients who are hypersensitive to this product.

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