Felodipine 10 MG 24 HR Extended Release Oral Tablet
Generic Name: FELODIPINE
Brand Name: Felodipine
- Substance Name(s):
- FELODIPINE
DRUG INTERACTIONS
Drug Interactions CYP3A4 Inhibitors – Felodipine is metabolized by CYP3A4.
Co-administration of CYP3A4 inhibitors (e.g., 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 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 felodipine extended-release tablets 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 (e.g.
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 mg -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.
DESCRIPTION
Felodipine is a calcium antagonist (calcium channel blocker).
Felodipine is a dihydropyridine derivative that is chemically described as ± ethyl methyl 4-(2, 3-dichlorophenyl)-1, 4-dihydro-2, 6-dimethyl-3, 5-pyridinedicarboxylate.
Its empirical formula is C18H19Cl2NO4 and its structural formula is: Felodipine, USP is a light yellow to yellow, crystalline powder with a molecular weight of 384.26.
It is insoluble in water and is freely soluble in acetone and in methanol; very slightly soluble in heptane.
Felodipine is a racemic mixture.
Felodipine extended-release tablets, USP provide extended release of felodipine.
They are available as tablets containing 2.5 mg, 5 mg or 10 mg of felodipine, USP for oral administration.
Inactive ingredients are: polyoxyl 40 hydrogenated castor oil, magnesium aluminum silicate, hypromellose 2208, lactose monohydrate, hydroxypropyl cellulose, sodium stearyl fumarate, hypromellose 2910 5cP, titanium dioxide and PEG 400.
The 2.5 mg tablet strength also contains Iron oxide yellow, D&C yellow #10 aluminum lake and the 5 mg tablet strength also contains Iron oxide yellow.
USP dissolution test pending.
structure
HOW SUPPLIED
Felodipine Extended-Release Tablets, USP are available containing 2.5 mg, 5 mg or 10 mg of felodipine, USP.
The 2.5 mg tablet is a yellow colored, circular shaped, biconvex, film coated tablet de-bossed with ‘I31’ on one side and plain on other side.
They are available as follows: NDC 23155-048-01 bottles of 100 tablets The 5 mg tablet is a light yellow colored, circular shaped, biconvex, film coated tablet de-bossed with ‘I32’ on one side and plain on other side.
They are available as follows: NDC 23155-049-01 bottles of 100 tablets The 10 mg tablet is a white colored, circular shaped, biconvex, film coated tablet de-bossed with ‘I33’ on one side and plain on other side.
They are available as follows: NDC 23155-050-01 bottles of 100 tablets Storage: Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room Temperature.] Protect from light.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Manufactured for: Heritage Pharmaceuticals Inc .
Eatontown, NJ 077241.
866.901.DRUG (3784) Made in India.
Issued 11/16
GERIATRIC USE
Geriatric Use Clinical studies of felodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
Pharmacokinetics, however, indicate that the availability of felodipine is increased in older patients (see CLINICAL PHARMACOLOGY , Geriatric Use ).
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
MECHANISM OF ACTION
Mechanism of Action Felodipine is a member of the dihydropyridine class of calcium channel antagonists (calcium channel blockers).
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.
In vitro studies show that the effects of felodipine on contractile processes are selective, with greater effects on vascular smooth muscle than cardiac muscle.
Negative inotropic effects can be detected in vitro , but such effects have not been seen in intact animals.
The effect of felodipine on blood pressure is principally a consequence of a dose related decrease of peripheral vascular resistance in man, with a modest reflex increase in heart rate (see Cardiovascular Effects ).
With the exception of a mild diuretic effect seen in several animal species and man, the effects of felodipine are accounted for by its effects on peripheral vascular resistance.
INDICATIONS AND USAGE
Felodipine extended-release tablets, USP are indicated for the treatment of hypertension, to lower blood pressure.
Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.
These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including felodipine.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.
Many patients will require more than 1 drug to achieve blood pressure goals.
For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits.
The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit.
Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (eg, on angina, heart failure, or diabetic kidney disease).
These considerations may guide selection of therapy.
Felodipine extended-release tablets, USP may be administered with other antihypertensive agents.
PEDIATRIC USE
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
PREGNANCY
Pregnancy Pregnancy Category C Teratogenic Effects – Studies in pregnant rabbits administered doses of 0.46, 1.2, 2.3 and 4.6 mg/kg/day (from 0.8 to 8 times1 the maximum recommended human dose on a mg/m2 basis) showed digital anomalies consisting of reduction in size and degree of ossification of the terminal phalanges in the fetuses.
The frequency and severity of the changes appeared dose related and were noted even at the lowest dose.
These changes have been shown to occur with other members of the dihydropyridine class and are possibly a result of compromised uterine blood flow.
Similar fetal anomalies were not observed in rats given felodipine.
In a teratology study in cynomolgus monkeys, no reduction in the size of the terminal phalanges was observed, but an abnormal position of the distal phalanges was noted in about 40% of the fetuses.
Nonteratogenic Effects – A prolongation of parturition with difficult labor and an increased frequency of fetal and early postnatal deaths were observed in rats administered doses of 9.6 mg/kg/day (8 times1 the maximum human dose on a mg/m2 basis) and above.
Significant enlargement of the mammary glands, in excess of the normal enlargement for pregnant rabbits, was found with doses greater than or equal to 1.2 mg/kg/day (2.1 times the maximum human dose on a mg/m2 basis).
This effect occured only in a pregnant rabits and regressed during lactation.
Similar changes in the mammary glands were not observed in rats or monkeys.
There are no adequate and well-controlled studies in pregnant women.
If felodipine is used during pregnancy, or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus, possible digital anomalies of the infant, and the potential effects of felodipine on labor and delivery and on the mammary glands of pregnant females.
1Based on patient weight of 50 kg
NUSRING MOTHERS
Nursing Mothers It is not known whether this drug is secreted in human milk and because of the potential for serious adverse reactions from felodipine in the infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
INFORMATION FOR PATIENTS
Information for Patients Patients should be instructed to take felodipine extended-release tablets 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 extended-release tablets are 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.
DOSAGE AND ADMINISTRATION
The recommended starting dose is 5 mg once a day.
Depending on the patient’s response, the dosage can be decreased to 2.5 mg or increased to 10 mg once a day.
These adjustments should occur generally at intervals of not less than 2 weeks.
The recommended dosage range is 2.5-10 mg once daily.
In clinical trials, doses above 10 mg daily showed an increased blood pressure response but a large increase in the rate of peripheral edema and other vasodilatory adverse events (see ADVERSE REACTIONS ).
Modification of the recommended dosage is usually not required in patients with renal impairment.
Felodipine extended-release tablets should regularly be taken either without food or with a light meal (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism ).
Felodipine extended-release tablets should be swallowed whole and not crushed or chewed.
Geriatric Use – Patients over 65 years of age are likely to develop higher plasma concentrations of felodipine (see CLINICAL PHARMACOLOGY ).
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range (2.5 mg daily).
Elderly patients should have their blood pressure closely monitored during any dosage adjustment.
Patients with Impaired Liver Function – Patients with impaired liver function may have elevated plasma concentrations of felodipine and may respond to lower doses of felodipine extended-release tablets; therefore, patients should have their blood pressure monitored closely during dosage adjustment of felodipine extended-release tablets (see CLINICAL PHARMACOLOGY ).