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Felodipine

Pronunciation

Class: Dihydropyridines
VA Class: CV200
Chemical Name: 4-(2,3-Dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5 -pyridinedicarboxylic acid ethyl methyl ester
Molecular Formula: C18H19Cl2NO4
CAS Number: 72509-76-3
Brands: Lexxel, Plendil

Introduction

Calcium-channel blocking agent; a 1,4-dihydropyridine derivative.1 2

Uses for Felodipine

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 46 51

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One of several preferred initial therapies in hypertensive patients with a high risk of developing coronary artery disease and/or diabetes mellitus.77

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.77

Hypertensive Crises

Extended-release felodipine tablets are not suitable for acute treatment of hypertensive urgencies nor in hypertensive emergencies7 9 46 51 but may be useful when severe BP elevations continue after initial management of the hypertensive crisis with an appropriate agent.46

Felodipine Dosage and Administration

General

Hypertension

  • Fixed-combination felodipine/enalapril tablets should not be used for initial treatment of hypertension.51 68

Administration

Oral Administration

Administer felodipine alone or in fixed combination with enalapril orally once daily without food or with a light meal.1 51 Avoid concomitant administration with grapefruit juice.1 (See Specific Drugs and Foods under Interactions.)

Swallow extended-release tablets intact; do not chew or crush.1 51

Dosage

Pediatric Patients

Hypertension
Felodipine Monotherapy
Oral

Initially, 2.5 mg of felodipine once daily.80 Increase dosage as necessary up to a maximum dosage of 10 mg once daily.80

Adults

Hypertension
Felodipine Monotherapy
Oral

Initially, 2.5–5 mg of felodipine once daily.1 9 46 Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.46

Usual felodipine dosage: 2.5–10 mg daily.1 Some experts (JNC 7) state that dosage can be increased to 20 mg daily if necessary and tolerated.46

Felodipine/Enalapril Combination Therapy
Oral

If BP is not adequately controlled by monotherapy with felodipine (or another dihydropyridine-derivative calcium-channel blocking agent) or enalapril (or another ACE inhibitor), can switch to fixed-combination tablets (felodipine 5 mg and enalapril 5 mg; then felodipine 10 mg and enalapril 10 mg).51 If BP control is still inadequate, consider addition of thiazide diuretic.51

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Maximum 10 mg of felodipine daily.80

Adults

Hypertension
Oral

Maximum 20 mg of felodipine daily.46

Special Populations

The following information addresses dosage of felodipine in special populations.51 Dosages of drugs administered in fixed combination with felodipine also may require adjustment in certain patient populations; the need for such dosage adjustments must be considered in the context of cautions, precautions, and contraindications specific to that population and drug.51

Hepatic Impairment

Usual initial felodipine dosage: 2.5 mg daily.1 51 68 Closely monitor BP response with each dosage adjustment.1

Felodipine/Enalapril Combination Therapy

May use the fixed combination if the optimum maintenance dosage of felodipine and enalapril administered separately corresponds to the amount of the drugs in the fixed combination.51 Amount of felodipine in the fixed combination exceeds the recommended initial dosage for patients with hepatic impairment.51

Renal Impairment

Adjustment of felodipine dosage generally not required.1

Felodipine/Enalapril Combination Therapy

May use the fixed combination if the optimum maintenance dosage of felodipine and enalapril administered separately corresponds to the amount of the drugs in the fixed combination.51 Amount of enalapril in the fixed combination exceeds the recommended initial dosage for patients with severe renal impairment.51

Geriatric Patients

Usual initial felodipine dosage: 2.5 mg daily.1 51 68 Closely monitor BP response with each dosage adjustment.1

Risk of peripheral edema increased substantially with felodipine dosages >10 mg daily.1

Felodipine/Enalapril Combination Therapy

May use the fixed combination if the optimum maintenance dosage of felodipine and enalapril administered separately corresponds to the amount of the drugs in the fixed combination.51 Amount of felodipine in the fixed combination exceeds the recommended initial dosage for geriatric patients.51

Cautions for Felodipine

Contraindications

  • Known hypersensitivity to felodipine or any ingredient in the formulation.1 51

Warnings/Precautions

General Precautions

Angina

Possible hypotension and/or syncope resulting in reflex tachycardia and precipitation of angina pectoris in susceptible patients.1 51

Heart Failure

Safety not established in patients with heart failure; use with caution in patients with heart failure or compromised ventricular function, particularly when used in combination with a β-adrenergic blocker.1

Peripheral Edema

Mild peripheral edema possible within 2–3 weeks of initiating therapy, particularly in older patients (e.g., >60 years of age) receiving higher felodipine dosages (e.g., 20 mg daily).1 51

Use of Fixed Combinations

When felodipine is used in fixed combination with enalapril, consider the cautions, precautions, and contraindications associated with enalapril.51

Specific Populations

Pregnancy

Felodipine: Category C.1 51

Lactation

Not known whether felodipine is distributed into milk; discontinue nursing or the drug.1 51

Pediatric Use

Safety and efficacy remain to be fully established in children;1 51 however, some experts have recommended dosages for hypertension based on current limited clinical experience.80

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.1 51 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Felodipine clearance may be decreased.1 (See Special Populations under Pharmacokinetics.) Manufacturer recommends lower initial dosage in patients with hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Peripheral edema, headache, flushing.1

Interactions for Felodipine

Metabolized by CYP3A4.1 51

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential for increased plasma felodipine concentrations, with possible reduction in BP and increase in heart rate; use with caution.1 51

Specific Drugs and Foods

Drug or Food

Interaction

Comment

Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)

Decreased plasma felodipine concentrations1 51

Consider use of alternative antihypertensive agents1 51

Antifungals, azoles (itraconazole, ketoconazole)

Increased plasma felodipine concentrations; decreased BP and increased heart rate reported with itraconazole1 51

Cimetidine

Increased plasma felodipine concentrations1 51

Digoxin

Pharmacokinetic interaction unlikely1 51

Erythromycin

Increased plasma felodipine concentrations1 51

Grapefruit juice

Increased oral bioavailability of felodipine1 51

Avoid concomitant use1 51

Indomethacin

Pharmacokinetic interaction unlikely1 51

Metoprolol

Increased plasma metoprolol concentrations1 51

Not considered clinically important1 51

Orange juice

Pharmacokinetic interaction unlikely1 51

Spironolactone

Pharmacokinetic interaction unlikely1 51

Tacrolimus

Increased plasma tacrolimus concentrations1 51

Monitor plasma tacrolimus concentrations1 51

Felodipine Pharmacokinetics

Absorption

Bioavailability

Almost completely absorbed following oral administration but undergoes extensive first-pass metabolism.1 51

Systemic bioavailability of felodipine is approximately 20%.1 51

Onset

Antihypertensive effect evident within 2–5 hours,1 with maximum BP reduction after 1–2 weeks.51

Duration

During chronic administration, substantial BP control lasts for 24 hours, with trough reductions in DBP approximately 40–50% of peak reductions.1

Food

High-fat or high-carbohydrate meal increases peak plasma concentrations but does not affect extent of absorption;1 51 when administered as fixed-combination felodipine/enalapril tablets, high-fat or high-carbohydrate meal also decreases trough (24-hour) plasma concentrations.51 A light meal (e.g., orange juice, toast, and cereal) does not alter felodipine pharmacokinetics.1 51

Distribution

Extent

Crosses the blood-brain barrier.51

Crosses the placenta in animals.1 51

Plasma Protein Binding

>99%.1 51

Elimination

Metabolism

Metabolized in the liver by CYP3A4.1 51

None of the 6 metabolites identified to date has substantial vasodilating activity.1 51

Elimination Route

Eliminated as metabolites, mainly in urine and to a lesser extent in feces.1 51

Half-life

Mean terminal half-life is approximately 11–16 hours following administration as an immediate-release formulation.1 51

Special Populations

Hepatic impairment: Clearance is decreased to about 60% of that observed in young healthy individuals.1 51

Geriatric patients: Felodipine clearance is decreased to about 45% of that observed in young healthy individuals.1 51

Stability

Storage

Oral

Tablets

Felodipine: Tightly closed container at <30°C.1 Protect from light.1

Felodipine/enalapril fixed-combination preparation: Tightly closed container at 25°C (may be exposed to 15–30°C).51 Protect from light and moisture.51

Actions

  • Inhibits the transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations.c

  • Hypotensive effect is principally a consequence of a dose-related reduction in peripheral vascular resistance, with a modest reflex increase in heart rate.1

  • Negative inotropic effects observed in vitro but not in intact animals.1

  • Has no substantial effect on cardiac conduction (PR, PQ, and HV intervals).1

Advice to Patients

  • Risk of mild gingival hyperplasia; importance of good dental hygiene.1

  • Importance of taking felodipine exactly as prescribed.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 51

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 51

  • Importance of informing patients of other important precautionary information.1 51 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Felodipine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

2.5 mg

Plendil

AstraZeneca

5 mg

Plendil

AstraZeneca

10 mg

Plendil

AstraZeneca

Felodipine Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release core (felodipine only), film-coated

5 mg with Enalapril Maleate 5 mg

Lexxel

AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Felodipine 10MG 24-hr Tablets (MYLAN): 100/$194.98 or 200/$388.98

Felodipine 2.5MG 24-hr Tablets (MYLAN): 30/$43.99 or 60/$87.98

Felodipine 5MG 24-hr Tablets (MYLAN): 30/$42.99 or 90/$119.98

Plendil 10MG 24-hr Tablets (ASTRAZENECA LP): 30/$89.99 or 90/$259.95

Plendil 2.5MG 24-hr Tablets (ASTRAZENECA LP): 30/$51.99 or 90/$137.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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