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Felodipine

Class: Dihydropyridines
- Calcium-Channel Blocking Agents, Dihydropyridine
- Calcium Antagonists
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: Plendil

Medically reviewed by Drugs.com on Mar 8, 2021. Written by ASHP.

Introduction

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

Uses for Felodipine

Hypertension

Management of hypertension alone or in combination with other classes of antihypertensive agents.

Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics. While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension. (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.</

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Calcium-channel blockers may be beneficial in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease) and in geriatric patients, including those with isolated systolic hypertension.

Calcium-channel blockers may be particularly useful in black patients with hypertension; such patients generally respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists). However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.

Felodipine Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, thiazide diuretic).

  • Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved with 2 antihypertensive agents, add a third drug.

Administration

Oral Administration

Administer once daily without food or with a light meal. Avoid concomitant administration with grapefruit juice. (See Specific Drugs and Foods under Interactions.)

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

Dosage

Pediatric Patients

Hypertension†
Oral

Children ≥6 years of age: Some experts recommend an initial dosage of 2.5 mg once daily. Experts state that dosage may be increased every 2–4 weeks until BP controlled, maximum dosage reached (10 mg once daily), or adverse effects occur.

Adults

Hypertension
Oral

Initially, 2.5–5 mg once daily.

Usual maintenance dosage: 2.5–10 mg daily. Dosages >10 mg daily associated with increased BP response but also with exaggerated adverse vasodilatory effects (e.g., peripheral edema).

Prescribing Limits

Pediatric Patients

Hypertension†
Oral

Maximum 10 mg of felodipine daily.

Special Populations

Hepatic Impairment

Usual initial dosage: 2.5 mg daily. Closely monitor BP response with each dosage adjustment.

Renal Impairment

Dosage adjustment generally not required.

Geriatric Patients

Usual initial dosage: 2.5 mg daily. Closely monitor BP response with each dosage adjustment.

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

Cautions for Felodipine

Contraindications

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

Warnings/Precautions

General Precautions

Angina

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

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.

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).

Specific Populations

Pregnancy

Felodipine: Category C.

Lactation

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

Pediatric Use

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

Geriatric Use

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

Hepatic Impairment

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

Common Adverse Effects

Peripheral edema, headache, flushing.

Interactions for Felodipine

Metabolized by CYP3A4.

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.

Specific Drugs and Foods

Drug or Food

Interaction

Comment

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

Decreased plasma felodipine concentrations

Consider use of alternative antihypertensive agents

Antifungals, azoles (itraconazole, ketoconazole)

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

Cimetidine

Increased plasma felodipine concentrations

Digoxin

Pharmacokinetic interaction unlikely

Erythromycin

Increased plasma felodipine concentrations

Grapefruit juice

Increased oral bioavailability of felodipine

Avoid concomitant use

Indomethacin

Pharmacokinetic interaction unlikely

Metoprolol

Increased plasma metoprolol concentrations

Not considered clinically important

Orange juice

Pharmacokinetic interaction unlikely

Spironolactone

Pharmacokinetic interaction unlikely

Tacrolimus

Increased plasma tacrolimus concentrations

Monitor plasma tacrolimus concentrations

Felodipine Pharmacokinetics

Absorption

Bioavailability

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

Systemic bioavailability of felodipine is approximately 20%.

Onset

Antihypertensive effect evident within 2–5 hours.

Duration

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

Food

High-fat or high-carbohydrate meal increases peak plasma concentrations but does not affect extent of absorption. A light meal (e.g., orange juice, toast, and cereal) does not alter felodipine pharmacokinetics.

Distribution

Extent

Crosses the blood-brain barrier.

Crosses the placenta in animals.

Plasma Protein Binding

>99%.

Elimination

Metabolism

Metabolized in the liver by CYP3A4.

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

Elimination Route

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

Half-life

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

Special Populations

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

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

Stability

Storage

Oral

Tablets

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

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.

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

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

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

Advice to Patients

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

  • Importance of taking felodipine exactly as prescribed.

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

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Felodipine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

2.5 mg*

Felodipine Extended-release Tablets

Plendil

AstraZeneca

5 mg*

Felodipine Extended-release Tablets

Plendil

AstraZeneca

10 mg*

Felodipine Extended-release Tablets

Plendil

AstraZeneca

AHFS DI Essentials™. © Copyright 2021, Selected Revisions March 18, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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