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Nicardipine

Pronunciation

Class: Dihydropyridines
VA Class: CV200
CAS Number: 54527-84-3
Brands: Cardene

Introduction

Calcium-channel blocking agent; dihydropyridine derivative.1

Uses for Nicardipine

Hypertension

Oral management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 500

Therapy with extended-release capsules generally is preferred because of less frequent dosing, potentially smoother BP control,500 and concerns raised by experience with short-acting (conventional, immediate-release) nifedipine.35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 61 72 73

Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 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).500 501 502 503 504 515

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Calcium-channel blockers may be preferred in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease)523 and in geriatric patients, including those with isolated systolic hypertension.502 510

Black hypertensive 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).500 501 504 However, diminished response to these other drug classes is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

IV, short-term management of hypertension when oral therapy is not feasible or desirable.18

IV management of hypertensive crises (e.g., emergencies) in adults.18 500

IV, rapid reduction of BP in the management of severe hypertension in pediatric patients 1–17 years of age.99

Angina

Management of chronic stable angina pectoris (alone or in combination with other antianginal agents).1 3 25

Nicardipine Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

  • Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Administer orally1 2 5 or by IV infusion.18 22 23

Oral Administration

Conventional Capsules

Administer orally 3 times daily.1

Extended-release Capsules

Administer orally twice daily.2

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow, continuous IV infusion.18 22 23

Must dilute commercially available injection concentrate containing 2.5 mg/mL with a compatible IV infusion solution prior to administration.18

Alternatively, administer as premixed solution (0.1 mg/mL in either 4.8% dextrose or 0.86% sodium chloride injection, 0.2 mg/mL in either 5% dextrose or 0.83% sodium chloride injection).600 601

If administered via a peripheral vein, change infusion site every 12 hours to minimize risk of venous irritation.18

Monitor BP closely during and after completion of IV administration; avoid rapid or excessive reduction in systolic or diastolic BP.18

Dilution

Injection concentrate: Dilute each 25-mg ampul containing 2.5 mg/mL with 240 mL of a compatible IV solution (see Solution Compatibility under Stability) to provide a solution containing 0.1 mg/mL.18 c

Dosage

Available as nicardipine hydrochloride; dosage is expressed in terms of the salt.a b c

Pediatric Patients

Severe Hypertension
Rapid Reduction of BP
IV

Children and adolescents 1–17 years of age: 1–3 mcg/kg per minute as infusion.99

Adults

Hypertension
Conventional Capsules
Oral

Initially, 20 mg 3 times daily.1 5

Adjust dosage according to patient’s peak (approximately 1–2 hours after dosing, particularly during initiation of therapy) and trough (8 hours after dosing) BP responses, but generally no more frequently than at 3-day intervals.1

Usual dosage is 20–40 mg 3 times daily.1

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Extended-Release Capsules
Oral

Initially, 30 mg twice daily.2 70

Adjust dosage according to BP response 2–4 hours after dosing as well as just prior to next dose.2

Usual dosage range is 30–60 mg twice daily.2 500

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Switching to Extended-Release Capsules
Oral

Total daily dose of conventional tablets not a useful guide to judging effective dose of extended-release capsules.2 c However, may administer the currently effective total daily dose of conventional capsules and adjust dosage according to BP response.2 c

Short-term Management with IV Therapy
IV

Initially, 5 mg/hour.18 70

If target BP is not achieved, increase rate by 2.5 mg/hour every 15 minutes, up to 15 mg/hour.18 70

For more rapid reduction, initially, 5 mg/hour. If the target BP is not achieved, increase rate by 2.5 mg/hour every 5 minutes, up to 15 mg/hour.18 70

Following achievement of desired BP response, decrease rate to 3 mg/hour;18 adjust rate as necessary to maintain desired BP response.18

Conversion From Oral to IV Therapy
IV
Recommended Infusion Rates for Patients Previously Maintained on Oral Therapy.

Oral Dosage (as Conventional Capsules)

Equivalent IV Infusion Rates

20 mg every 8 hours

0.5 mg/hour

30 mg every 8 hours

1.2 mg/hour

40 mg every 8 hours

2.2 mg/hour

Hypertensive Emergency
IV

5–15 mg/hour; adjust according to BP response and tolerance.500

Initially, reduce mean arterial BP by no more than 25% within minutes to 1 hour, then further reduce if stable toward 160/100 to 110 mm Hg within the next 2–6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia.500

If patient is stable, can further reduce BP toward normal in the next 24–48 hours.500

Angina
Conventional Capsules
Oral

Initially, 20 mg 3 times daily.1 5 Adjust dosage according to patient tolerance and response at ≥3-day intervals.1

Usual dosage range is 20–40 mg 3 times daily.1

Prescribing Limits

Adults

Hypertension
IV

15 mg/hour.18

Special Populations

Hepatic Impairment

Conventional capsules: Initially, 20 mg twice daily in patients with severe hepatic impairment.1 Individualize dosage, but maintain a twice-daily dosing schedule.1

IV infusion: Consider dosage reduction.18 Use with caution in patients with portal hypertension.18

Renal Impairment

Conventional capsules: Initially, 20 mg 3 times daily.1 5 Titrate dosage carefully.1

Extended-release capsules: Initially, 30 mg twice daily.2 Titrate dosage carefully.2

IV infusion: Titrate dosage carefully.18

Geriatric Patients

Cautious dosing recommended.a b For conventional and extended-release capsules, initiate therapy at low end of dosage range.20 68

Cautions for Nicardipine

Contraindications

  • Known hypersensitivity to nicardipine or any ingredient in the formulation.1 2 18

  • Advanced aortic stenosis, since reduction in diastolic pressure may worsen myocardial oxygen balance.1 2 18

Warnings/Precautions

Warnings

Increased Angina

Increased frequency, duration, and severity of angina upon initiation or dosage increase of calcium channel blockers.1 2 18

Heart Failure

Use with caution in patients with heart failure or substantial left ventricular dysfunction, especially in those receiving concomitant β-adrenergic blocking agents.1 2 18

β-Blocker Withdrawal

Taper dosage of β-adrenergic blocking agent, preferably over 8–10 days before initiation of nicardipine.1 2 18 Nicardipine is not a β-adrenergic blocking agent and offers no protection against abrupt withdrawal of these agents.1 2 18

General Precautions

Hypotension

Possible symptomatic hypotension from decreased peripheral resistance.1 2 18 Use with caution in patients with acute cerebral infarction or hemorrhage; avoid systemic hypotension in these patients.1 2 18

Monitor BP carefully, especially during initiation of therapy or upward adjustment of dosage.1

Pheochromocytoma

Limited clinical experience in patients with hypertension associated with pheochromocytoma.18 Use with caution.18

Specific Populations

Pregnancy

Category C.1 2 18

Lactation

Distributed into milk in high concentrations in rats.1 2 18 Use not recommended.1 2 18

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 2 18

Use with caution for rapid reduction of BP in pediatric patients 1–17 years of age; may cause reflex tachycardia.99

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.a b Select dosage with caution; initiate dosage at lower end of recommended range.a b

Hepatic Impairment

Use with caution in patients with hepatic impairment or reduced hepatic blood flow; dosage adjustments recommended.1 2 18 24 (See Hepatic Impairment under Dosage and Administration.)

Use of extended-release capsules has not been studied in patients with severe hepatic impairment.2

Renal Impairment

Use with caution; careful dosage titration recommended.1 2 18 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

With oral therapy, pedal edema, dizziness, headache, asthenia, flushing, increased angina, vasodilation, palpitation.a b

With IV therapy, headache, hypotension, nausea/vomiting, tachycardia.c

Interactions for Nicardipine

Specific Drugs

Drug

Interaction

Comments

Antacids (magnesium hydroxide)

Pharmacokinetic interaction unlikely1 2 18

β-Adrenergic blockers (e.g., propranolol)

Pharmacokinetic interaction (e.g., effect on plasma protein binding of nicardipine) unlikely1 2 18

Cimetidine

Increased plasma nicardipine concentrations1 2 18

Monitor carefully1 2 18

Cyclosporine

Increased plasma cyclosporine concentrations1 2 18

Monitor plasma cyclosporine concentrations closely and adjust dosage accordingly1 2 18

Digoxin

Potential for increased plasma digoxin concentrations1 2 18

Monitor serum digoxin concentrations1 2 18

Dipyridamole

No effect on plasma protein binding of nicardipine1 2 18

Fentanyl

Potential for severe hypotension with concomitant use of a β-adrenergic blocker and a calcium channel blocker1 2 18

Increase circulating fluid volume if hypotension occurs1 2 18

Furosemide

No effect on plasma protein binding of nicardipine1 2 18

Naproxen

No effect on plasma protein binding of nicardipine1 2 18

Quinidine

No effect on plasma protein binding of nicardipine1 2 18

Warfarin

No effect on plasma protein binding of nicardipine1 2 18

Nicardipine Pharmacokinetics

Absorption

Bioavailability

Completely absorbed from the GI tract following oral administration; peak plasma concentrations of conventional and extended-release capsules are attained within 0.5–2 and 1–4 hours, respectively.1 2

Minimum plasma levels of equivalent doses of conventional and extended-release capsules are similar.2

Bioavailability of conventional capsules is about 35%;1 2 extended-release capsules have a slightly lower bioavailability, except at the highest doses.2

Food

High-fat meal decreases bioavailability of conventional and extended-release capsules.1 2

Special Populations

In patients with severe hepatic impairment, peak plasma concentrations and AUC increased by 1.8 and 4-fold, respectively, and terminal half-life prolonged to 19 hours.1 2

In patients with moderate renal impairment, peak plasma concentrations and AUC increased by 2- to 3-fold following administration of conventional or extended-release capsules.1 2

Distribution

Extent

Distributed into milk in rats.1 2

Plasma Protein Binding

>95%.1 2 18

Elimination

Metabolism

Extensively metabolized in the liver.1 2 18

Elimination Route

Excreted in urine (49–60%) and feces (35–43%).1 2 18

Half-life

Multi-phasic; terminal elimination half-life is 8.6 and 14.4 hours following oral and IV administration, respectively.1 2 18

Stability

Storage

Oral

Conventional Capsules and Extended-release Capsules

Light resistant containers at 15–30°C.a b

Parenteral

Injection Concentrate

20–25°C; protect from light.c Avoid exposure to increased temperatures.c

Premixed Injection for Infusion

20–25°C; protect from light, freezing, and excessive heat.600 601

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.45% or 0.9%

Dextrose 5% in water with potassium chloride 0.3%

Sodium chloride 0.9%

Incompatible

Sodium bicarbonate 5%

Variable

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45%

Drug CompatibilityHID
Admixture Compatibility

Compatible

Potassium chloride

Y-Site CompatibilityHID

Compatible

Amikacin sulfate

Aminophylline

Aztreonam

Butorphanol tartrate

Calcium gluconate

Cefazolin sodium

Chloramphenicol sodium succinate

Clindamycin phosphate

Co-trimoxazole

Dextran 40 in dextrose 5%

Diltiazem HCl

Dobutamine HCl

Dopamine HCl

Enalaprilat

Epinephrine HCl

Erythromycin lactobionate

Esmolol HCl

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Gentamicin sulfate

Hetastarch in sodium chloride 0.9%

Hydrocortisone sodium succinate

Hydromorphone HCl

Labetalol HCl

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Methylprednisolone sodium succinate

Metronidazole

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nafcillin sodium

Nesiritide

Nitroglycerin

Norepinephrine bitartrate

Penicillin G potassium

Potassium chloride

Potassium phosphates

Ranitidine HCl

Sodium acetate

Sodium nitroprusside

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Incompatible

Ampicillin sodium

Ampicillin sodium-sulbactam sodium

Cefepime HCI

Furosemide

Micafungin sodium

Variable

Ceftazidime

Heparin sodium

Actions

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

  • Peripheral arterial vasodilator; acts directly on vascular smooth muscle causing reduction in peripheral vascular resistance (afterload) and BP.a b c

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 2 18

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 18

  • Importance of informing patients of other important precautionary information.1 2 18 (See Cautions.)

Preparations

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

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

Nicardipine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

20 mg*

Nicardipine Hydrochloride Capsules

30 mg*

Nicardipine Hydrochloride Capsules

Capsules, extended-release

30 mg

Cardene SR

Chiesi

60 mg

Cardene SR

Chiesi

For injection, concentrate, for IV infusion

2.5 mg/mL*

Cardene I.V.

Chiesi

Nicardipine Hydrochloride Injection

Nicardipine Hydrochloride in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

0.1 mg/mL (20 mg) in 4.8% Dextrose

Cardene I.V.

Chiesi

0.2 mg/mL (40 mg) in 5% Dextrose

Cardene I.V.

Chiesi

Nicardipine Hydrochloride in Sodium Chloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

0.1 mg/mL (20 mg) in 0.86% Sodium Chloride

Cardene I.V.

Chiesi

0.2 mg/mL (40 mg) in 0.83% Sodium Chloride

Cardene I.V.

Chiesi

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 12/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Cardene SR 30MG 12-hr Capsules (EKR THERAPEUTICS): 60/$105.99 or 180/$305.98

Cardene SR 45MG 12-hr Capsules (EKR THERAPEUTICS): 60/$169.98 or 180/$499.97

Cardene SR 60MG 12-hr Capsules (EKR THERAPEUTICS): 60/$199.99 or 180/$549.98

NiCARdipine HCl 20MG Capsules (MYLAN): 90/$45.99 or 270/$120.97

NiCARdipine HCl 30MG Capsules (MYLAN): 90/$60.99 or 270/$170.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 17, 2014. 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.

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