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Nicardipine Hydrochloride

Pronunciation

Pronunciation: nye-KAR-di-peen HYE-droe-KLOR-ide
Class: Calcium channel blocking agent

Trade Names

Cardene I.V.
- Injection, solution, premixed 0.1 mg/mL in dextrose 4.8%
- Injection, solution, premixed 0.1 mg/mL in sodium chloride 0.86%
- Injection, solution, premixed 0.2 mg/mL in dextrose 5%
- Injection, solution, premixed 0.2 mg/mL in sodium chloride 0.83%
- Injection, solution, concentrate 2.5 mg/mL

Cardene SR
- Capsules, ER, oral 30 mg
- Capsules, ER, oral 45 mg
- Capsules, ER, oral 60 mg

Nicardipine hydrochloride
- Capsules, oral 20 mg
- Capsules, oral 30 mg

Pharmacology

Inhibits movement of calcium ions across cell membrane in systemic and coronary vascular smooth muscle and myocardium.

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Pharmacokinetics

Absorption

Nicardipine is approximately 100% absorbed following oral administration. C max is 36 to 133 ng/mL (immediate release) and 13.4 to 58.4 ng/mL (ER); steady state is 24 to 48 h (IV); T max is 0.5 to 2 h (immediate release) and 1 to 4 h (ER); absolute bioavailability is 35%. When administered 1 to 3 h after a high-fat meal, C max and AUC were lower (20% to 30% for immediate release). When ER capsules were administered with a high-fat breakfast, the C max and AUC were 45% and 25% lower, respectively.

Distribution

Following infusion, plasma concentrations decline triexponetially with a rapid early-distribution phase, intermediate phase, and a slow terminal phase. Vd is 8.3 L/kg; protein binding is approximately 95%.

Metabolism

Metabolized extensively by the liver.

Elimination

Eliminated by urine (less than 1% unchanged, 49% [IV] and 60% [oral] of dose recovered) and feces (43% [IV] and 35% [oral]). Plasma Cl is 0.4 L/h/kg; plasma half-life is 8.6 h (oral); half-life is 2 to 4 h (oral); alpha half-life is 2.7 min (IV); beta half-life is 44.8 min (IV); gamma half-life is 14.4 h (IV).

Onset

Approximately 20 min (oral).

Special Populations

Renal Function Impairment

In patients with mild to moderate renal impairment, there was a reduction in glomerular filtration rate (GFR), decreased systemic Cl, and higher AUC and C max .

Hepatic Function Impairment

In patients with severe hepatic impairment, plasma concentrations were elevated and the half-life was prolonged to 19 h (oral immediate release). Nicardipine ER has not been studied in patients with severe liver disease.

Elderly

Pharmacokinetics are similar in hypertensive patients older than 65 y of age compared with younger healthy individuals.

Indications and Usage

Treatment of chronic stable (effort-associated) angina (immediate-release capsules); management of hypertension (immediate-release and ER capsules; IV when oral therapy is not feasible or desirable).

Unlabeled Uses

Pediatric hypertensive urgency or emergency.

Contraindications

Hypersensitivity to any component of the product; advanced aortic stenosis.

Dosage and Administration

Angina (Immediate Release Only)
Adults

PO 20 mg 3 times daily initially. Allow at least 3 days before increasing the dose. Maintenance dosage is 20 to 40 mg 3 times daily.

Hypertension
Adults ER

PO 30 mg twice daily initially. Maintenance dosage is 30 to 60 mg 2 times daily.

Immediate release

PO 20 mg 3 times daily initially. Allow at least 3 days before increasing the dose. Maintenance dosage is 20 to 40 mg 3 times daily.

IV

IV Individualize dose based on severity of hypertension and response of patient during dosing. As a substitute for oral therapy, the following may be given: For an oral nicardipine dosage of 20 mg every 8 h, an equivalent IV infusion rate is 0.5 mg/h. For an oral nicardipine dosage of 30 mg every 8 h, an equivalent IV infusion rate is 1.2 mg/h. For an oral nicardipine dosage of 40 mg every 8 h, an equivalent IV infusion rate is 2.2 mg/h. For initiation of therapy in a drug-free patient, IV infusion rate is 5 mg/h.

Titration

May increase by 2.5 mg/h every 5 to 15 min up to a max of 15 mg/h until desired BP is achieved. Following achievement of the BP goal, decrease the infusion rate to 3 mg/h.

Hypotension/Tachycardia

Discontinue infusion; when BP has stabilized, restart at 3 to 5 mg/h and adjust dose to maintain desired BP.

Special risk patients Adults

PO Titrate carefully in patients with renal and/or hepatic impairment and in patients with CHF.

General Advice

  • Injection
  • Nicardipine IV is administered by slow continuous infusion by a central line or through a large peripheral vein.
  • When switching from IV to oral therapy, administer the first dose 1 h prior to discontinuation of the infusion.
  • Change site of infusion every 12 h to minimize the risk of peripheral venous irritation.
  • For premixed injection, do not use plastic container in series connections because it could result in air embolism.
  • For vials, further dilution is required before infusion. Each vial (25 mg) should be diluted with 240 mL of a compatible IV diluent, resulting in 250 mL of solution at a concentration of 0.1 mg/mL.
  • The premixed container and vials are for single use; any unused portion should be discarded.
  • Inspect nicardipine visually for particulate matter and discoloration prior to administration.
  • Nicardipine in vials has been found compatible and stable in glass or polyvinyl chloride containers with dextrose 5% injection, dextrose 5% and sodium chloride 0.45% injection, dextrose 5% and sodium chloride 0.9% injection, dextrose 5% with potassium 40 mEq, sodium chloride 0.45% injection, and sodium chloride 0.9% injection.
  • Nicardipine in vials is not compatible with sodium bicarbonate 5% injection or Ringer's lactate injection.
  • Premixed injection should not be combined with any product in the same IV line or premixed container.
  • Oral
  • Do not crush, chew, or open ER capsules.
  • Patients currently receiving immediate-release capsules may be titrated with ER capsules starting at their current total daily dose of immediate-release capsules.

Storage/Stability

Capsules

Store between 59° and 86°F. Protect from light.

IV

Store between 68° and 77°F. The diluted solution is stable for 24 h at room temperature. Protect from freezing. Freezing does not adversely affect the product in the vials, but exposure to elevated temperatures should be avoided. Avoid excessive heat. Protect from light; store vials in carton until ready to use.

Drug Interactions

Cimetidine, grapefruit

Nicardipine plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Closely monitor the clinical response. Avoid grapefruit juice during oral administration.

Cyclosporine

May cause increased cyclosporine levels, with possible toxicity. Monitor cyclosporine concentrations and the patient for evidence of renal toxicity. Reduce the dose accordingly. The cyclosporine dose may need to be increased when nicardipine is discontinued.

Digoxin

Some calcium channel blockers may increase digitalis serum concentrations; evaluate serum digoxin concentrations after concomitant nicardipine treatment is initiated. Adjust the digoxin dose as needed.

Fentanyl

Severe hypotension has been reported with concomitant use of a beta-blocker and a calcium channel blocker; monitor BP. An increase of circulating fluid volume may be needed if such an interaction occurs.

Other hypertensive agents

May have additive effects.

Protease inhibitors (eg, amprenavir, indinavir, nelfinavir, ritonavir)

Protease inhibitors may increase the antihypertensive and pharmacologic effects of nicardipine. Administer with caution. Closely monitor the clinical response and adjust the nicardipine dose as needed.

Adverse Reactions

Cardiovascular

Hypotension, increased angina (6%); vasodilation (5%); palpitations, tachycardia (4%); ECG abnormality, extrasystoles, hemopericardium, hypertension, postural hypotension, supraventricular tachycardia, sustained tachycardia, syncope, ventricular extrasystoles, ventricular tachycardia (1%).

CNS

Headache (15%); dizziness (7%); asthenia (6%); hypesthesia, insomnia, intracranial hemorrhage, malaise, nervousness, paresthesia, somnolence, tremor (1%).

Dermatologic

Flushing (10%); rash, sweating (1%).

GI

Nausea/vomiting (5%); dyspepsia, nausea (2%); abdominal pain, constipation, dry mouth (1%).

Genitourinary

Hematuria, increased urinary frequency, polyuria (1%).

Local

Injection-site pain, injection-site reaction (1%).

Musculoskeletal

Myalgia (1%).

Miscellaneous

Pedal edema (8%); chest pain, dyspnea, edema, hypokalemia, pain (1%).

Precautions

Monitor

Monitoring of BP and heart rate during IV administration is required. When initiating oral therapy, measure BP 1 to 2 h (immediate release) or 2 to 4 h (ER) after dosing and during dose increases, as well as at the end of a dosing interval. Monitor response carefully in patients with hepatic impairment or reduced hepatic blood flow and when combining nicardipine and a beta-blocker in the treatment of CHF.


Pregnancy

Category C .

Lactation

Minimally excreted into human milk.

Children

Safety and efficacy not established.

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Renal Function

Adjust dosage in patients with renal impairment.

Hepatic Function

Adjust dosage and use drug with caution in patients with hepatic impairment or reduced hepatic blood flow.

Special Risk Patients

Use with caution in patients who have sustained an acute cerebral infarction or hemorrhage, or in patients with pheochromocytoma.

Beta-blocker withdrawal

Patients withdrawn from beta-blockers while taking nicardipine may experience increased angina. Gradually taper beta-blocker dose.

CHF

Use drug with caution in patients with CHF, particularly in combination with a beta-blocker.

Hypotension

Symptomatic hypotension may occur.

Increased angina

Occasionally, patients have increased frequency, duration, or severity of angina when starting or increasing dose.

Infusion sites

To reduce the possibility of venous thrombosis, phlebitis, local irritation, swelling, extravasation, and the rare occurrence of vascular impairment, administer drug through large peripheral veins or central veins.

Withdrawal

Abrupt withdrawal may cause increased frequency and duration of angina.

Overdosage

Symptoms

Bradycardia, confusion, drowsiness, flushing, marked hypotension, palpitations, slurred speech.

Patient Information

  • Instruct patients not to open, crush, or chew the ER capsules.
  • Caution patient that increased angina may occur initially when starting, changing dose, or stopping medication.
  • Advise patient to avoid alcohol and grapefruit juice while taking nicardipine.
  • Instruct patient to rise slowly from a sitting or supine position because drug may cause symptomatic hypotension.
  • Instruct patient to report the following symptoms to health care provider: any unusual bleeding, bruising, change in angina, changes in gums, constipation, dizziness, irregular heartbeat, nausea, palpitations, rash, shortness of breath, or swelling in the hands or feet.
  • Advise patient that drug may cause dizziness or drowsiness, and to use caution while driving or performing other tasks requiring mental alertness.

Copyright © 2009 Wolters Kluwer Health.

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