NiCARdipine

Pronunciation

(nye KAR de peen)

U.S. Brand Names

Cardene®; Cardene® I.V.; Cardene® SR

Synonyms

Nicardipine Hydrochloride

Generic Available

Yes: Capsule

Use

Chronic stable angina (immediate-release product only); management of essential hypertension (immediate and sustained release; parenteral only for short time that oral treatment is not feasible)

Use - Unlabeled/Investigational

Congestive heart failure

Pregnancy Risk Factor

Pregnancy Implications

Crosses the placenta; may exhibit tocolytic effect

Lactation

Enters breast milk/not recommended

Contraindications

Hypersensitivity to nicardipine or any component of the formulation; advanced aortic stenosis; severe hypotension; cardiogenic shock; ventricular tachycardia

Warnings/Precautions

Blood pressure lowering should be done at a rate appropriate for the patient's condition. Rapid drops in blood pressure can lead to arterial insufficiency. Use with caution in CAD (can cause increase in angina), CHF (can worsen heart failure symptoms), and pheochromocytoma (limited clinical experience). Peripheral infusion sites (for I.V. therapy) should be changed ever 12 hours. Titrate I.V. dose cautiously in patients with CHF, renal, or hepatic dysfunction. Use the I.V. form cautiously in patients with portal hypertension (can cause increase in hepatic pressure gradient). Safety and efficacy have not been demonstrated in pediatric patients. Abrupt withdrawal may cause rebound angina in patients with CAD.

Adverse Reactions

1% to 10%:

Cardiovascular: Flushing (6% to 10%), palpitation (3% to 4%), tachycardia (1% to 4%), peripheral edema (dose related 7% to 8%), increased angina (dose related 6%), hypotension (I.V. 6%), orthostasis (I.V. 1%)

Central nervous system: Headache (6% to 15%), dizziness (4% to 7%), somnolence (4% to 6%), paresthesia (1%)

Dermatologic: Rash (1%)

Gastrointestinal: Nausea (2% to 5%), dry mouth (1%)

Genitourinary: Polyuria (1%)

Local: Injection site reaction (I.V. 1%)

Neuromuscular & skeletal: Weakness (4% to 6%), myalgia (1%)

Miscellaneous: Diaphoresis

<1% (Limited to important or life-threatening): Abnormal ECG, insomnia, malaise, abnormal dreams, vomiting, constipation, nocturia, tremor, nervousness, malaise, dyspnea, gingival hyperplasia, syncope, sustained tachycardia, injection site pain (I.V.), hypokalemia, intracranial hemorrhage, dyspnea

Case report: Parotitis

Overdosage/Toxicology

The primary cardiac symptoms of calcium blocker overdose include hypotension and bradycardia. Noncardiac symptoms include confusion, stupor, nausea, vomiting, metabolic acidosis, and hyperglycemia. Following initial gastric decontamination, if possible, repeated calcium administration may promptly reverse the depressed cardiac contractility (but not sinus node depression or peripheral vasodilation). Glucagon and epinephrine may treat refractory hypotension. Glucagon and epinephrine also increase the heart rate (outside the U.S., 4-aminopyridine may be available as an antidote). Dialysis and hemoperfusion are not effective in enhancing elimination although repeat-dose activated charcoal may serve as an adjunct with sustained-release preparations.

Drug Interactions

Substrate of CYP1A2 (minor), 2C8/9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (major); Inhibits CYP2C8/9 (strong), 2C19 (moderate), 2D6 (moderate), 3A4 (strong)

Azole antifungals may inhibit the calcium channel blocker's metabolism; avoid this combination. Try an antifungal like terbinafine (if appropriate) or monitor closely for altered effect of the calcium channel blocker.

Calcium may reduce the calcium channel blocker's effects, particularly hypotension.

Cyclosporine's serum concentrations are increased by nicardipine; avoid this combination. Use another calcium channel blocker or monitor cyclosporine trough levels and renal function closely. Tacrolimus may be affected similarly.

CYP2C8/9 substrates: Nicardipine may increase the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, and warfarin.

CYP2C19 substrates: Nicardipine may increase the levels/effects of CYP2C19 substrates. Example substrates include citalopram, diazepam, methsuximide, phenytoin, propranolol, and sertraline.

CYP2D6 substrates: Nicardipine may increase the levels/effects of CYP2D6 substrates. Example substrates include amphetamines, selected beta-blockers, dextromethorphan, fluoxetine, lidocaine, mirtazapine, nefazodone, paroxetine, risperidone, ritonavir, thioridazine, tricyclic antidepressants, and venlafaxine.

CYP2D6 prodrug substrates: Nicardipine may decrease the levels/effects of CYP2D6 prodrug substrates. Example prodrug substrates include codeine, hydrocodone, oxycodone, and tramadol.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of nicardipine. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of nicardipine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, propofol, protease inhibitors, quinidine, and verapamil.

CYP3A4 substrates: Nicardipine may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, mirtazapine, nateglinide, nefazodone, tacrolimus, and venlafaxine. Selected benzodiazepines (midazolam and triazolam), cisapride, ergot alkaloids, selected HMG-CoA reductase inhibitors (lovastatin and simvastatin), and pimozide are generally contraindicated with strong CYP3A4 inhibitors.

Metoprolol: Concentration of metoprolol is increased by 25% with concurrent use.

Nafcillin decreases plasma concentration of nicardipine; avoid this combination.

Propranolol: May decrease the metabolism of nicardipine.

Protease inhibitor like amprenavir and ritonavir may increase nicardipine's serum concentration.

Rifampin increases the metabolism of the calcium channel blocker; adjust the dose of the calcium channel blocker to maintain efficacy.

Sildenafil, tadalafil, vardenafil: Blood pressure-lowering effects may be additive; use caution.

Vecuronium: Clearance of vecuronium is decreased by 25% with use of I.V. nicardipine; reduce dose of muscle relaxant.

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (may increase CNS depression).

Food: Nicardipine average peak concentrations may be decreased if taken with food. Serum concentrations/toxicity of nicardipine may be increased by grapefruit juice; avoid concurrent use.

Herb/Nutraceutical: St John's wort may decrease levels. Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).

Stability

Compatible with D5W, D5¹ /2NS, D5NS, and D5W with 40 mEq potassium chloride; 0.45% and 0.9% NS; do not mix with 5% sodium bicarbonate and lactated Ringer's solution; store at room temperature; protect from light; stable for 24 hours at room temperature

Compatibility

Stable in D5W with KCl 40 mEq, D5¹ /2NS, D5NS, D5W, ¹ /2NS, NS; incompatible with sodium bicarbonate 5%, LR

Y-site administration: Compatible: Diltiazem, dobutamine, dopamine, epinephrine, fentanyl, gatifloxacin, hydromorphone, labetalol, linezolid, lorazepam, midazolam, milrinone, morphine, nitroglycerin, norepinephrine, ranitidine, vecuronium. Incompatible: Furosemide, heparin, thiopental

Mechanism of Action

Inhibits calcium ion from entering the "slow channels" or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina

Pharmacodynamics/Kinetics

Onset of action: Oral: 1-2 hours; I.V.: 10 minutes; Hypotension: ~20 minutes

Duration: 2-6 hours

Absorption: Oral: ~100%

Protein binding: 95%

Metabolism: Hepatic; extensive first-pass effect

Bioavailability: 35%

Half-life elimination: 2-4 hours

Time to peak, serum: 20-120 minutes

Excretion: Urine (as metabolites)

Dosage

Adults:

Oral:

Immediate release: Initial: 20 mg 3 times/day; usual: 20-40 mg 3 times/day (allow 3 days between dose increases)

Sustained release: Initial: 30 mg twice daily, titrate up to 60 mg twice daily

Note: The total daily dose of immediate-release product may not automatically be equivalent to the daily sustained-release dose; use caution in converting.

I.V. (dilute to 0.1 mg/mL):

Acute hypertension: Initial: 5 mg/hour increased by 2.5 mg/hour every 15 minutes to a maximum of 15 mg/hour; consider reduction to 3 mg/hour after response is achieved. Monitor and titrate to lowest dose necessary to maintain stable blood pressure.

Substitution for oral therapy (approximate equivalents):

20 mg every 8 hours oral, equivalent to 0.5 mg/hour I.V. infusion

30 mg every 8 hours oral, equivalent to 1.2 mg/hour I.V. infusion

40 mg every 8 hours oral, equivalent to 2.2 mg/hour I.V. infusion

Dosing adjustment in renal impairment: Titrate dose beginning with 20 mg 3 times/day (immediate release) or 30 mg twice daily (sustained release). Specific guidelines for adjustment of I.V. nicardipine are not available, but careful monitoring/adjustment is warranted.

Dosing adjustment in hepatic impairment: Starting dose: 20 mg twice daily (immediate release) with titration. Specific guidelines for adjustment of I.V. nicardipine are not available, but careful monitoring/adjustment is warranted.

Administration

Oral: The total daily dose of immediate-release product may not automatically be equivalent to the daily sustained-release dose; use caution in converting. Do not chew or crush the sustained release formulation, swallow whole. Do not open or cut capsules.

I.V.: Ampuls must be diluted before use. Administer as a slow continuous infusion.

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber.

I.V.: Report immediately any swelling, redness, burning, or pain at infusion site.

Oral: Take as directed; do not alter dose or decrease without consulting prescriber. Do not crush or chew sustained release forms; swallow whole. Take with nonfatty food. Avoid caffeine and alcohol. Consult prescriber before increasing exercise routine (decreased angina does not mean it is safe to increase exercise). May cause orthostatic hypotension (change position slowly from sitting or lying to standing, or when climbing stairs); sore mouth (inspect gums for swelling or redness - use soft toothbrush, waxed dental floss, and frequent mouth rinses); dizziness or fatigue (use caution when driving or engaging in tasks that require alertness until response to drug is known); or nausea and dry mouth (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report chest pain, palpitations, rapid heartbeat; swelling of extremities; muscle weakness or pain; respiratory difficulty; or nervousness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.

Anesthesia and Critical Care Concerns/Other Considerations

I.V. ampuls must be diluted; dilute each ampul in 240 mL to result in 250 mL of 0.1 mg/mL nicardipine. Nicardipine should be used with caution in patients with heart failure.

Cardiovascular Considerations

Nicardipine alone or in combination with other agents is effective in the management of hypertension and angina. Nicardipine should be used with caution in patients with heart failure.

In the treatment of unstable angina/non-ST-segment elevation MI, a nondihydropyridine calcium antagonist (diltiazem or verapamil) may be considered in patients with continuing or frequently recurring ischemia when beta-blockers are contraindicated (Class I). Oral long-acting calcium antagonists may also be considered in addition to beta-blockers and nitrates (Class IIa).

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). Other drugs of this class can cause gingival hyperplasia (ie, nifedipine). The first case of nicardipine-induced gingival hyperplasia has been reported in a child taking 40-50 mg daily for 20 months.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Drowsiness and dizziness are common; may rarely cause insomnia

Mental Health: Effects on Psychiatric Treatment

Concurrent use with propranolol may increase AV nodal effects

Dosage Forms

Capsule (Cardene®): 20 mg, 30 mg

Capsule, sustained release (Cardene® SR): 30 mg, 45 mg, 60 mg

Injection, solution (Cardene® IV): 2.5 mg/mL (10 mL)

References

Braunwald E, Antman EM, Beasley JW, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina)," J Am Coll Cardiol , 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

Erstad BL and Barletta JF, "Treatment of Hypertension in the Perioperative Patient," Ann Pharmacother , 2000, 34(1):66-79.

"Randomized Double-Blind Comparison of a Calcium Antagonist and a Diuretic in Elderly Hypertensives. National Intervention Cooperative Study in Elderly Hypertensives Study Group," Hypertension , 1999, 34(5):1129-33.

Steele RM, Schuna AA, and Schreiber RT, "Calcium Antagonist-Induced Gingival Hyperplasia," Ann Intern Med , 1994, 120(8):663-4.

Wallin JD, Fletcher E, Ram CV, et al, "Intravenous Nicardipine for the Treatment of Severe Hypertension. A Double-Blind, Placebo-Controlled Multicenter Trial," Arch Intern Med , 1989, 149(12):2662-9.

International Brand Names

Antagonil® (DE); Barizin® (SI); Bionicard® (IT); Cardene® (GB, IE, NL); Cardene I.V.® (NL); Cardene SR® (GB, IE); Cardepine® (TH); Cardibloc® (SG); Cardioten® (IT); Cardip® (IT); Dafil® (AR); Dagan® (ES); Flusemide® (ES); Karden® (AT); Lecibral® (ES); Lincil® (EG, ES, HU); Lisanirc® (IT); Loxen® (FR); Lucenfal® (ES); Nerdipina® (ES, PT); Nerdipine® (RU); Neucor® (IT); Nicant® (IT); Nicapress® (IT); Nicardal® (IT); Nicardipina Dorom® (IT); Nicardipina Merck® (IT); Nicardipine® (GB); Nicardipino Ratiopharm® (ES); Nicardipino Seid® (ES); Nicarel® (CL); Nicarpin® (IT); Nicaven® (IT); Nimicor® (IT); Niven® (IT); Perdipina® (IT); Perdipine® (JP); Ranvil® (IT); Ridene® [caps] (MX); Rydene® (BE, LU); Vasodin® (IT); Vasonase® (ES)

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process . A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2007 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

Home > Medical Reference > Complementary Medicine