Cardene - Drug Monograph

Introduction

Cardene (nicardipine hydrochloride) is a dihydropyridine calcium channel blocker used primarily in the management of hypertension and chronic stable angina. As a second-generation calcium antagonist, it offers vascular selectivity with minimal negative inotropic effects compared to non-dihydropyridine calcium channel blockers.

Mechanism of Action

Nicardipine inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle through selective blockade of L-type calcium channels. This inhibition produces:

• Coronary and peripheral vasodilation
• Reduction in peripheral vascular resistance
• Decreased afterload without significantly affecting cardiac contractility
• Increased coronary blood flow through coronary artery dilation

The drug exhibits greater selectivity for vascular smooth muscle than cardiac muscle, resulting in potent vasodilation with minimal negative inotropic effects.

Indications

• Chronic stable angina (effort-associated angina) in patients who remain symptomatic despite adequate doses of beta-blockers and/or nitrates
• Hypertension (alone or in combination with other antihypertensive agents)

• Hypertensive emergencies (using intravenous formulation)
• Subarachnoid hemorrhage-associated vasospasm
• Pediatric hypertension

Dosage and Administration

• Immediate-release capsules: 20 mg three times daily
• Maintenance dose: 20-40 mg three times daily
• Maximum dose: 120 mg daily

• Hepatic impairment: Start with 20 mg twice daily
• Renal impairment: No initial adjustment necessary
• Elderly patients: Start with lower doses (20 mg twice daily)
• Titration: Increase doses at 3-day intervals

• Take with or without food (consistent administration pattern recommended)
• Swallow capsules whole; do not crush or chew
• Blood pressure monitoring during dose titration

Pharmacokinetics

• Rapidly absorbed from GI tract
• Bioavailability: ~35% due to first-pass metabolism
• Peak plasma concentrations: 0.5-2 hours
• Food may decrease peak concentrations but not overall bioavailability

• Protein binding: >95%
• Volume of distribution: 8.3 L/kg
• Crosses blood-brain barrier and placenta

• Extensive hepatic metabolism via cytochrome P450 system (CYP2C8, CYP2C9, CYP3A4)
• Active metabolites: none significant

• Half-life: 2-4 hours
• Excretion: primarily urine (60%) as metabolites, feces (35%)
• Clearance: reduced in elderly and hepatic impairment

Contraindications

• Hypersensitivity to nicardipine or other dihydropyridines
• Advanced aortic stenosis
• Acute myocardial infarction with cardiogenic shock
• Severe hypotension (SBP <90 mmHg)

Warnings and Precautions

• Reflex tachycardia may occur
• May precipitate angina in patients with severe coronary artery disease
• Use caution in heart failure patients (may worsen symptoms)

• Extensive hepatic metabolism requires caution in liver impairment
• Monitor liver function periodically

• Abrupt discontinuation may cause rebound hypertension or angina

• Peripheral edema (dose-related)
• Use caution in elderly patients (increased bioavailability)
• Pregnancy Category C: use only if potential benefit justifies potential risk

Drug Interactions

• Ketoconazole, itraconazole: ↑ nicardipine levels
• Clarithromycin, erythromycin: ↑ nicardipine levels
• Ritonavir: ↑ nicardipine levels

• Rifampin: ↓ nicardipine levels
• Phenytoin: ↓ nicardipine levels
• St. John's wort: ↓ nicardipine levels

• Beta-blockers: additive hypotension and bradycardia
• Digoxin: possible ↑ digoxin levels
• Cimetidine: ↑ nicardipine levels
• Cyclosporine: ↑ cyclosporine levels
• Anesthetic agents: enhanced hypotensive effect

Adverse Effects

• Headache (28%)
• Peripheral edema (15%)
• Flushing (10%)
• Dizziness (8%)
• Asthenia (7%)
• Palpitations (5%)
• Nausea (5%)

• Hypotension
• Angina exacerbation
• Myocardial infarction
• Heart failure exacerbation
• Severe tachycardia
• Allergic reactions
• Hepatitis
• Leukopenia

Monitoring Parameters

• Blood pressure (standing and sitting)
• Heart rate
• Liver function tests
• Renal function
• ECG (if cardiac history)

• Blood pressure at each dose adjustment
• Heart rate regularly
• Signs/symptoms of heart failure
• Peripheral edema assessment
• Liver function (periodically)
• Therapeutic efficacy (angina frequency, BP control)

• Elderly: frequent BP checks
• Hepatic impairment: closer monitoring
• Concomitant digoxin: monitor levels

Patient Education

• Take exactly as prescribed
• Do not stop abruptly
• Report missed doses; do not double dose

• Avoid grapefruit juice (may increase drug levels)
• Rise slowly from sitting/lying position
• Limit alcohol consumption

• Report swelling in ankles/feet
• Monitor for dizziness or lightheadedness
• Report rapid heartbeat or chest pain
• Seek immediate care for fainting episodes

• Regular blood pressure monitoring
• Keep all medical appointments
• Inform all healthcare providers of medication use
• Use caution when driving or operating machinery

References

1. FDA Prescribing Information: Cardene (nicardipine hydrochloride) 2. Chobanian AV, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252 3. Frishman WH, et al. Nicardipine: a new calcium channel blocker for hypertension and angina pectoris. J Clin Pharmacol. 1988;28(11):1004-1019 4. Saseen JJ, et al. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina. J Am Coll Cardiol. 1999;33:2092-2197 5. McTavish D, et al. Nicardipine: a review of its pharmacology and therapeutic efficacy in older patients. Drugs Aging. 1993;3(2):165-187 6. Abernethy DR. Pharmacokinetics and pharmacodynamics of nicardipine in hypertension. Am J Cardiol. 1989;64(17):7H-11H 7. Micromedex Solutions: Nicardipine Drug Information 8. Lexicomp Online: Nicardipine Monograph