Nicardipine - Drug Monograph

Introduction

Nicardipine hydrochloride is a dihydropyridine calcium channel blocker used primarily for the management of hypertension and angina pectoris. As a potent vasodilator, it selectively inhibits calcium ion influx across cardiac and vascular smooth muscle cell membranes, resulting in decreased peripheral vascular resistance and blood pressure without significantly affecting cardiac conduction.

Mechanism of Action

Nicardipine exerts its pharmacological effects by selectively blocking L-type calcium channels in vascular smooth muscle cells. This inhibition prevents calcium influx during depolarization, leading to relaxation of vascular smooth muscle and subsequent vasodilation. The drug demonstrates greater selectivity for vascular smooth muscle than cardiac muscle, resulting in peripheral and coronary vasodilation with minimal negative inotropic effects at therapeutic doses.

Indications

• Hypertension (oral formulation)
• Chronic stable angina (oral formulation)
• Acute hypertension (intravenous formulation)
• Short-term treatment of hypertension when oral therapy is not feasible (IV)

Dosage and Administration

• Hypertension: Initial dose 20 mg three times daily; range 20-40 mg TID
• Angina: Initial dose 20 mg three times daily; range 20-40 mg TID

• Initial infusion: 5 mg/hour; titrate by 2.5 mg/hour every 15 minutes
• Maximum dose: 15 mg/hour

• Hepatic impairment: Reduce initial dose
• Renal impairment: Use with caution; dose adjustment may be necessary
• Elderly: Start with lower doses

Pharmacokinetics

• Absorption: Well absorbed orally (≥95%); extensive first-pass metabolism
• Distribution: Protein binding >95%; Vd: 8.3 L/kg
• Metabolism: Extensive hepatic metabolism via cytochrome P450 system (CYP3A4, CYP2C8, CYP2D6)
• Elimination: Half-life: 2-4 hours; primarily renal excretion (60%) with fecal elimination (35%)
• Onset of action: Oral: 20 minutes; IV: 1-2 minutes
• Duration: Oral: 4-8 hours; IV: 3-6 hours after discontinuation

Contraindications

• Hypersensitivity to nicardipine or other dihydropyridines
• Advanced aortic stenosis
• Severe hypotension
• Acute myocardial infarction with cardiogenic shock

Warnings and Precautions

• Hypotension: May cause significant blood pressure reduction
• Hepatic impairment: Requires dose reduction and careful monitoring
• Angina exacerbation: Rare reports of increased angina at initiation
• Peripheral edema: Common side effect requiring monitoring
• Use in heart failure: Use with caution in patients with heart failure
• Withdrawal syndrome: Avoid abrupt discontinuation

Drug Interactions

• Strong CYP3A4 inhibitors: (ketoconazole, itraconazole) - Increase nicardipine levels
• Beta-blockers: Enhanced hypotensive effects; monitor for bradycardia
• Digoxin: May increase digoxin levels
• Cimetidine: Increases nicardipine bioavailability
• Fentanyl: Risk of severe hypotension
• Grapefruit juice: Increases bioavailability

Adverse Effects

• Headache (28%)
• Peripheral edema (7-15%)
• Flushing (10%)
• Dizziness (8%)
• Nausea (6%)

• Hypotension (2-4%)
• Tachycardia (1-3%)
• ECG abnormalities (<2%)
• Elevated liver enzymes (1%)
• Allergic reactions (<1%)

Monitoring Parameters

• Blood pressure (frequent monitoring during initiation)
• Heart rate and rhythm
• Peripheral edema assessment
• Liver function tests (periodically)
• Renal function
• Signs and symptoms of hypotension
• ECG monitoring in patients with cardiac conditions

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• Rise slowly from sitting/lying position to prevent dizziness
• Monitor for swelling in ankles or feet
• Avoid grapefruit and grapefruit juice
• Report chest pain, palpitations, or severe dizziness
• Regular blood pressure checks are essential
• Inform all healthcare providers about nicardipine use
• Be aware of potential drug interactions

References

1. FDA Prescribing Information: Nicardipine Hydrochloride 2. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition 3. Lexicomp Online: Nicardipine Monograph 4. Joint National Committee on Hypertension (JNC 8) Guidelines 5. American Heart Association/American College of Cardiology Guidelines for Hypertension Management 6. Micromedex Solutions: Nicardipine Drug Information 7. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Nicardipine monograph 8. manufacturer's product information