What is nicardipine?

What is Nicardipine?

Nicardipine is a dihydropyridine calcium channel blocker that inhibits calcium influx into vascular smooth muscle and cardiac muscle, producing potent vasodilation with greater selectivity for vascular tissue than cardiac tissue. 1

Drug Classification and Mechanism

• Nicardipine is a calcium entry blocker (slow channel blocker or calcium ion antagonist) that inhibits transmembrane calcium ion influx into cardiac muscle and smooth muscle without changing serum calcium concentrations 1
• It belongs to the dihydropyridine subclass of calcium channel blockers, which produce more marked peripheral arterial vasodilation compared to other calcium channel blocker classes like diltiazem or verapamil 2
• The drug's effects are more selective to vascular smooth muscle than cardiac muscle, producing coronary and peripheral arterial dilation at drug levels that cause little or no negative inotropic effect 1, 3

Pharmacokinetic Properties

• Nicardipine is completely absorbed following oral administration, with plasma levels detectable within 20 minutes and maximal levels reached within 30 minutes to 2 hours (mean Tmax = 1 hour) 1
• The systemic bioavailability is approximately 35% following a 30-mg oral dose at steady-state due to saturable first-pass hepatic metabolism 1
• The pharmacokinetics are nonlinear—increasing doses result in disproportionate increases in plasma levels (e.g., increasing from 20 to 40 mg every 8 hours increases Cmax more than threefold) 1
• The terminal plasma half-life averages 8.6 hours at steady-state, though elimination over the first 8 hours is much faster with a half-life of 2 to 4 hours 1
• Nicardipine is highly protein bound (>95%) in human plasma over a wide concentration range 1
• All calcium channel blockers, including nicardipine, are metabolized in the liver by cytochrome P450 3A4 2

Clinical Indications

Hypertensive Emergencies (Intravenous Formulation)

• Nicardipine is a first-line intravenous agent for most hypertensive emergencies alongside labetalol, and should be the default choice when labetalol fails 4, 5
• It is specifically recommended for acute renal failure, eclampsia/preeclampsia, and perioperative hypertension 4
• The initial IV dose is 5 mg/h, increasing every 5 minutes by 2.5 mg/h to a maximum of 15 mg/h 4
• Nicardipine has a longer onset and duration of action compared to clevidipine, providing more sustained blood pressure control 6

Chronic Stable Angina

• Nicardipine is effective in treating chronic stable exercise-induced angina pectoris and possibly angina at rest due to coronary artery spasm 3
• In clinical trials, nicardipine increased treadmill exercise duration by 9%, time to angina by 15%, and time to 1-mm ST-segment depression by 16% 7
• All calcium channel blockers, including nicardipine, are effective alone or in combination with nitrates in the treatment of vasospastic angina 2

Hypertension

• Nicardipine is useful as initial monotherapy or in combination with other antihypertensive drugs for mild to moderate hypertension 3
• It may have advantages over other vasodilators in that it is not as frequently associated with fluid retention or weight gain 3

Hemodynamic Effects

• Nicardipine mildly increases heart rate at rest and mildly decreases blood pressure at rest 7
• In patients with left ventricular failure, IV nicardipine (20 mg) increased cardiac index by 64%, stroke volume index by 35%, and heart rate by 20%, while reducing systemic vascular resistance by 50% 8
• The drug improves both systolic and diastolic left ventricular function—increasing ejection fraction from 31% to 38% and peak filling rate by 54% in heart failure patients 9

Adverse Effects

• The major adverse effects of dihydropyridines like nicardipine are systemic hypotension, headache, dizziness, flushing, palpitations, and leg edema 2
• Reflex tachycardia is not uncommon, especially with short-acting dihydropyridines 2
• Side effects appear to be dose-related and more frequent within the first few weeks of therapy, but most are minor and transient 3
• Vasodilatory side effects are generally mild and well tolerated, with drug discontinuation required in only rare cases 7

Important Clinical Considerations

• Calcium channel blockers do not improve survival in patients with chronic stable angina with or without myocardial infarction or left ventricular dysfunction, and when used in patients with heart failure, they might have deleterious effects on outcome 2
• However, nicardipine may have an advantage over other calcium channel blockers in that it does not depress cardiac conduction or left ventricular function, even in patients with compromised cardiac pumping ability 3
• When administered 1 or 3 hours after a high-fat meal, mean Cmax and AUC are 20-30% lower than when given to fasting subjects 1
• In hepatic cirrhosis patients, AUC of nicardipine increases by 5-fold compared to control subjects 10