General Administration Information
For storage information, see the specific product information within the How Supplied section.
-May administer without regard to meals.
-Avoid coadministration with grapefruit juice or grapefruit.
Oral Solid Formulations
-Extended-release capsule: Swallow whole; do not crush, break, or chew.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Nicardipine is usually a clear, colorless to yellow solution.
Dilution of Single-Dose Vials
-Dilute each vial (25 mg) with 240 mL of compatible IV solution to yield a 0.1 mg/mL concentration. Nicardipine injection is compatible with 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose Injection with 40 mEq/L potassium chloride, 0.9% Sodium Chloride Injection, and 0.45% Sodium Chloride Injection. Nicardipine is NOT compatible with Lactated Ringer's Injection or Sodium Bicarbonate Injection.
-A more concentrated solution (0.5 mg/mL) has been used in patients as young as neonates to avoid fluid overload; occasional superficial thrombophlebitis has occurred.
-Storage: When diluted with a compatible solution, nicardipine 0.1 mg/mL is stable in polyvinyl chloride (PVC) containers for 24 hours at room temperature. Nicardipine 0.5 mg/mL is stable in PVC containers for 24 hours and glass containers for up to 7 days, both at room temperature (18 to 28 degrees C) under fluorescent light.
Premixed IV Solution
-Available as single-use, ready-to-use solution. No further dilution required.
-Do not combine nicardipine premixed injection with any product in the same intravenous line or premixed container. Do not add supplementary medication to the bag.
-Protect from light until ready to use.
-Do not use plastic containers in series connections, which may result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete.
Continuous IV Infusion
-Administer via a central line or large peripheral vein. Change the infusion site every 12 hours if administered via peripheral vein.
-Adjust the rate of infusion as needed to maintain the desired response.
-Monitor blood pressure and heart rate during and after the infusion to avoid tachycardia or too rapid or excessive reduction in blood pressure. When used for the treatment of hypertensive emergency, intra-arterial blood pressure monitoring may be necessary, especially for patients with labile and difficult to control blood pressure.
Most adverse reactions associated with nicardipine are secondary to vasodilation. Generally, adverse reactions are not serious and respond well to dosage reduction.
An injection site reaction of phlebitis has been associated with intravenous nicardipine use. Administer nicardipine injection through a central or large peripheral vein to reduce the possibility of extravasation, venous thrombosis, phlebitis, local irritation, swelling, and vascular impairment. Avoid arteries and small peripheral veins, such as those on the dorsum of the hand or wrist. Change the peripheral infusion site every 12 hours to minimize the risk of venous irritation.
Headache (6.2% to 15%), dizziness (1.6% to 6.9%), syncope (0.8%), asthenia (0.9% to 5.8%), somnolence/drowsiness (1.1% to 1.4%), malaise (0.6%), paresthesias (1%), insomnia (0.6%), nervousness (0.6%), tremor (0.6%), abnormal dreams (0.4%), and hypertonia have been reported during nicardipine clinical trials. Hot flashes, vertigo, hyperkinesis, depression, confusion, and anxiety have been reported rarely with oral use.
Flushing (5.6% to 9.7%), peripheral vasodilation (4.7% to 5.5%), hypotension (6%), orthostatic hypotension (0.9%), sinus tachycardia (0.8% to 4%), generalized edema (0.6% to 1%), peripheral edema (4.4% to 8%), palpitations (2.8% to 4.1%), chest pain (unspecified), AV block, ST-T wave changes including ST-segment depression and inverted T-wave, abnormal ECG (0.6%), and deep vein thrombophlebitis have been reported during nicardipine clinical trials. Sinus node dysfunction and myocardial infarction have been reported in adults on chronic oral therapy; however, these effects may be attributed to disease progression. Rarely, atypical chest pain, peripheral vascular disorder, atrial fibrillation, exertional hypotension, pericarditis, ventricular extrasystoles, ventricular tachycardia, and cerebral ischemia have been reported with oral nicardipine use. Decreased oxygen saturation (possibly pulmonary shunting) has been reported during postmarketing use of intravenous nicardipine. In addition, nicardipine can precipitate or exacerbate heart failure due to its negative inotropic effects; this may be more common in patients receiving concomitant beta-blocker therapy.
Increases in frequency, duration, or severity of angina (6% to 7% vs. 4% for placebo) have been reported with chronic oral nicardipine therapy in adults. Similarly, induction or exacerbation of angina has occurred in less than 1% of patients with coronary artery disease treated with intravenous nicardipine. Comparisons with beta-blockers also show a greater frequency of increased angina, 4% vs. 1%. Although the mechanism of this effect has not been established, angina may result from excessive hypotension, coronary steal, or reflex tachycardia.
Gynecomastia has been associated with the use of calcium channel blockers such as nicardipine.
Nausea/vomiting (4% to 5%) and dyspepsia have been reported in adults receiving intravenous nicardipine. Nausea (1.9%), vomiting (0.4% to 0.6%), dyspepsia (0.8% to 1.5%), constipation (0.6%), diarrhea, xerostomia (0.4% to 1.4%), and sore throat (rare) have been reported with oral nicardipine use.
Gingival hyperplasia is a class effect of calcium channel blockers, which appears to be more common with dihydropyridine derivatives, and may occur within 1 month after drug initiation. Counsel patients who take nicardipine and their caregivers on good oral hygiene and gum massage, as the presence of dental plaque may contribute to hyperplasia.
Less commonly, pain (0.6%), neck pain, myalgia (1%), arthralgia (rare), fever, diaphoresis (0.6%), dyspnea (0.6%), respiratory disorder, and unspecified infection (rare) have been associated with nicardipine use.
Elevated hepatic enzymes have rarely been associated with nicardipine use. Thrombocytopenia and hypophosphatemia have been reported with intravenous nicardipine.
An allergic reaction has rarely been associated with nicardipine use. Rash (0.4% to 1.2%) and facial edema have been reported with nicardipine.
Increased urinary frequency (0.6%) and nocturia (0.4%) have been associated with nicardipine use.
Conjunctivitis, ear disorder, tinnitus have been reported during nicardipine clinical trials. Rhinitis, sinusitis, blurred vision, and abnormal vision have rarely been associated with nicardipine use.
Nicardipine is contraindicated in patients with hypersensitivity to the drug.
Nicardipine gives no protection against the effects of abrupt beta-blocker withdrawal. Withdraw beta-blockers by gradual dose reduction, preferably over 8 to 10 days.
Nicardipine is contraindicated in patients with advanced aortic stenosis; reduction of diastolic pressure in these patients may worsen myocardial oxygen balance.
Use nicardipine with caution in patients with heart failure or significant left ventricular dysfunction, particularly in those receiving concomitant beta-blocker therapy. The negative inotropic effects produced by nicardipine can exacerbate heart failure.
Use caution to avoid systemic hypotension in patients who have sustained an acute stroke or intracranial bleeding, as sequelae of these conditions may worsen if adequate blood pressure and organ perfusion are not maintained. Monitor blood pressure carefully during initiation and titration of nicardipine in all patients.
Titrate nicardipine dosages carefully in patients with renal impairment; increased drug exposure may occur.
Use nicardipine with caution in patients with severe hepatic disease or portal hypertension. Consider lower dosages and closely monitor responses in patients with impaired liver function or reduced hepatic blood flow. Nicardipine is metabolized in the liver; increased drug exposure and prolonged half-life are expected in patients with severe hepatic disease.
Administer nicardipine injection through a central or large peripheral vein to reduce the possibility of extravasation, venous thrombosis, phlebitis, local irritation, swelling, and vascular impairment. Avoid arteries and small peripheral veins, such as those on the dorsum of the hand or wrist. Change the peripheral infusion site every 12 hours to minimize the risk of venous irritation.
Description: Nicardipine is an oral and intravenous dihydropyridine calcium channel blocker used for the treatment of hypertension. Nicardipine is a potent peripheral vasodilator, similar to nifedipine and other members of the dihydropyridine class. It is more selective to vascular smooth muscle than cardiac muscle and does not alter myocardial contractility or function. When given as a continuous intravenous infusion, nicardipine can be used as a first-line agent for severe hypertension, including hypertensive crisis, caused by a variety of etiologies. Intravenous nicardipine is useful for severely hypertensive patients with life-threatening symptoms. Nicardipine is preferred when labetalol and nitroprusside are not favorable, as there is no concern for bradycardia, bronchospasm, or toxic metabolite buildup with renal impairment or prolonged use. Though pediatric studies are limited, clinically apparent side effects appear scarce; reflex tachycardia and superficial phlebitis have been reported but are usually not clinically significant. Nicardipine is not FDA-approved for pediatric use, but has been used in patients as young as neonates.
For the treatment of chronic hypertension*:
Oral dosage (immediate-release):
Children and Adolescents: 0.5 mg/kg/dose PO every 8 hours. Maximum dosage is undefined; however, effective doses in adult clinical trials range from 20 to 40 mg PO 3 times daily. There is no data regarding the conversion of nicardipine IV infusion to oral dosing in pediatric patients. In a case report of a 14-year-old, 68-kg girl, who was initially maintained on a nicardipine infusion at 1 to 4 mcg/kg/minute, nicardipine 30 mg PO every 8 hours was initiated once the patient was able to tolerate oral medication. Blood pressure was well controlled with oral nicardipine and labetalol. Another case describes the successful use of nicardipine 20 mg PO every 8 hours, eventually titrated to 30 mg PO every 8 hours, in a 14-year-old, 78-kg boy.
Continuous Intravenous Infusion dosage:
Neonates: 0.5 to 1 mcg/kg/minute continuous IV infusion, initially. Titrate every 15 to 30 minutes until goal blood pressure is attained. Usual dose: 0.5 to 2 mcg/kg/minute. Most neonates are controlled with doses less than 3 mcg/kg/minute, although maintenance infusion rates up to 6 mcg/kg/minute have been reported in term neonates.
Infants, Children, and Adolescents: 0.5 to 1 mcg/kg/minute continuous IV infusion, initially. Titrate by 1 mcg/kg/minute every 15 to 30 minutes until goal blood pressure is attained. Usual dose: 1 to 3 mcg/kg/minute. Max: 10 mcg/kg/minute. Gradually discontinue IV infusion after oral antihypertensives are introduced, weaning by 1 mcg/kg/minute increments.
For the short-term treatment of acute severe hypertension, including postoperative hypertension*, perioperative hypertension*, hypertensive emergency*, and hypertensive urgency*:
Continuous Intravenous Infusion dosage:
Neonates: 0.5 to 1 mcg/kg/minute continuous IV infusion, initially. Titrate every 15 to 30 minutes until goal blood pressure is attained. Usual dose: 0.5 to 2 mcg/kg/minute. Most patients require 3 mcg/kg/minute or less, although maintenance infusion rates up to 6 mcg/kg/minute have been reported in term neonates.
Infants, Children, and Adolescents: 30 mcg/kg (Max: 2 mg) IV, then 0.5 to 4 mcg/kg/minute continuous IV infusion, initially. Titrate by 1 mcg/kg/minute every 15 to 30 minutes until goal blood pressure is attained. Max: 10 mcg/kg/minute. Gradually discontinue IV infusion after oral antihypertensives are introduced, weaning by 1 mcg/kg/minute increments.
Maximum Dosage Limits:
Safety and efficacy have not been established; however, doses up to 6 mcg/kg/minute IV have been used off-label.
Safety and efficacy have not been established; however, doses up to 10 mcg/kg/minute IV have been used off-label.
Safety and efficacy have not been established; however, doses up to 10 mcg/kg/minute IV have been used off-label. A maximum oral dose has not been defined.
Safety and efficacy have not been established; however, doses up to 10 mcg/kg/minute IV have been used off-label. A maximum oral dose has not been defined.
Patients with Hepatic Impairment Dosing
Consider lower dosages and closely monitor responses in patients with impaired liver function or reduced hepatic blood flow. Specific guidelines for pediatric patients are not available; in adults, it is recommended to initiate immediate-release nicardipine at 20 mg PO twice daily and titrate maintaining a twice-daily interval.
Patients with Renal Impairment Dosing
Titrate nicardipine dosages carefully in patients with renal impairment.
Monograph content under development
Mechanism of Action: Nicardipine inhibits the influx of extracellular calcium across the cell membranes of myocardial and vascular smooth muscle without altering serum calcium concentrations. Nicardipine is more selective to vascular smooth muscle than to cardiac muscle. Thus, nicardipine relaxes the peripheral vasculature without affecting inotropy. While verapamil and diltiazem exert balanced effects on calcium channels in the sinoatrial (SA) node, atrioventricular (AV) node, and vasculature, nicardipine and other members of the dihydropyridine class predominantly act on the vasculature, making these agents more potent peripheral vasodilators.
The decrease in intracellular calcium inhibits the contractile processes of the vascular smooth muscle cells, resulting in dilation of the coronary arteries. These effects elicit an increased oxygen delivery to the myocardial tissue, and a decreased total peripheral resistance, systemic blood pressure, and afterload. Although originally it was believed that dihydropyridine calcium channel blockers improved oxygen supply, it now appears that their effectiveness as anti-ischemic agents arises from their ability to alter the systemic balance between supply and demand. Reduced afterload and reduced myocardial wall tension lead to reduced myocardial oxygen demand, which now seems to explain best the benefit of nicardipine and other dihydropyridines in the treatment of angina. Thus, nicardipine increases myocardial oxygen supply (secondary to coronary vasodilation) and also decreases myocardial oxygen demand (secondary to decreased afterload).
Nicardipine does not affect the AV or SA nodal cardiac conduction systems. Negative inotropic effects rarely are noted clinically with nicardipine, presumably due to a reflex increase in heart rate in response to vasodilatory activity as well as a negligible effect on myocardial contractility. Nicardipine therapy usually does not affect hemodynamic parameters in patients with normal ventricular function; however, patients with decreased left ventricular function can experience an increase in ejection fraction and a decrease in left ventricular filling pressures. Nicardipine equals or exceeds nifedipine as an arterial and coronary artery vasodilator, with its vasodilatory effects being more pronounced in hypertensive than in normotensive patients.
Pharmacokinetics: Nicardipine is administered orally and intravenously. More than 95% of nicardipine is protein bound to alpha1-acid glycoproteins, albumin, and lipoproteins; protein binding is pH-dependent and increases with increased serum pH. Nicardipine also binds to erythrocytes. Vd is 8.3 L/kg in adults. Extensive metabolism via hepatic CYP2C8, CYP2D6, and CYP3A4 isoenzymes results in the formation of inactive metabolites, which are glucuronidated and eliminated primarily via renal (49% to 60%) and fecal (35% to 43%) routes. Less than 1% of unchanged drug is excreted in the urine.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, CYP2C19, CYP2D6, CYP3A4
Nicardipine is rapidly and extensively metabolized by CYP2C8, CYP2D6, and CYP3A4. While it does not induce or inhibit its own metabolism, nicardipine is a strong inhibitor of CYP2D6 and also inhibits CYP2C19, CYP3A4, and CYP2C8.
Nicardipine is rapidly and completely absorbed after oral administration but undergoes extensive first-pass metabolism, resulting in a bioavailability of about 35%. Oral nicardipine pharmacokinetics are nonlinear due to saturable first-pass metabolism.
Peak plasma concentrations occur 30 to 120 minutes (mean Tmax = 60 minutes) after administration. In adults, steady-state Cmax after 20 mg, 30 mg, and 40 mg doses every 8 hours averages 36 ng/mL, 88 ng/mL, and 133 ng/mL, respectively. Increasing the dose from 20 to 30 mg more than doubled Cmax, while increasing the dose from 20 to 40 mg increased the Cmax more than 3-fold. Disproportionate increases in AUC were also observed. Pharmacokinetics after drug absorption are also nonlinear. In adults, half-life over the first 8 hours after oral administration is 2 to 4 hours, but mean terminal half-life is 8.6 hours. The bioavailability of nicardipine is reduced when administered with food; mean Cmax and AUC are 20% to 30% lower than those of fasting subjects when given 1 to 3 hours after a high-fat meal.
Bioavailability of extended-release nicardipine is somewhat lower than that of immediate-release nicardipine, except when given at the highest dose. Peak plasma concentrations occur 1 to 4 hours after administration. When compared to an equivalent daily dose of immediate-release nicardipine, Cmin is similar while Cmax is significantly reduced, hence a reduction in plasma concentration fluctuation. In adults, steady-state Cmax after 30 mg, 45 mg, and 60 mg doses every 12 hours averages 13.4 ng/mL, 34 ng/mL, and 58.4 ng/mL, respectively. Doubling the dose increased Cmax 4-fold to 5-fold. Disproportionate increases in AUC were also observed. In adults, mean terminal half-life is 8.6 hours. When given with a high-fat meal, mean Cmax is 45% lower, AUC is 25% lower, and Cmin is 75% higher than those of fasting subjects.
Onset of action is 2 to 5 minutes, and antihypertensive effects persist for 30 minutes to 4 hours. Rapid, dose-related increases in plasma concentrations are seen within 2 hours of initiation. After this, plasma concentrations increase at a slower rate and approach steady-state at 24 to 48 hours. Nicardipine plasma concentrations decrease tri-exponentially, with a rapid early distribution phase (alpha half-life = 3 minutes), an intermediate phase (beta half-life = 45 minutes), and slow terminal phase (gamma half-life = 14 hours) that is only seen after long-term IV infusion. Plasma clearance is 0.4 L/kg/hour in adults. After IV infusion discontinuation, plasma concentrations decrease rapidly with at least a 50% reduction within the first 2 hours. The pharmacokinetics of IV nicardipine are linear over the dosage range of 0.5 to 40 mg/hour in adults.
Cmax and AUC are 1.8- and 4-fold higher, respectively, and the half-life is prolonged in patients with severe hepatic disease.
Significantly lower systemic clearance and 2- to 3-fold higher Cmax and AUC occurs in patients with moderate renal impairment.