Each mL contains: Nicardipine Hydrochloride 1 mg and Water for Injection BP qs.
Pharmacology: Nicardipine inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentrations. The contractile processes upon the movement of extracellular calcium ions into these cells through specific ion channels. The effects of Nicardipine are more selective to vascular smooth muscle than cardiac muscle. In animal models, Nicardipine produced relaxation of coronary vascular smooth muscle at drug levels which cause little or no negative inotropic effect.
Pharmacokinetics: Following infusion, Nicardipine plasma concentrations decline tri-exponentially, with a rapid early distribution phase (a half life of 2.7 minutes), an intermediate phase (β-half-life of 44.8 minutes), and a slow terminal phase (y-half-life of 14.4 hours) that can only be detected after long-term infusions. Total plasma clearance (Cl) is 0.4 L/hr/kg, and the apparent volume of distribution (Vd) using a non-compartment model is 8.3 L/kg. The pharmacokinetics of Nicardipine hydrochloride injection are linear over the dosage range of 0.5 to 40 mg/hr.
Rapid dose-related increases in Nicardipine plasma concentrations are seen during the first two hours after the start of an infusion of Nicardipine hydrochloride injection. Plasma concentrations increase at much slower rate after the first few hours, and approach steady state at 24 to 48 hours. On termination of infusion, Nicardipine concentrations decrease, with at least a 50% decrease during the first two hours post-infusion. The effects of Nicardipine on blood pressure significantly correlate with plasma concentrations.
Nicardipine is highly protein bound (>95%) in human plasma over a wide concentration range.
Nicardipine hydrochloride injection has been shown to be rapidly and extensively metabolized by the liver. After coadministration of a radioactive intravenous dose of Nicardipine hydrochloride injection with an oral 30 mg dose given every 8 hours, 49% of the radioactivity was recovered in the urine and 43% in the feces within 96 hours. None of the dose was recovered as unchanged Nicardipine. Nicardipine does not include or inhibits its own metabolism and does not induce or inhibit hepatic microsomal enzymes. The steady-state pharmacokinetics of Nicardipine are similar in elderly hypertensive patients (>65 years) and young healthy adults.
Used in the management of hypertension and angina pectoris.
As a Substitute for Oral Nicardipine Therapy:
The intravenous infusion rate required to produce an average plasma concentration equivalent to a given oral dose at steady state is shown in the following table (see table).
Click on icon to see table/diagram/image
For Initiation of Therapy in a Drug Free Patient:
The time course of blood pressure decrease is dependent on the initial rate of infusion and the frequency of dosage adjustment. Nicardipine hydrochloride is administered by slow continuous infusion at a concentration of 0.1 mg/mL. With constant infusion, blood pressure begins to fall within minutes. It reaches about 50% of its ultimate decrease in about 45 minutes and does not reach final steady state for about 50 hours.
When treating acute hypertensive episodes in patients with chronic hypertension, discontinuation of the infusion is followed by a 50% offset of action in 30 ± 7 minutes but plasma levels of drug and gradually decreasing antihypertensive effects exist for about 50 hours.
Titration: For gradual reduction in blood pressure, initiate therapy at 50 mL/hr (5 mg/hr). If desired blood pressure reduction is not achieved at this dose, the infusion rate may be increased by 25 mL/hr (2.5 mg/hr) every 5 minutes up to a maximum of 150 mL/hr (15 mg/hr), until desired blood pressure reduction is achieved. Following achievement of blood pressure goal, the infusion rate should be decreased to 30 mL/hr (3 mg/hr).
Maintenance: The rate of infusion should be adjusted as needed to maintain desired response.
Several overdosages with orally administered Nicardipine have been reported. One adult patient allegedly ingested 600 mg of Nicardipine [standard (immediate release) capsules]. and another patient, 2160 mg of the sustained release formulation of Nicardipine. Symptoms included marked hypotension, bradycardia, palpitations, flushing, drowsiness, confusion and slurred speech. All symptoms resolved without sequelae. An overdosage occurred in a one-year-old child who ingested half of the powder in a 30 mg Nicardipine standard capsule. The child remain asymptomatic.
Based on results obtained in laboratory animals, lethal overdose may cause systemic hypotension, bradycardia (following initial tachycardia) and progressive atrioventricular conduction block.
Reversible hepatic function abnormalities and sporadic focal hepatic necrosis were noted in some animal species receiving very large dose of Nicardipine.
For treatment of overdosage, standard measures including monitoring of cardiac and respiratory functions should be implemented. The patient should be positioned so as to avoid cerebral anoxia. Frequent blood pressure determinations are essential. Vasopressors are clinically indicated for patients exhibiting profound hypotension. Intravenous Calcium Gluconate may help reverse the effects of Calcium entry blockade.
Nicardipine hydrochloride injection is contraindicated in patients with known hypersensitivity to the drug. Nicardipine hydrochloride injection is also contraindicated in patients with advanced aortic stenosis because part of the effect of Nicardipine hydrochloride injection is secondary to reduced afterload. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance.
Beta-Blocker Withdrawal: Nicardipine is not beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of dose of beta-blocker.
Rapid Decrease in Blood Pressure: No clinical events have been suggestive of a too rapid decrease in blood pressure with Nicardipine hydrochloride injection. However, as with antihypertensive agent, blood pressure lowering should be accomplished over as long a time as is compatible with the patient's clinical status.
Use in Patients with Angina: Increases in frequency, duration, or severity of angina have been seen in chronic oral therapy with Nicardipine hydrochloride capsules. Induction or exacerbation of angina has been seen in less than 1% of coronary artery disease patients treated with Nicardipine hydrochloride injection. The mechanism of this effect has not been established.
Use in Patients with Congestive Heart Failure: Nicardipine hydrochloride injection reduced afterload without impairing myocardial contractility in preliminary hemodynamic studies of CHF patients. However, in vitro and in some patients, a negative inotropic effect has been observed. Therefore, caution should be exercised when using Nicardipine hydrochloride injection, particularly in combination with a beta-blocker, in patients with CHF or significant left ventricular dysfunction.
Use in Patients with Pheocromocytoma: Only limited clinical experience exist in use of Nicardipine hydrochloride injection for patients with hypertension associated with pheocromocytoma. Caution should be therefore be exercised when using the drug in these patients.
Peripheral Vein Infusion Site: To minimize the risk of peripheral venous irritation, it is recommended that the site of infusion of Nicardipine hydrochloride injection be changed every 12 hours.
General: Blood Pressure: Because Nicardipine hydrochloride injection decreases peripheral resistance, monitoring of blood pressure during administration is required. Nicardipine hydrochloride injection, like other calcium channel blockers, may occasionally produce symptomatic hypotension. Caution is advised to avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or haemorrhage.
Use in Patients with Impaired Hepatic Function: Since Nicardipine is metabolized in the liver, the drug should be used with caution in patients with impaired liver functions or reduced hepatic blood flow. The use of lower dosages should be considered. Nicardipine administered intravenously has been reported to increase hepatic venous pressure gradient by 4 mmHg in cirrhotic patients at a high doses (5 mg/20 min). Nicardipine hydrochloride injection should therefore be used with caution in patients with portal hypertension.
Use in Patients with Impaired Renal Function: When Nicardipine hydrochloride injection was given to mild to moderate hypertensive patients with moderate renal impairment, a significantly lower systemic clearance and higher AUC was observed. These results are consistent with those seen after oral administration of Nicardipine. Careful dose titration is advised when treating renal impaired patients.
Effects on ability to drive and use machines: Not known.
Two hundred forty-four patients participated in two multicenter, double-blind, placebo-controlled trials of Nicardipine hydrochloride injection. Adverse experiences were generally not serious and most were expected consequences of vasodilation. Adverse experiences occasionally required dosage adjustment. Therapy was discontinued in approximately 12% of patients, mainly due to hypotension, headache, and tachycardia.
Since Nicardipine hydrochloride injection may be administered to patients already being treated with other medications, including other antihypertensive agents, careful monitoring of these patients in necessary to detect and promptly treat any undesired effects from concomitant administration.
Beta-Blockers: In most patients, Nicardipine hydrochloride injection can safely be used concomitantly with beta-blocker. However, caution should be exercised when using Nicardipine hydrochloride injection in combination with beta-blocker in congestive heart failure patients.
Cimetidine: Cimetidine has been shown to increase Nicardipine plasma concentrations with Nicardipine hydrochloride capsule administration. Patients receiving the two drugs concomitantly should be carefully monitored. Data with other histamine-2 antagonists are not available.
Digoxin: Studies have shown that Nicardipine hydrochloride capsules usually do not alter Digoxin plasma concentrations. However, as a precaution, digoxin levels should be evaluated when concomitant therapy with Nicardipine hydrochloride is initiated.
Fentanyl Anesthesia: Hypotension has been reported during Fentanyl anaesthesia with concomitant use of a beta-blocker and a calcium channel blocker. Even though such interactions were not seen during clinical studies with Nicardipine hydrochloride injection (Nicardipine hydrochloride), an increased volume of circulating fluids might be required if such an interaction were to occur.
Cyclosporine: Concomitant administration of Nicardipine hydrochloride capsules and Cyclosporine results in elevated plasma cyclosporine levels. Plasma concentrations of Cyclosporine should therefore be closely monitored during Nicardipine hydrochloride injection administration, and the dose of Cyclosporine reduced accordingly.
In Vitro Hydrochloride: The plasma protein binding of Nicardipine was not altered when therapeutic concentrations of furosemide, propranolol, dipyridamole, warfarin, quinidine, or naproxen were added to human plasma in vitro.
Store at temperatures not exceeding 30°C. Protect from light.
C08CA04 - nicardipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.
Soln for inj (amp) 1 mg/mL x 10 mL x 5's.