Nicardipine hydrochloride injection is indicated for the short-term treatment of hypertension when oral therapy is not feasible or not desirable. For prolonged control of blood pressure, patients should be transferred to oral medication as soon as their clinical condition permits (see DOSAGE AND ADMINISTRATION ).
CONTRAINDICATIONS
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.
Warnings
CONTRAINDICATIONS
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.
WARNINGS
Directions And Dosage
OVERDOSAGE
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 remained 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 doses 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.
DOSAGE AND ADMINISTRATION
Nicardipine hydrochloride injection is intended for intravenous use. DOSAGE MUST BE INDIVIDUALIZED depending upon the severity of hypertension and the response of the patient during dosing. Blood pressure should be monitored both during and after the infusion; too rapid or excessive reduction in either systolic or diastolic blood pressure during parenteral treatment should be avoided.
Nicardipine hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium channel blocker). Nicardipine hydrochloride injection for intravenous administration contains 2.5 mg/mL of nicardipine hydrochloride. Nicardipine hydrochloride is a dihydropyridine derivative with IUPAC (International Union of Pure and Applied Chemistry) chemical name (±)-2-(benzyl-methyl amino) ethyl methyl 1,4-dihydro-2, 6-dimethyl-4-( m -nitrophenyl)-3,5-pyridinedicarboxylate monohydrochloride and has the following structure: Nicardipine hydrochloride is a greenish-yellow, odorless, crystalline powder that melts at about 169º C. It is freely soluble in chloroform, methanol, and glacial acetic acid, sparingly soluble in anhydrous ethanol, slightly soluble in n-butanol, water, 0.01 M potassium dihydrogen phosphate, acetone, and dioxane, very slightly soluble in ethyl acetate, and practically insoluble in benzene, ether, and hexane. It has a molecular weight of 515.99. Nicardipine hydrochloride injection is available as a sterile, non-pyrogenic, clear, yellow solution in 10 mL vials for intravenous infusion after dilution. Each mL contains 2.5 mg nicardipine hydrochloride in water for injection, USP with 48 mg sorbitol, NF, buffered to pH 3.5 with 0.525 mg citric acid monohydrate, USP and 0.09 mg sodium hydroxide, NF. Additional citric acid and/or sodium hydroxide may have been added to adjust pH.
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Nicardipine hydrochloride injection is indicated for the short-term treatment of hypertension when oral therapy is not feasible or not desirable. For prolonged control of blood pressure, patients should be transferred to oral medication as soon as their clinical condition permits (see DOSAGE AND ADMINISTRATION ).
CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
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.
WARNINGS
WARNINGS SECTION
PRECAUTIONS
PRECAUTIONS SECTION
ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
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. Percent of Patients with Adverse Experiences During the Double-Blind Portion of Controlled Trials Adverse Experience Nicardipine Hydrochloride (n=144) Placebo (n=100) Body as a Whole Headache 14.6 2.0 Asthenia 0.7 0.0 Abdominal pain 0.7 0.0 Chest pain 0.7 0.0 Cardiovascular Hypotension 5.6 1.0 Tachycardia 3.5 0.0 ECG abnormality 1.4 0.0 Postural hypotension 1.4 0.0 Ventricular extrasystoles 1.4 0.0 Extrasystoles 0.7 0.0 Hemopericardium 0.7 0.0 Hypertension 0.7 0.0 Supraventricular tachycardia 0.7 0.0 Syncope 0.7 0.0 Vasodilation 0.7 0.0 Ventricular tachycardia 0.7 0.0 Digestive Nausea/vomiting 4.9 1.0 Injection Site Injection site reaction 1.4 0.0 Injection site pain 0.7 0.0 Metabolic and Nutritional Hypokalemia 0.7 0.0 Nervous Dizziness 1.4 0.0 Hypesthesia 0.7 0.0 Intracranial hemorrhage 0.7 0.0 Paresthesia 0.7 0.0 Respiratory Dyspnea 0.7 0.0 Skin and Appendages Sweating 1.4 0.0 Urogenital Polyuria 1.4 0.0 Hematuria 0.7 0.0
OVERDOSAGE
OVERDOSAGE SECTION
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 remained 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 doses 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.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
Nicardipine hydrochloride injection is intended for intravenous use. DOSAGE MUST BE INDIVIDUALIZED depending upon the severity of hypertension and the response of the patient during dosing. Blood pressure should be monitored both during and after the infusion; too rapid or excessive reduction in either systolic or diastolic blood pressure during parenteral treatment should be avoided.
HOW SUPPLIED
HOW SUPPLIED SECTION
Nicardipine hydrochloride injection 25 mg/10 mL (2.5 mg/mL) single dose vials are available in cartons of 10 as follows: 25 mg/10 mL (2.5 mg/mL) – NDC 40042-047-10 Store at 20ºC to 25ºC (68ºF to 77ºF) [see USP Controlled Room Temperature]. Freezing does not adversely affect the product, but exposure to elevated temperatures should be avoided. Protect from light. Store vials in carton until used. Manufactured for: PharmaForce, Inc. Columbus, OH 43229 Revised August 2009
