Nicardipine Hydrochloride

NICARDIPINE HYDROCHLORIDE- nicardipine hydrochloride injection
Hikma Pharmaceuticals USA Inc.

1 INDICATIONS AND USAGE

1.1 Hypertension

Nicardipine hydrochloride injection is indicated for the short-term treatment of hypertension when oral therapy is not feasible or desirable. For prolonged control of blood pressure, transfer patients to oral medication as soon as their clinical condition permits [see Dosage and Administration (2.6)].

2 DOSAGE AND ADMINISTRATION

2.1 General Information

Individualize dosing based on the severity of hypertension and the response of the patient during dosing. Monitor blood pressure and heart rate both during and after the infusion to avoid tachycardia or too rapid or excessive reduction in either systolic or diastolic blood pressure.

Administer Nicardipine Hydrochloride by slow continuous infusion by a central line or through a large peripheral vein. Change the infusion site every 12 hours if administered via peripheral vein [see Intravenous Infusion Site (5.7)].

2.2 Inspection and Preparation

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use the solution if particulate matter, precipitate, or crystallization is present, or if the container appears damaged.

Single Dose Vials

Dilution

Single dose vials must be diluted before infusion.

Each vial (25 mg) must be diluted with 240 mL of compatible intravenous fluid (see below), resulting in 250 mL of solution at a concentration of 0.1 mg/mL.

Compatability

Nicardipine hydrochloride injection has been found compatible and stable in polyvinyl chloride containers for 24 hours at controlled room temperature with:

Dextrose (5%) Injection, USP
Dextrose (5%) and Sodium Chloride (0.45%) Injection, USP
Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP
Dextrose (5%) with 40 mEq Potassium, USP
Sodium Chloride (0.45%) Injection, USPSodium Chloride (0.9%) Injection, USP

Nicardipine hydrochloride is not compatible with Sodium Bicarbonate (5%) Injection, USP or Lactated Ringer’s Injection, USP.

2.3 Dosage 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:

Oral Nicardipine Dose			Equivalent Intravenous Infusion Rate
20 mg q8h			0.5 mg/hr
30 mg q8h			1.2 mg/hr
40 mg q8h			2.2 mg/hr

2.4 Dosage 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 injection 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.

When treating acute hypertensive episodes in patients with chronic hypertension, discontinuation of infusion is followed by a 50% offset of action in 30 minutes ± 7 minutes but plasma levels of drug and gradually decreasing antihypertensive effects exist for many hours.

Titration

For a gradual reduction in blood pressure, initiate therapy at a rate of 5 mg/hr. If desired blood pressure reduction is not achieved at this dose, increase the infusion rate by 2.5 mg/hr every 15 minutes up to a maximum of 15 mg/hr, until desired blood pressure reduction is achieved. For more rapid blood pressure reduction, titrate every 5 minutes.

Maintenance

Adjust the rate of infusion as needed to maintain desired response.

2.5 Conditions Requiring Infusion Adjustment

Hypotension or Tachycardia: In case of hypotension or tachycardia, discontinue infusion. When blood pressure and heart rate stabilize, restart infusion at low doses such as 30 mL/hr to 50 mL/hr (3 mg/hr to 5 mg/hr) and titrate to maintain desired blood pressure.

Infusion Site Changes: Change infusion site every 12 hours if administered via peripheral vein.

Impaired Cardiac, Hepatic, or Renal Function: Monitor closely when titrating nicardipine hydrochloride injection in patients with congestive heart failure or impaired hepatic or renal function [see Warnings and Precautions (5.4, 5.5 and 5.6)].

2.6 Transfer to Oral Antihypertensive Agents

If treatment includes transfer to an oral antihypertensive agent other than nicardipine capsules, initiate oral therapy upon discontinuation of nicardipine hydrochloride injection.

When switching to a TID regimen of nicardipine capsules, administer the first dose 1 hour prior to discontinuation of the infusion.

3 DOSAGE FORMS AND STRENGTHS

Nicardipine hydrochloride is available in the following presentations:

• 25 mg nicardipine hydrochloride in 10 mL injection (2.5 mg/mL) in a single dose vial
  

4 CONTRAINDICATIONS

4.1 Advanced Aortic Stenosis

Do not use nicardipine in patients with advanced aortic stenosis because of the afterload reduction effect of nicardipine. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance.

5 WARNINGS AND PRECAUTIONS

5.1 Excessive Pharmacologic Effects

In administrating nicardipine, close monitoring of blood pressure and heart rate is required. Nicardipine may occasionally produce symptomatic hypotension or tachycardia. Avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or hemorrhage.

5.2 Rapid Decreases in Blood Pressure

No clinical events have been reported suggestive of a too rapid decrease in blood pressure with nicardipine. However, as with any antihypertensive agent, blood pressure lowering should be accomplished over as long a time as is compatible with the patient’s clinical status.

5.3 Use in Patients with Angina

Increases in frequency, duration, or severity of angina have been seen in chronic oral therapy with nicardipine capsules. Induction or exacerbation of angina has been seen in less than 1% of coronary artery disease patients treated with nicardipine. The mechanism of this effect has not been established.

5.4 Use in Patients with Congestive Heart Failure

Nicardipine 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, monitor vital signs carefully when using nicardipine, particularly in combination with a beta-blocker, in patients with CHF or significant left ventricular dysfunction.

5.5 Use in Patients with Impaired Hepatic Function

Since nicardipine is metabolized in the liver, consider lower dosages and closely monitor response. Nicardipine administered intravenously increased hepatic venous pressure gradient by 4 mmHg in cirrhotic patients at high doses (5 mg/20 min) in one study. Use caution in patients with portal hypertension.