Nidepine

Light yellow, clear sterile solution for IV infusion.
Each mL contains: Nicardipine HCl 1 mg.

Pharmacology: Pharmacodynamics: Nicardipine is a dihydropyridine calcium channel blockers which share the ability to inhibit movement of calcium ions across the cell membrane of the myocardium and vascular smooth muscle. The effects on the cardiovascular system include depression of mechanical contraction of myocardial and smooth muscle and depression of both impulse formation and conduction velocity.
Pharmacokinetics: Nicardipine has a volume of distribution about 8.3 L/kg and protein binding >95%. The elimination half-life varies from about 2-4 hours. It is metabolised in the liver. Excretion in urine is about 49% (as <1% unchanged form) and in feces is about 43%.

Use in short-term treatment of hypertension when oral therapy is not feasible or not desirable.

Dosage: NIDEPINE is intended for IV infusion use. Ampoules must be diluted with compatible intravenous fluids at a concentration of 0.1 mg/mL before infusion.
Administer 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 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/h (5 mg/h). If desired blood pressure reduction is not achieved at this dose, the infusion rate may be increased by 25 mL/h (2.5 mg/h) 15 minutes up to a maximum of 150 mL/h until desired reduction of blood pressure is achieved.
For more rapid blood pressure reduction, initiate therapy at 50 mL/hr (5 mg/h). If desired blood pressure reduction is not achieved at this dose, the infusion rate may be increased by 25 mL/hr (2.5 mg/h) every 5 minutes up to a maximum of 150mL/h (15 mg/h), until desired blood pressure reduction is achieved. Following achievement of the blood pressure goal, the infusion rate should be decreased to 30 mL/h (3 mg/h).
Conditions requiring infusion adjustment: Hypotension or tachycardia: If there is concern of impending hypotension or tachycardia, the infusion should be discontinued. When blood pressure has stabilized, infusion of NIDEPINE may be restarted at low doses such as 30 to 50 mL/hr (3 to 5 mg/hr) and adjusted to maintain desired blood pressure.
Infusion-site should be changed every 12 hours if administered via peripheral vein.
Mode of Administration: NIDEPINE is intended for intravenous use. Ampoules must be diluted before infusion at a concentration of 0.1 mg/mL.
Solution for dilution: The drug could be diluted with compatible solution as follows: 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, USP; Sodium chloride (0.9%) injection, USP.
Remark: NIDEPINE is not compatible with sodium bicarbonate (5%) injection or Ringer's lactate injection.
The diluted solution is stable in glass or polyvinyl chloride containers for 24 hours at room temperature (20-25°C).

Overdosage may be associated with bradycardia and hypotension, hyperglycaemia, metabolic acidosis, and coma may also occur.
Supportive and symptomatic care should be given. Hypotension may respond to placing the patient in the supine position with the feet raised. If hypotension is not corrected, calcium should be given intravenously. The usual initial dose is 10 to 20 mL of 10% calcium gluconate given by slow intravenous injection or infusion; alternatively, up to 10 mL of 10% calcium chloride may be given. Glucagon may also be used. If hypotension persists, an intravenous sympathomimetic such as isoprenaline, dopamine, or noradrenaline may also be necessary. Bradycardia may be treated with atropine, isoprenaline, or cardiac pacing.

Do not use in patients with a history of: Acute heart failure, Advanced aortic stenosis, Hypersensitivity to nicardipine or any ingredients in the formulation.

Caution in patients with congestive heart failure or impaired hepatic or renal function. Doses should be reduced and administer at longer dosing intervals.
Be cautious in patient with coronary ischemia.
Increased angina: Occasional patients have increased frequency, duration, or severity of angina on starting nicardipine, or at the time of dosage increases.
Blood pressure should be monitored both during and after the infusion, too rapid or excessive reduction in blood pressure during treatment should be avoided.
Use in Children: Safety and efficacy of nicardipine in pediatric have not been established. Use of NIDEPINE in the pediatric population is not recommended.

Pregnancy: Category C. Not advisable for pregnant women.
Lactation: Significant concentration of nicardipine appear in maternal milk of rats. Not advisable for nursing mother. Decide whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.

The most common adverse effect are associated with its vasodilator action and often diminish on continued therapy. They include dizziness, flushing, headache, hypotension, peripheral oedema, tachycardia, and palpitations. Nausea and other gastrointestinal disturbances, increased micturition frequency, lethargy, eye pain, visual disturbances, and mental depression have also occurred. A paradoxical increase in ischaemic chest pain may occur at the start of treatment and in a few patients excessive fall in blood pressure has led to cerebral or myocardial ischemia or transient blindness.

Coadministration with beta-blockers agents may cause additive or synergistic effects. Nicardipine may inhibit the metabolism of certain beta-blockers. Monitor cardiac function and adjust dosage as needed.
Cyclosporine level and toxicity may be increased when given concurrently with nicardipine.
Serum concentrations of nicardipine may be increased when given concurrent with cimetidine. Adjust dose as needed.
Coadministration with rifampin may decrease the therapeutic effects of nicardipine. Monitor cardiovascular status closely. Adjust dose as needed.
Grapefruit juice may increase the serum concentrations of nicardipine.

Store below 30°C. Protect from light.

Calcium Antagonists

C08CA04 - nicardipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.

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