Nikem

Each mL contains: Nicardipine Hydrochloride 1 mg.
Nicardipine hydrochloride is 2-[Benzyl(methyl)amino]ethyl methyl (4RS)-2,6-dimethyl-4-(3nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylatemonohydrochloride, Molecular formula:C₂₆H₂₉N₃O₆ HCl.

Pharmacotherapeutic group: Selective calcium inhibitors with vascular effects. ATC code: C08CA04.
Pharmacology: Pharmacodynamics: Mechanism of action: Nicardipine is a second generation slow calcium channel inhibitor, and belongs to the phenyl-dihydropyridine group. Nicardipine has a greater selectivity for L-type calcium channels in vascular smooth muscle than cardiac myocytes. At very low concentrations it inhibits the influx of calcium into the cell. Its action is produced mainly on arterial smooth muscle. This is slurred speech and hyperglycaemia. In laboratory animals, overdosage also resulted in reversible hepatic function abnormalities, sporadic focal hepatic necrosis and progressive atrio-ventricular conduction block.
Pharmacological: Mechanism of action: Nicardipine is a second generation slow calcium channel inhibitor, and belongs to the phenyl-dihydropyridine group. Nicardipine has a greater selectivity for L-type calcium channels in vascular smooth muscle than cardiac myocytes. At very low concentrations it inhibits the influx of calcium into the cell. Its action is produced mainly on arterial smooth muscle. This is reflected in relatively large and rapid changes in blood pressure, with minimal inotropic changes in cardiac function (baroreflex effect).
Pharmacodynamic: Administered by systemic route, nicardipine is a potent vasodilator which diminishes total peripheral resistance and lowers blood pressure. Heart rate is temporarily increased; as a result of a decrease in after-load, cardiac output is markedly and durably increased. In humans, the vasodilator action also occurs in both acute dose administration and chronic administration in the large and small arteries, increasing blood flow and improving arterial compliance. Renal vascular resistance is decreased.
Pharmacokinetics: Absorption: Following intravenous administration, Nicardipine is rapidly absorbed with studies showing the time to onset ranging between 5-15 minutes. Peak plasma levels can reach 184 ng/ml and steady state plasma concentrations of 157 ng/ml achieved within 24-48 hours of continuous infusion.
Distribution: Nicardipine is highly protein bound in human plasma over a wide concentration range.
Metabolism: Nicardipine is metabolized by cytochrome P450 3A4. Studies involving either a single dose, or administration 3 times daily for 3 days, have shown that less than 0.03% of unchanged nicardipine is recovered in the urine in humans after oral or intravenous administration. The most abundant metabolite in human urine is the glucuronide of the hydroxy form, which is formed by the oxidative cleaving of the N-methylbenzyl moiety and the oxidation of the pyridine ring.
Elimination: After co-administration of a radioactive intravenous dose of nicardipine 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 in the urine. The elimination profile of the drug following an intravenous dose consists of three phases, with corresponding half-life: distribution 6.4 min, elimination 1.5 hours, terminal elimination 7.9 hours. Studies have shown clinical offset of action to be approximately 15 minutes.
Renal impairment: The pharmacokinetics of intravenously administered nicardipine was studied in subjects with severe renal dysfunction requiring hemodialysis (creatinine clearance <10 ml/min), mild/moderate renal dysfunction (creatinine clearance 10-50 ml/min) and normal renal function (creatinine clearance >50 ml/min).
At steady state, Cmax and AUC were significantly higher and clearance significantly lower in subjects with mild/moderate renal function compared to subjects with normal renal function. There were no significant differences in the principal pharmacokinetic parameters between severe renal dysfunction and normal renal dysfunction.

Used in the management of hypertension and angina pectoris.

Method of Administration: Nicardipine Hydrochloride Injection should be administered by continuous intravenous infusion only. It should only be administered by specialists in well controlled environments, such as hospitals and intensive care units, with continuous monitoring of blood pressure. The speed of administration must be accurately controlled by the use of an electronic syringe driver or a volumetric pump.
Blood pressure and heart rate must be monitored at least every 5 minutes during the infusion, and then until vital signs are stable, but at least for 12 hours after the end of the administration of Nicardipine.
The antihypertensive effect will depend on the administered dose. The dosage regimen to achieve the desired blood pressure can vary depending on the targeted blood pressure, the response of the patient, and the age or status of the patient.
Unless given by a central venous line, dilute to a concentration of 0.1-0.2 mg/ml before use.
Adults: Initial dose: Treatment should start with the continuous administration of Nicardipine at a rate of 3-5 mg/h for 15 minutes. Rates can be increased by increments of 0.5 or 1 mg every 15 minutes.
The infusion rate should not exceed 15 mg/h.
Maintenance dose: When the target pressure is reached, the dose should be reduced progressively, usually to between 2 and 4 mg/h, to maintain the therapeutic efficacy.
Older patients: Elderly patients may be more sensitive to Nicardipine effects because of impaired renal and/or hepatic function. It is recommended to provide a continuous infusion of Nicardipine starting at the dose of 1 to 5 mg/h, depending on the blood pressure and clinical situation. After 30 minutes, depending on the effect observed, the rate should be increased or decreased by increments of 0.5 mg/h. The rate should not exceed 15 mg/h.

Symptoms: Overdose with nicardipine hydrochloride can potentially result in marked hypotension, bradycardia, palpitations, flushing, drowsiness, collapse, peripheral oedema, confusion, slurred speech and hyperglycaemia. In laboratory animals, overdosage also resulted in reversible hepatic function abnormalities, sporadic focal hepatic necrosis and progressive atrio-ventricular conduction block.

Known hypersensitivity to nicardipine or to any of the excipients; Severe aortic stenosis; Compensatory hypertension, i.e. in case of an arteriovenous shunt or aortic Coarctation; Unstable angina; Within 8 days after myocardial infarction; Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Hepatic Impairment: Nicardipine should be used with particular caution in these patients. It is recommended to use the same dose regimens as for elderly patients in patients with impaired liver function or reduced hepatic blood flow.
Renal Impairment: Nicardipine should be used with particular caution in these patients. It is recommended to use the same dose regimens as for elderly patients in patients with renal impairment.
Use in Children: Nicardipine Hydrochloride Injection safety and efficacy has not been established in low birth weight infants, newborns, nursing infants, infants, and children.
Nicardipine should only be used for life-threatening hypertension in pediatric intensive care settings or post-operative contexts.
Initial dose: In case of emergency, a starting dose of 0.5 to 5 mcg/kg/min is recommended.
Maintenance dose: The maintenance dosage of 1 to 4 mcg/kg/min is recommended.
Nicardipine should be used with particular caution in children with renal impairment. In this case, only the lowest posology should be used.

It is recommended to use the same dose regimens as for elderly patients in pregnant women.
Pregnancy: Limited pharmacokinetic data have shown that nicardipine i.v. does not accumulate and has a low placental transfer. In clinical practice, the use of nicardipine during the first two trimesters in a limited number of pregnancies has not revealed any malformative or particular foetotoxic effect to date. The use of nicardipine for severe pre-eclampsia during the third trimester of pregnancy could potentially produce an undesirable tocolytic effect which could potentially interfere with the spontaneous induction of labour.
Acute pulmonary oedema has been observed when nicardipine has been used as tocolytic during pregnancy, especially in cases of multiple pregnancy (twins or more), with the intravenous route and/or concomitant use of beta-2 agonists. Nicardipine should not be used in multiple pregnancies or in pregnant women with compromised cardio-vascular condition, except if there is no other acceptable alternative.
Lactation: Nicardipine and its metabolites are excreted in human milk at very low concentrations. There is insufficient information on the effects of nicardipine in newborns/infants. Nicardipine should not be used during breast-feeding.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Headache is the most common side effect, and may affect more than 1 in 10 people.
Other common side effects (these may affect up to 1 in 10 people) are: Dizziness, Swollen legs or ankles, Increased heart rate, feeling your heart beat (palpitations); Low blood pressure, especially on standing up. This may cause dizziness, lightheadedness or fainting.
Feeling sick or being sick, Flushing of the skin.
Other side effects (Frequency unknown): Reduction in blood platelets, which may increase the risk of bleeding or bruising; Slow heart rhythm; Chest pain; Heart problems leading to increased fluid in the lungs and shortness of breath; Abdominal pain; Redness of the skin; Inflammation of the vein where the medicine has been given; Changes in blood tests of how your liver is working.

Store at temperatures not exceeding 30°C. Protected 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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