Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Mercury Pharmaceuticals Limited, Capital House, 85 King William Street, London, EC4N 7BL, UK
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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.
Rapid pharmacologic reductions in blood pressure may produce systemic hypotension and reflex tachycardia. If either occurs with nicardipine, consider decreasing the dose by half or stopping the infusion.
Bolus administration or intravenous administration not controlled by the use of an electronic syringe driver or a volumetric pump is not recommended and can increase the risk of serious hypotension, particularly in the elderly, in children, in patients with renal or hepatic impairment and in pregnancy.
Nicardipine should be used with caution in patients with congestive heart failure or pulmonary oedema, particularly when these patients are receiving concomitant beta-blockers, as worsening of cardiac insufficiency may occur.
Ischaemic cardiovascular disease.
Nicardipine is contra-indicated in unstable angina and immediately following myocardial infarction (see section 4.3).
Nicardipine should be used with caution in patients with suspected coronary ischemia. Occasionally, patients have developed an increased frequency, duration, or severity of angina upon starting or increasing nicardipine dosage, or during the course of treatment.
Due to the risk of severe maternal hypotension and potentially fatal foetal hypoxia, the decrease in blood pressure should be progressive and always closely monitored. Due to the possible risk of pulmonary oedema or excessive decrease in blood pressure, caution should be taken if magnesium sulphate is used concomitantly
Rare cases of abnormal hepatic function possibly associated with the use of nicardipine have been reported. Potential risk groups are patients with a history of hepatic dysfunction or those with impaired hepatic function at the initiation of treatment with nicardipine.
Intravenous nicardipine at high doses has been reported to worsen portal vein hypertension and portal-systemic collateral blood flow index in cirrhotic patients.
Intracranial pressure should be monitored, to allow calculation of the cerebral perfusion pressure.
Nicardipine should be used with caution in patients with acute cerebral infarction. A hypertensive episode which often accompanies a stroke is not an indication for emergency antihypertensive therapy. The use of antihypertensive drugs is not recommended in ischemic stroke patients unless acute hypertension precludes the administration of an adequate treatment (e.g. thrombolysis) or there is other end-organ damage which is life-threatening in the short term.
Caution should be exercised when using nicardipine in combination with a beta-blocker in patients with decreased cardiac function. In such case, the posology of the beta blocker should be individualized to the clinical situation. (See section 4.5)
Infusion site reactions can occur, particularly with prolonged duration of administration and in peripheral veins. It is advised to change the infusion site in case of any suspicion of infusion site irritation. The use of a central venous line or of a greater dilution of the solution could reduce the risk of occurrence of infusion site reaction.
The safety and efficacy of nicardipine IV has not been tested in controlled clinical trials in infants or children, thus special care is required in this population (refer to section 4.2)
Nicardipine may enhance the negative inotropic effect of beta-blockers and may cause heart failure in patient with latent or uncontrolled heart failure (see section 4.4)
In animal studies, administration of verapamil and intravenous dantrolene has caused fatal ventricular fibrillation. The combination of a calcium channel inhibitor and dantrolene is therefore potentially dangerous.
Due to the possible risk of pulmonary oedema or excessive decrease in blood pressure, caution should be taken if magnesium sulphate is used concomitantly (see section 4.4)
Nicardipine is metabolized by cytochrome P450 3A4. Co-administration of CYP 3A4 enzyme-inducing agents (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone and rifampicin) may cause a decrease in the plasma concentrations of nicardipine.
Co-administration of CYP3A4 enzyme-inhibiting agents (e.g. cimetidine, itraconazole and grapefruit juice) may cause an increase in the plasma concentrations of nicardipine. Co-administration of calcium channel blockers with itraconazole has shown an increased risk of adverse events, in particular oedema due to a decreased metabolism of the calcium channel blocker in the liver.
Concomitant administration of nicardipine and cyclosporine, tacrolimus or sirolimus results in elevated plasma cyclosporine, tacrolimus or sirolimus levels. Cyclosporine, tacrolimus or sirolimus level should be monitored and dosage of immunosuppressant and/or nicardipine should be reduced, if required.
Nicardipine has been reported to increase the plasma levels of digoxin in pharmacokinetic studies. Digoxin levels should be monitored when concomitant therapy with nicardipine is initiated.
Concomitant medications which could potentiate the antihypertensive effect of nicardipine include baclofen, alpha-blockers, tricyclic antidepressants, neuroleptics, opiods and amifostine
Nicardipine in combination with intravenous corticosteroids and tetracosactide (except for hydrocortisone used as replacement therapy in Addison’s disease) may cause a decrease in the antihypertensive effect
The co-administration of nicardipine with inhalational anaesthetics could induce a potential additive or synergistic hypotensive effect, as well as an inhibition by anaesthetics of the baroreflex heart rate increase associated with peripheral vasodilators. Limited clinical data suggests that the effects of inhaled anaesthetics (e.g. isoflurane, sevoflurane and enflurane) on nicardipine appear to be moderate.
Limited data suggest that nicardipine, as other calcium channel blockers, enhances neuromuscular block possibly by acting at the post-junctional region. Vecuronium infusion dose requirements could be reduced by the concurrent use of nicardipine. Reversal of neuromuscular block by neostigmine appears not to be affected by nicardipine infusion. No additional monitoring is required.
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 (see section 4.8), 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.
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.
No data.
Nicardipine has no or negligible influence on the ability to drive and use machines.
The majority of undesirable effects are the consequence of the vasodilator effects of nicardipine. The most frequent events are headache, dizziness, peripheral oedema, palpitations and flushing
Adverse reactions listed below have been observed during clinical studies and/or during marketed use and are based on clinical trial data and classified according to MedDRA System Organ Class. Frequency categories are defined according to the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).
Not known: thrombocytopenia
Not known: anaphylactic reaction
Very common: headache
Common: dizziness
Common: lower limb oedema, palpitations, hypotension, tachycardia
Not known: atrioventricular block, angina pectoris
Common: orthostatic hypotension
Not known: pulmonary oedema*
Common: nausea, vomiting
Not known: paralytic ileus
Common: flushing
Not known: erythema
Not known: phlebitis
Not known: hepatic enzyme increased
* cases have been also reported when used as tocolytic during pregnancy (see section 4.6)
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
In the absence of studies of compatibility, this medicinal product should not be mixed with other medicinal products except those mentioned under section 4.2.
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