Inadvisable combinations: Dantrolene: Dantrolene administered by infusion: In animal studies, fatal ventricular fibrillation cases are consistently observed when verapamil and dantrolene are administered intravenously. The combination of a calcium channel inhibitor and dantrolene is therefore potentially dangerous.
However, a few patients received the combination of nifedipine and dantrolene without any inconvenience.
Combinations requiring precautions for use: Idelalisib: Increased adverse effects of nicardipine, such as orthostatic hypotension, especially in elderly patients.
Clinical monitoring and dosage adjustment of nicardipine should be performed during treatment with idelalisib and after its discontinuation.
Cyclosporine, tacrolimus and sirolimus: 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.
CYP3A4 inducers and inhibitors: Nicardipine is metabolised 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 due to its increased hepatic metabolism.
Clinical monitoring and possible dosage adjustment if nicardipine should be performed during treatment with the anticonvulsant and after its discontinuation.
Co-administration of potent CYP3A4 enzyme-inhibiting agents (e.g. cimetidine, clarithromycin, cobicistat, erythromycin, itraconazole, grapefruit juice, ketoconazole, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, voriconazole) may cause an increase in the plasma concentration of nicardipine.
Increased adverse effects of nicardipine, more commonly orthostatic hypotension, especially in elderly patients. Co-administration of calcium channel blockers with itraconazole has shown an increased risk of adverse effects, in particular oedema due to a decreased metabolism of the calcium channel blocker in the liver.
Clinical monitoring and dosage adjustment of nicardipine should be performed during treatment with a potent CYP3A4 enzyme inhibitor and after its discontinuation.
Combinations to be taken into account: Potential additive hypertensive effect: Medicinal products which could potentiate the antihypertensive effect of nicardipine during concomitant administration, with an increased risk of orthostatic hypotension, include baclofen, urologic alpha-blockers (alfuzosin, doxazosin, prazosin, silodosin, tamsulosin, terazosin), alpha-blocking antihypertensive agents (doxazosin, prazosin, urapidil), tricyclic antidepressants, imipramine antidepressants, neuroleptics, opioids and amifostine.
Nitrate derivatives and related agents: Increased risk of hypotension, particularly orthostatic hypotension.
Medicinal products that cause orthostatic hypotension: Increased risk of hypotension, particularly orthostatic hypotension.
Inhalational anaesthetics: 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.
Enhancement of negative inotropic effect: Nicardipine may enhance the negative inotropic effect of beta-blockers in cardiac failure (bisoprolol, carvedilol, metoprolol, nebivolol) and may cause hypotension, cardiac failure in patients with latent or uncontrolled cardiac failure (see Warnings and Precautions). Moreover, the presence of a beta-blocker treatment can minimise the reflex sympathetic reaction set into action in case of excessive haemodynamic repercussion.
Nicardipine may enhance the negative inotropic effect of beta-blockers (except for esmolol) and may cause hypotension, cardiac failure in patients with latent or uncontrolled cardiac failure (see Warnings and Precautions) (addition of negative inotropic effects). Moreover, the beta-blocker can minimise the reflex sympathetic reaction set into action in case of excessive haemodynamic repercussion.
Magnesium: 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 Warnings).
Digoxin: 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.
Decrease of antihypertensive effect: Nicardipine in combination with intravenous corticosteroids (glucocorticoids and mineralocorticoids) and tetracosactide (except for hydrocortisone used as replacement therapy in Addison's disease) may cause a decrease in the antihypertensive effect.
Competitive neuromuscular blockers: Limited data suggest that nicardipine, as other calcium channel blockers, enhances neuromuscular block possibly by acting on the post-synaptic 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.