CARDENE Hard capsule Ref.[8183] Active ingredients: Nicardipine

When Cardene is used as monotherapy, caution is advised to avoid an excessive decrease in blood pressure. If used in combination with diuretics or beta-blockers, careful titration of Cardene is advised.

Caution should be exercised when using nicardipine in combination with a beta-blocker in patients with decreased cardiac function.

If switching from beta-blockers to Cardene, gradually reduce the beta-blocker dose (preferably over 8-10 days) since nicardipine gives no protection against the dangers of abrupt beta-blocker withdrawal.

Stop Cardene in patients experiencing ischaemic pain within 30 minutes of starting therapy or after increasing the dose.

Ischemic heart disease

Short-acting dihydropyridines are associated with an increased risk of ischemic cardiovascular events.

Use in patients with congestive heart failure or poor cardiac reserve

Haemodynamic studies in patients with heart failure have shown that nicardipine reduces afterload and improves overall haemodynamics. In one study, intravenous nicardipine reduced myocardial contractility in patients with severe heart failure despite increases in cardiac index and ejection fraction noted in the same patients.

Since nicardipine has not been extensively studied in patients with severe left ventricular dysfunction and cardiac failure one must consider that worsening of cardiac failure may occur.

Use in patients with impaired hepatic or renal function

Since Cardene is subject to first-pass metabolism, use with caution in patients with impaired liver function or reduced hepatic blood flow. Patients with severe liver disease showed elevated blood levels and the half-life of nicardipine was prolonged. Cardene blood levels may also be elevated in some renally impaired patients. Therefore the lowest starting dose and extending the dosing interval should be individually considered in these patients.

Use in patients following a stroke (infarction or haemorrhage)

Avoid inducing systemic hypotension when administering Cardene to these patients.

Laboratory tests

Transient elevations of alkaline phosphatase, serum bilirubin, SGPT, SGOT and glucose, have been observed. BUN and creatinine may also become elevated. While out-of-range values were seen in T₃, T₄ and TSH, the lack of consistent alterations suggest that any changes were not drug-related.

Treatment with short acting nicardipine may induce an exaggerated fall in blood pressure and reflex tachycardia which can cause cardiovascular complications such as myocardial and cerebrovascular ischaemia.

There has been some concern about increased mortality and morbidity in the treatment of ischaemic heart disease using higher than recommended doses of some other short-acting dihydropyridines.

Inhibitors and inducers of cytochrome P450 3A4

Nicardipine is metabolized by cytochrome P450 3A4. Concomitant administration of nicardipine with inducers (e.g. carbamazepine and rifampicin) or inhibitors (e.g. cimetidine and grapefruit juice) of cytochrome P450 3A4 may alter the plasma levels of nicardipine.

Clinical monitoring during treatment with an enzyme inducing or inhibiting agent, and after its discontinuation, is required.

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.

Digoxin

Careful monitoring of serum digoxin levels is advised in patients also receiving Cardene as levels may be increased.

Beta-blockers and other anti-hypertensive drugs

Cardene may be used in combination with beta-blocking and other anti-hypertensive drugs but the possibility of an additive effect resulting in postural hypotension should be considered.

Propranolol, Dipyridamole, Warfarin, Quinidine, Naproxen

Therapeutic concentrations of these drugs does not change the in vitro plasma protein binding of nicardipine.

Fentanyl Anaesthesia

Severe hypotension has been reported during fentanyl anaesthesia with concomitant use of a beta-blocker and calcium blockade. Even though such interactions have not been seen in clinical trials, such hypotensive episodes should be vigorously treated with conventional therapy such as intravenous fluids.

Pregnancy

See contra-indications (section 4.3).

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.

Breast-feeding

Because nicardipine was found in maternal milk, breast-feeding must be discontinued during nicardipine treatment (see section 5.3).

Caution should be exercised because the hypotensive effects of this drug may cause dizziness.

Majority are not serious and are expected consequences of the vasodilator effects of Cardene.

The most frequent side-effects reported are headache, oedema peripheral, heat sensation and/or flushing, palpitations, nausea and dizziness.

Other side-effects noted in clinical trials include the following:

Cardiac disorders: Tachycardia

As with the use of other short-acting dihydropyridines in patients with ischaemic heart disease, exacerbation of angina pectoris may occur frequently at the start of treatment with nicardipine capsules. The occurrence of myocardial infarction has been reported although it is not possible to distinguish such an event from the natural course of ischaemic heart disease.

Gastro-intestinal disorders: Gastro-intestinal upset, Gingival hyperplasia, Vomiting

General disorders and administration site conditions: Asthenia

Hepatobiliary disorders: Hepatic function abnormal

Renal and urinary disorders: Renal function abnormal, Frequency of micturition

Nervous system disorders: Drowsiness, Insomnia, Tinnitus, Paraesthesia, Functional disorders

Respiratory, thoracic and mediastinal disorders: Dyspnoea

Frequency: unknown, Pulmonary oedema*

* cases have been also reported when used as tocolytic during pregnancy (see section 4.6)

Skin and subcutaneous tissue disorders: Erythema, Pruritis, Rash

Vascular disorders: Hypotension, Orthostatic hypotension

Immune system disorders: Anaphylactic reaction

Frequency: Unknown

Investigations: Hepatic enzyme increased

Frequency: Unknown

Rarely, depression, impotence and thrombocytopenia have been reported.

The above mentioned listed adverse reactions have been observed during clinical studies and/or during marketed use.

Reporting of suspected adverse reactions

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.

None known.