Calcium-channel blockers (class II calcium antagonists).

Nicardipine - hypertension

Nicardipine hydrochloride 30 mg Nicardipine hydrochloride 45 mg

Sustained release capsules

Treatment of mild to moderate hypertension.

Starting dose: 30 mg every 12 hours titrating upwards as required.

Usual effective dose: 45 mg every 12 hours (range 30 mg to 60 mg every 12 hours).

Individually adjust the dose for each patient. Where appropriate Cardene SR may also be used in combination with beta-blockers and/or diuretics

Cardene SR is not recommended for use in patients under the age of 18.

Starting dose: 30 mg every 12 hours. Titrate upwards with care as nicardipine may lower systolic pressure more than diastolic pressure in these patients.

i) Use in pregnancy and lactation.

ii) Hypersensitivity to nicardipine hydrochloride or other dihydropyridines because of the theoretical risk of cross reactivity.

iii) As part of the effect of nicardipine is secondary to reduced afterload, the drug should not be given to patients with advanced aortic stenosis. Reduction in diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance.

iv) Cardene should not be used in cardiogenic shock, clinically significant aortic stenosis and during or within one month of a myocardial infarction.

v) Cardene should not be used for secondary prevention of myocardial infarction

If used in combination with diuretics or beta-blockers, careful titration of Cardene SR is advised to avoid excessive reduction in blood pressure.

If switching from beta-blockers to Cardene SR, 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 SR in patients experiencing ischaemic pain within 30 minutes of starting therapy or after increasing the dose.

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 SR 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.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Digoxin

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

Propranolol, Dipyridamole, Warfarin, Quinidine, Naproxen:

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

Cimetidine:

Cimetidine increases nicardipine plasma levels. Carefully monitor patients receiving both drugs.

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.

Ciclosporin:

Monitor ciclosporin plasma levels and reduce dosage accordingly in patients concomitantly receiving nicardipine as elevated cyclosporin levels have been reported.

Rifampicin:

Rifampicin can interact with other dihydropyridines to substantially reduce their plasma levels and so rifampicin and nicardipine should be used together with caution.

As with other dihydropyridines, nicardipine should not be taken with grapefruit juice because bioavailability may be increased.

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.

Most are expected consequences of the vasodilator effects of Cardene SR.

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

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

Cardiovascular System: As with the use of other sustained release dihydropyridines in patients with ischaemic heart disease, exacerbation of angina pectoris may occur rarely at the start of treatment with Cardene SR. 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.

Central Nervous System: Drowsiness, insomnia, tinnitus, paraesthesia, functional disorders.

Skin: Itching, rashes.

Hepato-Renal: Impairment, frequency.

Dyspnoea, gastro-intestinal upset and, rarely, depression, impotence and thrombocytopenia, have also been reported.

Astellas Pharma

(POM)