Nicardipine Hydrochloride 30mg Capsules
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nicardipine Hydrochloride 30 mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 30 mg of nicardipine hydrochloride For the full list of excipients, see 6.1.
3 PHARMACEUTICAL FORM
Capsule
Hard gelatin capsule filled with a light yellow granule.
Size 2, orange opaque body, violet opaque cap.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
The prophylaxis of patients with chronic stable angina, and the treatment of mild to moderate hypertension.
4.2 Posology and method of administration
Posology
Adults
Angina: Initial dose; 20 mg three times a day, titrating upwards as required. Usual effective dose; 30 mg three times a day (range of total daily dose 60 mg - 120 mg). Allow at least 3 days before increasing the dose to ensure steady-state plasma levels have been achieved. Hypertension: Initial dose; 20 mg three times a day, titrating upwards as required. Usual effective dose; 30 mg three times a day (range of total daily dose 60 mg - 120 mg per day).
Nicardipine may be used in combination with beta-blockers, diuretics and nitrates. When used concomitantly with beta-blockers additive anti-anginal efficacy has been demonstrated (see section 4.5 - 'Interaction with Other Medicaments and Other Forms of Interaction').
Elderly
Initial dose; 20 mg three times a day. Titrate upwards with care as nicardipine may lower systolic pressure more than diastolic pressure in elderly patients.
Children
Nicardipine is not recommended in patients under the age of 18 years since safety and efficacy have not been established.
Method of administration
Nicardipine Hydrochloride 30 mg Capsules are for oral administration. They should be swallowed whole with a drink of water.
4.3 Contraindications
i) Hypersensitivity to nicardipine hydrochloride, other dihydropyridines because of the theoretical risk of cross-reactivity or to any of the excipients listed in section 6.1.
ii) Pregnancy and lactation.
iii) Advanced aortic stenosis (since part of the effect of nicardipine is secondary to reduced afterload). Reduction of diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance.
iv) Cardiogenic shock, clinically significant aortic stenosis, unstable angina, and during or within one month of a myocardial infarction.
v) Nicardipine should not be used for acute attacks of angina.
vi) Nicardipine should not be used for secondary prevention of myocardial infarction.
vii) Acute porphyria
4.4 Special warnings and precautions for use
If used in combination with diuretics or beta-blockers, careful titration of the dose of nicardipine is advised to avoid excessive reduction in blood pressure.
If switching from beta-blockers to nicardipine, 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 nicardipine 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 the occurrence of worsening of cardiac failure must be considered.
Use in patients with impaired hepatic or renal function Since nicardipine 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. Nicardipine 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 nicardipine 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 suggests 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.
Nicardipine hydrochloride 30 mg capsules contain the Azo colouring agent Sunset yellow (E110). This may cause an allergic reaction in some individuals.
4.5 Interaction with other medicinal products and other forms of interaction
Digoxin
Careful monitoring of serum digoxin levels is advised in patients also receiving nicardipine as levels may be increased.
Cimetidine
Cimetidine increases nicardipine plasma levels. Carefully monitor patients receiving both drugs.
Cyclosporin
Monitor cyclosporin plasma levels and reduce dosage accordingly in patients concomitantly receiving nicardipine as elevated cyclosporin levels have been reported.
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.
Propanolol, dipyridamole, warfarin, quinidine, naproxen
Therapeutic concentrations of these drugs do not change the in vitro plasma protein binding of nicardipine.
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.
Nicardipine may be used in combination with beta-blocking and other antihypertensive drugs but possibility of an additive effect resulting in postural hypotension should be considered.
4.6 Fertility, pregnancy and lactation
Pregnancy
Nicardipine is contra-indicated in pregnancy and lactation due to the lack of experience in this patient group.
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.
4.7 Effects on ability to drive and use machines
Drowsiness, nausea and dizziness can occur, which may impair the ability to perform hazardous tasks such as driving or operating machinery.
4.8 Undesirable effects
The majority of side effects are not serious and are expected consequences of the vasodilatory effects of nicardipine.
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 short-acting dihydropyridines in patients with ischaemic heart disease, exacerbation of angina pectoris may occur frequently
at the start of treatment with nicardipine. 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 (depression, lassitude, nervousness).
Skin
Itching, rash.
Hepatorenal Impairment, frequency of micturition.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema*
*cases have been also reported when used as tocolytic during pregnancy (see section 4.6)
Dyspnoea, gastro-intestinal upset and, rarely, depression impotence and thrombocytopenia have also been reported.
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 internet at www.mhra.gov.uk/yellowcard.
4.9 Overdose
Symptoms may include marked hypotension, bradycardia, palpitations, flushing, drowsiness, confusion and slurred speech. In laboratory animals overdosage also resulted in reversible hepatic function abnormalities, sporadic focal hepatic necrosis and progressive atrioventricular conduction block.
Use routine measures (e.g. gastric lavage), including monitoring of cardiac and respiratory functions. Position the patient to avoid cerebral anoxia. Frequent blood pressure determinations are essential. Vasopressors may be clinically indicated for patients exhibiting the effects of calcium entry blockade. Intravenous calcium gluconate may help reverse the effects of calcium entry blockade.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Nicardipine is a potent calcium antagonist. Pharmacological studies demonstrate its preferential high selectivity for the peripheral vasculature over the myocardium, which accounts for its minimal negative inotropic effects. Nicardipine produces smooth muscle relaxation and marked peripheral vasodilatation.
In humans nicardipine produces a significant decrease in systemic vascular resistance, the degree of vasodilatation being more predominant in hypertensive patients than in normotensive subjects. Haemodynamic studies in patients with coronary artery disease and normal left ventricular function have shown significant increases in cardiac index and coronary blood flow, with little if any increase in left ventricular end-diastolic pressure.
Electrophysiologic effects
Electrophysiological studies in man show that nicardipine does not depress sinus node function or atrial or ventricular conduction in patients with either normal or decreased electrical conduction systems. Refractory periods of the His-Purkinje system were actually shortened slightly by nicardipine and SA conduction time was improved.
5.2 Pharmacokinetic properties
Nicardipine is rapidly and completely absorbed with plasma levels detectable 20 minutes after an oral dose. Maximum plasma levels are observed within 30 minutes to 2 hours
(mean tmax = 1 hour). When given with a high fat meal peak plasma levels are reduced by 30%. Nicardipine is subject to saturable first-pass metabolism and the bioavailability is about 35% following a 30 mg oral dose at steady state.
The pharmacokinetics of nicardipine are non-linear due to saturable hepatic first-pass metabolism.
Steady-state plasma levels are achieved after about 3 days of dosing at 20 mg and 30 mg tds and remain relatively constant over 28 days of dosing at 30 mg tds. Considerable intersubject variability in plasma levels is observed. Following dosing to steady state using doses of 30 mg and 40 mg tds, the terminal plasma half-life of nicardipine averaged 8.6 hours. Nicardipine is highly protein bound (>99%) in human plasma over a wide concentration range.
Nicardipine does not induce its own metabolism and does not induce hepatic microsomal enzymes.
5.3 Preclinical safety data
Chronic toxicity studies in rats and dogs have shown that first toxic effects may be expected after oral dosages of 25 mg/kg, corresponding to 1750 mg per day in patients, far in excess of the maximum recommended therapeutic dose of 120 mg per day.
Embryo-foetal and perinatal toxicity tests in rats and mice revealed that doses at least 10-fold higher than the therapeutic dose are needed to induce embryotoxic effects. Abnormalities were observed during experiments with Xenopus embryos at relatively low nicardipine concentrations, indicating potential teratogenic effects.
Bacteriological tests have indicated that nicardipine does not demonstrate mutagenic potential. There is no information on the carcinogenic potential of nicardipine, and no evidence in the literature that there are any grounds for suspicion that would necessitate testing.
PHARMACEUTICAL PARTICULARS
6
6.1 List of excipients
Maize starch
Sodium starch glycollate Maize starch, pregelatinised Capsule:
Gelatin
Titanium dioxide (E171) Sunset yellow (E110) Erythrosine (E127)
Patent blue V (E131)
6.2 Incompatibilities
Not applicable.
6.3. Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original container.
6.5 Nature and contents of container
Al/PVC blister pack, (PE-HD) tablet container and closure. Pack sizes: 200 mg: 25 and 100
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements for disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Tillomed Laboarories Ltd
3 Howard Road
Eaton Socon
St. Neots
Cambs
PE19 3ET
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 11311/0102
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
3 November 2000
10 DATE OF REVISION OF THE TEXT
16/12/2013