Cardilate Mr 10mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Cardilate MR® 10mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient: nifedipine (INN) Ph Eur 10mg
3 PHARMACEUTICAL FORM
Modified Release Tablet for oral administration
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Cardilate MR® 10mg is indicated for the treatment of hypertension and for prophylaxis of chronic stable angina pectoris.
4.2 Posology and method of administration
Cardilate MR® 10mgis not recommended for treatment of children.
For adults and adolescents over 16 years:
Cardilate MR® 10mg is suitable for long-term treatment of hypertension and for prophylaxis of chronic stable angina pectoris. Dosage must be determined for each patient on the basis of disease severity and the patient's individual response.
The recommended starting dose of Cardilate MR® 10mgis 10mg every 12 hours swallowed with water, with subsequent titration of dosage according to response. The dose may be adjusted to 40mg every 12 hours.
Cardilate MR® 10mg/ 10mg tablets should be taken with a little water.
Tablets must be swallowed whole and not broken or chewed.
The pharmacokinetics of nifedipine are altered in the elderly, so that lower maintenance doses of nifedipine may be required compared to younger patients.
Nifedipine is metabolised primarily by the liver and therefore patients with liver dysfunction should be carefully monitored. Patients with renal impairment should not require adjustment of dosage.
Route of administration :
Oral.
Paediatric population
The safety and efficacy of nifedipine in children under the age 18 years have not been established.
Currently available data for the use of nifedipine in hypertension are described in section 5.1
4.3 Contraindications
Cardilate MR® 10mg should not be given to patients with known hypersensitivity to nifedipine, other tablet constituents, or other dihydropyridines, because of the theoretical risk of cross reactivity.
It is contra-indicated in women of child-bearing potential and those breast-feeding their babies.
Cardilate MR® 10mg is contra-indicated in patients with clinically significant aortic stenosis, unstable angina, porphyria, or those in cardiogenic shock. It should not be used during or within one month of a myocardial infarction.
Cardilate MR® 10mg tablets should not be used for the treatment of acute attacks of angina.
The safety of nifedipine in malignant hypertension has not been established.
Cardilate MR® 10mg tablets should not be used for secondary prevention of myocardial infarction.
Cardilate MR® 10mg tablets should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction.
4.4 Special warnings and precautions for use
Cardilate MR® 10mg should be administered to patients with low cardiac reserve or with severe hypotension with caution. Patients at risk of hypotensive crisis should begin any therapy under close medical supervision.
4.5 Interaction with other medicinal products and other forms of interaction
As with other dihydropyridines, nifedipine should not be taken with grapefruit juice because bioavailability is increased.
Cardilate MR® 10mg can be administered concomitantly with other antihypertensives including beta-receptor blockers. These may have additive antihypertensive effects and postural hypotension may therefore occur.
Cardilate MR® 10mg will not prevent the possibility that there might be a rebound effect when other antihypertensive treatment is stopped. Concomitant therapy with cimetidine may potentiate the anti hypertensive action of nifedipine. Nifedipine administration may suppress serum levels of quinidine
The simultaneous administration of nifedipine and digoxin may lead to reduced digoxin clearance, and hence an increase in the plasma digoxin. Digoxin levels should be monitored and if necessary, the digoxin dose reduced.
Cardilate MR® 10mg may modify insulin and glucose responses, requiring adjustment in therapy of treated diabetics.
Cardilate MR® 10mg tablets should not be administered concomitantly with rifampicin, since effective plasma levels of nifedipine may not be achieved owing to enzyme induction (see Contra-indications).
4.6 Pregnancy and lactation
Cardilate MR® 10mg is contra-indicated in pregnant women and women of childbearing potential because foetal risks, observed in animal experiments and during human use, far outweigh the potential benefits.
Nifedipine is secreted into breast milk, so Cardilate MR® 10mg should not be administered during lactation.
4.7 Effects on ability to drive and use machines
Infrequently, Cardilate MR® 10mg may cause headaches, dizziness, nausea and tiredness to such a degree that reaction time is affected. These effects can be aggravated by concurrent alcohol. If this occurs, the patient should not be allowed to drive or operate machines.
4.8 Undesirable effects
Cardilate MR® 10mg may cause headaches, facial reddening and dizziness and leg oedema. These effects are secondary to vasodilation. Less common side-effects include rash, nausea, lethargy and urinary frequency. Rarely, gingival hyperplasia may occur; this may resolve when treatment is discontinued. Chest pain due to myocardial ischaemia may occur 1-4 hours after ingestion of Cardilate MR® 10mg. A 'steal' effect has not been observed up to now with Cardilate MR® 10mg, but treatment should be discontinued in patients in which this does occur. Cases of hypersensitivity to nifedipine resulting in jaundice have been reported.
Exacerbation of angina pectoris may occur rarely at the start of treatment with sustained release formulations of nifedipine. The occurrence of myocardial infarction has been described, although it is not possible to distinguish such an event from the natural course of ischaemic heart disease.
4.9 Overdose
Toxic effects arise from the three main actions of nifedipine in overdose: dilatation of vascular smooth muscles (predominant effect); decreased myocardial contractility; and depression of AV nodal conduction. Hypotension and tachycardia of
bradycardia are the most likely manifestations of overdose. Other toxic effects include nausea, vomiting, drowsiness, dizziness, confusion, lethargy, flushing, coma and convulsions. Cardiac effects may include heart block, AV dissociation and asystole; metabolic disturbances include hyperglycaemia, acidosis, hypo - or hyperkalaemia and hypocalcaemia; pulmonary oedema has been reported.
Primary treatment involves removal of nifedipine by gastric lavage or ipecac and administration of activated charcoal (50g adults; 10-15g children). Cardilate MR® 10mg is a modified release product, therefore activated charcoal should be repeated at 4- hourly intervals (25g adults; 10g children). The patient should be closely monitored and treated according to predominating signs:
for hypotension: the feet should be raised and plasma expanders given. If this is not effective, 10% calcium gluconate or chloride can be given intravenously (calcium chloride should not be given to acidotic patients). If this fails, dopamine may be tried (large doses may be needed). Glucagon may also be of value;
for bradycardia: treatment with atropine, isoprenaline and cardiac pacing should be given as required.
The value of extracorporeal methods of removal of nifedipine have not been established.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Nifedipine inhibits the influx of calcium into myocardial cells, the smooth muscle cells of the coronary arteries and the peripheral capillaries. Nifedipine brings about a substantial improvement in the oxygen supply to the myocardium while reducing oxygen demand. It has been shown to exhibit anti-anginal properties. High blood pressure is normalised due to a reduction in the peripheral resistance (vasodilatation).
Paediatric population:
Limited information on comparison of nifedipine with other antihypertensives is available for both acute hypertension and long-term hypertension with different formulations in different dosages. Antihypertensive effects of nifedipine have been demonstrated but dose recommendations, long term safety and effect on cardiovascular outcome remain unestablished. Paediatric dosing forms are lacking.
5.2 Pharmacokinetic properties
Absorption: Nifedipine is absorbed rapidly and almost completely following oral administration. Nifedipine can be detected in plasma 30 - 60 minutes after administration of Cardilate MR® and reaches maximal concentration between 0.75 and 5 hours.
Distribution: Nifedipine is more than 90% serum protein bound. Animal studies with labelled nifedipine have shown that distribution of the fraction not protein bound is throughout all organs and tissues, with higher concentrations in myocardium than in skeletal muscle. Neither nifedipine nor its metabolites are stored selectively in any tissue.
Metabolism: Nifedipine is converted almost completely to inactive metabolites.
Elimination: 70 to 80% of administered nifedipine is excreted as metabolites by the kidneys with an elimination half-life of approximately 10 hours.
Elimination may be retarded by renal failure or insufficiency.
5.3 Preclinical safety data
None stated.
6.1 List of excipients
Tablet Core
Microcrystalline cellulose PhEur Carboxymethyl sodium starch BP Mannitol PhEur
Colloidal anhydrous silica PhEur Polyvidone PhEur Magnesium stearate PhEur Sodium lauryl sulphate PhEur
Tablet Coating
Methylhydroxypropyl cellulose PhEur Polyoxyethylene glycol 6000 PhEur Polyoxyethylene glycol 400 PhEur Red ferric oxide (El72) PF Titanium dioxide (E171) PhEur Talc PhEur Purified Water PhEur Alcohol (Industrial) PhEur
6.2 Incompatibilities
None known.
6.3 Shelf life
Three years.
6.4 Special precautions for storage
Cardilate MR® should be stored in the original pack below 25°C, in a dry place and protected from light.
Nifedipine is highly sensitive to light and is therefore protected both by materials in the tablet and in the packaging. Nonetheless tablets should not be exposed to direct sunlight and should only be removed from the blister pack when about to be taken.
6.5 Nature and contents of container
Thermoformed blister packs of PVC/red transparent PVDC/aluminium in boxes of 7, 14, 20, 21, 28, 30, 56, 60, 84, 90, 100, 112 and 120 tablets.
6.6 Special precautions for disposal
None.
7 MARKETING AUTHORISATION HOLDER
Norton Healthcare Ltd
T/A IVAX Pharmaceuticals UK
Ridings Point,
Whistler Drive,
Castleford,
West Yorkshire,
WF10 5HX
8 MARKETING AUTHORISATION NUMBER(S)
PL 00530/0517
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22/05/1996 / 10/09/2002
10 DATE OF REVISION OF THE TEXT
07/01/2013