Coracten SR Capsules 10mg

BIDNIF 10

Coracten SR Capsules 20mg

BIDNIF 20

Each capsule contains 10mg Nifedipine USP in sustained release form.

Each capsule contains 20mg Nifedipine USP in sustained release form.

For excipients, see 6.1

Modified-release capsule, hard

10 mg - Sustained release capsules with opaque grey body and opaque brownish-pink cap, overprinted in white with 'Coracten' on the body and '10mg' on the cap, and filled with yellow pellets.

20 mg - Sustained release capsules with opaque brownish-pink body and opaque reddish-brown cap, overprinted in white with 'Coracten' on the body and '20mg' on the cap, and filled with yellow pellets.

Coracten SR Capsules are indicated for the prophylaxis of chronic stable angina pectoris and the treatment of hypertension.

They are also indicated for the treatment of Prinzmetal (variant) angina when diagnosed by a cardiologist.

Adults only: The recommended starting dose of Coracten SR Capsules is 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.

Children: Coracten SR Capsules are not recommended for use in children.

Elderly: The pharmacokinetics of nifedipine are altered in the elderly so that lower maintenance doses of nifedipine may be required compared to younger patients.

Hepatic impairment: Caution should be exercised in treating patients with hepatic impairment. In these patients the use of one 10mg Coracten SR Capsule every 12 hours, together with careful monitoring, is suggested when commencing therapy.

Renal impairment: Dosage adjustments are not usually required in patients with renal impairment.

Coracten SR Capsules are contra-indicated in patients with known hypersensitivity to nifedipine or other dihydropyridines because of the theoretical risk of cross reactivity. They should not be used in women who are or who may become pregnant (see section 4.6. Pregnancy and Lactation).

Coracten SR Capsules should not be used in clinically significant aortic stenosis, unstable angina, or during or within one month of a myocardial infarction. They should not be used in patients in cardiogenic shock.

Coracten SR Capsules should not be used for the treatment of acute attacks of angina, or in patients who have had ischaemic pain following its administration previously.

The safety of Coracten SR Capsules in malignant hypertension has not been established.

Coracten SR Capsules should not be used for secondary prevention of myocardial infarction.

Coracten SR Capsules are contra-indicated in patients with acute porphyria.

Coracten SR Capsules should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction.

The dose of nifedipine should be reduced in patients with hepatic impairment (see section 4.2. Posology and Method of Administration). Nifedipine should be used with caution in patients who are hypotensive; in patients with poor cardiac reserve; in patients with heart failure or significantly impaired left ventricular function as their condition may deteriorate; in diabetic patients as they may require adjustment of their diabetic therapy; and in dialysis patients with malignant hypertension and irreversible renal failure with hypovolaemia, since a significant drop in blood pressure may occur due to the vasodilator effects of nifedipine.

Excessive falls in blood pressure may result in transient blindness. If affected the patient should not attempt to drive or use machinery (see section 4.8. Undesirable Effects).

Since nifedipine has no beta-blocking activity, it gives no protection against the dangers of abrupt withdrawal of beta-blocking drugs. Withdrawal of any previously prescribed beta-blockers should be gradual, preferably over 8 to 10 days.

The dose of nifedipine should be reduced in patients with hepatic impairment (see section 4.2.Posology and Method of Administration).

Nifedipine may be used in combination with beta-blockers and other antihypertensive agents, but the possibility of an additive effect resulting in postural hypotension and/or cardiac failure must be borne in mind.

As with other dihydropyridines, nifedipine should not be taken with grapefruit juice because bioavailability is increased.

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.

Nifedipine may increase the spectrophotometric values of urinary vanillylmandelic acid falsely. However, HPLC measurements are unaffected.

Coracten SR Capsules should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction (see section 4.3. Contra-indications).

Increased plasma levels of nifedipine have been reported during concomitant use of H₂-receptor antagonists (specifically cimetidine), other calcium channel blockers (specifically diltiazem), alcohol, cyclosporin, macrolide antibiotics, gingko biloba and ginseng. Azole antifungals may increase serum concentrations of nifedipine.

Plasma levels of nifedipine are possibly decreased by the concomitant use of antiepileptics and St John's Wort.

When used in combination with nifedipine, plasma concentrations of quinidine have been shown to be suppressed regardless of quinidine dosage. The plasma concentrations of phenytoin, theophylline and non-depolarising muscle relaxants (e.g. tubocurarine) are increased when used in combination with nifedipine. Tacrolimus concentrations may be increased by nifedipine.

Enhanced hypotensive effect of nifedipine may occur with: aldesleukin, alprostadil, anaesthetics, antipsychotics, diuretics, phenothiazides, prazosin and intravenous ionic X-ray contrast medium. Profound hypotension has been reported with nifedipine and intravenous magnesium sulphate in the treatment of pre-eclampsia.

Ritonavir and quinupristin/dalfopristin may result in increased plasma concentrations of nifedipine.

Effective plasma levels of nifedipine may not be achieved due to enzyme induction with concurrent administration of erythromycin carbamazepine and phenobarbitone.

There is an increased risk of excessive hypotension, bradycardia and heart failure with β-blockers.

An increased rate of absorption of nifedipine from sustained release preparation may occur if given concurrently with cisapride.

Nifedipine may result in increased levels of mizolastine due to inhibition of cytochrome CYP3A4.

Nifedipine may increase the neuromuscular blocking effects of vecuronium.

Pregnancy

Because animal studies show embryotoxicity and teratogenicity, Coracten SR Capsules are contra-indicated during pregnancy (see also section 4.3. Contra-indications). Embryotoxicity was noted at 6 to 20 times the maximum recommended dose for Coracten SR Capsules given to rats, mice and rabbits, and teratogenicity was noted in rabbits given 20 times the maximum recommended dose for Coracten SR Capsules.

Lactation

Nifedipine is excreted in breast milk, therefore Coracten SR Capsules are not recommended during lactation.

Dizziness and lethargy are potential undesirable effects. If affected do not attempt to drive or use machinery (see also section 4.8. Undesirable Effects).

Excessive falls in blood pressure may result in transient blindness. If affected do not attempt to drive or use machinery (see also section 4.8. Undesirable Effects).

Most side-effects are consequences of the vasodilatory effects of nifedipine.

Side-effects are generally transient and mild, and usually occur at the start of treatment only. They include headache, flushing and, usually at higher dosages, nausea, dyspepsia, heartburn, constipation, diarrhoea, dizziness, lethargy, skin reactions (such as rash, pruritus and urticaria), paraesthesia, hypotension, palpitation, tachycardia, dependent oedema, increased frequency of micturition, eye pain, depression, fever, gingival hyperplasia, telangiectasia and erythema multiforme

Other less frequently reported side effects include myalgia, tremor, pemphigoid reaction and visual disturbances. Impotence may occur rarely. Mood changes may occur rarely.

Excessive falls in blood pressure may result in cerebral or myocardial ischaemia or transient blindness.

As with other sustained release dihydropyridines, 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.

lschaemic pain has been reported in a small proportion of patients following the introduction of nifedipine therapy. Although a 'steal' effect has not been demonstrated, patients experiencing this effect should discontinue nifedipine therapy.

There are reports in older men on long-term therapy of gynaecomastia, which usually regresses upon withdrawal of therapy.

Side-effects which may occur in isolated cases are photosensitivity, exfoliative dermatitis, systemic allergic reactions, purpura and a worsening of myasthenia gravis. Usually, these regress after discontinuation of the drug.

Rare cases of hypersensitivity-type jaundice have been reported. In addition, disturbances of liver function such as intra-hepatic cholestasis may occur. These regress after discontinuation of therapy.

Human experience:

Reports of nifedipine overdosage are limited and symptoms are not necessarily dose-related. Severe hypotension due to vasodilation, and tachycardia or bradycardia are the most likely manifestations of overdose.

Metabolic disturbances include hyperglycaemia, metabolic acidosis and hypo- or hyperkalaemia.

Cardiac effects may include heart block, AV dissociation and asystole, and cardiogenic shock with pulmonary oedema.

Other toxic effects include nausea, vomiting, drowsiness, dizziness, confusion, lethargy, flushing, hypoxia, unconsciousness and coma.

Management of overdose in man:

As far as treatment is concerned, elimination of nifedipine and the restoration of stable cardiovascular conditions have priority.

After oral ingestion, gastric lavage is indicated, if necessary in combination with irrigation of the small intestine. Ipecacuanha should be given to children.

Elimination must be as complete as possible, including the small intestine, to prevent the otherwise inevitable subsequent absorption of the active substance.

Activated charcoal should be given in 4-hourly doses of 25g for adults, 10g for children.

Blood pressure, ECG, central arterial pressure, pulmonary wedge pressure, urea and electrolytes should be monitored.

Hypotension as a result of cardiogenic shock and arterial vasodilation should be treated with elevation of the feet and plasma expanders. If these measures are ineffective, hypotension may be treated with 10% calcium gluconate 10-20 ml intravenously over 5-10 minutes. If the effects are inadequate, the treatment can be continued, with ECG monitoring. In addition, beta-sympathomimetics may be given, e.g. isoprenaline 0.2 mg slowly i.v. or as a continuous infusion of 5µg/min. If an insufficient increase in blood pressure is achieved with calcium and isoprenaline, vasoconstricting sympathomimetics such as dopamine or noradrenaline should be administered. The dosage of these drugs should be determined by the patient's response.

Bradycardia may be treated with atropine, beta-sympathomimetics or a temporary cardiac pacemaker, as required.

Additional fluids should be administered with caution to avoid cardiac overload.

ATC Code: C08C A05

Nifedipine is a potent calcium-channel blocker which, by dilating peripheral arterial smooth muscle, decreases cardiac work and myocardial oxygen requirement. It also dilates coronary arteries, thereby improving myocardial perfusion and reducing coronary artery spasm. In hypertension, it reduces blood pressure but has little or no effect in normotensive subjects. It has no therapeutic antiarrhythmic effect.

Coracten SR Capsules are a sustained release formulation of nifedipine designed to provide less fluctuation and more prolonged nifedipine blood concentrations than standard immediate release preparations.

Nifedipine is highly protein bound. It undergoes hepatic oxidation to inactive metabolites which are excreted in the urine (80%) and faeces (20%).

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.

Capsule contents:

Sucrose Ph.Eur., Maize Starch Ph.Eur., Lactose Ph.Eur., Povidone K30 Ph.Eur., Methacrylic acid copolymer type A (Eudragit L100) NF, Talc Ph.Eur., Purified Water Ph.Eur.

Capsule shells 10 mg:

Gelatin , Red iron oxide (E172), Yellow iron oxide (E172), Black iron oxide (E172), Titanium dioxide (E171).

Capsule shells 20 mg:

Gelatin , Red iron oxide (E172), Yellow iron oxide (E172), Titanium dioxide (E171).

None known.

36 months.

Store in original pack at a temperature not exceeding 30°C and protect from light.

Coracten SR Capsules are presented in blister strips packed in cartons containing 60 capsules. The blister strips are formed from PVC with a coating of PVdC backed with aluminium foil.

(Cartons of 10, 15, 30, 56, 100, 150, 250, 500 and 600 capsules are licenced but not marketed.)

None.

UCB Pharma Limited

208 Bath Road

Slough

Berkshire

SL1 3WE

UK

10 mg - PL 00039/0365

20 mg - PL 00039/0367

31 July 1991

April 2009