Informations for option: Coracten Xl 60mg, show other option

Select option:

1. Coracten Xl 60mg
2. Coracten Xl 60mg

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Coracten XL 60mg.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 60mg Nifedipine Ph.Eur in sustained release form.

For excipients, see 6.1

3 PHARMACEUTICAL FORM

Prolonged release capsule, hard.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Coracten XL capsules are indicated for the treatment of hypertension and the prophylaxis of chronic stable angina pectoris.

4.2    Posology and method of administration

The capsules are for oral administration and should be swallowed whole with a little fluid.

Dosage - Angina Pectoris and Hypertension

Adults only: Normally treatment is initiated with one 30mg Coracten XL capsule every 24 hours. Dosage may be titrated to a higher level as clinically warranted. The dose may be adjusted to 90mg every 24 hours.

Children: Coracten XL capsules are not recommended for use in children.

Elderly ^ 65 years): The pharmacokinetics of nifedipine are altered in the elderly so that lower maintenance doses of nifedipine may be required.

Hepatic impairment: As Coracten XL is a long acting formulation, it should not be administered to patients with hepatic impairment.

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

4.3 Contraindications

Coracten XL capsules are contraindicated in patients with known hypersensitivity to nifedipine or other dihydropyridines because of the theoretical risk of cross reactivity. They should also not be used in cases of known hypersensitivity to any of the excipients (see Section 6.1). They should not be used in nursing mothers and women who are or who may become pregnant (see section 4.6. Pregnancy and Lactation).

Coracten XL 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 XL 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 XL capsules in malignant hypertension has not been established.

Coracten XL capsules should not be used for secondary prevention of myocardial infarction.

Coracten XL capsules are contraindicated in patients with acute porphyria.

Coracten XL should not be used in patients with Kock pouch (ileostomy after proctocolectomy).

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

As Coracten XL is a long acting formulation, it should not be administered to patients with hepatic impairment.

4.4 Special warnings and precautions for use

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 do not attempt to drive or use machinery (see also section 4.8. Undesirable Effects).

Although a ‘steal’ effect has not been demonstrated, patients experiencing this effect should discontinue nifedipine therapy.

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.

Nifedipine may be used in combination with beta-blocking drugs and other antihypertensive agents, but the possibility of an additive effect resulting in postural hypotension should be borne in mind. Nifedipine will not prevent possible rebound effects after cessation of other anti-hypertensive therapy.

Nifedipine is metabolised via the cytochrome P450 3 A4 system. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass or the clearance of nifedipine.

Drugs, which are inhibitors on the cytochrome P450 3A4 system and therefore may lead to increased plasma concentrations of nifedipine are, e.g.:

•    macrolide antibiotics (e.g. erythromycin)

•    anti-HIV protease inhibitors (e.g. ritonavir)

•    azole antimycotics (e.g. ketoconazole)

•    the antidepressants nefazodone and fluoxetine

•    quinupristin/dalfopristin

•    valproic acid

•    cimetidine.

Upon co-administration with these drugs, the blood pressure should be monitored and if necessary, a reduction of the nifedipine dose should be considered.

Since this medicinal product contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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.

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 XL 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 and cyclosporin, macrolide antibiotics, gingko biloba and ginseng. Azole antifungals (e.g. ketoconazole) may increase serum concentrations of nifedipine.

Decreased plasma levels of nifedipine have been reported during concomitant use of antibacterials (specifically rifampicin), and probably also antiepileptics (such as phenytoin, carbamazepine and phenobarbitone) 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, non-depolarising muscle relaxants (e.g. tubocurarine) and possibly digoxin are increased when used in combination with nifedipine. Tacrolimus concentrations may be increased by nifedipine. Data recently published indicate that the dose of tacrolimus administered simultaneously with nifedipine may be reduced in individual cases. Upon co-administration of both drugs the tacrolimus plasma concentrations should be monitored and if necessary a reduction in the tacrolimus dose considered.

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.

Anti-protease inhibitors (e.g. ritonavir),Ritonavir fluoxetine, nefazodone, valproic acid and quinupristin/dalfopristin may result in increased plasma concentrations of nifedipine.

No interaction studies have been carried out between nifedipine and macrolide antibiotics. Certain macrolide antibiotics are known to inhibit the cytochrome P450 3A4 mediated metabolism of other drugs. Therefore the potential for an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded (see Section 4.4).

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

An increased rate of absorption of nifedipine from sustained release preparation may occur if given concurrently with cisapride. Simultaneous administration of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.

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

Nifedipine may increase the neuromuscular blocking effects of vecuronium.

4.6 Fertility, pregnancy and lactation

Pregnancy

Because animal studies show embryotoxicity and teratogenicity, nifedipine is contraindicated during pregnancy (see also section 4.3. Contra-indications). Embryotoxicity was noted at 6 to 20 times the maximum recommended dose for

nifedipine given to rats, mice and rabbits, and teratogenicity was noted in rabbits given 20 times the maximum recommended dose for nifedipine.

An increase in perinatal asphyxia, caesarean delivery as well as prematurity and intrauterine growth retardation has been reported, however it is unclear whether these reports are due to the underlying hypertension, its treatment or to a specific drug effect.

Lactation

Nifedipine is secreted in breast milk, therefore, Coracten XL capsules are not recommended during lactation.

Fertility

In single cases of in-vitro fertilization calcium-antagonists like nifedipine have been associated with reversible biochemical change in the spermatozoa’s head section that may result in impaired sperm function. Nifedipine should be considered as a possible cause if there is no other explanation for unsuccessful fathering.

4.7    Effects on ability to drive and use machines

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).

4.8    Undesirable effects

ADRs listed under “common” were observed with a frequency below 3% with the exception of oedema (9.9%) and headache (3.9%). Most side-effects are consequences of the vasodilatory effects of nifedipine.

The frequencies of ADRs reported with nifedipine containing products are summarised in the table below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as common (> 1/100 to < 1/10), uncommon (> 1/1,000 to < 1/100) and rare (> 1/10,000 to < 1/1,000). The ADRs identified only during the ongoing postmarketing surveillance and for which a frequency could not be estimated, are listed under “Not known”.

System Organ Class (MedDRA)	Common	Uncommon	Rare	Not known
Blood and lymphatic system disorders				Agranulocytosis Leukopenia
Immune system disorders		Allergic reaction Allergic oedema / angioedema (incl. larynx oedema 1)	Pruritus Urticaria Rash	Anaphylactic/ anaphylactoid reaction Systemic allergic reactions
Psychiatric disorders		Anxiety reactions Sleep disorders	Mood changes	Depression
Metabolism and nutrition disorders				Hyperglycaemia

System Organ Class (MedDRA)	Common	Uncommon	Rare	Not known
Nervous system disorders	Headache	Vertigo Migraine Dizziness Tremor	Par-/ Dysaesthesia	Hypoaesthesia Somnolence Lethargy Cerebral ischemia (due to excessive fall in blood pressure)
Eye disorders		Visual disturbances		Eye pain Transient blindness (due to excessive fall in blood pressure)
Cardiac disorders		Tachycardia Palpitations		Chest pain (Angina Pectoris) Myocardial infarction2 Myocardial ischemia (due to excessive fall in blood pressure)
Vascular disorders	Oedema (incl. peripheral oedema) Vasodilatation	Hypotension Syncope		Flushing
Respiratory, thoracic, and mediastinal disorders		Nosebleed Nasal congestion		Dyspnea
Gastrointestinal disorders	Constipation	Gastrointestinal and abdominal pain Nausea Dyspepsia Flatulence Dry mouth	Gingival hyperplasia	Vomiting Gastrooesophageal sphincter insufficiency Diarrhoea
Hepatobiliary disorders		Transient increase in liver enzymes		Jaundice Intra-hepatic cholestasis
Skin and subcutaneous tissue disorders		Erythema		Toxic Epidermal Necrolysis Photosensitivity allergic reaction Palpable purpura Telangiectasia Erythema multiforme Pemphigoid reaction Exfoliative dermatitis Purpura
Musculoskeletal and connective tissue disorders		Muscle cramps Joint swelling		Arthralgia Myalgia Worsening of

System Organ Class (MedDRA)	Common	Uncommon	Rare	Not known
				myasthenia gravis
Renal and urinary disorders		Polyuria Dysuria
Reproductive system and breast disorders		Erectile dysfunction		Gynaecomastia (long-term therapy)
General disorders and administration site conditions	Feeling unwell	Unspecific pain Chills		Fever

= may result in life-threatening outcome.

² = 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.

In dialysis patients with malignant hypertension and hypovolaemia a distinct fall in blood pressure can occur as a result of vasodilation.

Reporting of Suspected Adverse Reactions

Reporting suspected adverse after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Health care professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov .uk/yellowcard.

4.9 Overdose

Clinical effects

Reports of nifedipine overdosage are limited and symptoms are not necessarily dose-related. Severe hypotension due to vasodilation, and tachycardia and 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 and unconsciousness to the point of coma.

Treatment

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.

Haemodialysis serves no purpose, as nifedipine is not dialyzable, but as plasmapheresis is advisable (high plasma protein binding, relatively low volume of distribution).

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 5pg/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.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

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.

5.2    Pharmacokinetic properties

Coracten XL 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%).

5.3    Preclinical safety data

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.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Capsule contents:

Lactose monohydrate

Microcrystalline Cellulose

Hydroxylpropyl methylcellulose K100

Povidone K30

Magnesium Stearate

Hydroxypropylcellulose

Ammonio methacrylate copolymer type B

Polyethylene Glycol 6000

Dibutylphthalate

Titanium dioxide E171

Talc

Capsule shells (size 1):

Red iron oxide E172 Titanium dioxide E171 Gelatin

The printing ink is made of shellac, purified water, black iron oxide (E172) with 2-ethoxyethanol, soya lecithin, anitfoam and IMS or with ethyl alcohol, isopropyl alcohol, n-butyl alcohol, propylene glycol, ammonium hydroxide and potassium hydroxide.

6.2    Major incompatibilities

None known.

6.3    Shelf life

36 months.

6.4    Special precautions for storage