1. Name Of The Medicinal Product
SECTRAL CAPSULES 100mg
or
ACEBUTOLOL 100mg CAPSULES
2. Qualitative And Quantitative Composition
The active component of SECTRAL Capsules 100mg / ACEBUTOLOL 100mg CAPSULES is:
Acebutolol hydrochloride 111.0mg (equivalent to 100mg of base).
For a full list of excipients, see section 6.1
3. Pharmaceutical Form
Hard gelatin capsules, the bodies being opaque yellowish-buff and the caps opaque white in colour. Length approximately 17mm, diameter of body approximately 6mm. Both body and cap are printed in black:
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The capsules contain a white or almost white powder.
4. Clinical Particulars
4.1 Therapeutic Indications
SECTRAL capsules 100 mg / ACEBUTOLOL 100mg CAPSULES are indicated for the following:
The management of all grades of hypertension, angina pectoris and the control of tachyarrhythmias.
4.2 Posology And Method Of Administration
Hypertension: Initial dosage of 400mg orally once daily at breakfast or 200mg orally twice daily. If response is not adequate within two weeks, dosage may be increased up to 400mg orally twice daily; if the hypertension is still not adequately controlled consideration should be given to adding a second antihypertensive agent such as the calcium antagonist nifedipine or small doses of a thiazide diuretic.
Angina pectoris: Initial dosage of 400mg orally once daily at breakfast or 200mg twice daily. In severe forms up to 300mg three times daily may be required. Up to 1200mg daily has been used.
Cardiac Arrhythmias: When given orally, an initial dose of 200mg is recommended. The daily dose requirement for long term anti arrhythmic activity should lie between 400 and 1200mg daily. The dose can be gauged by response, and better control may be achieved by divided doses rather than single doses. It may take up to three hours for maximal anti-arrhythmic effect to become apparent.
Elderly: There are no specific dosage recommendations for the elderly with normal glomerular filtration rate. Dose reduction is necessary if moderate to severe renal impairment is present (see Section 4.4)
Children: Paediatric dose has not been established.
For all indications, it is advised that the lowest recommended dosage be used initially.
4.3 Contraindications
Cardiogenic shock is an absolute contraindication. Extreme caution is required in patients with blood pressures of the order of 100/60 mmHg or below. SECTRAL/ACEBUTOLOL is also contraindicated in patients with second and third degree heart block, sick sinus syndrome, marked bradycardia (< 45-50 bpm), uncontrolled heart failure, metabolic acidosis, severe .peripheral circulatory disorders, hypersensitivity to acebutolol, any of the excipients or to beta blockers, and untreated phaeochromocytoma.
4.4 Special Warnings And Precautions For Use
Renal impairment is not a contraindication to the use of SECTRAL/ACEBUTOLOL which has both renal and non-renal excretory pathways. Some caution should be exercised when administering high doses to patients with severe renal failure as accumulation could possibly occur in these circumstances.
The dosage frequency should not exceed once daily in patients with renal impairment. As a guide, the dosage should be reduced by 50% when glomerular filtration rates are between 25-50ml/min and by 75% when they are below 25ml/min (see Section 4.2).
Drug-induced bronchospasm is usually at least partially reversible by the use of a suitable agonist.
Although cardio-selective beta blockers may have less effect on lung function than non-selective beta blockers as with all beta blockers they should be avoided in patients with obstructive airways disease unless there are compelling clinical reasons for their use. Where such reasons exist, cardio-selective β-blockers should be used with the utmost care (from Section 4.3).
Beta-blockers may induce bradycardia. In such cases, the dosage should be reduced.
They may be used with care in patients with controlled heart failure (see Section 4.3).
Use with caution in patients with Prinzmetal's angina.
Beta blockers may aggravate peripheral circulatory disorders. They may mask signs of thyrotoxicosis and hypoglycaemia. They should only be used in patients with phaeochromocytoma with comcomitant alpha-adrenoceptor therapy
Patients with known psoriasis should take beta-blockers only after careful consideration.
Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.
Withdrawal of treatment by beta blockers should be achieved by gradual dosage reduction; this is especially important in patients with ischaemic heart disease
When it has been decided to interrupt beta-blockade prior to surgery, therapy should be discontinued for at least 24 hours. Continuation of therapy reduces the risk of arrhythmias but the risk of hypotension may be increased. If treatment is continued, caution should be observed with the use of certain anaesthetic drugs. The patient may be protected against vagal reactions by intravenous administration of atropine.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Sectral/Acebutolol should not be used with Verapamil or within several days of Verapamil therapy (and vice versa). Use with great care with any other calcium antagonists, particularly Diltiazem.
Class I anti-arrhythmic drugs (such as disopyramide) and amiodarone may increase atrial conduction time and induce negative inotropic effects when used concomitantly with beta-blockers.
In patients with labile and insulin-dependent diabetes, the dosage of the hypoglycaemic agent (ie insulin or oral diabetic drugs) may need to be reduced. However beta-blockers have also been known to blunt the effect of glibenclamide. Beta-adrenergic blockade may also prevent the appearance of signs of hypoglycaemia (tachycardia, see Section 4.4).
Cross reactions due to displacement of other drugs from plasma protein binding sites are unlikely due to the low degree of plasma protein binding exhibited by acebutolol and diacetolol.
If a beta-blocker is used concurrently with clonidine the latter should not be withdrawn until several days after the former is discontinued.
Acebutolol may antagonize the effect of sympathomimetic and xanthine bronchodilators.
Concurrent use of digoxin and beta blockers may occasionally induce serious bradycardia. The anti-hypertensive effects of beta blockers may be attenuated by non-steroidal anti-inflammatory agents.
Concomitant administration of tricyclic antidepressants, barbiturates and phenothiazines as well as other anti-hypertensive agent- may increase the blood pressure lowering effect of beta-blockers.
There is a theoretical risk that concurrent administration of monoamine oxidase inhibitors and high doses of beta-blockers, even if they are cardio-selective can produce hypertension.
SECTRAL/ACEBUTOLOL therapy should be brought to the attention of the anaesthetist prior to general anaesthesia (see Section 4.4). If treatment is continued, special care should be taken when using anaesthetic agents causing myocardial depression such as ether, cyclopropane and trichlorethylene.
4.6 Pregnancy And Lactation
Pregnancy: SECTRAL/ACEBUTOLOL should not be administered to female patients during the first trimester of pregnancy unless the physician considers it essential. In such cases the lowest possible dose should be used.
Beta blockers administered in late pregnancy may give rise to bradycardia, hypoglycaemia and cardiac or pulmonary complications in the foetus/neonate.
Beta-blockers can reduce placental perfusion, which may result in intrauterine foetal death, immature and premature deliveries
Animal studies have shown no teratogenic hazard.
Lactation: Acebutolol and its active metabolite are excreted in breast milk and the half life of acebutolol in the neonate is double that in adults. The risks of hypoglycaemia and bradycardia occurring in the nursing infant have not been evaluated. Therefore, breast-feeding is not recommended during treatment.
4.7 Effects On Ability To Drive And Use Machines
As with all beta-blockers, dizziness or fatigue may occur occasionally. This should be taken into account when driving or operating machinery.
4.8 Undesirable Effects
SECTRAL/ACEBUTOLOL possesses antihypertensive effects but these are unlikely to be noted in normotensive subjects. The side-effects common to beta-blockade include: bradycardia, heart failure, a slowing of AV conduction or increase of an existing AV block, hypotension, gastrointestinal effects (such as nausea, vomiting and diarrhoea), cold and cyanotic extremities, paraesthesia, Raynaud's syndrome, intermittent claudication, confusion, dizziness, impaired vision, headaches, shortness of breath, nightmares, hallucinations, psychoses and depression, loss of libido and lethargy. The low lipid solubility and lack of accumulation in CNS tissues of acebutolol and its active metabolite reduce the likelihood of sleep disturbances, depression or other central effects and such occurrences are rare.
Pulmonary infiltration and pneumonitis appear to be rare but potentially serious complications of beta-blockade therapy. Cases of pneumonitis have been reported with acebutolol.
There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenoceptor blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when treatment was withdrawn. Discontinuation of the drug should be considered in such cases.
Cessation of therapy with a beta-blocker should be gradual. (see Section 4.4)
Although some patients have developed anti-nuclear factor titres, the incidence of associated clinical symptoms is rare and when present, these clear promptly on discontinuation of treatment. Rare cases of a Lupus-like syndrome have been reported.
Bronchospasm has occurred rarely during treatment with acebutolol.
4.9 Overdose
In the event of excessive bradycardia or hypotension, 1mg atropine sulphate administered intravenously should be given without delay. If this is insufficient it should be followed by a slow intravenous injection of isoprenaline (5mcg per minute) with constant monitoring until a response occurs. In severe cases of self-poisoning with circulatory collapse unresponsive to atropine and catecholamines the intravenous injection of glucagon 10-20mg may produce a dramatic improvement. Cardiac pacing may be employed if bradycardia becomes severe.
Judicious use of vasopressors, diazepam, phenytoin, lidocaine, digoxin and bronchodilators should be considered depending on the presentation of the patient. Acebutolol can be removed from blood by haemodialysis. Other symptoms and signs of overdosage include cardiogenic shock, AV block, conduction defects, pulmonary oedema, depressed level of consciousness, bronchospasm, hypoglycaemia and rarely hyperkalaemia.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Mode of action: SECTRAL/ACEBUTOLOL is a beta adrenoceptor antagonist which is cardioselective, i.e. acts preferentially on beta-1 adrenergic receptors in the heart. Its principal effects are to reduce heart rate especially on exercise and to lower blood pressure in hypertensive subjects. SECTRAL/ACEBUTOLOL and its equally active metabolite, diacetolol have anti-arrhythmic activity, the combined plasma half-life of the active drug and metabolite being 7-10 hours. Both have partial agonist activity (PAA) also known as intrinsic sympathomimetic activity (ISA). This property ensures that some degree of stimulation of beta receptors is maintained. Under conditions of rest, this tends to balance the negative chronotropic and negative inotropic effects. SECTRAL/ACEBUTOLOL blocks the effects of excessive catecholamine stimulation resulting from stress.
5.2 Pharmacokinetic Properties
After oral administration, acebutolol is rapidly and almost completely absorbed. Absorption appears to be unaffected by the presence of food in the gut. There is rapid formation of a major equiactive metabolite, diacetolol, which possesses a similar pharmacological profile to acebutolol. Peak plasma concentrations of active material (i.e. acebutolol plus diacetolol) are achieved within 2-4 hours and the terminal plasma elimination half-life is around 8-10 hours. Because of biliary excretion and direct transfer across the gut wall from the systemic circulation to the gut lumen, more than 50% of an oral dose of SECTRAL/ACEBUTOLOL is recovered in the faeces with acebutolol and diacetolol in equal proportions; the rest of the dose is recovered in the urine, mainly as diacetolol. Both acebutolol and diacetolol are hydrophilic and exhibit poor penetration of the CNS.
5.3 Preclinical Safety Data
No particulars.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Starch Potato
Silica colloidal anhydrous (E551)
Magnesium Stearate (E572)
Capsule Shell
Body:
Yellow iron oxide (E172)
Titanium dioxide (E171)
Gelatin
Cap:
Titanium dioxide (E171)
Gelatin
Ink
Opacode S-1-8100 Black containing
shellac
Iron oxide (E172)
Lecithin
Antifoam DC 1501
6.2 Incompatibilities
Not applicable
6.3 Shelf Life
The shelf-life of SECTRAL Capsules 100mg / ACEBUTOLOL 100mg CAPSULES is 60 months.
6.4 Special Precautions For Storage
Store in a dry place below 25°C. Protect from light
6.5 Nature And Contents Of Container
Aluminium foil/UPVC blister strip packs of 84 tablets.
6.6 Special Precautions For Disposal And Other Handling
None
7. Marketing Authorisation Holder
Aventis Pharma Ltd
50 Kings Hill Avenue
Kings Hill
West Malling
Kent
ME19 4AH
United Kingdom
Trading as:-
Sanofi-aventis
One Onslow Street
Guildford
Surrey, GU1 4YS, UK
8. Marketing Authorisation Number(S)
PL 04425/0262
9. Date Of First Authorisation/Renewal Of The Authorisation
13th July 2001
10. Date Of Revision Of The Text
November 2006
LEGAL CLASSIFICATION
POM
