INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo APO-ATENOLOL 50 mg tablet
APO-ATENOLOL 100 mg tablet

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

APO-ATENOLOL 50 mg tablet
APO-ATENOLOL 100 mg tablet

COMPOSITION:
Each tablet contains 50 or 100 mg of
Atenolol

PHARMACOLOGICAL CLASSIFICATION:
A 5.2 Medicines affecting Autonomic functions: Adrenolytics (Sympathicolytics)

PHARMACOLOGICAL ACTION:
Atenolol is a beta 1 selective beta-blocker without intrinsic sympathomimetic and membrane stabilising activity.
Absorption of atenolol following oral dosing is consistent but incomplete (approximately 40-50%) with peak plasma concentrations occurring 2-4 hours after dosing. There is no significant hepatic metabolism of atenolol and more than 90% of that absorbed reaches the systemic circulation unaltered. The plasma half-life is about 6 hours but this may rise in severe renal impairment since the kidney is the major route of elimination. Atenolol penetrates tissues poorly due to its low lipid solubility and its concentration in brain tissue is low. Plasma protein binding is low (approximately 3%).

INDICATIONS:
APO-ATENOLOL is indicated in patients with mild or moderate hypertension.
APO-ATENOLOL is indicated in the management of angina pectoris.

CONTRA-INDICATIONS:
APO-ATENOLOL should not be used in the following instances:
1. Hypersensitivity to any of the ingredients.
2. Patients with bronchospasm or asthma, or patients with a history of obstructive airways disease.
3. In the presence of second degree or third degree heart block.
4. In patients with cardiogenic shock.
5. After prolonged fasting.
6. In patients with metabolic acidoses (e.g. in diabetes).
7. Special care should be taken with patients whose cardiac reserve is poor. Atenolol should be avoided in cardiac failure, unless or until signs of failure are controlled with digitalis or diuretics.
8. Uncontrolled cardiac failure, excluding that due to hypertrophic obstructive cardiomyopathy.
9. Pregnancy: Atenolol crosses the placental barrier and appears in cord blood. Administration to pregnant women has been associated with intra-uterine growth retardation. Administration of atenolol to pregnant mothers shortly before giving birth, or during labour may result in the newborn infants being born hypotonic, collapsed and hypoglycaemic.
10. There is significant accumulation in breast milk. Breastfeeding patients must not take atenolol.
11. Atenolol is not recommended for the emergency treatment of hypertensive crises.

WARNINGS:
While taking atenolol, patients with a history of anaphylactic reactions to a variety of allergens, may have a more severe reaction on repeated challenge. Such patients may be unresponsive to the usual dose of adrenaline used to treat allergic reactions. Particular caution should be exercised with patients suffering from the following:
Bradycardia of less that 50 pulse beats a minute
Peripheral vascular disease
Raynaud's phenomenon
The normal dose should be reduced in elderly patients, or in patients suffering from renal dysfunction. Elderly patients may not respond as well to atenolol as younger patients.
In the perioperative period it is generally unwise to reduce the dosage to which the patient is accustomed, as there may be danger of aggravation of angina pectoris or of hypertension. A patient’s normal tachycardic response to hypovolemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard.

DOSAGE AND DIRECTIONS FOR USE:
Hypertension:
50-100 mg daily, given orally as a single dose. It is unlikely that additional benefit will be gained by increasing the dose.
Atenolol is compatible with diuretics and other hypotensive agents. In refractory cases a further reduction of blood pressure may be achieved by combining atenolol with other antihypertensive agents for example, co-administration of a diuretic.
Atenolol may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two medicines are co-administered, the atenolol should be withdrawn several days before discontinuing clonidine. If replacing clonidine by Atenolol therapy, the introduction of the latter should be delayed for several days after clonidine administration has stopped.
Angina Pectoris:
The usual dose is 100 mg daily given as a single or divided dose. Additional benefit is not obtained from higher doses.
Patients with Renal Impairment:
Since atenolol is eliminated predominantly via the kidneys, dosage should be adjusted in patients with severe renal impairment. Significant accumulation of atenolol occurs when creatinine clearance falls below 35 mL/min/1,73 m² (normal range is 100-150 mL/min/1,73 m²). The following maximum dosages are recommended for patients with renal impairment:

CREATININE
CLEARANCE
(mL/min/1,73 m²)
ATENOLOL
ELIMINATION
HALF-LIFE
MAXIMUM
DOSAGE
15 - 35 16 - 27 50 mg daily or 100 mg every two days
< 15 > 27 25 mg daily or 50 mg every other day or 100 mg once every four days
Patients on haemodialysis should be given 50 mg after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.
Children: There is no experience in children.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
SIDE-EFFECTS
The most serious side-effects include heart failure, heart block and bronchospasm. Other side-effects include fatigue and coldness of the extremities. Cardiovascular effects include bradycardia and hypotension. Congestive heart failure may be precipitated in patients with underlying cardiac disorders.
Pneumonitis and pleurisy have been reported. Central nervous system effects include depression, confusion and sleep disturbances.
Fatigue is a common side-effect. Paraesthesia, peripheral neuropathy and myopathies have been reported. Gastro-intestinal side-effects include nausea, vomiting, diarrhoea, constipation and abdominal cramping.
Skin rash, pruritus and reversible alopecia have been reported.
Ocular symptoms experienced include decreased tear production, blurred vision and soreness.
Haematological reactions include non-thrombocytopenic purpura, thrombocytopenia and less frequently agranulocytosis. Transient eosinophilia can occur.
Metabolic changes can affect glucose control and cholesterol concentrations.
Other reported side-effects include a lupus-like syndrome, male impotence, sclerosing peritonitis and retroperitoneal fibrosis.
Adverse reactions are more common in patients with renal decompensation.
PRECAUTIONS
Patients with phaeochromocytoma should not receive atenolol without concomitant alpha-adrenoreceptor blocking therapy.
Bronchoconstriction may occur in patients suffering from asthma, bronchitis and other chronic pulmonary diseases.
Abrupt discontinuation of therapy may cause exacerbation of angina pectoris in patients suffering from ischaemic heart disease. Discontinuation of therapy should be gradual and patients should be advised to limit the extent of their physical activity during the period that the medicine is discontinued.
Atenolol may mask the symptoms of hyperthyroidism and of hypoglycaemia. Atenolol may unmask myasthenia gravis.
Psoriasis may be aggravated.
One of the pharmacological actions of atenolol is to reduce the heart rate. Bradycardia (usually less than 50-55 beats /minute)indicates that the dosage should not be further increased.
INTERACTIONS
Anaesthetics: Care should be taken when anaesthetic agents are used with atenolol. The patient should be warned to inform the anaesthetist.
It can be dangerous to administer APO-ATENOLOL concomitantly with the following agents: hypoglycaemic agents, phenothiazines and Class 1 antiarrhythmic agents such as disopyramide. Such interactions can have life-threatening consequences.
It should be noted that digitalisation of patients receiving long term atenolol therapy may be necessary if congestive cardiac failure is likely to develop. This combination can be considered despite the potentiation of negative chronotropic effect of the two medicines. Careful control of dosages and of the individual patient’s response (and notably pulse rate) is essential in this situation.
Combined use of atenolol and calcium channel blockers with negative inotropic effects such as verapamil and diltiazem can lead to an exaggeration of these effects, particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities. Neither medicine should be administered intravenously within 48 hours of discontinuing the other.
Patients with phaeochromocytoma require treatment with an alpha-adrenergic blocker.
If atenolol and clonidine are given concurrently, the clonidine should not be discontinued until several days after the withdrawal of the atenolol as severe rebound hypertension may occur.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF IT'S TREATMENT
Overdosage may produce bradycardia and severe hypotension. Bronchospasm and heart failure may be produced in certain individuals.
Cases of mild overdose should be observed for at least four hours as apnoea and cardiovascular collapse may appear suddenly.
Gastric lavage should be performed if within four hours of suspected overdose. Repeated activated charcoal is necessary in severe overdoses.
Atropine may be used to treat bradycardia. If the response is inadequate, glucagon may be given intravenously. Alternatively, dobutamine or isoprenaline may be used for the management of hypotension. Large doses of isoprenaline may be required to counteract the beta-blockade. Transvenous cardiac pacing may be required for severe bradycardia. Bronchospasm should be treated with IV aminophylline or inhaled or IV beta-agonist, eg salbutamol.

IDENTIFICATION:
APO-ATENOLOL 50 mg is a round, white, biconvex, scored, compressed tablet, engraved "APO" over "A50" on one side.
APO-ATENOLOL 100 mg is a round, white, biconvex, scored, compressed tablet, engraved "APO" over "A100" on one side.

PRESENTATION:
Both strenghts of APO-ATENOLOL tablets, 50 & 100 mg, are available in white high density polyethylene bottles of 30, 100 and 500.

STORAGE INSTRUCTIONS:
APO-ATENOLOL tablets, 50 & 100 mg, should be protected from light and moisture while stored at room temperature below 25°C.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
50 mg : 30/5.2/0026
100 mg : 30/5.2/0035

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
APOTEX S.A.
PHARMACEUTICAL INNOVATION
Apotex S.A. (Pty) Ltd.
Cnr Fleming & Watt Streets
Meadowdale Ext. 1

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
22 September 1995

7550K-1

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