Atenolol Tablets Atenolol Accord 25 mg tablets

Atenolol Tablets
Summary of Product Characteristics
1.
NAME OF THE MEDICINAL PRODUCT
Atenolol Accord 25 mg tablets
Atenolol Accord 50 mg tablets
Atenolol Accord 100 mg tablets
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Atenolol Accord 25 mg tablets
Each tablet contains 25 mg of atenolol
Atenolol Accord 50 mg tablets
Each tablet contains 50 mg of atenolol
Atenolol Accord 100 mg tablets
Each tablet contains 100 mg of atenolol
For the full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Tablets
Atenolol Accord 25 mg tablets
White, round, flat, bevelled tablets with the inscription 'AA' on one side and a scoreline
on the other.
The tablet can be divided into equal doses.
Atenolol Accord 50 mg tablets
White, round, flat, bevelled tablets with the inscription 'AB' on one side and a scoreline
on the other
The tablet can be divided into equal doses.
Atenolol Accord 100 mg tablets
White, round, flat, bevelled tablets with the inscription 'AC' on one side and a scoreline
on the other
The tablet can be divided into equal doses.
4.
CLINICAL PARTICULARS
4.1
Therapeutic indications
 Hypertension
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 Chronic stable angina pectoris
 Secondary prevention after acute myocardial infarction: early intervention within 12
hours.

Supraventricular arrhythmias:
- paroxysmal supraventricular tachycardia (in therapeutic or prophylactic treatment)
- atrial fibrillation and atrial flutter: in case of inadequate response to maximum
dosages of cardiac glycosides; in cases where cardiac glycosides may be contraindicated or may be associated with an unfavorable risk/benefit ratio.
 Ventricular arrhythmias:
- ventricular extrasystoles (prophylactic or therapeutic treatment), if the extrasystoles are the result of increased sympathetic activity
- ventricular tachycardias and ventricular fibrillation (prophylactic treatment), especially when the ventricular abnormality is the result of elevated sympathetic activity.
4.2
Posology and method of administration
Posology and method of administration
The dosage should be determined on an individual basis, especially based on the clinical
effect. It is recommended to start with the lowest possible dosage so that heart failure,
bradycardia and bronchial symptoms are noticed timely.
Hypertension: A starting dose of 50 mg is recommended. The usual maintenance dosage
in hypertension is one tablet (50-100 mg) daily. The maximum effect will be reached after 1-2 weeks. If further improvement of the blood pressure is desired, atenolol may be
combined with another anti-hypertensive e.g., a diuretic.
The 25 mg dose is only indicated in patients with severe renal insufficiency or for elderly
patients as initiation therapy if necessary.
Angina pectoris: 50-100 mg daily depending, on the clinical effect. Increasing the dose
above 100 mg daily does not generally lead to an increased antianginous effect. If desired the dosage of 100 mg daily can be divided in two dosages.
Arrhythmias: The regular oral maintenance dose is 50 to 100 mg atenolol daily.
Secondary prevention after myocardial infarction: Oral maintenance therapy until hospital discharge is 50 - 100 mg daily in 1-2 dosages in patients that are hemodynamically
stabilised.
Children:
There is no experience with use of atenolol in children. It is therefore not recommended
to use atenolol in children.
Elderly patients:
In elderly therapy should be started with a lower dosage. Dosage should be titrated according to clinical effect.
Renal impairment:
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Glomerular filtration rate
(ml/min/1.73 m2 body surface
> 35
15-35
< 15
Recommended atenolol dose
(mg/day)
No dose modification
25-50 (or 50-100 / 2 days)
25 – 50 / 2 days
In haemodialysis a 50 mg tablet is administered after each dialysis. The administration
should be done in hospital since sudden decrease of the arterial pressure may occur.
Hepatic impairment: No dose modifications necessary.
Atenolol should be swallowed with a sufficient amount of fluid (e.g. one glass of water)
before food intake.
It is not recommended that atenolol treatment is stopped abruptly since this might lead to
a worsening of hypertension, heart failure or ischaemic heart disease which could lead to
myocardial infarction. The dosage of atenolol should always be reduced gradually.
4.3
Contraindications
Contra-indications
 Cardiogenic shock
 Uncontrolled heart failure
 Sick sinus syndrome (including sino-atrial block)
 Second and third degree heart block
 Untreated phaeochromocytoma
 Metabolic acidosis
 Bradycardia (< 50 bpm before treatment initiation)
 Hypotension
 Hypersensitivity to the active substance atenolol or any of the excipients listed in section 6.1.
 Severe peripheral circulatory disturbances
 Floctafenine
 Severe asthma and severe chronic obstructive pulmonary disorders, such as airway
obstructions
 The intravenous application of calcium channel blockers (verapamil / diltiazem type)
is contraindicated in patients who use atenolol (except in intensive care unit)
4.4
Special warnings and precautions for use
Ischaemic heart diseases
Especially in patients with ischaemic heart disease, treatment should not be discontinued
suddenly. The dosage should gradually be reduced, i.e. over 1-2 weeks, if necessary at
the same time initiating replacement therapy, to prevent exacerbation of angina pectoris.
In addition, hypertension and arrhythmias may develop.
Furthermore there is a risk on myocardial infarction and sudden death.
Atenolol should not be used in patients with untreated congestive heart failure. This condition should first be stabilised.
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Surgery:
When it has been decided to interrupt a beta-blockade in preparation for surgery, therapy
should be discontinued for at least 24 hours. Continuation of beta-blockade reduces the
risk of arrhythmias during induction and intubation, however the risk of hypotension
may be increased as well.
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.
Peripheral circulatory disorders:
In patients with peripheral circulatory disorders (Raynauds’s disease or syndrome, intermittent claudication), atenolol should be used with great caution as aggravation of these
disorders may occur.
Severe peripheral circulatory disorders are a contra-indication (see contraindications)
Heart rate:
Atenolol may induce bradycardia. If the pulse rate decreases to less than 50-55 beats per
minute at rest and the patient experiences symptoms related to the bradycardia, the dosage should be reduced.
Airways:
In patients with chronic obstructive pulmonary disorders, airway obstructions may be
aggravated. Therefore, atenolol should only be used for these patients with the utmost
care.
Heart block:
Due to its negative effect on conduction time, atenolol should only be given with caution
to patients with first degree heart block.
Renal impairment:
In patients with renal impairment dosage should be adjusted to reduced glomerular filtration rate (see section 4.2. Posology)
Elderly:
The elderly should be treated with caution (see section 4.2. Posology).
Prinzmetal’s angina:
Atenolol may increase the number and the duration of anginal attacks in patients with
Prinzmetal’s angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction. For these patients atenolol should only be used with the utmost care.
Psoriasis:
Patients with anamnestically known psoriasis should take atenolol only after careful consideration.
Allergens:
Atenolol may increase both the sensitivity toward allergens and the seriousness of anaphylactic reactions. Atenolol may reduce the efficacy of epinephrine.
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Hypersensitivity:
Atenolol may cause a hypersensitivity reaction including angioedema and urticaria.
Diabetics
The symptoms of hypoglycaemia may be masked by atenolol, in particular tachycardia.
Insulin sensitivity may be reduced in patients treated with atenolol.
Thyrotoxicosis:
Beta-blockade may mask cardiovascular signs of thyrotoxicosis.
Treated pheochromocytoma:
Patients with pheochromocytoma (adrenal gland tumour; a pre-treatment with alphareceptor inhibitors is necessary)
4.5
Interactions with other medicinal products and other forms of interaction
Combinations contra-indicated:


Floctafenine:
Beta-adrenergic blocking agents may impede the compensatory cardiovascular reactions associated with hypotension or shock that may be induced by floctafenine.
Calcium antagonists: verapamil and to a lesser extent diltiazem:
negative influence on the contractility and AV-conduction.
Not recommended association:
 Digitalis glycosides:
association with atenolol may increase the AV-conduction time.
 Monoamineoxidase inhibitors (except MAO-B inhibitors)
 Clonidine:
Betablockers increase the risk of rebound hypertension.
 Sultopride:
Atenolol should not be concomitantly administered with sultopride since there is an
increased risk of ventricular arrhythmias, e.g. torsades de pointes.
Precautions for use:



Class I anti-arrhythmic drugs (e.g. disopyramide, quinidine) and amiodaron:
may have potentiating effect on atrial-conduction time and induce a negative inotropic effect.
Insulin and oral antidiabetic drugs:
may intensify the blood sugar lowering effect (especially non-selective betablockers)
Beta-adrenergic blockade may prevent the appearance of signs of hypoglycaemia
(tachycardia).
Anaesthetic drugs:
attenuation of the reflex tachycardia and increase the risk of hypotension.
Continuation of beta-blockades reduce the risk of arrhythmia during induction and
intubation. The anaesthesiologist should be informed when the patient is receiving a
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beta-blocking agent.
Anaesthetic agents causing myocardial depression, such as cyclopropane and trichlorethylene, lidocaine, procainamide and beta-adrenoceptor stimulants such as noradrenaline (norepinephrine) are best avoided.
 Baclofen:
Causes an increased antihypertensive activity.
 Contrast media, iodinated:
Atenolol may impede the compensatory cardiovascular reactions associated with hypotension or shock induced by iodated contrast products.
 Amiodaron:Combination with atenolol may result in additive depressant effects on
conduction and negative inotropic effects, especially in patients with underlying sinus
node dysfunction or atrioventricular node dysfunction.
Take into account:
 Calcium antagonists: dihydropyridine derivates such as nifedipine:
the risk of hypotension may be increased. In patients with latent cardiac insufficiency, treatment with atenolol may lead to cardiac failure.
 Prostaglandin synthetase inhibiting drugs:
(like NSAID’s) may decrease the hypotensive effects of atenolol.
 Sympathicomimetic agents:
(f.e. adrenaline) may counteract the effect of atenolol.
 Concomitant administration of tricyclic antidepressants, barbiturates and phenothiazines as well as other antihypertensive agents:
may increase the bloodpressure lowering effect.
Ampicillin:
May reduce the bioavailability of atenolol. Therefore the physician should watch for evidence of altered atenolol response especially when large doses of ampicillin are administered concomitantly
Antihypertensives, diuretics, vasodilatators, tricyclic antidepressants, barbiturate and
phenothiacine could increase the antihypertensive effect of atenolol.
Peripheral muscle relaxants (e.g. Suxamethonium halogenide, Tubocurarine): concomitant use of atenolol could increase and extent the relaxative effect of muscle relaxants.
4.6
Fertility, pregnancy and breastfeeding
Pregnancy and lactation
Pregnancy
Beta-blockers reduce placental perfusion, which may result in intrauterine foetal death,
immature and premature deliveries. In addition, adverse effects (especially hypoglycaemia and bradycardia) may occur in foetus and neonate. There is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period. Therefore the
neonate should be monitored carefully.
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Atenolol crosses the placenta. If atenolol is used regularly during pregnancy a medical
practitioner should be consulted.
Atenolol was used with good results, under careful surveillance, for hypertension of
pregnancy. There were no indications for foetal abnormalities, it should be mentioned
that atenolol was used only after the 20th week of pregnancy. Furthermore there are no
indications for adverse effects during childbirth or during the lactation period. Nevertheless a harmful effect on the foetus may not be excluded.
Breastfeeding
The concentration in mothers milk is three times higher than in blood. During lactation
only low levels of atenolol are found in the child. Nevertheless the occurrence of beta
blocking properties in the child can not be excluded in the long term. If possible, it is advised, to keep a six hour time interval between atenolol intake and breastfeeding. During
this interval the child may be bottle-fed.
When used during pregnancy and lactation the advantages and disadvantages should be
carefully weighed.
4.7
Effects on ability to drive and use machines
This medicinal product has minor influence on the ability to drive and use machines.
The individual response to react with the ability to drive or operate the machinery can be
affected due to occasional dizziness or fatigue.
4.8
Undesirable effects
The following terminologies have been used in order to classify the occurrence of undesirable effects
Very common:
Common:
Uncommon:
Rare:
Very rare:
ta)
≥1/10
≥1/100 and <1/10
≥1/1000 and <1/100
≥1/10 000 and <1/1000
<1/10 000, not known (cannot be estimated from the available da-
Blood and lymphatic system disorders
Rare: Thrombocytopenia, leukopenia
Endocrine disorders
Beta-blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia.
Psychiatric disorders
Uncommon: Sleep disturbances
Rare: Hallucinations, psychoses, confusion, depression, nightmares, anxiety
Nervous system disorders
Rare: Headaches, dizziness, paraesthesia of the extremities,
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Eye disorders
Rare: Impaired vision, visual disturbances, dry eyes
Cardiac disorders
Common: Bradycardia,
Rare: Slow AV-conduction or increase of an existing AV-block, aggravation of heart
failure
Vascular disorders
Common: Cold and cyanotic extremities
Rare: Hypotension (sometimes associated with syncope), Raynaud phenomenon, increase of an existing intermittent claudication.
Respiratory, thoracic and mediastinal disorders
Rare: Bronchospasm in patients with bronchial asthma or a history of asthmatic complaints.
Gastrointestinal disorders
Common: Gastro-intestinal problems, nausea, vomiting, diarrhoeaand constipation.
Rare: Dry mouth.
Skin and subcutaneous tissue disorders
Rare: Rash, alopecia, psoriasis like skin reactions, aggravation of psoriasis, purpura
Frequency not known: Hypersensitivity reactions, including angioedema and urticaria.
General disorders and administration site conditions
Common: Fatigue, sweating
Investigations
Very rare: An increase in Anti Nuclear Antibodies has been seen; its clinical relevance is
not clear.
Hepato-biliary disorders:
Uncommon: Elevations of transaminase levels.
Rare: Hepatic toxicity including intrahepatic cholestasis.
Reproductive system and breast disorders
Rare: Impotence
4.9
Overdose
Overdose
Symptoms of overdosage are:
Bradycardia, hypotension, bronchospasm and acute cardiac insufficiency.
After ingestion of an overdose or in case of hypersensitivity, the patient should be kept
under close supervision and be treated in an intensive-care ward. Absorption of atenolol
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still present in the gastro-intestinal tract can be prevented by gastric lavage, administration of activated charcoal and a laxative. Artificial respiration may be required. Bradycardia or extensive vagal reactions should be treated by administering atropine or methylatropine. Hypotension and shock should be treated with plasma/plasma substitutes and,
if necessary, catecholamines. The beta-blocking effect can be counteracted by slow intravenous administration of isoprenaline hydrochloride, starting with a dose of approximately 5 micrograms/minute, or dobutamine, starting with a dose of 2,5 microgram/minute, until required effect has been obtained. In refractory cases isoprenaline
can be combined with dopamine. If this does not produce the desired effect either, intravenous administration of 8-10 mg glucagon may be considered. If required the injection
should be repeated within one hour, to be followed - if required - by an i.v. infusion of
glucagon at an administration rate of 1-3 mg/hour. Administration of calcium ions, or the
use of a cardiac pacemaker may also be considered. As for the hydrophylic character, the
low plasma protein binding and the small distribution volume of atenolol hemodialysis
or hemoperfusion may be considered.
5.
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Pharmacodynamic properties
ATC code: C07AB03
Atenolol is a selective beta-1-adrenergic blocking agent, without intrinsic sympathomimetic of membrane stabilising characteristics. Clinical effects are reached fast and will
maintain at least 24 hours after the intake of atenolol. Therefore both Atenolol 50 and
Atenolol 100 can be taken once daily, which simplifies the therapy. Atenolol is a very
hydrophylic compound which passes the blood-brain barrier only in very limited
amounts. This causes a relatively low incidence of CNS-side effects. Atenolol mainly
acts on the beta receptors of the heart and can therefore, contrary to non-selective beta
adrenergic blocking agents, be administered, under carefull surveillance and check-up of
the lung function, to patients with chronic obstructive pulmonal diseases, who can not
bear a non-selective beta adrenergic blocking agent.
The beta-1-selectivity is reduced with increased dose. Beta-adrenergic blocking agents
have a negative inotropic and chronotropic effect and inhibit the effect of catecholamines
resulting in reduced heart rate and blood pressure.
5.2
Pharmacokinetic properties
The oral bioavailability is about 50 to 60%. The bioavailability is decreased by 20%
when taken with food. Peak plasma concentrations are found 2 -4 hours after repeated
oral administration. There is a linear relationship between dosage and plasma concentration. The inter-subject variability in AUC and Cmax is about 30-40%. The volume of
distribution is 50 to 75 L. The protein binding is less then 5%. Metabolism of atenolol is
minimal. Most of an absorbed dose (85-100%) is excreted unchanged via the urine. The
clearance is about 6 l/h and the half-life is about 6 to 9 hours. In elderly patients, clear-
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ance is decreased and elimination half-life increased. The clearance is correlated to renal
function and the elimination is prolonged in patients with renal impairment. Impaired
liver function does not influence the pharmacokinetics of atenolol.
5.3
Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of
safety, pharmacology, repeated dose toxicity, genotoxicity and carcinogenicity.
Reproduction studies show that atenolol has no teratogenic potential; however a study in
rats showed that dosages of 200 mg/kg/day on the 6th and 15th day of the pregnancy did
result in a decrease in number of fetuses per dam and an increased incidence of embryo
resorptions.
6.
PHARMACEUTICAL PROPERTIES
6.1
List of excipients
Heavy magnesium carbonate
Maize starch
Sodium lauryl sulphate
Gelatine
Magnesium stearate (E572)
Cellulose, microcrystalline
Talc
6.2
Incompatibilities
Not applicable
6.3
Shelf-life
3 years
6.4
Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5
Nature and contents of container
Atenolol Accord 25 mg tablets are packed in PVC/PVDC/aluminium blisters.
Pack sizes: 14, 20, 28, 30, or 90 tablets.
Atenolol Accord 50 mg tablets are packed in PVC/PVDC/aluminium blisters.
Pack sizes: 14, 20, 28, 30, 50, 90 or 100 tablets.
Atenolol Accord 100 mg tablets are packed in PVC/PVDC/aluminium blisters.
Pack sizes: 14, 20, 28, 30, 50 or 90 tablets.
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Atenolol Accord 25 mg tablets are available in an HDPE tablet container with a PP
screw cap.
Pack sizes: 100, 500, 1000, or 5000 tablets.
Atenolol Accord 50 mg and 100 mg tablets are available in an HDPE tablet container
with a PP screw cap.
Pack sizes: 500 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handlings
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.
7.
MARKETING AUTHORISATION HOLDER
Accord Healthcare Limited
Sage House, 319 Pinner Road, North Harrow, Middlesex
HA1 4HF, United Kingdom
8.
MARKETING AUTHORISATION NUMBER
To be completed nationally.
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
To be completed nationally.
10.
DATE OF REVISION OF THE TEXT
To be completed nationally.
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