atenolol 25 mg / 5 ml oral solution. (atenolol) pl 13931 ... · atenolol 25 mg / 5 ml oral...

ATENOLOL 25 MG / 5 ML ORAL SOLUTION.

(Atenolol)

PL 13931/0060

UKPAR

TABLE OF CONTENTS Lay Summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

1

Steps taken after authorisation – summary

Page 12

Summary of Product Characteristics Page 13

Product Information Leaflet

Page 20

Labelling Page 22

MHRA PAR – Atenolol 25 mg / 5 ml oral Solution (PL 13931/0060) 1 -


PL 13931/0060

LAY SUMMARY The MHRA granted Chanelle Medical a Marketing Authorisation (licence) for the medicinal product Atenolol 25 mg / 5 ml Oral Solution on 08 December 2011. This product is a prescription-only medicine (POM). Atenolol 25 mg / 5 ml Oral Solution contains the active ingredient atenolol which belongs to a group of medicines called beta-blockers. Atenolol is used to:

• treat high blood pressure (hypertension) and some arrhythmias (irregular heart beats)

• help treat angina (chest pain) • protect the heart after a heart attack

No new or unexpected safety concerns arose from this application and it was therefore judged that the benefits of taking Atenolol 25 mg / 5 ml Oral Solution outweigh the risks and a Marketing Authorisation was granted.



PL 13931/0060

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS Introduction

Page 4

Pharmaceutical assessment

Page 5

Non-clinical assessment

Page 8

Clinical assessment

Page 9

Overall conclusions and risk benefit assessment Page 10


INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the MHRA granted Chanelle Medical, a Marketing Authorisation for the medicinal product Atenolol 25 mg / 5 ml Oral Solution (PL 13931/0060) on 08 December 2011. This product is a prescription-only medicine (POM). Atenolol 25 mg / 5 ml Oral Solution is used for the following indications:

• management of hypertension • management of angina • management of cardiac arrhythmias • myocardial infarction. Early intervention in the acute phase.

This is an abridged application submitted under Article 10(1) of Directive 2001/83/EC as amended, cross-referring to Tenormin 25 mg/5 ml Syrup (PL 17901/0051, AstraZeneca Limited, UK) which was originally licensed as PL 00029/0195 (Imperial Chemical Industries Plc, UK), prior to 01 October 1993. Atenolol is a beta-blocker which is beta1-selective, (i.e. acts preferentially on beta1-adrenergic receptors in the heart). Selectivity decreases with increasing dose. Atenolol is without intrinsic sympathomimetic and membrane-stabilising activities and as with other beta-blockers, has negative inotropic effects (and is therefore contraindicated in uncontrolled heart failure). As with other beta-blockers, the mode of action of atenolol in the treatment of hypertension is unclear. It is probably the action of atenolol in reducing cardiac rate and contractility which makes it effective in eliminating or reducing the symptoms of patients with angina. No new non-clinical data have been submitted, which is acceptable given that the application was based on being a generic medicinal product of an originator product that has been in clinical use for over 10 years. No new clinical studies were performed, which is acceptable given that the application was based on being a generic medicinal product of an originator product that has been in clinical use for over 10 years. No new or unexpected safety concerns were raised during the assessment of this application and it was therefore judged that the benefits of taking Atenolol 25 mg / 5 ml Oral Solution outweigh the risks and a Marketing Authorisation was granted.


PHARMACEUTICAL ASSESSMENT

ACTIVE SUBSTANCE INN: Atenolol. Chemical name: 2-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide Structure:

Molecular formula: C14H22N2O3Molecular weight: 266.3 Appearance: Atenolol is a white or almost white powder, sparingly soluble in

water, soluble in ethanol, slightly soluble in methylene chloride and practically insoluble in ether.

Atenolol is the subject of a European Pharmacopoeia monograph. All aspects of the manufacture and control of the active substance atenolol are covered by a European Directorate for the Quality of Medicines (EDQM) Certificate of Suitability. MEDICINAL PRODUCT Other ingredients Other ingredients consist of the pharmaceutical excipients, citric acid monohydrate, Lemon and lime flavour (containing ethanol), methyl hydroxybenzoate, propyl hydroxybenzoate, purified water, saccharin sodium, sodium citrate, sorbitol solution and mono propylene glycol. Appropriate justification for the inclusion of each excipient has been provided. All of the excipients comply with their respective European Pharmacopoeia monograph with the exception of Lemon and lime flavour which is controlled to suitable in-house specifications and is in compliance with current EEC directives concerning the use of colouring agents. Satisfactory Certificates of Analysis have been provided for all excipients. No genetically modified organisms (GMO) have been used in the preparation of this product. Pharmaceutical development The aim of the development programme was to formulate a safe, efficacious, stable oral solution that could be considered a generic medicinal product of Tenormin 25 mg/5 ml Syrup (AstraZeneca Limited, UK). Suitable pharmaceutical development data have been provided for this application. Comparable impurity profiles have been provided for the proposed and originator products.


Manufacture A description and flow-chart of the manufacturing method has been provided. Satisfactory batch formulae have been provided for the manufacture of the product, along with an appropriate account of the manufacturing process. The manufacturing process has been validated and has shown satisfactory results. In addition, the manufacturing authorisation holder has also committed to perform process validation on the first three commercial scale batches. Finished product specification The finished product specifications are satisfactory. Test methods have been described and have been adequately validated, as appropriate. Batch data have been provided and comply with the release specification. Certificates of Analysis have been provided for any working standards used. Container Closure System The finished product is packaged in amber polyethylene terephthalate (PET) bottles with tamper evident high density polyethylene (HDPE) cap with low density polyethylene (LDPE) plug containing 300 ml of oral solution. Satisfactory specifications and certificates of analysis have been provided for all packaging components. All primary packaging complies with the current European regulations concerning materials in contact with food. Stability Stability studies were performed in accordance with current guidelines on batches of finished product packed in the packaging proposed for marketing. The data from these studies support a shelf-life of 3 years for the unopened bottle which decreases to 3 months once opened with the storage conditions ‘Store below 25°C. Keep the bottle upright. Store in the original container.’ Bioequivalence/Bioavailability A bioequivalence study is not required to support an application of this type as per European guidance. Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labelling The SmPC, PIL and labelling are satisfactory. A package leaflet has been submitted to the MHRA along with results of consultations with target patient groups ("user testing"), in accordance with Article 59 of Council Directive 2001/83/EC, as amended. The results indicate that the package leaflet is well-structured and organised, easy to understand and written in a comprehensive manner. The test shows that the patients/users are able to act upon the information that it contains.


MAA (Marketing Authorisation Application) Form The MAA form is satisfactory. Expert Report The quality overall summary is written by an appropriately qualified person and is a suitable summary of the pharmaceutical aspects of the dossier. Conclusion It is recommended that a marketing authorisation is granted for this application.


NON-CLINICAL ASSESSMENT PHARMACODYNAMICS, PHARMACOKINETICS AND TOXICOLOGY No new non-clinical data were submitted, which is acceptable given that the proposed product is a generic medicinal product of an originator product that has been licensed for over 10 years. NON-CLINICAL EXPERT REPORT The non-clinical overview has been written by an appropriately qualified person and is a suitable summary of the non-clinical aspects of the dossier. ENVIRONMENTAL RISK ASSESSMENT Suitable justification has been provided for the non-submission of an Environmental Risk Assessment. As this product is intended for generic substitution with products that are already marketed, no increase in environmental burden is anticipated. Thus, the justification for non-submission of an Environmental Risk Assessment is accepted. CONCLUSION It is recommended that a marketing authorisation is granted for this application.


CLINICAL ASSESSMENT

CLINICAL PHARMACOLOGY Pharmacokinetics In accordance with the Note for Guidance on the investigation of bioavailability and bioequivalence (CPMP/EWP/QWP/1401/98), a bioequivalence study is not required if the product is to be administered as an aqueous oral solution at time of administration and contains the same active substance in the same concentration as the currently licensed product. EFFICACY No new efficacy data have been submitted and none are required for an application of this type. SAFETY No new safety data have been submitted and none are required for this application.

SUMMARY OF PRODUCT CHARACTERISTICS (SmPC), PATIENT INFORMATION LEAFLET (PIL) AND LABELLING The SmPC, PIL and labelling are acceptable. The SmPC is consistent with that for the respective originator product. The PIL is consistent with the SmPC and is in line with current guidance. The labelling is in line with current guidance. CLINICAL EXPERT REPORT The clinical expert report has been written by an appropriately qualified physician and is a suitable summary of the clinical aspects of the dossier. PHARMACOVIGILANCE SYSTEM AND RISK MANAGEMENT PLAN The pharmacovigilance system, as described by the applicant, fulfils the requirements and provides adequate evidence that the applicant has the services of a qualified person responsible for pharmacovigilance, and has the necessary means for the notification of any adverse reaction suspected of occurring either in the Community or in a third country. Suitable justification has been provided for not submitting a Risk Management Plan for this product. CONCLUSION There are no objections to the approval of this product from a clinical viewpoint.


IV OVERALL CONCLUSION AND BENEFIT-RISK ASSESSMENT QUALITY The important quality characteristics of Atenolol 25 mg / 5 ml Oral Solution are well-defined and controlled. The specifications and batch analytical results indicate consistency from batch to batch. There are no outstanding quality issues that would have a negative impact on the benefit-risk balance. NON-CLINICAL No new non-clinical data have been submitted and none are required for an application of this type. EFFICACY No new data have been submitted and none are required for an application of this type. SAFETY No new or unexpected safety concerns arose from this application. PRODUCT LITERATURE The SmPCs, PIL and labelling are satisfactory and consistent with those for the reference product, where appropriate. BENEFIT-RISK ASSESSMENT The quality of the products is acceptable and no new non-clinical or clinical safety concerns have been identified. Extensive clinical experience with atenolol is considered to have demonstrated the therapeutic value of the compound. The benefit-risk ratio is therefore considered to be positive.


ATENOLOL 25 MG / 5 ML ORAL SOLUTION

PL 13931/0060

STEPS TAKEN FOR ASSESMENT

1 The MHRA received the marketing authorisation application on 05 January

2009.

2 Following standard checks and communication with the applicant the MHRA considered the application valid on 14 January 2009.

3 Following assessment of the application the MHRA requested further information on 03 July 2009, 30 June 2010, 30 November 2010 and 03 October 2011

4 The applicant responded to the MHRA’s requests, providing further information on 26 February 2010, 02 November 2010, 08 September 2011 and 07 November 2011.

5 The application was determined on 08 December 2011.



PL 13931/0060

STEPS TAKEN AFTER ASSESSMENT

Date submitted

Application type

Scope Outcome


SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

ATENOLOL 25 mg / 5 ml ORAL SOLUTION 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Atenolol 25 mg / 5 ml For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Oral solution The solution is a clear, colourless and viscous liquid.

4 CLINICAL PARTICULARS 4.1 Therapeutic Indications

i. Management of hypertension. ii. Management of angina. iii. Management of cardiac arrhythmias. iv. Myocardial infarction. Early intervention in the acute phase.

4.2 Posology and method of administration

Oral administration. Atenolol Solution is intended for patients unable to swallow Atenolol tablets. The dose must always be adjusted to individual requirements of the patients, with the lowest possible starting dosage. The following are guidelines: Adults Hypertension Two or four 5 ml spoonfuls daily i.e. 50 mg or 100 mg in patients unable to take 50 mg or 100 mg tablets. Most patients respond to 100 mg once daily. Some patients, however, will respond to 50 mg given as a single daily dose. The effect will be fully established after one to two weeks. A further reduction in blood pressure may be achieved by combining Atenolol with other antihypertensive agents. Angina Most patients with angina pectoris will respond to 100 mg (four 5 ml spoonfuls) given orally once a day, or 50 mg (two 5 ml spoonfuls) given twice daily. It is unlikely that additional benefit will be gained by increasing the dose. Cardiac arrhythmias A suitable initial dose of Atenolol injection is 2.5 mg (5 ml) injected intravenously over a 2.5 minute period (i.e. 1 mg/minute). (See also prescribing information for Atenolol Injection.) This may be repeated at 5 minute intervals, until a response is observed up to a maximum dosage of 10 mg. If Atenolol is given by infusion, 0.15 mg/kg bodyweight may be administered over a 20 minute period. If required, the injection or infusion may be repeated every 12 hours. Having controlled the arrhythmias with intravenous Atenolol, a suitable oral maintenance dosage is 50–100 mg (two to four 5 ml spoonfuls of Atenolol Solution) daily, given as a single dose. Myocardial infarction For patients suitable for treatment with intravenous beta-blockade and presenting within 12 hours of the onset of chest pain, Atenolol 5–10 mg should be given by slow intravenous injection (1 mg/minute) followed by Atenolol 50 mg orally about 15 minutes later, provided no untoward effects have occurred from the intravenous dose. This should be followed by a further 50 mg orally 12 hours after the intravenous dose, and then 12 hours later by 100 mg orally, once daily. If bradycardia


and/or hypotension requiring treatment, or any other untoward effects occur, Atenolol should be discontinued. Elderly Dosage requirements may be reduced, especially in patients with impaired renal function. Children There is no pediatric experience with Atenolol and for this reason it is not recommended for use in children. Renal failure Since Atenolol is excreted via the kidneys, the dosage should be adjusted in cases of severe impairment of renal function. No significant accumulation of Atenolol occurs in patients who have a creatinine clearance greater than 35 ml/min/1.73 m2 (normal range is 100–150 ml/min/1.73 m2). For patients with a creatinine clearance of 15–35 ml/min/1.73 m2 (equivalent to serum creatinine of 300–600 micromol/litre), the oral dose should be 50 mg daily and the intravenous dose should be 10 mg once every two days. For patients with a creatinine clearance of less than 15 ml/min/1.73 m2 (equivalent to serum creatinine of greater than 600 micromol/litre), the oral dose should be 25 mg daily or 50 mg on alternate days and the intravenous dose should be 10 mg once every four days. Patients on haemodialysis should be given 50 mg orally after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.

4.3 Contraindications

Atenolol, as with other beta-blockers, should not be used in patients with any of the following: cardiogenic shock uncontrolled heart failure sick sinus syndrome second-or third-degree heart block untreated phaeochromocytoma metabolic acidosis bradycardia (<45 bpm) hypotension known hypersensitivity to the active substance, or any of the excipients severe peripheral arterial circulatory disturbances.

4.4 Special warnings and precautions for use

Atenolol as with other beta-blockers: • Should not be withdrawn abruptly. The dosage should be withdrawn gradually over a period of 7–14 days, to facilitate a reduction in beta-blocker dosage. Patients should be followed during withdrawal, especially those with ischaemic heart disease. • When a patient is scheduled for surgery, and a decision is made to discontinue beta-blocker therapy, this should be done at least 24 hours prior to the procedure. The risk-benefit assessment of stopping beta-blockade should be made for each patient. If treatment is continued, an anaesthetic with little negative inotropic activity should be selected to minimise the risk of myocardial depression. The patient may be protected against vagal reactions by intravenous administration of atropine. • Although contraindicated in uncontrolled heart failure (see section 4.3), may be used in patients whose signs of heart failure have been controlled. Caution must be exercised in patients whose cardiac reserve is poor. • May increase the number and duration of angina attacks in patients with Prinzmetal's angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction. Atenolol is a beta1-selective beta-blocker; consequently, its use may be considered although utmost caution must be exercised.


• Although contraindicated in severe peripheral arterial circulatory disturbances (see section 4.3), may also aggravate less severe peripheral arterial circulatory disturbances. • Due to its negative effect on conduction time, caution must be exercised if it is given to patients with first-degree heart block. • May mask the symptoms of hypoglycaemia, in particular, tachycardia. • May mask the signs of thyrotoxicosis. • Will reduce heart rate as a result of its pharmacological action. In the rare instances when a treated patient develops symptoms which may be attributable to a slow heart rate and the pulse rate drops to less than 50–55 bpm at rest, the dose should be reduced. • May cause a more severe reaction to a variety of allergens when given to patients with a history of anaphylactic reaction to such allergens. Such patients may be unresponsive to the usual doses of adrenaline (epinephrine) used to treat the allergic reactions. • May cause a hypersensitivity reaction including angioedema and urticaria. • Should be used with caution in the elderly, starting with a lesser dose (see Section 4.2). Since Atenolol is excreted via the kidneys, dosage should be reduced in patients with a creatinine clearance of below 35 ml/min/1.73 m2. Although cardioselective (beta1) beta-blockers may have less effect on lung function than non-selective beta-blockers, as with all beta-blockers, these should be avoided in patients with reversible obstructive airways disease, unless there are compelling clinical reasons for their use. Where such reasons exist, Atenolol may be used with caution. Occasionally, some increase in airways resistance may occur in asthmatic patients however, and this may usually be reversed by commonly used dosage of bronchodilators such as salbutamol or isoprenaline. The label and patient information leaflet for this product state the following warning: “If you have ever had asthma or wheezing, you should not take this medicine unless you have discussed these symptoms with the prescribing doctor”. As with other beta-blockers, in patients with a phaeochromocytoma, an alpha-blocker should be given concomitantly.

4.5 Interaction with other medicinal products and other forms of interaction

Combined use of beta-blockers and calcium channel blockers with negative inotropic effects, e.g. verapamil and diltiazem, can lead to an exaggeration of these effects particularly in patients with impaired ventricular function and/or sinoatrial or atrioventricular conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure. Neither the beta-blocker nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other. Concomitant therapy with dihydropyridines, e.g. nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency. Digitalis glycosides, in association with beta-blockers, may increase atrioventricular conduction time. Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are co-administered, the beta-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped. (See also prescribing information for clonidine.). Class I anti-arrhythmic drugs (e.g. disopyramide) and amiodarone may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.


Concomitant use of sympathomimetic agents, e.g. adrenaline (epinephrine), may counteract the effect of beta-blockers. Concomitant use with insulin and oral antidiabetic drugs may lead to the intensification of the blood sugar lowering effects of these drugs. Symptoms of hypoglycaemia, particularly tachycardia, may be masked (see section 4.4). Concomitant use of prostaglandin synthetase-inhibiting drugs, e.g. ibuprofen and indometacin, may decrease the hypotensive effects of beta-blockers. Caution must be exercised when using anaesthetic agents with Atenolol. The anaesthetist should be informed and the choice of anaesthetic should be an agent with as little negative inotropic activity as possible. Use of beta-blockers with anaesthetic drugs may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anaesthetic agents causing myocardial depression are best avoided.

4.6 Pregnancy and lactation

Atenolol crosses the placental barrier and appears in the cord blood. No studies have been performed on the use of Atenolol in the first trimester and the possibility of foetal injury cannot be excluded. Atenolol has been used under close supervision for the treatment of hypertension in the third trimester. Administration of Atenolol to pregnant women in the management of mild to moderate hypertension has been associated with intra-uterine growth retardation. The use of Atenolol in women who are, or may become, pregnant requires that the anticipated benefit be weighed against the possible risks, particularly in the first and second trimesters, since beta-blockers, in general, have been associated with a decrease in placental perfusion which may result in intra-uterine deaths, immature and premature deliveries. There is significant accumulation of Atenolol in breast milk. Neonates born to mothers who are receiving Atenolol at parturition or breast-feeding may be at risk of hypoglycaemia and bradycardia. Caution should be exercised when Atenolol is administered during pregnancy or to a woman who is breast-feeding.

4.7 Effects on ability to drive and use machines

Use is unlikely to result in any impairment of the ability of patients to drive or operate machinery. However, it should be taken into account that occasionally dizziness or fatigue may occur.

4.8 Undesirable effects

Atenolol is well tolerated. In clinical studies, the undesired events reported are usually attributable to the pharmacological actions of atenolol. The following undesired events, listed by body system, have been reported with the following frequencies: very common ( 10%), common (1–9.9%), uncommon (0.1–0.9%), rare (0.01–0.09%), very rare (<0.01%) including isolated reports, not known (cannot be estimated from the available data). Blood and lymphatic system disorders: Rare: Purpura, thrombocytopenia. Psychiatric disorders: Uncommon: Sleep disturbances of the type noted with other beta-blockers. Rare: Mood changes, nightmares, confusion, psychoses and hallucinations. Nervous system disorders: Rare: Dizziness, headache, paraesthesia. Eye disorders: Rare: Dry eyes, visual disturbances.


Cardiac disorders: Common: Bradycardia. Rare: Heart failure deterioration, precipitation of heart block. Vascular disorders: Common: Cold extremities. Rare: Postural hypotension which may be associated with syncope, intermittent claudication may be increased if already present, in susceptible patients Raynaud's phenomenon. Respiratory, thoracic and mediastinal disorders: Rare: Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints. Gastrointestinal disorders: Common: Gastrointestinal disturbances. Rare: Dry mouth. Hepato-biliary disorders: Uncommon: Elevations of transaminase levels. Rare: Hepatic toxicity including intrahepatic cholestasis. Skin and subcutaneous tissue disorders: Rare: Alopecia, psoriasiform skin reactions, exacerbation of psoriasis, skin rashes. Not known: Hypersensitivity reactions, including angioedema and urticaria. Reproductive system and breast disorders: Rare: Impotence. General disorders and administration site conditions: Common: Fatigue. Investigations: Very rare: An increase in ANA (Antinuclear Antibodies) has been observed, however the clinical relevance of this is not clear. Discontinuance of the drug should be considered if, according to clinical judgement, the well-being of the patient is adversely affected by any of the above reactions.

4.9 Overdose The symptoms of overdosage may include bradycardia, hypotension, acute cardiac insufficiency and bronchospasm. General treatment should include: close supervision; treatment in an intensive care ward; the use of gastric lavage; activated charcoal and a laxative to prevent absorption of any drug still present in the gastrointestinal tract; the use of plasma or plasma substitutes to treat hypotension and shock. The possible uses of haemodialysis or haemoperfusion may be considered. Excessive bradycardia can be countered with atropine 1–2 mg intravenously and/or a cardiac pacemaker. If necessary, this may be followed by a bolus dose of glucagon 10 mg intravenously. If required, this may be repeated or followed by an intravenous infusion of glucagon 1–10 mg/hour depending on response. If no response to glucagon occurs or if glucagon is unavailable, a beta-adrenoceptor stimulant such as dobutamine 2.5 to 10 micrograms/kg/minute by intravenous infusion may be given. Dobutamine, because of its positive inotropic effect could also be used to treat hypotension and acute cardiac insufficiency. It is likely that these doses would be inadequate to reverse the cardiac effects of beta-blocker blockade if a large overdose has been taken. The dose of dobutamine should therefore be increased if necessary to achieve the required response according to the clinical condition of the patient. Bronchospasm can usually be reversed by bronchodilators.


5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Beta-blocking agents, plain, selective. CO7AB03. Atenolol is a beta-blocker which is beta1-selective, (i.e. acts preferentially on beta1-adrenergic receptors in the heart). Selectivity decreases with increasing dose. Atenolol is without intrinsic sympathomimetic and membrane-stabilising activities and as with other beta-blockers, has negative inotropic effects (and is therefore contraindicated in uncontrolled heart failure). As with other beta-blockers, the mode of action of atenolol in the treatment of hypertension is unclear. It is probably the action of atenolol in reducing cardiac rate and contractility which makes it effective in eliminating or reducing the symptoms of patients with angina. It is unlikely that any additional ancillary properties possessed by S (-) atenolol, in comparison with the racemic mixture, will give rise to different therapeutic effects. Atenolol is effective and well-tolerated in most ethnic populations although the response may be less in black patients. Atenolol is effective for at least 24 hours after once daily dosing with 10 ml or 20 ml Atenolol Solution. Atenolol Solution facilitates compliance by its acceptability to patients and the once daily dosing regimen. The narrow dose range and early patient response ensure that the effect of the drug in individual patients is quickly demonstrated. Atenolol is compatible with diuretics, other hypotensive agents and antianginals (see section 4.5). Since it acts preferentially on beta-adrenergic receptors in the heart, Atenolol may, with care, be used successfully in the treatment of patients with respiratory disease, who cannot tolerate non-selective beta-blockers. Early intervention with Atenolol in acute myocardial infarction reduces infarct size and decreases morbidity and mortality. Fewer patients with a threatened infarction progress to frank infarction; the incidence of ventricular arrhythmias is decreased and marked pain relief may result in reduced need of opiate analgesics. Early mortality is decreased. Atenolol is an additional treatment to standard coronary care.

5.2 Pharmacokinetic Properties

Absorption of atenolol following oral dosing is consistent but incomplete (approximately 40–50%) with peak plasma concentrations occurring 2–4 hours after dosing. The atenolol blood levels are consistent and subject to little variability. 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%).

5.3 Preclinical safety data

Atenolol is a drug on which extensive clinical experience has been obtained. Relevant information for the prescriber is provided elsewhere in the Summary of Product Characteristics.

6 PHARMACEUTICAL PARTICULARS 6.1 List of excipients

Citric acid monohydrate Lemon and lime flavour (containing ethanol) Methyl hydroxybenzoate Propyl hydroxybenzoate Purified water


Saccharin sodium Sodium citrate Sorbitol solution Mono Propylene glycol

6.2 Incompatibilities

Not applicable. 6.3 Shelf life

Unopened: 3 years Opened: 3 months

6.4 Special precautions for storage

Store below 25°C. Keep the bottle upright. Store in the original container.

6.5 Nature and contents of container

Amber Polyethylene Terephthalate (PET) bottle with tamper evident High Density Polyethylene (HDPE) cap with Low Density Polyethylne (LDPE) plug, containing 300 ml.

6.6 Special precautions for disposal

Not applicable 7 MARKETING AUTHORISATION HOLDER

Chanelle Medical, Loughrea, Galway Co. Ireland. 8 MARKETING AUTHORISATION NUMBER(S)

PL 13931/0060 9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 08/12/2011 10 DATE OF REVISION OF THE TEXT

08/12/2011


Module 3

PATIENT INFORMATION LEAFLET


LABELLING CARTON:

BOTTLE LABEL:


atenolol 25 mg / 5 ml oral solution. (atenolol) pl 13931 ... · atenolol 25 mg / 5 ml oral...

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