CARDATEN Atenalol Injection

 5 mg/10 ml


For the use of a Registered Medical Practitioner or a Hospital or a Institution only. 

Myocardial Infarction

CARDATEN (Atenolol) a synthetic, beta1-selective (cardioselective) adrenoreceptor blocking agent, may be chemically described as benzeneacetamide, 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-. The molecular formula is C14H22N2O3. Atenolol (free base) has a molecular weight of 266.34.



Its structural formula is :
       Atenolol Injection

A clear colourless solution filled in 10 ml amber ampoule. 

Each ml contains :
Atenolol I.P.                          0.500 mg
Water for Injections I.P.             q.s. 

CARDATEN is a beta1-selective (cardioselective) beta-adrenergic receptor blocking agent without membrane stabilizing or intrinsic sympathomimetic (partial agonist) activities. This preferential effect is not absolute, however, and at higher doses, CARDATEN inhibits beta2-adrenoreceptors, chiefly located in the bronchial and vascular musculature. 

In man, absorption of an oral dose is rapid and consistent but incomplete. Approximately 50 % of an oral dose is absorbed from the gastrointestinal tract, the remainder being excreted unchanged in the faeces. Peak blood levels are reached between two and four hours after ingestion. Unlike Propranolol or Metoprolol, but like Nadolol, CARDATEN undergoes little or no metabolism by the liver and the absorbed portion is eliminated primarily by renal excretion. Over 85 % of an intravenous dose is excreted in urine within 24 hours compared with approximately 50 % for an oral dose. CARDATEN also differs from Propranolol in that only a small amount (6 % - 16 %) of Atenolol is bound to proteins in the plasma. This kinetic profile results in relatively consistent plasma drug levels with about a fourfold interpatient variation. The  elimination  half-life  of  oral  CARDATEN  is  approximately 6 to 7 hours and there is no alteration of the kinetic profile of the drug by chronic administration. Following intravenous administration, peak plasma levels are reached within 5 minutes. Declines from peak levels are rapid (5 to 10 fold) during the first 7 hours; thereafter, plasma levels decay with a half-life similar to that of orally administered drug. Following oral doses of 50 mg or 100 mg, both beta-blocking and antihypertensive effects persist for at least 24 hours. When renal function is impaired, elimination of CARDATEN is closely related to the glomerular filtration rate; significant accumulation occurs when the creatinine clearance falls below 35 mL/min/1.73m2.
Elderly patients present higher Atenolol plasma levels with total clearance values about 50 % lower than younger subjects. The half life is markedly longer in elderly compare to younger subjects.

Arrhythmias :
CARDATEN is indicated in the management of arrhythmias. For the early intervention treatment of Acute 
Myocardial Infarction : 
CARDATEN is indicated in the management of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality. Treatment can be initiated as soon as the patients clinical condition allows. Some subgroups (e.g. elderly patients with systolic blood pressure below 120 mm Hg) are less likely to benefit.  

CARDATEN Injection is administered  by the intravenous route.

The ampoule used in this product is equipped with O.P.C. (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.

                   Ampoules equipped with One Point Cut (OPC) technology  

Adults :
Arrhythmias : 
A suitable initial dose of CARDATEN Injection is 2.5 mg (5 ml) injected intravenously over a 2.5 minute period (i.e. 1 mg/minute). This may be repeated at 5 minutes intervals until a response is observed upto a maximum dosage of 10 mg. If CARDATEN Injection is given by infusion, 0.15 mg/kg body weight 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 IV CARDATEN, a suitable oral maintenance dosage is 50 to 100 mg daily.

Acute Myocardial Infarction :
In patients with definite or suspected acute myocardial infarction, treatment with CARDATEN Injection should be initiated as soon as possible after the patients arrival in the hospital and after eligibility is established. Such treatment should be initiated in a coronary care or similar unit immediately after the patients hemodynamic condition has stabilized. Treatment should begin with the intravenous administration of 5 mg CARDATEN Injection over 5 minutes followed by another 5 mg intravenous injection 10 minutes later. CARDATEN Injection should be administered under carefully controlled conditions including monitoring of blood pressure, heart rate and electrocardiogram. Dilutions of CARDATEN Injection in Dextrose Injection USP, Sodium Chloride Injection USP, or Sodium Chloride and Dextrose Injection may be used. These admixtures are stable for 48 hours if they are not used immediately. In patients who tolerate the full intravenous dose (10 mg), Atenolol Tablets 50 mg should be initiated 10 minutes after the last intravenous dose followed by another 50 mg oral dose 12 hours later. Thereafter, Atenolol Tablets can be given orally either 100 mg once daily or 50 mg twice a day for a further 6-9 days or until discharge from the hospital. If bradycardia or hypotension requiring treatment or any other untoward effects occur, Atenolol Tablets should be discontinued.

Data from other beta blocker trials suggest that if there is any question concerning the use of IV beta blocker or clinical estimate that there is a contraindication, the IV beta blocker may be eliminated and patients fulfilling the safety criteria may be given Atenolol Tablets 50 mg twice daily or 100 mg once a day for at least seven days (if the IV dosing is excluded). Although the demonstration of efficacy of Atenolol Tablets is based entirely on data from the first seven postinfarction days, data from other beta blocker trials suggest that treatment with beta blockers that are effective in the postinfarction setting may be continued for one to three years if there are no contraindications. CARDATEN is an additional treatment to standard coronary care unit therapy.

Elderly patients or patients with Renal Impairment : 
Since Atenolol is excreted via the kidneys, dosage should be adjusted in cases of severe impairment of renal function. No significant accumulation of CARDATEN occurs until creatinine clearance falls below 35 mL/min/1.73m2 (normal range is 100 - 150 mL/min/1.73m2). For Patients with a creatinine clearance of 15 to 35 mL/min/1.73m2 (equivalent to serum creatinine of 300 to 600 micromol/litre) the oral dose should be 50 mg daily and intravenous dose should be 10 mg once every two days. For patients with creatinine clearance of < 15 mL/min/1.73m2 (equivalent to serum creatinine of > 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.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Evaluation of patients with hypertension or myocardial infarction should always include assessment of renal function. Atenolol excretion would be expected to decrease with advancing age.Patients on hemodialysis should be given 50 mg after each dialysis; this should be done under hospital supervision as marked falls in blood  pressure can occur.
Cessation of Therapy : 
If withdrawal of CARDATEN therapy is planned, it should be achieved gradually over a period of about two weeks. Patients should be carefully observed and advised to limit physical activity to a minimum.
CARDATEN is contraindicated in sick sinus syndrome, bradycardia, heart block greater than first degree, cardiogenic shock, metabolic  acidosis, severe peripheral arterial circulatory disturbances, untreated phaeochromocytoma and overt cardiac failure. CARDATEN is contraindicated in those patients with a history of hypersensitivity to Atenolol or any of the drug products components. 

Cardiac failure :  
Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure and beta blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In patients who have congestive heart failure controlled by digitalis and/or diuretics,  CARDATEN should be administered cautiously. Both digitalis and Atenolol slow AV conduction. In patients with acute myocardial infarction, cardiac failure which is not promptly and effectively controlled by 80 mg of intravenous furosemide or equivalent therapy is a contraindication to beta-blocker treatment.

In patients without a history of Cardiac Failure :
Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be treated appropriately according to currently recommended guidelines and the response observed closely. If cardiac failure continues despite adequate treatment, CARDATEN Injection should be withdrawn.
Concomitant Use of Calcium Channel Blockers : 
Bradycardia and heart block can occur and the left ventricular end diastolic pressure can rise when beta blockers are administered with Verapamil or diltiazem. Patients with pre-existing conduction abnormalities or left ventricular dysfunction are particularly susceptible. 
Bronchospastic Diseases : 
PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT  RECEIVE  BETA   BLOCKERS. Because of its relative beta1 selectivity, however, CARDATEN may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Since beta1 selectivity is not absolute, the lowest possible dose of CARDATEN should be used with therapy initiated at 50  mg  and  a  beta2-stimulating  agent  (bronchodilator) should be made available. If dosage must be increased, dividing the dose should be considered in order to achieve lower peak blood levels. 
Anaesthesia and Major Surgery : 
It is not advisable to withdraw beta adrenoreceptor blocking drugs prior to surgery in the majority of patients. However, care should be taken when using anaesthetic agents such as those which may depress the myocardium. Vagal dominance, if it occurs, may be corrected with atropine (1- 2 mg IV). Additionally, caution should be used when CARDATEN Injection is administered concomitantly with such agents. CARDATEN, like other beta blockers, is a competitive inhibitor of betareceptor agonists and its effects on the heart can be reversed by administration of such agents : e.g. Dobutamine or Isoproterenol with caution.
Diabetes and Hypoglycemia :
CARDATEN should be used with caution in diabetic patients if a beta-blocking agent is required. Beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. At recommended doses CARDATEN does not potentiate insulin-induced hypoglycemia and unlike nonselective beta blockers, does not delay recovery of blood glucose to normal levels.

Thyrotoxicosis : 
Beta-adrenergic blockade may mask certain clinical signs (e.g. tachycardia) of hyperthyroidism. Patients suspected of having thyroid disease should be monitored closely when administering CARDATEN Injection. Abrupt withdrawal of beta blockade might precipitate a thyroid storm; therefore, patients  suspected of developing thyrotoxicosis from whom CARDATEN therapy is to be withdrawn should be monitored closely.

Patients already on a  beta blocker must be evaluated carefully before CARDATEN is administered. Initial and subsequent CARDATEN dosages can be adjusted downward depending on clinical observations including pulse and blood pressure. CARDATEN may aggravate peripheral arterial circulatory disorders. CARDATEN should be used with caution in patients with impaired renal function.

Pregnancy Category D :
CARDATEN can cause foetal harm when administered to a pregnant woman. CARDATEN crosses the placental barrier and appears in cord blood. Administration of CARDATEN, starting in the second trimester of pregnancy, has been associated with the birth of infants that are small for gestational age. No studies have been performed on the use of CARDATEN in the first trimester and the possibility of foetal injury cannot be excluded. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the foetus.  

Nursing mothers : 
CARDATEN is excreted in human breast milk at a ratio of 1.5 to 6.8 when compared to the concentration in plasma. Caution should be exercised when CARDATEN is administered to a nursing woman. Clinically significant bradycardia has been reported in breast fed infants. Premature infants, or infants with impaired renal function may be more likely to develop adverse effects.
Paediatric Use : 
Safety and effectiveness in paediatric patients have not been established. Digitalis glycosides, in association with beta-adrenoreceptor blocking drugs, may increase atrio-ventricular conduction time.

Catecholamine-depleting drugs (e.g. Reserpine) may have an additive effect when given with beta-blocking agents. Patients treated with CARDATEN plus a catecholamine depletor should therefore be closely observed for evidence of hypotension and/or marked bradycardia which may produce vertigo, syncope or postural hypotension. Calcium channel blockers may also have an additive effect when given with CARDATEN. 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 the gradual withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta blockers should be delayed for several days after clonidine administration has stopped.

Concomitant use of prostaglandin synthetase inhibiting drugs, e.g. Ibuprofen or Indomethacin, may decrease the hypotensive effects of beta blockers. 
Caution should be exercised with CARDATEN Injection when given in close proximity with drugs that may also have a depressant effect on myocardial contractility. On rare occasions, concomitant use of intravenous beta blockers and intravenous Verapamil has resulted in serious adverse reactions, especially in patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction. Information on concurrent usage of Atenolol and Aspirin is limited. While taking beta blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction. Caution must be exercised when prescribing a beta-adrenoceptor blocking drug with class I antiarrhythmic agents such as disopyramide concomitant therapy with dihydropyridines e.g. Nifedipine, may increase the risk of hypotension and cardiac failure may occur in patients with latent cardiac insufficiency.

Most adverse effects have been mild and transient. Cardio Vascular : Bradycardia, heart failure deterioration, postural hypotension which may be associated with syncope, cold extremities. In susceptible patients : precipitation of heart block, intermittent claudication, Raynauds phenomenon.

Respiratory : Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints.
Hematologic : Agranulocytosis, purpura, thrombo-cytopenia.
Allergic :  Fever, combined with aching and sore throat, laryngospasm and respiratory distress. 
Central Nervous System :
Confusion, dizziness, headache, mood changes, nightmares, psychoses and hallucinations, sleep disturbances of the type noted with other beta-adrenoreceptor blocking drugs.
Gastrointestinal : 
Mesenteric arterial thrombosis, ischemic colitis, dry mouth, gastrointestinal disturbances, rare cases of hepatic toxicity including intrahepatic cholestasis have been reported.

Other : Erythematous rash, fatigue.

Neurological : Paraesthesia.
Integumentary : Alopecia.
Special Senses : Visual disturbances.

Miscellaneous : 
There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The reported incidence is small, and in most cases, the symptoms have cleared when treatment was withdrawn. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable.  Patients  should be closely monitored following cessation of therapy. The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with CARDATEN. Furthermore, a number of patients who had previously demonstrated established practolol reactions were transferred to CARDATEN therapy with subsequent resolution or quiescence of the reaction. In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and may be considered potential adverse effects of CARDATEN. 

Overdosage with CARDATEN has been reported with patients surviving acute doses as high as 5 g. One death was reported in a man who may have taken as much as 10 g acutely. The predominant symptoms reported following CARDATEN overdose are lethargy, disorder of respiratory drive, wheezing, sinus pause and bradycardia. Additionally, common effects associated with overdosage of any beta-adrenergic blocking agent and which might also be expected in CARDATEN overdose are congestive heart failure, hypotension, bronchospasm and/or hypoglycemia. 

Treatment of overdose should be directed to the removal of any unabsorbed drug by induced emesis, gastric lavage, or administration of activated charcoal. CARDATEN can be removed from the general circulation by hemodialysis. Other treatment modalities should be employed at the physicians discretion and may include :

Bradycardia : 
Atropine intravenously. If there is no response to vagal blockade, give Isoproterenol cautiously. In refractory cases, a transvenous cardiac pacemaker may be indicated.
Heart Block (Second or Third Degree) :  
Isoproterenol or transvenous cardiac pacemaker.
Cardiac Failure : 
Digitalize the patient and administer a diuretic. Glucagon has been reported to be useful.
Hypotension : 
Vasopressors such as Dopamine or Norepinephrine (Levarterenol). Monitor blood pressure continuously.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Store at controlled room temperature 15 - 25°C (59 - 77°F), protected from light. Do not refrigerate.
24 months from the date of manufacture.
CARDATEN is supplied as 5 mg Atenolol in 10 ml aqueous solution. Available as 5 x 10 ml in a box.

Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.

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