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

Logo TENCHLOR® TABLETS
TENCHLOR® HS TABLETS

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

TENCHLOR® TABLETS
TENCHLOR
® HS TABLETS

COMPOSITION:
Each tablet contains
TENCHLOR:         100 mg atenolol and 25 mg chlorthalidone.
TENCHLOR HS:         50 mg atenolol and 12,5 mg chlorthalidone.

PHARMACOLOGICAL CLASSIFICATION:
A 7.1.3 Other hypotensives.

PHARMACOLOGICAL ACTION:
Atenolol is a cardio-selective beta1-adrenergic receptor blocking agent with insignificant partial agonist activity and weak membrane-stabilising properties. As it is highly hydrophilic it does not readily cross the blood brain barrier. Chlorthalidone has the same actions as the thiazide diuretics although not chemically the same. Chlorthalidone acts directly on the kidney to increase the excretion of sodium chloride and an accompanying volume of water, it also increases the excretion of potassium. The major hypotensive effect during chronic administration appears to be due to vasodilatation, rather than to loss of water per se. However, the effect on peripheral vascular resistance may be secondary to diuretic-induced changes in sodium balance. Tenchlor has a narrow dose range and early patient response allows assessment of the effect within one or two weeks, in those patients who respond.

INDICATIONS:
For the management of mild to moderate hypertension.

CONTRA-INDICATIONS:
Hypersensitivity to the active ingredients.
Tenchlor should not be given to patients with partial heart block, heart failure, metabolic acidosis or sinus bradycardia and should never be given to patients with phaeochromocytoma without concomitant alpha-adrenoceptor blocking therapy. It should not be given together with verapamil and neither drug should be administered within several days of discontinuing the other.
Tenchlor is contra-indicated in patients with bronchial asthma, bronchitis, bronchospasm or chronic respiratory diseases, metabolic acidosis, atrioventricular block, marked bradycardia, (less than 50 per minute), heart failure refractory to digitalis, uraemia, hypoglycaemia, second and third degree heart block, peripheral vascular diseases and Raynaud’s phenomenon. It should be avoided in patients with severe hepatic impairment, in whom encephalopathy may be precipitated.
Tenchlor is contra-indicated in pregnancy and lactation. Tenchlor should not be used in elderly patients, or in patients suffering from renal dysfunction without reducing the normal dose of Tenchlor. It should not be given to patients with severe renal impairment or anuria. Tenchlor should not be given to patients with Addison's disease.
It is contra-indicated in patients with metabolic acidosis (e.g. in diabetes) and after prolonged fasting.
In the peri-operative period, it is generally unwise to reduce the dosage to that which the patient is accustomed, as there may be danger of aggravation of angina pectoris or of hypertension. A patient’s normal tachycardiac response to hypo-volaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard. Chlorthalidone should not be given to patients with pre-existing hypercalcaemia.

WARNING:
Tenchlor should be given to patients with congestive heart failure only when they are fully digitalised and only then with great caution. Great care should be exercised in giving Tenchlor to patients undergoing general anaesthesia, and myocardial depressants, such as chloroform and ether must be avoided.
If a beta-blocker and clonidine are given concurrently, the clonidine should not be discontinued until several days after the withdrawal of the beta-blocker as severe rebound hypertension may occur. Caution should be exercised when transferring a patient from clonidine. The withdrawal of clonidine may result in the release of large amounts of catecholamines which may give rise to a hypertensive crisis. If beta-blockers are administered in these circumstances, the unopposed alpha-receptor stimulation may potentiate this effect.
Tenchlor should be used with caution in patients with impaired hepatic or renal function, or adrenal disease.
Atenolol is excreted into breast milk. Consult your physician.

DOSAGE AND DIRECTIONS FOR USE:
Tenchlor:         Half to one tablet daily in the morning.
Tenchlor HS:         One to two tablets daily in the morning.
There is little or no further fall in blood pressure with increased dosage. Tenchlor is not recommended for children.
Patients should be warned not to stop taking the medicine except on the advice of their medical doctor and the importance of compliance with therapy should be stressed. Patients should be advised not to take other medicines without professional advice.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side effects
Atenolol
The most frequent and serious adverse effects are related to the beta adrenergic blocking activity. Among the most serious adverse effects are heart failure. heart block and bronchospasm.
Adverse gastro-intestinal effects include nausea. vomiting, diarrhoea, constipation, and abdominal cramping.
Cardiovascular effects include bradycardia and hypotension; heart failure or heart block may be precipitated in patients with underlying cardiac disorders.
Reduced peripheral circulation can produce coldness of the extremities and may exacerbate peripheral vascular disease such as Raynaud’s syndrome. Abrupt withdrawal of beta blockers may exacerbate angina and may lead to sudden death.
Central nervous system effects include depression, dizziness, hallucinations, confusion, psychotic episodes, and disturbances of sleep, including nightmares. Paraesthesia, peripheral neuropathy, and myopathies, including muscle cramps, and loss of hearing have been reported. Bronchospasm may occur, particularly in susceptible individuals. Fatigue is a common side-effect.
Haematological reactions include non-thrombocytopenic purpura, thrombocytopenia, and less frequently agranulocytosis.
Transient eosinophilia can occur.
Skin rash, pruritus and reversible alopecia have occurred.
Other adverse effects reported include: allergic reactions, metabolic disturbances, fluid retention and weight gain, stomatitis, a lupus-like syndrome, male impotence, sclerosing peritonitis, and retroperitoneal fibrosis.
Decreased tear production, blurred vision, and soreness are among the ocular symptoms which have been reported.
Pneumonitis, pulmonary fibrosis, and pleurisy have been reported.
Chlorthalidone
Chlorthalidone may cause a number of metabolic disturbances at high doses and may cause hyperuricaemia and precipitate attacks of gout in some patients.
Chlorthalidone may provoke hyperglycaemia and glycosuria in diabetic and other susceptible patients.
Administration of chlorthalidone may be associated with electrolyte imbalances including hypochloraemic alkalosis, hyponatraemia, and hypokalaemia.
They may cause hyperglycaemia and aggravate or unmask diabetes mellitus. Chlorthalidone may increase the concentration of low-density and very low-density lipoprotein cholesterol, as well as of triglycerides. Acute interstitial pneumonitis and acute pulmonary oedema are less frequent but potentially dangerous complications of chlorthalidone therapy and may be due to a hypersensitivity reaction. Hypokalaemia in patients treated with chlorthalidone may be avoided or treated by concurrent administration of potassium or a potassium-sparing diuretic.
The urinary excretion of calcium is reduced, sometimes resulting in mild hypercalcaemia. Hypomagnesaemia has also occurred.
There is some evidence to suggest that electrolyte imbalances during long-term treatment with chlorthalidone may be associated with an increased incidence of cardiac arrhythmias.
Signs of electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain and cramps, seizures, oliguria, hypotension, and gastro-intestinal disturbances.
Other side-effects include anorexia, gastric irritation, nausea, vomiting, constipation, diarrhoea, headache, dizziness, photosensitivity reactions, postural hypotension, paraesthesia, impotence, and yellow vision. Hypersensitivity reactions include skin rashes, fever, pulmonary oedema, and pneumonitis. Cholestatic jaundice, pancreatitis, and blood dyscrasias including thrombocytopenia and, less frequently granulocytopenia, leucopenia, and aplastic and haemolytic anaemia have been reported.
Special Precautions
Atenolol
Atenolol may mask the symptoms of hyperthyroidism. It may also mask the symptoms of hypoglycaemia, as well as enhance the effects of hypoglycaemic agents in patients with diabetes mellitus.
Beta blockers may unmask myasthenia gravis.
Special precaution must be taken in patients with psoriasis, as this may be aggravated.
Patients with a history of anaphylaxis to an antigen may be more reactive to repeated challenge with the antigen while taking atenolol.
The dose may need to be reduced in patients with renal or hepatic dysfunction.
Important:
Digitalisation of patients receiving long-term beta-blocker therapy may be necessary if congestive heart failure is likely to develop. This combination can be considered despite the potentiation negative chronotropic effects of the two medicines. Careful control of dosages and of the individual patient’s response (and notably pulse-rate) is essential in this situation.
Abrupt withdrawal of therapy has sometimes resulted in angina, myocardial infarction, ventricular arrhythmias and death..
Discontinuation of therapy should be gradual (1-2 weeks) and patients should be advised to limit the extent of their physical activity during the period that the medicine is being discontinued.
Administration to pregnant women shortly before giving birth, or during labour has resulted in bradycardia and other adverse effects such as hypoglycaemia and hypotension in the neonate and it may result in the newborn infants being born hypotonic, collapsed and hypoglycaemic.
Tenchlor should not be administered to patients with phaeochromocytoma without concurrent alpha-adrenergic blocking therapy.
Chlorthalidone
Chlorthalidone may provoke hyperglycaemia and glycosuria in diabetic and other susceptible patients.
Chlorthalidone may cause hypokalaemia which intensifies the effect of digitalis on cardiac muscle and administration of digitalis or its glycosides may have to be temporarily suspended. Patients with severe coronary artery disease and cirrhosis of the liver are particularly at risk from hypokalaemia. Hyponatraemia may occur in patients with severe congestive heart failure who are very oedematous, particularly with large doses in conjunction with restricted salt in the diet.
Chlorthalidone should be used with caution in patients with existing fluid and electrolyte disturbances or who are at risk from changes in fluid and electrolyte balance, such as the elderly.
There is an increased risk of patients taking chlorthalidone developing cholecystitis.
Chlorthalidone should be used with caution in patients with impaired hepatic function since it may increase the risk of hepatic encephalopathy. It should also be given with caution in renal impairment since it can further reduce renal function. It may precipitate attacks of gout in susceptible patients. All patients should be carefully observed for signs of fluid and electrolyte imbalance, especially in the presence of vomiting or during parenteral fluid therapy. Chlorthalidone may exacerbate or activate systemic lupus erythematosus in susceptible patients.
Blood-glucose concentrations should be monitored in patients taking antidiabetics, since requirements may change.
Chlorthalidone crosses the placenta and there have been reports of neonatal jaundice, thrombocytopenia, and electrolyte imbalances following maternal treatment. Reductions in maternal blood volume could also adversely affect placental perfusion. Chlorthalidone is excreted and distributed in the breast milk. Treatment with chlorthalidone can inhibit lactation.
INTERACTIONS
Atenolol interferes with carbohydrate and lipid metabolism and can produce hypoglycaemia, hyperglycaemia and changes in blood concentrations of triglycerides and cholesterol.
Both pharmacodynamic and pharmacokinetic interactions have been reported with beta blockers. Pharmacodynamic interactions may occur with medicines whose actions enhance or antagonise the various effects of beta blockers at beta1 and beta2 receptors.
Interactions may occur with medicines that interfere with the antihypertensive effect, cardiodepressant effect, effect on carbohydrate metabolism, or effects on bronchial beta2 receptors of beta blockers. Medicines that enhance the antihypertensive effects of beta blockers, such as ACE inhibitors, calcium -channel blockers, and clonidine may be useful in controlling hypertension.
Medicines that cause hypotension such as aldesleukin and general anaesthetics also enhance the antihypertensive effects of beta blockers while other medicines, for example nonsteriodal anti-inflammatories antagonise the antihypertensive effects.
If beta blockers are not discontinued prior to anaesthesia, an agent such as atropine may be given to counter increases in vagal tone.
Anaesthetics that cause myocardial depression, such as ether, cyclopropane, and trichloroethylene are best avoided. Awareness by the anaesthetist that beta-blockers are being taken is of the greatest importance.
Concomitant use of beta blockers with other cardiac depressants such as amiodarone, diltiazem, and verapamil can precipitate bradycardia and heart block. Concurrent administration of calcium-channel blockers and beta blockers has resulted in hypotension, bradycardia, conduction defects and cardiac failure.
Sotalol is particularly prone to interactions with other medicines affecting cardiac conduction.
The effects of other myocardial depressant agents, including anti-arrhythmics such as quinidine, procainamide, or lignocaine, phenytoin, and medicines which interfere with calcium transport, such as verapamil, may also be enhanced by atenolol.
An enhanced antihypertensive effect is seen when other antihypertensives are given concomitantly.
Beta blockers can potentiate the severe postural hypotension that may follow the initial dose of prazosin and can exacerbate rebound hypertension following withdrawal of clonidine treatment.
The effects of atenolol are diminished by beta-adrenoceptor stimulating agents such as isoprenaline; the hypotensive effects of atenolol may be dangerously reversed and the peripheral vasoconstrictor effects enhanced by alpha-adrenoceptor stimulating agents such as noradrenaline or those with mixed alpha- and beta-adrenoceptor stimulating properties such as adrenaline; bradycardia may also occur.
The effects of atenolol may be enhanced by adrenergic neurone blocking agents such as guanethidine or bethanidine, or catecholamine-depleting agents such as reserpine, and the hypotensive effects by diuretics.
Atenolol may enhance some of the cardiac effects of digitalis and diminish others. Beta blockers may potentiate bradycardia due to digoxin.
It has been suggested that clonidine withdrawal symptoms may be exacerbated in patients who are concurrently taking a beta blocker.
In diabetic patients, beta blockers can reduce the response to insulin and oral hypoglycaemics through their effects on pancreatic beta receptors. Blockade of peripheral beta receptors interferes with the effects of sympathomimetics; patients on beta blockers, especially non-selective beta blockers, may develop elevated blood pressure if they are given adrenaline. The bronchodilator effects of adrenaline are also inhibited. The response to adrenaline given for anaphylaxis may be reduced in patients on long-term treatment with beta blockers.
Pharmacokinetic interactions occur with medicines that alter the absorption or metabolism of beta blockers.
Medicines that reduce absorption include aluminium salts, and bile-acid binding resins such as cholestyramine. Metabolism of beta blockers can be increased by concomitant treatment with medicines such as barbiturates and rifampicin and decreased with medicines such as cimetidine, erythromycin, fluvoxamine, and hydralazine.
Drugs that alter hepatic blood flow also affect metabolism of beta blockers, eg. cimetidine and hydralazine decreases hepatic blood flow and this contributes to the decreased hepatic clearance seen with these medicines.
Medicines that influence hepatic metabolism affect beta blockers, such as labetalol, propranolol and timolol, that are extensively metabolised while beta blockers that are excreted largely unchanged, eg. atenolol and nadolol, are unaffected. Serum-atenolol concentrations were reduced by concurrent administration of ampicillin given in doses of 1 gram per mouth.
Please note: Such interactions can have life-threatening consequences.
Chlorthalidone
Many of the interactions of chlorthalidone are due to the effects on fluid and electrolyte balance. Diuretic-induced hypokalaemia may enhance the toxicity of digitalis glycosides by depleting serum-potassium concentrations and may also increase the risk of arrhythmias with agents such as astemizole, terfenadine, halofantrine, pimozide, and sotalol.
It may enhance the neuromuscular blocking action of competitive muscle relaxants, such as tubocurarine probably by the hypokalaemic effect. It may enhance the effect of other antihypertensive agents, particularly the first-dose hypotension that occurs with alpha blockers or angiotensin converting enzyme inhibitors, while postural hypotension associated with chlorthalidone therapy may be enhanced by concomitant ingestion of alcohol, barbiturates or opioids. The potassium-depleting effect of chlorthalidone may be enhanced by corticosteroids, corticotrophin, beta2 agonists such as salbutamol, carbenoxolone, or amphotericin.
The antihypertensive effects of diuretics may be antagonised by agents that cause fluid retention, such as corticosteroids, nonsteroidal anti-inflammatories, or carbenoxolone.
Concomitant administration of chlorthalidone and lithium is not generally recommended as the association may lead to toxic blood concentrations of lithium. Other agents for which increased toxicity has been reported when given concomitantly with chlorthalidone include allopurinol and tetracyclines. Blood-glucose concentrations should be monitored in patients taking antidiabetic agents, since requirements may change. Chlorthalidone may alter the requirements for hypoglycaemic agents in diabetic patients.
Gastro-intestinal absorption has been reported to be reduced by cholestipol and cholestyramine. The milk-alkali syndrome is characterised by hypercalcaemia, metabolic alkalosis, and renal failure. Patients taking chlorthalidone may be at increased risk of developing the milk-alkali syndrome, because of their reduced ability to excrete excess calcium. Hypercalcaemia may also occur in patients taking chlortalidone with agents that increase calcium levels. such as vitamin D.
Chlorthalidone may interfere with a number of diagnostic tests, including tests for parathyroid function., serum concentrations of protein-bound iodine may increase without signs of thyroid disturbance. Reported to diminish the response to pressor amines, such as noradrenaline.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdosage with atenolol may produce bradycardia and severe hypotension. Bronchospasm and heart failure may be produced in certain individuals. Coma and convulsions have been reported following beta-blocker (atenolol) overdosage.
Cases of mild overdose should be observed for at least 4 hours, as apnoea and cardiovascular collapse may appear suddenly. Gastric lavage should be performed if within 4 hours of suspected overdose. Repeated activated charcoal is necessary in severe overdosage. 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 intra-venous aminophylline or inhaled, or intra-venous beta-agonist, eg salbutamol. With overdosage of chlorthalidone, treatment should be symptomatic and supportive and directed at fluid and electrolyte replacement.

IDENTIFICATION:
Tenchlor tablets: A white to cream biconvex film-coated tablet, bisected on one side and engraved with the word “TENCHLOR”on the other side.
Tenchlor HS tablets: A white to cream, film-coated tablet, bisected on one side.

PRESENTATION:
Securitainers of 30 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C.
Store in well-closed containers.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
Tenchlor tablets:         W/7.1.3/53
Tenchlor HS tablets:         Z/7.1.3/96

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pharmacare Limited
7 Fairclough Road
Korsten
PORT ELIZABETH
6020

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
11 April 1989
                        D828
A&S PRINTERS

Updated on this site: October 2004
Source: Community Pharmacy

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