Tenchlor, Tenchlor Hs 100 mg/25 mg/50 mg/12,5 mg

TENCHLOR is indicated for:

• The management of mild to moderate hypertension.

Posology

Adults

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. 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.

Special populations

Elderly population TENCHLOR should not be used in elderly patients, without reducing the normal dose (see section 4.3).

Renal impairment TENCHLOR should not be given to patients with severe renal impairment or anuria (see section 4.3).

Hepatic impairment TENCHLOR should be avoided in patients with severe hepatic impairment, in whom encephalopathy may be precipitated (see section 4.3).

Paediatric population TENCHLOR is not recommended for children.

Method of administration For oral administration.

TENCHLOR is contraindicated in:

• Patients with hypersensitivity to atenolol and chlorthalidone or any excipients in TENCHLOR (see section 6.1).
• Patients with partial heart block, heart failure, metabolic acidosis or sinus bradycardia, and should never be given to patients with untreated phaeochromocytoma without concomitant alpha-adrenoceptor blocking therapy.
• Patients taking verapamil concomittently, neither medicine should be administered within several days of discontinuing the other.
• Patients with bronchial asthma, bronchitis, bronchospasm or chronic respiratory diseases, atrioventricular block, marked bradycardia (less than 50 beats per minute), heart failure refractory to digitalis, uraemia, hypoglycaemia, second and third degree heart block, peripheral vascular diseases and Raynaudu2019s phenomenon.
• Patients with severe hepatic impairment, in whom encephalopathy may be precipitated.
• Pregnancy and lactation.
• Elderly patients, or in patients suffering from renal dysfunction without reducing the normal dose of TENCHLOR.
• Patients with severe renal impairment or anuria.
• Patients with Addisonu2019s disease.
• Patients 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 patientu2019s normal tachycardiac response to hypo -volaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard.
• Patients with pre-existing hypercalcaemia.
• Cardiogenic shock.
• Hypotension.
• Sick sinus syndrome.
• Severe renal failure.
• Uncontrolled heart failure.
• Patients with metabolic acidosis (e.g. in diabetes) and after prolonged fasting.

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 when 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 (see section 4.3). Due to its beta-blocker component in TENCHLOR tablets:

• Atenolol as contained in TENCHLOR may mask the symptoms of hyperthyroidism. It may also mask the symptoms of hypoglycaemia, as well as enhance the effects of hypoglycaemic medicines 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, as in TENCHLOR.
• 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 of negative chronotropic effects of the two medicines. Careful control of dosages and of the individual patientu2019s response (and notably pulse -rate) is essential in this situation.
• Abrupt withdrawal of therapy has sometimes resulted in angina, myocardial infarction, ventricular dysrhythmias and death. Discontinuation of therapy should be gradual (1 to 2 weeks) and patients should be advised to limit the extent of their physical activity during the period that the medicine is being discontinued.
• Although contraindicated in uncontrolled heart failure (see section 4.3) it 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, as in TENCHLOR, is a beta 1 -selective beta-blocker; consequently the use of TENCHLOR tablets may be considered although utmost caution must be exercised.
• Although contraindicated in severe peripheral arterial circulatory disturbances (see section 4.3) it 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 modify warning signs of hypoglycaemia such as tachycardia, palpitation and sweating.
• May mask the cardiovascular 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, the dose may be reduced.
• Should not be discontinued abruptly in patients suffering from ischaemic heart disease.
• 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 used to treat the allergic reactions.
• May cause a hypersensitivity reaction including angioedema and urticaria (see section 4.8).
• Patients with bronchospastic disease should, in general, not receive beta-blockers due to an increase in airways resistance. Atenolol, as in TENCHLOR, is a beta 1 -selective beta-blocker; however this selectivity is not absolute. Therefore the lowest possible dose of TENCHLOR tablets should be used and utmost caution must be exercised. If increased airways resistance does occur, TENCHLOR tablets should be discontinued and bronchodilator therapy (e.g. salbutamol) administered if necessary.
• The label and patient information leaflet for this medicine state the following warning: u201cIf you have ever had asthma or wheezing, do not take this medicine without first checking with your healthcare professionalu201d.
• Systemic effects of oral beta-blockers may be potentiated when used concomitantly with ophthalmic beta-blockers.
• In patients with phaeochromocytoma it must be administered only after alfa-receptor blockade. Blood pressure should be monitored closely.
• Caution must be exercised when using anaesthetic medicines with TENCHLOR tablets. The anaesthetist should be informed and the choice of anaesthetic should be a medicine with as little negative inotropic activity as possible. Use of beta-blockers with anaesthetic medicines may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anaesthetic medicines causing myocardial depression are best avoided.

Chlorthalidone

Due to its chlorthalidone component:

• Chlorthalidone as contained in TENCHLOR 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.
• Plasma electrolytes should be periodically determined in appropriate intervals to detect possible electrolyte imbalance especially hypokalaemia and hyponatraemia.
• Hypokalaemia and hyponatraemia may occur. Measurement of electrolytes is recommended, especially in the older patient, those receiving digitalis preparations for cardiac failure, those taking an abnormal (low in potassium) diet or those suffering from gastrointestinal complaints. Hypokalaemia may predispose to dyshythmias in patients receiving digitalis.
• Impaired glucose tolerance may occur and diabetic patients should be aware of the potential for increased glucose levels. Close monitoring of glycaemia is recommended in the initial phase of therapy and in prolonged therapy testing for glucosuria should be carried out at regular intervals.
• There is an increased risk of patients taking chlorthalidone as contained in TENCHLOR developing cholecystitis.
• Chlorthalidone as contained in TENCHLOR 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 as contained in TENCHLOR may exacerbate or activate systemic lupus erythematosus in susceptible patients.
• In patients with impaired hepatic function or progressive liver disease, minor alterations in fluid and electrolyte balance may precipitate hepatic coma.
• Hyperuricaemia may occur. Only a minor increase in serum uric acid usually occurs but in cases of prolonged elevation, the concurrent use of a uricosuric medicine will reverse the hyperuricaemia.

TENCHLOR is contraindicated in pregnancy and lactation (see section 4.3).

Pregnancy 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. Chlorthalidone as contained in TENCHLOR 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.

Breastfeeding Atenolol as contained in TENCHLOR is excreted into breast milk. Consult your medical practitioner. Chlorthalidone as contained in TENCHLOR is excreted and distributed in the breast milk. Treatment with chlorthalidone as contained in TENCHLOR can inhibit lactation.

Fertility No data on fertility available.

TENCHLOR has minor influence on the ability to drive and use machines. Since adverse reactions such as dizziness, drowsiness and visual disturbances have been reported in patients receiving TENCHLOR, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that TENCHLOR does not adversely affect their ability to do so (see section 4.4 and 4.8).

a) Tabulated list of adverse reactions

System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data)

• Blood and the lymphatic system disorders Purpura, thrombocytopenia, leucopenia (related to chlorthalidone) granulocytopenia, aplastic and haemolytic anaemia, agranulocytosis Blood dyscrasias, transient eosinophilia
• Immune system disorders Hypersensitivity reactions, photosensitivity reactions
• Metabolism and nutrition disorders Fluid retention, weight gain Hyperglycaemia, glycosuria hypochloraemic alkalosis, hyponatraemia, gout, hypokalaemia, hypercalcaemia, hypomagnesaemia, increased concentration of low-density and very low-density lipoprotein cholesterol, as well as of triglycerides, electrolyte imbalance, anorexia
• Psychiatric disorders Mood changes, nightmares, confusion, psychoses, hallucinations, sleep disturbances of the type noted with other beta blockers
• Nervous system disorders Dizziness, headache, paraesthesia Depression, peripheral neuropathy, myopathies
• Eye disorders Dry eyes, visual disturbances Decreased tear production, blurred vision, and soreness are among the ocular symptoms, yellow vision, choroidal effusion
• Ear and labyrinth disorders Loss of hearing
• Cardiac disorders Bradycardia Heart failure, deterioration, precipitation of heart block
• Vascular disorders Cold extremities 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 Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints, acute interstitial pneumonitis, acute pulmonary oedema, Pneumonitis, pleurisy, pulmonary fibrosis
• Gastrointestinal disorders Gastrointestinal disturbances (including nausea related to chlorthalidone) Dry mouth Constipation vomiting, diarrhoea, abdominal cramping, pancreatitis, stomatitis, sclerosing peritonitis, retroperitoneal fibrosis, gastric irritation
• Hepato-biliary disorders Hepatic toxicity including intrahepatic cholestasis, pancreatitis (related to chlorthalidone), Cholestatic jaundice
• Skin and subcutaneous tissue disorders Alopecia (reversible), psoriasiform skin reaction, exacerbation of psoriasis, skin rashes Angioedema and urticaria, pruritus
• Musculoskeletal and connective tissue disorders Lupus-like syndrome, muscle cramps
• Reproductive system and breast disorders Male impotence
• General disorders and administrative site conditions Fatigue Weakness, fever
• Investigations Elevations of transaminase levels, increase in ANA (Antinuclear Antibodies)

b) Description of selected adverse reactions

Atenolol Cardiac disorders Cardiovascular effects may be precipitated in patients with underlying cardiac disorders. Vascular disorder Reduced peripheral circulation can produce coldness of the extremities and may exacerbate peripheral vascular disease such as Raynaudu2019s syndrome. Abrupt withdrawal of beta-blockers may exacerbate angina and may lead to sudden death.

Respiratory, thoracic and mediastinal disorders Bronchospasm may occur, particularly in susceptible individuals..

Chlorthalidone Eye disorders Cases of choroidal effusion with visual field defect have been reported after the use of thiazide and thiazide-like diuretics.

Investigations 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 dysrhythmias. Signs of electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain and cramps, seizures, oliguria, hypotension, and gastrointestinal disturbances.

Immune system disorders 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.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to: SAHPRA: via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 Aspen Pharmacare: E-mail: [email protected] Tel: 0800 118 088

Symptoms 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.

Treatment General treatment should include close supervision, treatment in an intensive care ward, activated charcoal and a laxative to prevent absorption of any medicine still present in the gastrointestinal tract, the use of plasma or plasma substitutes to treat hypotension and shock. The possible use of haemodialysis or haemoperfusion may be considered. Excessive bradycardia may be countered with atropine 1 to 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 to 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 effects could 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. Excessive diuresis should be countered by maintaining normal fluid and electrolyte balance.