Presentation and Status in Health Basket
30 x 25 mg
30 x 50 mg
30 x 100 mg
The dose must always be adjusted to individual requirements of the patients, with the lowest possible starting dosage. The following are guidelines.
Angina Pectoris: Initially 50 mg once a day, the dosage being increased gradually to 100 mg after 1 week, as needed and tolerated.
Hypertension: Initially 25-50 mg once a day, the dosage being increased gradually to 100 mg a day after two weeks, as needed and tolerated.
Late Intervention after Acute Myocardial Infarction: For patients who present some days after suffering an acute myocardial infarction, an oral dose of Normiten 100 mg daily is recommended for long-term prophylaxis of myocardial infarction.
Elderly: Dosage requirements may be reduced, especially in patients with impaired renal function.
Children: There is no paediatric experience with Normiten and for this reason it is not recommended for use in children.
Renal Failure: Since Normiten is excreted via the kidneys the dosage should be adjusted in cases of severe impairment of renal function. No significant accumulation of Normiten occurs in patients who have a creatinine clearance greater than 35 ml/min/1.73 m2 (normal range is 100-150 ml/min/1.73m2 ). For patients with a creatinine clearance of 15-35 ml/min/1.73m2 (equivalent to serum creatinine of 300-600 micromol/litre) the oral dose should be 50 mg daily, or 100 mg once every 2 days. For patients with a creatinine clearance of less than 15 ml/min/1.73m2 (equivalent to serum creatinine of more than 600 micromol/litre) the oral dose should be 25 mg daily, or 50 mg on alternate days, or 100 mg every 4 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.
Hypertension, angina pectoris, 100 mg. Late intervention of myocardial infarction.
Normiten, 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 (<45bpm); hypotension; known hypersensitivity to the active substance, or any of the excipients; severe peripheral arterial circulatory disturbances.
Hypotension: Patients dependent on sympathetic stimulation to maintain adequate cardiac output and blood pressure, such as patients with hypotension in the setting of myocardial infarction, may not benefit from β-adrenergic blockade; studies of β-adrenergic blockade in the treatment of myocardial infarction excluded patients with systolic pressures less than 100 mm Hg. 2nd or 3rd degree AV block, sinus bradycardia, sick sinus syndrome, severe peripheral arterial disease, Printzmetal’s angina, uncompensated cardiac failure (except carvedilol), cardiogenic shock, hypotension, right ventricular failure secondary to pulmonary hypertension, significant cardiomegaly, untreated phaeochromocytoma, metabolic acidosis. Non-cardioselective ?blockers (nadolol, oxprenolol, penbutolol, pindolol, propranolol, timolol) are also generally contraindicated in patients with obstructive airways disease or a history of bronchospasm.
Normiten 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, 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 medi
ated coronary artery vasoconstriction. Normiten 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, 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 50-55bpm 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 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. Since Normiten is excreted via the kidneys, dosage should be reduced in patients with a creatinine clearance of below 35ml/min/1.7m2 . 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, Normiten 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. As with other beta-blockers, in patients with a phaeochromocytoma, an alphablocker should be given concomitantly.
Cold extremities, CNS and sleep disturbances (particularly with the more lipophilic drugs), bradycardia (less with carvedilol, pindolol), exertional tiredness, bronchospasm, heart failure, hypotension, GI upset, alopecia, thrombocytopenia. Withdraw gradually in unexplained dry eyes or skin rash. For full details see prescribing information.
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 sino-atrial or atrio-ventricular 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 atrio ventricular 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. Class I anti-arrhythmic drugs (e.g. disopyramide, quinidine) and amiodarone may have a potentiating effect on atrial-conduction time and induce negative inotropic effect. Concomitant use of sympathomimetic agents, e.g. adrenaline, 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 Concomitant use of prostaglandin synthetase inhibiting drugs (e.g. ibuprofen and indomethacin), may decrease the hypotensive effects of beta-blockers. Caution must be exercised when using anaesthetic agents with Normiten. 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.
Pregnancy and Lactation
Normiten crosses the placental barrier and appears in the cord blood. No studies have been performed on the use of Normiten in the first trimester and the possibility of foetal injury cannot be excluded. Normiten has been used under close supervision for the treatment of hypertension in the third trimester. Administration of Normiten to pregnant women in the management of mild to moderate hypertension has been associated with intra-uterine growth retardation. The use of Normiten 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 Normiten in breast milk. Neonates born to mothers who are receiving Normiten at parturition or breastfeeding may be at risk of hypoglycaemia and bradycardia. Caution should be exercised when Normiten is administered during pregnancy or to a woman who is breast-feeding.
The symptoms of overdose 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 use 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.