Atenolol

Based on theoretical at least data, simultaneous administration of atenolol with MAO inhibitors should be avoided at least before a previous 2-week interruption.

Concomitant use of atenolol with sympathomimetic agents, e.g. adrenaline (epinephrine), may counteract the effect of beta-blockers.

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.

Concomitant use of atenolol 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.

Class I anti-arrhythmic drugs (e.g. disopyramide) may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.

Concomitant therapy with dihydropyridines, e.g. nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.

Concomitant administration of atenolol with neuromuscular inhibitors (tocouvarin, etc.) may result in an increase in their activity.

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/1.73m² (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 and the intravenous dose should be 10 mg once every two days.

For patients with a creatinine clearance of less than 15 ml/min/1.73m² (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.

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.

Co-administration of atenolol with aminophylline has a competitive effect.

Amiodarone may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.

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.

Digitalis glycosides, in association with beta-blockers, may increase atrioventricular conduction time.

Concomitant administration of atenolol with ergotamine and prenylamine increases peripheral vasospasm and myocardial suppression, respectively.

Concomitant use of prostaglandin synthetase-inhibiting drugs, e.g. ibuprofen and indometacin, may decrease the hypotensive effects of beta-blockers.

Atenolol co-administered with isoproterenol, norepinephrine, dopamine or dobutamine and generally sympathomimetic amines may inhibit the action of the drug. There is also a risk of severe hypertension or prolonged hypotension.

Co-administration of atenolol with intravenous phenytoin may result in synergistic myocardial suppressive action.

Concomitant administration of atenolol with prazosin may cause acute orthostatic hypotension at the start of treatment.

Atenolol with drugs causing catecholamine deprivation, such as reserpine, may have synergistic action.

Atenolol may reduce the clearance of theophylline, particularly in smokers.

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.

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”.

Due to its negative effect on conduction time, caution must be exercised if atenolol is given to patients with first-degree heart block.

Although contraindicated in severe peripheral arterial circulatory disturbances, may also aggravate less severe peripheral arterial circulatory disturbances.

May increase the number and duration of angina attacks in patients with Prinzmetal’s angina due to unopposed alphareceptor mediated coronary artery vasoconstriction. Atenolol is a beta₁-selective beta-blocker; consequently, its use may be considered although utmost caution must be exercised.

Atenolol may mask the signs of thyrotoxicosis.

Caution should be exercised when atenolol is administered during pregnancy.

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.

Caution should be exercised when atenolol is administered to a woman who is breast-feeding.

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.

Atenolol has no or negligible influence on the ability to drive and use machines. However, it should be taken into account that occasionally dizziness or fatigue may occur.