LABETALOL

Route of administration:

Oral Labetalol tablets should be taken with food.

Adults:

Hypertension: Treatment should start with one 100mg tablet twice daily. In patients already being treated with antihypertensives and in those of low body weight this may be sufficient to control blood pressure. In others, increases in dose of 100mg twice daily should be made at fortnightly intervals.

Many patients blood pressure is controlled by 200mg twice daily and up to 800mg daily may be given as a twice daily regimen. In severe, refractory hypertension, daily doses up to 2400mg have been given. Such doses should be divided into a three or four times a day regimen.

In hypertensive patients with angina:

The recommended dose of labetalol tablets will be that required to control the hypertension.

Use with other agents:

Hypertension is usually controlled by labetalol alone. Diuretic therapy is not usually necessary in patients receiving labetalol tablets, but may be introduced or continued if required. Diuretics usually increase the antihypertensive action of labetalol.

If labetalol tablets are prescribed together with another antihypertensive drug, such as methyldopa or clonidine, an additive effect may be expected. When transferring patients from other drugs, labetalol tablets should be introduced with a dosage of 100mg twice daily and the dosage of the existing therapy progressively decreased.

Abrupt withdrawal of clonidine or beta-adrenoceptor blockers is undesirable.

Children:

Safety and efficacy in children has not been established.

Elderly:

In elderly patients, an initial dose of 50mg twice daily is recommended. This has provided satisfactory control in some cases.

Side effects usually occur in the first few weeks of treatment and most are transient. Effects include headache, tiredness, depressed mood, lethargy, dizziness, sweating, nasal congestion and rarely ankle oedema. A few patients may get a transient tingling in the scalp early in treatment.

Postural hypotension is uncommon except at very high doses or if the initial dose it too high or doses are increased too rapidly. Reports of other effects include acute retention of urine, difficulty in micturition, ejaculatory failure, epigastric pain, nausea and vomiting.

There have been rare reports of positive anti-nuclear antibodies unassociated with disease as well as rare reports of systemic lupus erythematosus and very rarely drug fever. There are rare reports of bradycardia and heart block. There are very rare reports of toxic myopathy.

In the treatment of hypertension of pregnancy, tremor has been reported. If the initial dose is too high, adjustment of the dose is too rapid or the patient is on a very high dose, then postural hypotension may occur; this is otherwise uncommon.

There are rare reports of hypersensitivity including rash, pruritus, angioedema, dyspnoea and a reversible lichenoid rash. Reports of other effects which are not necessarily related to labetalol include blurred vision, eye irritation and cramps.

On rare occasions labetalol has been associated with jaundice (both hepatocellular and cholestatic), raised liver function tests, hepatitis and hepatic necrosis. It is therefore recommended that treatment with labetalol should be discontinued should a patient develop jaundice, since the latter has been shown to be reversible on stopping the drug.

Other possible side effects of beta-blockers are: heart failure, cold or cyanotic extremities, Raynaud’s phenomenon, paraesthesia of the extremities, increase of an existing intermittent claudication, hallucinations, psychoses, confusion, sleep disturbances, nightmares, diarrhoea, bronchospasm (in patients with asthma or a history of asthma), masking of the symptoms of thyrotoxicosis or hypoglycaemia.

Reproductive system and breast disorders Frequency ‘not known’:

Nipple pain, Raynaud's phenomenon of the nipple

4. Special Warnings and Special Precautions For Use Severe hepatocellular injury has rarely been reported and can occur after both short and long term treatment but is usually reversible. At the first sign or symptom of liver problems laboratory testing should be performed and if there is any evidence of liver injury, or if the patient is jaundiced then labetalol should be discontinued and not re-started.

There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenoceptor blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when the treatment was withdrawn. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable.

Care should be taken in patients whose cardiac reserve is poor. Heart failure should be controlled with a cardiac glycoside and diuretic therapy before treatment is initiated. Labetalol should not normally be given to patients with digitalis-resistant heart failure or atrio-ventricular block.

Especially in patients with ischaemic heart disease, treatment should not be discontinued suddenly. e. over 1-2 weeks, if necessary at the same time initiating replacement therapy, to prevent exacerbation of angina pectoris. In addition, hypertension and arrhythmias may develop.

Caution is required when administering anaesthetic agents to patients receiving Labetalol. The anaesthetist must always be informed of the use of a beta- adrenoceptor blocking drug. The patient should receive intravenous atropine prior to induction.

When it has been decided to interrupt a beta-blockade in preparation for surgery, therapy should be discontinued for at least 24 hours. g. cyclopropane, trichloroethylene) should be avoided. Labetalol may enhance the hypotensive effects of halothane.

In patients with peripheral circulatory disorders (Raynaud’s disease or syndrome, intermittent claudication), beta-blockers should be used with great caution as aggravation of these disorders may occur. Beta-blockers may induce bradycardia.

If the pulse rate decreases to less than 50-55 beats per minute at rest and the patient experiences symptoms related to the bradycardia, the dosage should be reduced. Due to a negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree heart block.

Patients with liver or kidney insufficiency may need a lower dosage, depending on the pharmacokinetic profile of the compound. The elderly should be treated with caution, starting with a lower dosage but tolerance is usually good in the elderly.

Labetalol should not be used to treat asthmatic patients or individuals prone to bronchospasm unless there is no alternative. The label will carry the following warning: “Do not take this medicine if you have a history of wheezing or asthma.

Consult your doctor or pharmacist first”. The risk of inducing bronchospasm must be appreciated and appropriate precautions taken. Any resultant bronchospasm may be controlled by an inhaled selectively-acting bronchodilator such as salbutamol; the required dose may be greater than the normal anti-asthmatic dose.

If further treatment is required, intravenous atropine 1mg should be given. Beta-blockers may increase the number and the duration of anginal attacks in patients with Prinzmetal’s angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction.

Non-selective beta-blockers should not be used for these patients, and beta-1 selective blockers only with the utmost care. Patients with a history of psoriasis should take beta-blockers only after careful consideration. In patients with a history of severe anaphylactic reaction the use of beta- blockers may mean the patient is more reactive to repeated challenge.

These patients may be unresponsive to the usual doses of adrenaline (epinephrine) used to treat allergic reaction. The label will state “Do not take labetalol if you have a history of wheezing or asthma as it can make your breathing worse”.

Patient with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.

3. Contra-Indications Labetalol tablets are contraindicated in patients with • Cardiogenic shock • Uncontrolled heart failure • Sick sinus syndrome (including sino-atrial block) • Second and third degree heart block • Printzmetal’s angina • History of bronchospasm and bronchial asthma • Untreated phaeochromocytoma • Metabolic acidosis • Bradycardia (<45-50 bpm) • Hypotension • Hypersensitivity to labetalol or any of the excipients used in the tablet • Severe peripheral circulatory disturbances