TRANDATE

Adults:

Trandate Injection/Labetalol Injection is intended for intravenous use in hospitalised patients. The plasma concentrations achieved after intravenous dose of labetalol in severe hypertension are substantially greater than those following oral administration of the drug and provide a greater degree of blockade of alpha-adrenoceptors necessary to control the more severe disease.

Patients should, therefore, always receive the drug whilst in the supine or left lateral position. Raising the patient into the upright position, within three hours of intravenous labetalol administration, should be avoided since excessive postural hypotension may occur.

Bolus injection If it is essential to reduce blood pressure quickly, as for example, in hypertensive encephalopathy, a dose of 50mg of labetalol hydrochloride should be given by intravenous injection over a period of at least one minute.

If necessary, doses of 50mg may be repeated at five minute intervals until a satisfactory response occurs. The total dose should not exceed 200mg. After bolus injection, the maximum effect usually occurs within five minutes and the effective duration of action is usually about six hours but may be as long as eighteen hours.

Intravenous infusion An alternative method of administering labetalol is intravenous infusion of a solution made by diluting the contents of two ampoules (200mg) to 200ml with Sodium Chloride and Dextrose Injection BP or 5% Dextrose Intravenous Infusion BP.

The resultant infusion solution contains 1mg/ml of labetalol hydrochloride. It should be administered using a paediatric giving set fitted with a 50ml graduated burette to facilitate dosage.

In the hypertension of pregnancy:

The infusion can be started at the rate of 20mg per hour and this dose may be doubled every thirty minutes until a satisfactory reduction in blood pressure has been obtained or a dosage of 160mg per hour is reached. Occasionally, higher doses may be necessary.

In hypertensive episodes following acute myocardial infarction:

The infusion should be commenced at 15mg per hour and gradually increased to a maximum of 120mg per hour depending on the control of blood pressure.

Trandate Injection/Labetalol Injection is usually well tolerated. Excessive postural hypotension may occur if patients are allowed to assume an upright position within three hours of receiving Trandate Injection/Labetalol Injection.

Most side-effects are transient and occur during the first few weeks of treatment with labetalol.

They include:

Blood and the lymphatic system disorders Rare reports of positive antinuclear antibodies unassociated with disease, hyperkalaemia, particularly in patients who may have impaired renal excretion of potassium, thrombocytopenia. Psychiatric disorders Depressed mood and lethargy, hallucinations, psychoses, confusion, sleep disturbances, nightmares.

Nervous system disorders Headache, tiredness, dizziness, tremor has been reported in the treatment of hypertension of pregnancy. Eye disorders Impaired vision, dry eyes. Cardiac disorders Bradycardia, heart block, heart failure, hypotension.

Vascular disorders Ankle oedema, increase of an existing intermittent claudication, postural hypotension, cold or cyanotic extremities, Raynaud’s phenomenon, paraesthesia of the extremities. Respiratory, thoracic and mediastinal disorders Bronchospasm (in patients with asthma or a history of asthma), nasal congestion, interstitial lung disease.

Gastrointestinal disorders Epigastric pain, nausea, vomiting, diarrhoea. Hepato-biliary disorders Raised liver function tests, jaundice (both hepatocellular and cholestatic), hepatitis and hepatic necrosis. Skin and subcutaneous tissue disorders Sweating, tingling sensation in the scalp, usually transient, may occur in a few patients early in treatment, reversible lichenoid rash, systemic lupus erythematosus, exacerbation of psoriasis.

Musculoskeletal, connective tissue and bone disorders:

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. Gradual discontinuance of the drug should be considered if any such reaction is not otherwise explicable.

The occurrence of intraoperative floppy iris syndrome (IFIS, a variation of Horner’s syndrome) has been observed during cataract surgeries in some patients who were being treated with tamsulosine, or have been treated with tamsulosine in the past.

IFIS has also been reported when other alpha-1-blockers were being used, and the possibility of a class effect cannot be excluded. Since IFIS can lead to a higher chance of complications during cataract surgeries, the ophthalmologist needs to be informed if alpha-1-blockers are currently being used, or have been used in the past.

There have been rare reports of severe hepatocellular injury with labetalol therapy. The hepatic injury is usually reversible and has occurred after both short and long term treatment. Appropriate laboratory testing should be done at the first sign or symptom of liver dysfunction.

If there is laboratory evidence of liver injury or the patient is jaundiced, labetalol therapy should be stopped and not re-started. Due to negative inotropic effects, special care should be taken with patients whose cardiac reserve is poor and heart failure should be controlled before starting labetalol therapy.

Patients, particularly those with ischemic heart disease, should not interrupt/discontinue abruptly labetalol therapy. 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. It is not necessary to discontinue labetalol therapy in patients requiring anaesthesia, but the anaesthetist must be informed and the patient should be given intravenous atropine prior to induction.

• Cardiogenic shock. • Uncontrolled, incipient or digitalis refractory heart failure. • Sick sinus syndrome (including sino-atrial block). • Second or third degree heart block. • Prinzmetal’s angina. • History of wheezing or asthma. • Untreated phaeochromocytoma.

• Metabolic acidosis. • Bradycardia (<45-50 bpm). • Hypotension. • Hypersensitivity to labetalol. • Severe peripheral circulatory disturbances. • Where peripheral vasoconstriction suggests low cardiac output, the use of Trandate Injection/Labetalol Injection to control hypertensive episodes following acute myocardial infarction is contra-indicated.