Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Trandate Tablets are indicated for the treatment of:

1. Mild, moderate or severe hypertension

2. Hypertension in pregnancy

3. Angina pectoris with existing hypertension

Adult Dosage

Trandate tablets should be taken orally with food.

Adults:

Hypertension

Treatment should start with 100mg 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 the hypertension of pregnancy

The initial dose of 100mg twice daily may be increased, if necessary, at weekly intervals by 100mg twice daily. During the second and third trimester, the severity of the hypertension may require further dose titration to a three times daily regimen, ranging from 100mg tds to 400mg tds. A total daily dose of 2400mg should not be exceeded.

Hospital in-patients with severe hypertension, particularly of pregnancy, may have daily increases in dosage.

General

If rapid reduction of blood pressure is necessary, see the SPC for Trandate Injection. If long-term control of hypertension following the use of Trandate Injection is required, oral therapy with Trandate tablets should start with 100mg twice daily.

Additive hypotensive effects may be expected if Trandate tablets are administered together with other antihypertensives e.g. diuretics, methyldopa etc. When transferring patients from such agents, Trandate tablets should be introduced with a dosage of 100mg twice daily and the previous therapy gradually decreased. Abrupt withdrawal of clonidine or beta-blocking agents is undesirable.

Angina co-existing with hypertension

In patients with angina pectoris co-existing with hypertension, the dose of Trandate will be that required to control the hypertension.

Child Dosage

Safety and efficacy in children have not been established.

Elderly Dosage

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

Contra Indications

• 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.

Special Precautions

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.

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 Trandate therapy.

Patients particularly those with ischemic heart disease, should not interrupt/ discontinue abruptly Trandate therapy. The dosage should gradually be reduced, ie. 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 Trandate therapy in patients requiring anaesthesia but the anaesthetist must be informed and the patient should be given intravenous atropine prior to induction. If beta-blockade is interrupted in preparation for surgery, therapy should be discontinued for at least 24 hours. Anaesthetic agents causing myocardial depression (eg. cyclopropane, trichloroethylene) should be avoided. Trandate 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.

Beta-blockers, even those with apparent cardioselectivity, should not be used in patients with asthma or a history of obstructive airways disease unless no alternative treatment is available. In such cases the risk of inducing bronchospasm should be appreciated and appropriate precautions taken. If bronchospasm should occur after the use of Trandate it can be treated with a beta2-agonist by inhalation, e.g. salbutamol (the dose of which may need to be greater than the usual in asthma) and, if necessary, intravenous atropine 1mg.

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.

Patients with a history of psoriasis should take beta-blockers only after careful consideration.

Risk of anaphylactic reaction: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

The label will state “Do not take Trandate if you have a history of wheezing or asthma as it can make your breathing worse.”

Trandate Tablets contain sodium benzoate which is a mild irritant to the eyes, nose and mucous membranes. It may increase the risk of jaundice in newborn babies.

Interactions

Concomitant use not recommended:

• Calcium antagonists such as verapamil and to a lesser extent diltiazem have a negative influence on contractility and atrio-ventricular conduction.

• Digitalis glycosides used in association with beta-blockers may increase atrio-ventricular conduction time.

• Clonidine: Beta-blockers increase the risk of rebound hypertension. When clonidine is used in conjunction with non-selective beta-blockers, such as propranolol, treatment with clonidine should be continued for some time after treatment with the beta-blocker has been discontinued.

• Monoamineoxidase inhibitors (except MOA-B inhibitors).

Use with caution:

• Class I antiarrhythmic agents (eg. disopyramide, quinidine) and amiodarone may have potentiating effects on atrial conduction time and induce negative inotropic effect.

• Insulin and oral antidiabetic drugs may intensify the blood sugar lowering effect, especially of non-selective beta-blockers. Beta- blockade may prevent the appearance of signs of hypoglycaemia (tachycardia).

• Anaesthetic drugs may cause attenuation of reflex tachycardia and increase the risk of hypotension. Continuation of beta-blockade reduces the risk of arrhythmia during induction and intubation. The anaesthesiologist should be informed when the patient is receiving a beta-blocking agent. Anaesthetic agents causing myocardial depression, such as cyclopropane and trichlorethylene, are best avoided.

• Cimetidine, hydralazine and alcohol may increase the bioavailability of labetalol.

Take into account:

• Calcium antagonists : dihydropyridine derivates such as nifedipine. The risk of hypotension may be increased. In patients with latent cardiac insufficiency, treatment with beta-blockers may lead to cardiac failure.

• Prostaglandin synthetase inhibiting drugs may decrease the hypotensive effect of beta-blockers.

• Sympathicomimetic agents may counteract the effect of beta-adrenergic blocking agents.

• Concomitant use of tricyclic antidepressants, barbiturates, phenothiazines or other antihypertensive agents may increase the blood pressure lowering effect of labetalol. Concomitant use of tricyclic antidepressants may increase the incidence of tremor.

• Labetalol has been shown to reduce the uptake of radioisotopes of metaiodobenzylguanidine (MIBG), and may increase the likelihood of a false negative study. Care should therefore be taken in interpreting results from MIBG scintigraphy. Consideration should be given to withdrawing labetalol for several days at least before MIBG scintigraphy, and substituting other beta or alpha-blocking drugs.

Adverse Reactions

Most side-effects are transient and occur during the first few weeks of treatment with Trandate. They include headache, tiredness, dizziness, depressed mood and lethargy, nasal congestion, sweating, and rarely, ankle oedema. Postural hypotension is uncommon except at very high doses or if the initial dose is too high or doses are increased too rapidly. A tingling sensation in the scalp, usually transient, also may occur in a few patients early in treatment. Tremor has been reported in the treatment of hypertension of pregnancy. Acute retention of urine, difficulty in micturition, ejaculatory failure, epigastric pain, nausea and vomiting have been reported.

There have been rare reports of positive anti-nuclear antibodies unassociated with disease, cases of systemic lupus erythematosus, drug fever, toxic myopathy, hypersensitivity (rash, pruritus, angioedema and dyspnoea), reversible lichenoid rash, impaired vision, dry eyes, cramps, raised liver function tests, jaundice (both hepatocellular and cholestatic), hepatitis and hepatic necrosis, bradycardia and heart block.

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.

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