Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

Liver disease
Care should be taken in liver disease. There have been very 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. However, hepatic necrosis, in some cases with fatal outcome, has been reported. Appropriate laboratory tests 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.

Particular care should be taken when labetalol is used in patients with hepatic impairment as these patients metabolise labetalol more slowly than patients without hepatic impairment.

Renal impairment
Caution is advised when labetalol is used for patients with severe renal impairment (GFR = 15-29 mL/min / 1.73m2).

Peripheral vascular disease
Labetalol should be used with caution in patients with peripheral vascular disease as their symptoms may be exacerbated. Caution is advised in patients with peripheral arterial disease (Raynauds syndrome, claudicatio intermittens), as labetalol may exacerbate their symptoms. Alpha-block may counter the unfortunate effect of beta-blockers.

Symptomatic bradycardia
If the patient develops symptomatic bradycardia, then the dosage of labetalol should be reduced.

First-degree atrio ventricular block
Given the negative effect of beta-adrenoceptor blocking medicinal products on atrioventricular conduction time, labetalol should be administered with caution to patients with first-degree atrio- ventricular block.

Diabetes mellitus
Care should be taken in case of uncontrolled or difficult-to-control diabetes mellitus. As with other beta-adrenoceptor blocking medicinal products, labetalol may mask the symptoms of hypoglycaemia (tachycardia and tremor) in diabetic patients. The hypoglycaemic effect of insulin and oral hypoglycaemic agents may be enhanced by beta blockers.

Labetalol S.A.L.F contains 49.5 mg/ml of glucose monohydrate. This should be taken into account in patients with diabetes mellitus.

Thyrotoxicosis
Beta blockers may mask the symptoms of thyrotoxicosis, but the thyroid function is not altered.

Hypersensitivity to beta blockers
Risk of anaphylactic reaction: When 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 an allergic reaction.

Adrenaline
If patients receiving labetalol require adrenaline treatment, a reduced dosage of adrenaline should be used as concomitant administration of labetalol with adrenaline may result in bradycardia and hypertension (see section 4.5 Interaction with other medicinal products and other forms of interaction).

Upon severe influence of adrenaline as in phaeochromocytoma, labetalol may cause a paradoxical blood pressure elevation.

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

Intraoperative Floppy Iris Syndrome
The occurrence of intraoperative Floppy Iris Syndrome (IFIS, a variant of Small Pupil Syndrome) has been observed during cataract surgery in some patients on, or previously treated with, or previously treated with tamsulosin. Isolated reports have also been received with other alpha-1 blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during the cataract operation, current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery.

Heart failure or poor left ventricular function
Special care should be taken with patients who suffer from heart failure or poor left ventricular systolic function. Labetalol is contraindicated in uncontrolled heart failure, but may be used with caution in patients who are well managed and free of symptoms. Heart failure should be controlled with appropriate therapy before use of labetalol.

Use of beta blockers implies a risk of inducing or exacerbating heart failure or obstructive lung disease. In case of heart failure the myocardial contractility should be maintained and the failure should be compensated. Patients with reduced contractility, particularly the elderly, should be monitored regularly for development of heart failure.
It is strongly recommended not to stop treatment with Labetalol Hydrochloride abruptly, especially in patients with heart failure and patients with angina pectoris (risk of exacerbation of angina, myocardial infarction and ventricular fibrillation).

Inhaled anaesthetics
Care should be taken with concomitant treatment with inhaled anaesthetics (see section 4.5 Interaction with other medicinal products and other forms of interaction). Labetalol need not be discontinued prior to anaesthesia but patients should receive I.V. atropine prior to induction.
Labetalol may enhance the hypotensive effects of volatile anaesthetics.

Metabolic acidosis and phaeochromocytoma
Care should be taken in case of metabolic acidosis and phaeochromocytoma. In patients with phaeochromocytoma, labetolol may be administered only after an adequate alpha-blockade is achieved.

Calcium antagonists
Care should be taken if labetalol is used concomitantly with calcium antagonists, particularly the “calcium entry blockers”, which influence contractility and AV conduction negatively.

Care should be taken with concomitant administration of adrenaline, verapamil or a class-1 antiarrhythmics (see section 4.5 Interaction with other medicinal products and other forms of interaction).

Beta blockers have a negative inotropic effect, but does not affect the positive inotropic effect of digitalis.

Sudden haemorrhage
During anaesthesia, labetalol may mask the compensatory physiological responses of sudden haemorrhage (tachycardia and vasoconstriction). Close attention must therefore be paid to blood loss and the blood volume maintained.

Administration
It desirable to monitor the blood pressure and heart rate after the injection and during infusion. In most patients, there is a small decrease in the heart rate; severe bradycardia is unusual but may be controlled by injecting atropine 1 to 2 mg intravenously.

Respiratory function should be observed, particularly in patients with any known impairment.
Once the blood pressure has been adequately reduced by bolus injection or infusion, maintenance therapy with labetalol tablets should be substituted with a starting dose of 100 mg twice daily.
Labetalol injection has been administered to patients with uncontrolled hypertension already receiving other hypotensive agents, including beta-blockers medicinal products, without adverse effects.

Important information about some of the excipients:

This medicine contains less than 1 mmol sodium (23 mg) per one ampoule of 20 ml, that is to say essentially ‘sodium-free’.
This medicine contains 49.5 mg/ml glucose monohydrate. This should be taken into account in patients with diabetes mellitus.


Effects on Driving

4.7    Effects on ability to drive and use machines
Not relevant.