Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Hepatic disease
Caution must be observed in the presence of 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-term and long-term treatment. However, hepatic necrosis has been reported and in some cases been fatal. Laboratory testing should be done at the first sign or symptom of hepatic dysfunction. If laboratory results show hepatic injury or the patient is jaundiced, labetalol therapy should be discontinued and not resumed.
Particular caution must be observed when labetalol is used in patients with hepatic impairment, as these patients metabolise labetalol slower than patients without hepatic impairment. Lower doses may be required (see section 4.2 Posology and method of administration and 5.2 Pharmacokinetic properties - Specific patient populations).

Renal impairment
Caution must be observed when labetalol is used in patients with severe renal impairment (GFR = 15– 29 ml/min/1.73 m2).

Peripheral vascular disease
Labetalol should be used with caution in patients with peripheral vascular disease as their symptoms may deteriorate. Caution should be observed for patients with peripheral arterial disease (Raynaud syndrome, intermittent claudication), as labetalol may aggravate symptoms. Alpha blockers can counteract the unwanted effect of beta blockers.

Symptomatic bradycardia
The labetalol dose should be decreased if the patient develops symptomatic bradycardia.

First degree atrioventricular block
Due to the negative effect of beta blockers on atrioventricular conduction time, labetalol should be administered with caution to patients with first degree atrioventricular block.

Diabetes mellitus
Caution must be observed in the presence of uncontrolled or difficult-to-control diabetes. As with other beta blockers, labetalol can mask the symptoms of hypoglycaemia (tachycardia and tremor) in diabetic patients. The hypoglycaemic effect of insulin and oral hypoglycaemic agents may be amplified by beta blockers.

Thyrotoxicosis
Beta blockers can mask the symptoms of thyrotoxicosis, however thyroid function is not affected.

Hypersensitivity to beta blockers
Risk of anaphylactic reaction: While taking beta blockers, patients with a history of severe anaphylactic reaction to various allergens may become more reactive to repeated challenges, regardless of whether these are accidental, diagnostic or therapeutic. Such patients might not respond to the usual doses of adrenaline used to treat allergic reactions.

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

Labetalol can cause a paradoxical rise in blood pressure if there is a significantly elevated level of adrenaline in the blood, such as in phaeochromocytoma.

Skin rash and/or dry eyes
Skin rash and/or dry eyes have been reported in connection with the use of beta blockers. The reported incidence is small and in most cases the symptoms subsided once the treatment was discontinued. Gradual discontinuation of the drug should be considered if a reaction of this type cannot otherwise be explained.

Intraoperative Floppy Iris Syndrome
The development of intraoperative floppy iris syndrome (IFIS, a type of small pupil syndrome) has been observed in connection with cataract surgery in some patients who were treated with, or previously treated with, tamsulosin. Isolated reports have also been received concerning other alpha-1 blockers; the risk of a drug class effect cannot be excluded. Since IFIS can involve an increase in complications in connection with cataract surgery, the eye surgeon must be informed prior to the procedure of current or previous use of alpha-1 blockers.

Heart failure or impaired left ventricular function
Particular caution must be observed in patients with heart failure or impaired systolic left ventricular function. Labetalol is contraindicated in uncontrolled heart failure, but may be used with caution in symptom-free patients whose condition is well controlled. Heart failure is to be controlled with adequate treatment before using labetalol.

The use of beta blockers indicates a risk of the development or deterioration of heart failure or obstructive lung disease. In the case of heart failure, the heart muscle's contraction capacity must be maintained, and the failure must be compensated. Patients with reduced contraction capacity, especially the elderly, must be monitored regularly with regard to the development of heart failure.

It is strongly recommended that Trandate therapy should not be discontinued abruptly, especially in patients with heart failure or angina pectoris (risk of aggravated angina, myocardial infarction and ventricular fibrillation).

Inhaled anaesthetics
Caution should be observed in cases of concurrent treatment with inhaled anaesthetics (see section 4.5 Interaction with other medicinal products and other forms of interaction). It is not necessary to discontinue labetalol therapy prior to anaesthesia however the patient should receive intravenous atropine prior to the administration of the anaesthetic. Labetalol can amplify the hypotensive effects of volatile anaesthetics.

Metabolic acidosis and pheochromocytoma
Caution should be observed in cases of metabolic acidosis and pheochromocytoma. Labetalol should only be administered to patients with pheochromocytoma once adequate alpha blockade has been achieved.

Calcium antagonists
Caution should be observed if labetalol is used concurrently with calcium antagonists, especially calcium channel antagonists, which negatively affect contraction capacity and AV conduction.

Caution should be observed in cases of concurrent administration of adrenaline, verapamil or class I antiarrhythmics (see section 4.5 Interaction with other medicinal products and other forms of interaction).

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


Ischemic heart disease
Patients -particularly those with ischemic heart disease- should not interrupt or abruptly discontinue labetalol therapy. For patients with ischemic heart disease, the treatment should be phased out gradually over 7-10 days if possible.

Warnings regarding excipients:
Lactose:
Patients with any of the following rare hereditary conditions should not take this medicinal product: galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Sunset yellow (E110):
The medicinal product contains the colouring agent sunset yellow, which can cause hypersensitivity reactions.

Sodium benzoate: This medicinal product contains benzoate.

Effects on Driving

4.7 Effects on ability to drive and use machines

The use of labetalol probably has no influence on the patient's ability to drive or use machines.
However, it must be remembered that transient dizziness or fatigue may occur.