Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Initiation of treatment
Prior to initiating propranolol therapy, screening for risks associated with propranolol use must be performed. An analysis of the medical history and a full clinical examination must be performed including heart rate, cardiac and pulmonary auscultation.
In case of suspected cardiac abnormality, a specialist advice must be sought before treatment initiation to determine any subjacent contra-indication.
In case of acute broncho-pulmonary abnormality, the initiation of the treatment should be postponed.

Hypoglycaemia
Propranolol prevents the response of endogenous catecholamines to correct hypoglycaemia. It masks the adrenergic warning signs of hypoglycaemia, particularly tachycardia, shakiness, anxiety and hunger. It can aggravate hypoglycaemia in children, especially during fasting period (e.g. poor oral food intake, infection, vomiting), when glucose demands are increased (cold, stress, infections), or in case of overdose.
Hypoglycaemic episodes associated with the taking of propranolol may present exceptionally in the form of seizures and/or coma. If clinical signs of hypoglycaemia occur, it is necessary to make the child drink a sugary liquid solution and to temporarily stop the treatment. Appropriate monitoring of the child is required until symptoms disappear.

Prescribers should inform carers/parents on the risk of serious hypoglycaemia that remains equally prominent throughout the whole treatment period and emphasize the need to respect the dosing recommendations (see section 4.2).

Carers should be provided guidance on how to recognise the clinical signs of hypoglycaemia in order to:
• immediately treat the hypoglycaemic condition to prevent life-threatening situations, • contact a doctor or to go straight to hospital,
• discontinue the treatment.

In children with diabetes, blood glucose monitoring should be more frequent and followed by the endocrinologist.

Respiratory disorders
In the event of lower respiratory tract infection associated with dyspnoea and wheezing, treatment should be temporarily discontinued. The administration of beta2 agonists and inhaled corticosteroids is possible. The readministration of propranolol may be considered when the child has fully recovered; in case of reoccurrence, treatment should be permanently discontinued.
In the event of isolated bronchospasm, treatment must be permanently discontinued.

Cardiovascular disorders
Propranolol, due to its pharmacological action, may cause or worsen bradycardia or blood pressure abnormalities. Bradycardia should be diagnosed if the heart rate declines by more than 30 bpm from baseline. Bradycardia is defined below the following limits: Age                         0-3 months            3-6 months            6-12 months Heart rate (beats/min)      100                   90                    80 
After the first intake and each dose increase, a clinical monitoring, including blood pressure and heart rate must be performed at least hourly for at least 2 hours. In case of symptomatic bradycardia or bradycardia under 80 bpm, immediate specialist advice must be sought.
In case of severe and/or symptomatic bradycardia or hypotension occurring at any time during treatment, treatment must be discontinued and a specialist advice should be sought.

Cardiac Failure:
Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta blockade may precipitate more severe failure. In children with cardiac failure, the treatment should be managed by the cardiologist.

PHACE syndrome
Very limited safety data of propranolol in PHACE syndrome patients are available.
Propranolol may increase the risk of stroke in PHACE syndrome patients with severe cerebrovascular anomalies by dropping blood pressure and attenuating flow through occluded, narrow, or stenotic vessels.
Infants with large facial infantile hemangioma should be thoroughly investigated for potential arteriopathy associated with PHACE syndrome, with magnetic resonance angiography of the head and neck and cardiac imaging to include the aortic arch, prior to considering propranolol therapy.
Specialized advice should be sought.

Breast-feeding:
Propranolol passes through breast milk, mothers being treated with propranolol who breastfeed their infant should inform their health care professional.

Liver or kidney failure
Propranolol is metabolised in the liver and excreted by the kidneys. In the absence of data in children, propranolol is not recommended in case of renal or hepatic impairment (see section 4.2).

Hypersensitivity
In patients likely to experience severe anaphylactic reaction, regardless of origin, particularly with iodinated contrast agents, beta-blocker treatment may lead to worsening of the reaction and resistance to its treatment with adrenaline at normal doses. In children who are at risk of anaphylaxis, the benefit risk of the medicinal product should be evaluated.

General anaesthesia
Beta-blockers will result in an attenuation of reflex tachycardia and an increased risk of hypotension. It is necessary to alert the anaesthetist to the fact that the patient is being treated with beta-blockers.
When a patient is scheduled for surgery, beta-blocker therapy should be discontinued at least 48 hours prior to the procedure.

Hyperkaliemia
Hyperkaliemia cases have been reported in patients with large ulcerated hemangioma. A monitoring of electrolyte should be performed in these patients.

Psoriasis
Worsening of disease has been reported with beta-blockers in patients suffering from psoriasis.
Therefore the need for treatment should be carefully weighed up.

Excipients with known effects
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’.
This medicinal product contains 2.08 mg of propylene glycol/kg/day. Caution should be taken into account in babies less than 4 weeks old, in particular if the baby is given other medicines that contain propylene glycol or alcohol.
Co-administration with any substrate for alcohol dehydrogenase such as ethanol may induce serious adverse effects in neonates.

Effects on Driving

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