Presentation and Status in Health Basket
The posology is expressed in propranolol base.
The recommended starting dose is 1 mg/kg/day which is divided into two separate doses of 0.5 mg/kg. It is recommended to increase the dose up to the therapeutic dose under medical supervision as follows: 1 mg/kg/day for 1 week, then 2 mg/kg/day for 1 week and then 3 mg/kg/day as a maintenance dose.
The therapeutic dose is 3 mg/kg/day, which is to be administered into 2 separate doses of 1.5 mg/kg, one in the morning and one in late afternoon, with a time interval of at least 9 hours between two intakes. The medicinal product is to be taken during or right after a feed.
If the child is not eating or is vomiting – skip the dose.
In case the child spits up a dose or does not take all of the medicine, no other dose should be given before the next scheduled dose.
During the titration phase, each dose increase must be managed and monitored by a physician in the same conditions as the administration of the initial dose. After the titration phase, the dose will be readjusted by the physician according to the changes in the child’s weight.
Clinical monitoring of the child condition, and dose readjustment, need to be performed at least monthly.
Duration of treatment: This medication should be administered for a 6-month period. Discontinuation of treatment does not require a progressive decrease in the dose. In the minority of patients showing a relapse of symptoms after treatment discontinuation, treatment may be re-initiated under the same conditions with a satisfactory response.
Specific populations: In the absence of clinical efficacy and safety data, this drug should not be used in children aged below 5 weeks.
There is no clinical efficacy and safety data in the clinical studies carried out with this drug to recommend its initiation in children aged above 5 months.
Infants with hepatic or renal impairment: In the absence of data, administration of the product is not recommended to infants with hepatic or renal impairment.
Method of administration: For oral use. This medication is to be given during or right after a feed to avoid the risk of hypoglycaemia. It should be administered directly into the child’s mouth using the graduated oral syringe, calibrated in mg of propranolol base, supplied with the oral solution bottle (see instructions for use in section 3 of the patient information leaflet).
The bottle should not be shaken before use.
Treatment of proliferating infantile haemangioma requiring systemic therapy:
– Life- or function-threatening haemangioma,
– Ulcerated haemangioma with pain and/or lack of response to simple wound car measures,
– Haemangioma with a risk of permanent scars or disfigurement.
It is to be initiated in infants aged 5 weeks to 5 months.
Premature infants, for whom the corrected age of 5 weeks has not been reached (the corrected age being calculated by subtracting the number of weeks of prematurity from the actual age).
Breastfed infants, if the mother is treated with medicines contraindicated with propranolol.
Hypersensitivity to the active substance or to any of the excipients.
Asthma or history of bronchospasm.
Second- or third-degree atrioventricular blocks.
Disease of the sinus node (including sinoatrial block).
Bradycardia below the following limits: child (0-3 months) whose heart beats = 100, child (3-6 months) whose heart beats = 90, child (6-12 months) whose heart beats = 80.
Low blood pressure below the following limits: child (0-3 months) whose blood pressure (mmhg) = 65/40, child (3-6 months) whose blood pressure (mmhg) = 70/50, child (6-12 months) whose blood pressure (mmhg) = 80/55.
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.
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.
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 in case of fasting, vomiting or overdose.
These 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.
In children with diabetes, blood glucose monitoring should be increased.
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.
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.
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.
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.
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.
See prescribing information for full details.
Bronchiolitis, Decreased appetite, Agitation Nightmares, Irritability, Somnolence, AV block, Peripheral coldness, Bronchospasm, Constipation, Abdominal pain, Erythema, Urticaria, Alopecia, Decreased blood pressure, Decreased blood glucose, Decreased heart rate, Neutropenia.
See prescribing information for full details.
In the absence of specific studies in children, the drug interactions with propranolol are those known in adults. Combinations should consider the 2 following situations (not mutually exclusive):
Infants given any other medicinal products, notably those mentioned below.
Infants breastfed by mothers taking any other medicinal products, notably those mentioned below. In this case, the need of stopping breast-feeding should be discussed.
A close clinical surveillance of any impaired tolerance of propranolol is requested.
Concommitant use not recommended: Bradycardia –inducing calcium-channel blockers (diltiazem, verapamil, bepridil): Co-administration with propranolol can cause altered automaticity (excessive bradycardia, sinus arrest), sino-atrial and atrio-ventricular conduction disorders, and increased risk of ventricular arrhythmias (torsades de pointes) along with heart failure.
This combination must only be administered under close clinical and ECG monitoring, particularly at the start of the treatment.
Interactions requiring caution
Cardiovascular Medicinal Products:
Antiarrhythmics: Propafenone has negative inotropic and beta-blocking properties that can be additive to those of propranolol, despite a reassuring study in healthy volunteers.
The metabolism of propranolol is reduced by co-administration of quinidine, leading to a two-three fold increased blood concentration and greater degrees of clinical beta-blockade.
Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with β-blockers such as propranolol. Automatism and conduction disorders are expected because of the suppression of sympathetic compensative mechanisms.
The metabolism of intravenous lidocaine is inhibited by co-administration of propranolol, resulting in a 25% increase in lidocaine concentrations. Lidocaine toxicity (neurological and cardiac adverse events) has been reported following co-administration with propranolol.
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
Dihydropyridines: Caution should be exercised when patients receiving a beta blocker are administered a dihydropyridine. Both agents may induce hypotension and/or heart failure in patients whose cardiac function is partially controlled because of additive inotropic effects. Concomitant use may reduce the reflex sympathetic response involved when excessive distal vasodilatation.
Antihypertensives (ACE Inhibitors, angiotensin II-receptors antagonists, diuretics, alpha-blockers whatever the indication, centrally-acting antihypertensives, reserpine, etc).
When combined with beta-blockers, drugs that decrease arterial pressure can cause or increase hypotension, notably orthostatic. With regard to centrally-acting antihypertensives, beta-blockers may exacerbate the rebound hypertension after clonidine abrupt withdrawal, and propranolol should be stopped several days before discontinuing clonidine.
Non-Cardiovascular Medicinal Products
Corticosteroids: Patients with infantile haemangioma may be at increased risk if they have received or are concomitantly receiving treatment with corticosteroids because adrenal suppression may result in loss of the counterregulatory cortisol response and increase the risk of hypoglycaemia. This also applies when children are breastfed by mothers treated with corticosteroids in case of high dosage or prolonged treatment.
Nonsteroidal Anti-Inflammatory Drugs: Non steroidal anti-inflammatory drugs (NSAIDS) have been reported to blunt the antihypertensive effect of beta-blocking agents.
Drugs inducing orthostatic hypotension: Drugs that induce postural hypotension (nitrates derivatives, type 5-phosphodiesterase inhibitors, tricyclic antidepressants, antipsychotics, dopaminergic agonists, levodopa, amifostine, baclofen…) may add their effects to that of beta-blockers.
Enzyme inducers: Blood levels of propranolol may be decreased by co-administration of enzyme inducers like rifampicin or phenobarbital.
Hypoglycaemic agents: All beta-blocking agents can mask certain symptoms of hypoglycaemia: palpitations and tachycardia.
Use of propranolol alongside hypoglycaemic therapy in diabetic patients should be with caution since it may prolong the hypoglycaemic response to insulin. In this case, inform the caregiver, and increase monitoring of blood glucose levels, particularly at the start of treatment.
Lipid lowering medicinal products: Co-administration of cholestyramine or colestipol with propranolol resulted in up to 50% decrease in propranolol concentrations.
They may depress myocardial contractility and vascular compensating response when administered with propranolol. Beta stimulating agents may be used to counteract the beta-blockade.
See prescribing information for full details.
Pregnancy and Lactation
Pregnancy: Not relevant.
Lactation: See prescribing information for full details.
The toxicity of beta-blockers is an extension of their therapeutic effects:
– Cardiac symptoms of mild to moderate poisoning are decreased heart rate and hypotension. Atrioventricular blocks, intraventricular conduction delays, and congestive heart failure can occur with more severe poisoning.
– Bronchospasm may develop particularly in patients with asthma.
– Hypoglycemia may develop and manifestations of hypoglycemia (tremor, tachycardia) may be masked by other clinical effects of beta-blocker toxicity.
Propranolol is highly lipid-soluble and may cross the blood brain barrier and cause seizures.
Support and treatment: The patient should be placed on a cardiac monitor, monitor vital signs, mental status and blood glucose. Intravenous fluids for hypotension and atropine for bradycardia should be given. Glucagon then catecholamines should be considered if the patient does not respond appropriately to intravenous fluid. Isoproterenol and aminophylline may be used for bronchospasm.
Compatibility: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage: Below 25°C. The drug should be kept in the bottle in the original carton in order to protect from light. Must not be freezed. The drug should be stored the bottle and the syringe together in the carton box between each use.