Hemangiol
1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 

1 NAME OF THE MEDICINAL PRODUCT 
 
HEMANGIOL 3.75 mg/mL oral solution 
 
 

2 QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 ml of solution contains 4.28 mg of propranolol hydrochloride equivalent to 3.75 mg of propranolol 
base. 
 
Excipients with known effect:  
1 ml of solution contains 
Propylene glycol………………………………………………….2.60 mg. 
 
 
For the full list of excipients, see section 6.1. 
 
 

3 PHARMACEUTICAL FORM 
 
Oral solution.  
Clear, colourless to slightly yellow oral solution, with a fruity odour. 
 

4 CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
HEMANGIOL is indicated in the 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 care measures, 
• Haemangioma with a risk of permanent scars or disfigurement. 
It is to be initiated in infants aged 5 weeks to 5 months (see section 4.2). 
 
4.2 Posology and method of administration 
 
Treatment with HEMANGIOL should be initiated by physicians who have expertise in the diagnosis, 
treatment and management of infantile haemangioma, in a controlled clinical setting where adequate 
facilities for handling of adverse reactions, including those requiring urgent measures, are available. 
 
Posology 
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. HEMANGIOL is to be given during or right after a feed to avoid the risk of hypoglycaemia. 
If the child is not eating or is vomiting it is recommended to skip the dose.  



3 

In case the child spits up a dose or does not take all of the medicinal product 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: 
HEMANGIOL 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. 
 
Paediatric populations 
In the absence of clinical efficacy and safety data, HEMANGIOL should not be used in infants aged 
below 5 weeks. 
There is no clinical efficacy and safety data in the clinical studies carried out with HEMANGIOL to 
recommend its initiation in infants and children aged above 5 months. 
 
Infants with hepatic or renal impairment  
In the absence of data, administration of the medicinal product is not recommended to infants with 
hepatic or renal impairment (see section 4.4). 
 
Method of administration  
Oral use. 
HEMANGIOL 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. 
If necessary, the medicinal product may be diluted in a small quantity of baby-milk or age-adapted 
apple and/or orange fruit juice. The medicine should not be put in the full filled bottle. 
The mixing may be done with one teaspoonful (approximately 5 mL) of milk for children weighing up 
to 5 kg, or with a tablespoonful (approximately 15 mL) of milk or fruit juice for children weighing 
more than 5 kg, delivered in a baby’s bottle. The mixing should be used within 2 hours. 
HEMANGIOL and the feed must be given by the same person in order to avoid the risk of 
hypoglycaemia. If different people are involved, good communication is essential in order to ensure 
the safety of the child. 
 
 
4.3 Contraindications 
 
• 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 medicinal products contraindicated with 

propranolol  
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1  
• Asthma or history of bronchospasm 
• Second- or third-degree atrioventricular blocks 
• Disease of the sinus node (including sinoatrial block) 
• Bradycardia below the following limits: 
Age 0-3 months 3-6 months 6-12 months 
Heart rate (beats/min) 100 90 80 



4 

 
• Low blood pressure below the following limits: 
Age 0-3 months 3-6 months 6-12 months 
Blood pressure (mmHg) 65/45 70/50 80/55 
 
• Cardiogenic shock 
• Heart failure not controlled by treatment 
• Prinzmetal’s angina 
• Severe peripheral arterial circulatory disturbances (Raynaud’s phenomenon) 
• Infants prone to hypoglycaemia  
• Phaeochromocytoma 
 
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. 
 
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. 
 
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 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. 
 



5 

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. 
Specialised 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. 
 



6 

4.5 Interaction with other medicinal products and other forms of interaction 
 
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 precautions for use 
 
Cardiovascular medicinal products 
 
Antiarrhythmics  
• Propafenone has negative inotropic and beta-blocking properties that can be additive to those of 

propranolol. 
• 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. 

 
Digitalis glycosides 
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. 
Concomitant use can increase the risk of bradycardia. The advice of a cardiologist should be sought. 
 
 
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, medicinal products 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. 
 



7 

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 (see section 4.4 concerning hypoglycaemia).  
 
 
Medicinal products inducing orthostatic hypotension 
Medicinal products 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. The advice of a cardiologist should be 
sought. 
 
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.  
 
Halogenated Anesthetic Agents 
They may depress myocardial contractility and vascular compensating response when administered 
with propranolol. Beta stimulating agents may be used to counteract the beta-blockade. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Not relevant. 
 
Breast-feeding 
Breastfeeding mothers: see section 4.4 and section 4.5. 
 
Fertility 
Although some reversible effects on male and female fertilities were reported in adult rats receiving 
high doses of propranolol in the literature, the study performed in juvenile animals did not show any 
effect on fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
In clinical trials for proliferating infantile haemangioma, the most frequently reported adverse 
reactions in infant treated with HEMANGIOL were sleep disorders (16.7%), aggravated respiratory 



8 

tract infections such as bronchitis and bronchiolitis associated with cough and fever, diarrhoea 
(16.5%), and vomiting (11.5%).  
Globally, the adverse reactions reported in the compassionate use program and in literature concerned 
hypoglycemia (and related event like hypoglycaemic seizure) and aggravated respiratory tract 
infections with respiratory distress. 
 
Tabulated list of adverse reactions 
The following table gives the adverse reactions, reported whatever dose and treatment duration, in 
three clinical studies, including 435 patients treated by HEMANGIOL at 1 mg/kg/day or 3 mg/kg/day 
for a maximum treatment duration of 6 months.  
Their frequency is defined using the following conventions: very common (≥ 1/10), common (≥ 1/100 
to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); 
not known (cannot be estimated from the available data). Due to the clinical trial database size rare 
and very rare categories are not represented. 
Within each system organ class, adverse reactions are presented in order of decreasing seriousness. 
 

 Very common  Common  Uncommon  Not known 
Infections and 
infestations 

Bronchitis  
 

Bronchiolitis   

Metabolism and 
nutrition 
disorders  

 Decreased 
appetite 

  

Psychiatric 
disorders 

Sleep disorder Agitation 
Nightmares 
Irritability 

  

Nervous system 
disorders 

 Somnolence  Hypoglycemic 
seizure 

Cardiac 
disorders 

  AV block Bradycardia 
 

Vascular 
disorders 

 Peripheral 
coldness 

 Hypotension 
Vasoconstriction 
Raynaud’s 
phenomenon 

Respiratory, 
thoracic and 
mediastinal 
disorders  

 Bronchospasm   

Gastrointestinal 
disorders  

Diarrhea 
Vomiting 

Constipation 
Abdominal pain  

  

Skin and 
subcutaneous 
tissue disorders  

 Erythema 
Dermatitis diaper 

Urticaria 
Alopecia 

Dermatitis 
psoriasiform 

Investigations  Decreased blood 
pressure 
 

Decreased blood 
glucose 
Decreased heart 
rate 
Neutropenia 

Agranulocytosis 
Hyperkaliemia 

 
Description of selected adverse reactions 
Concerning the lower respiratory tract infections like bronchitis or bronchiolitis, an aggravation of 
symptoms (including bronchospasm) has been observed in patients treated with HEMANGIOL due to 
the bronchoconstrictive effect of propranolol. These effects rarely led to definitive treatment 
discontinuation (see section 4.4). 



9 

 
Sleep disorders corresponded to insomnia, poor quality of sleep and hypersomnia. Other Central 
Nervous System disorders were principally observed during the early periods of treatment. 
 
Diarrhea was frequently reported and was not always associated with an infectious gastrointestinal 
disease. The occurrence of diarrhea seems to be dose-dependent between 1 and 3 mg/kg/day. None of 
cases was of severe intensity and led to treatment discontinuation. 
 
Cardiovascular events reported during clinical studies were asymptomatic. In the context of the 
4 hours cardiovascular monitoring during the titration days, it was observed a decrease of heart rate 
(about 7 bpm) and of systolic blood pressure (less than 3 mmHg) following drug administration. One 
case of second degree atrioventricular heart block in a patient with underlying conduction disorder led 
to definitive treatment discontinuation. Isolated cases of symptomatic bradycardia and hypotension 
have been reported in literature. 
 
Blood sugar decreases observed during clinical studies were asymptomatic. However, several reports 
of hypoglycaemia with related hypoglycaemic seizure were reported during the compassionate use 
program and in literature, especially in case of fasting period during intercurrent illness (see section 
4.4). 
 
Concomitant treatment with systemic corticosteroids may increase the risk of hypoglycemia (see 
section 4.5). 
 
Hyperkalaemia has been reported in the literature in few patients with large ulcerated haemangioma 
(see section 4.4). 
 
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
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.   
 
 



10 

5 PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Beta-Blocking agent, non-selective, ATC code: C07AA05 
 
Mechanism of action 
Potential mechanisms of action of propranolol in proliferating infantile haemangioma described in the 
literature could include various mechanisms all in close relationship: 
• a local haemodynamic effect (vasoconstriction which is a classical consequence of beta-

adrenergic blockade and a decrease of infantile haemangioma lesion perfusion); 
• an antiangiogenic effect (decrease of vascular endothelial cells proliferation, reduction of the 

neovascularization and formation of vascular tubules, reduction of the secretion of Matrix 
Metalloproteinase 9); 

• an apoptosis-triggering effect on capillary endothelial cells; 
• a reduction of both VEGF and bFGF signalling pathways and subsequent angiogenesis / 

proliferation. 
 
Pharmacodynamic effects 
Propranolol is a beta-blocker that is characterised by three pharmacological properties: 
• the absence of cardioselective beta-1 beta-blocking activity, 
• an antiarrhythmic effect, 
• lack of partial agonist activity (or intrinsic sympathomimetic activity). 
 
Clinical efficacy and safety in the paediatric population 
The efficacy of propranolol in infants (aged 5 weeks to 5 months at treatment initiation) with 
proliferating infantile haemangioma requiring systemic therapy has been demonstrated in a pivotal 
randomised, controlled, multicentre, multidose, adaptive phase II/III study aimed to compare four 
regimens of propranolol (1 or 3 mg/kg/day for 3 or 6 months) to placebo (double blind).  
 
Treatment was administered to 456 subjects (401 Propranolol at a dose of 1 or 3 mg/kg/day for 3 or 
6 months; 55 Placebo), including a titration phase over 3 weeks. Patients (71.3% female; 37% aged 
35-90 days old and 63% aged 91-150 days old) presented a target haemangioma on the head in 70% 
and majority of the infantile haemangiomas were localized (89%).  
 
Treatment success was defined as a complete or nearly complete resolution of the target 
haemangioma, which was evaluated by blinded centralized independent assessments made on 
photographs at Week 24, in the absence of premature treatment discontinuation. 
 
The regimen 3 mg/kg/day during 6 months (selected at the end of the phase II part of the study) 
presented 60.4% of success versus 3.6% in the placebo arm (p value < 0.0001). Age (35-90 days / 91-
150 days), gender and haemangioma location (head / body) subgroups did not identify differences in 
response to propranolol. Improvement of haemangioma was observed at 5 weeks of treatment by 
propranolol in 88% of patients. 11.4% of patients needed to be re-treated after treatment 
discontinuation. 
For ethical reasons related to the use of placebo, the demonstration of the efficacy was not established 
in patients with high-risk haemangioma. Evidence of the efficacy of propranolol in patients with high-
risk haemangioma is available both in literature and in a specific compassionate use program 
performed with Hemangiol. 
 
Based on a retrospective study, a minority of patients (12%) required a re-initiation of systemic 
treatment. When treatment was re-initiated, a satisfactory response was observed in a large majority of 
patients. 
 
 



11 

5.2 Pharmacokinetic properties 
 
Adults 
Absorption and distribution: 
Propranolol is almost completely absorbed after oral administration. However, it undergoes an 
extensive first-pass metabolism by the liver and on average only about 25% of propranolol reaches the 
systemic circulation. Peak plasma concentrations occur about 1 to 4 hours after an oral dose. 
Administration of protein-rich foods increases the bioavailability of propranolol by about 50% with no 
change in time to peak concentration. 
 
Propranolol is a substrate for the intestinal efflux transporter, P-glycoprotein (P-gp). However, studies 
suggest that P-gp is not dose-limiting for intestinal absorption of propranolol in the usual therapeutic 
dose range. 
 
Approximately 90% of circulating propranolol is bound to plasma proteins (albumin and alpha1 acid 
glycoprotein). The volume of distribution of propranolol is approximately 4 L/kg. Propranolol crosses 
the blood-brain barrier and the placenta, and is distributed into breast milk. 
 
Biotransformation and elimination: 
Propranolol is metabolized through three primary routes: aromatic hydroxylation (mainly 4-
hydroxylation), N-dealkylation followed by further side-chain oxidation, and direct glucuronidation. 
The percentage contributions of these routes to total metabolism are 42%, 41% and 17%, respectively, 
but with considerable variability between individuals. The four major final metabolites are propranolol 
glucuronide, naphthyloxylactic acid and glucuronic acid, and sulfate conjugates of 4-hydroxy 
propranolol. In vitro studies indicated that CYP2D6 (aromatic hydroxylation), CYP1A2 (chain 
oxidation) and to a less extent CYP2C19 were involved in propranolol metabolism. 
 
In healthy subjects, no difference was observed between CYP2D6 extensive metabolizers and poor 
metabolizers with respect to oral clearance or elimination half-life.  
The plasma half-life of propranolol ranges from 3 to 6 hours. Less than 1% of a dose is excreted as 
unchanged drug in the urine.  
 
Paediatric population 
The pharmacokinetics of repeated administrations of HEMANGIOL at 3 mg/kg/day given in 2 intakes 
has been investigated in 19 infants aged 35 to 150 days at the beginning of treatment. The 
pharmacokinetic evaluation was performed at steady-state, after 1 or 3 months of treatment. 
 
Propranolol was rapidly absorbed, the maximum plasma concentration generally occurring 2 hours 
after administration with a corresponding mean value around 79 ng/mL whatever the infant age. 
Mean apparent oral clearance was 2.71 L/h/kg in infants aged 65- 120 days and 3.27 L/h/kg in infant 
aged 181- 240 days. Once corrected by the body weight, primary pharmacokinetic parameters for 
propranolol (such as plasma clearance) determined in infants were similar to those reported in the 
literature for adults. 
The 4-hydroxy-propranolol metabolite was quantified, its plasma exposure accounting for less than 
7% of the parent drug exposure. 
 
During this pharmacokinetic study including infants with function-threatening haemangioma, 
haemangioma in certain anatomic locations that often leave permanent scars or deformity, large facial 
haemangioma, smaller haemangioma in exposed areas, severe ulcerated haemangioma, pedunculated 
haemangioma, efficacy was also studied as a secondary evaluation criteria. Treatment with 
propranolol resulted in a rapid improvement (within 7-14 days) in all patients and resolution of the 
target haemangioma was observed in 36.4% of patients by 3 months.  
 



12 

5.3 Preclinical safety data 
 
In animals, after an acute dosing, propranolol is considered as a moderately toxic drug with an oral 
LD50 of about 600 mg/kg. The main effects reported after repeated administration of propranolol in 
adult and juvenile rats were a transient decrease in body weight and body weight gain associated with 
a transient decrease in organ weight. These effects were completely reversible when treatment was 
discontinued. 
  
In dietary administration studies in which mice and rats were treated with propranolol hydrochloride 
for up to 18 months at doses of up to 150 mg/kg/day, there was no evidence of drug-related 
tumorigenesis.  
Although some data were equivocal, based on the overall available in vitro and in vivo data, it can be 
concluded that propranolol is devoid of genotoxic potential. 
 
In adult female rats, propranolol given into the uterus or by intravaginal administration is a powerful 
anti-implantation agent at dose ≥4 mg per animal, the effects being reversible. In adult male rats, 
repeated administration of propranolol at high dose levels (≥7.5 mg/kg) induced histopathological 
lesions of the testes, epididymis, and seminal vesicles, decrease in sperm motility, sperm cell 
concentration, plasma testosterone levels and significant increase in sperm head and tail abnormalities. 
The effects generally totally reversed after treatment cessation. Similar results were obtained 
following intra-testicular administration of propranolol and using in vitro models. However, in the 
study conducted in juvenile animals treated all over the development period corresponding to infancy, 
childhood and adolescence, no effect on male and female fertilities was observed (See section 4.6). 
 
The potential effects of propranolol on the development of juvenile rats were evaluated following 
daily oral administration from post-natal Day 4 (PND 4) to PND 21 at dose-levels of 0, 10, 20 or 
40 mg/kg/day.  
Mortality with unknown although unlikely relationship to treatment was observed at 40 mg/kg/day, 
leading to a NOAEL of 20 mg/kg/day for juvenile toxicity. 
In terms of reproductive development, growth and neurological development there were no 
propranolol-related effects or toxicologically significant findings at 40 mg/kg/day, correlating to safety 
margins of 1.2 in females and 2.9 in males, based on mean propranolol exposures on PND 21.  
 

6 PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
• Hydroxyethylcellulose 
• Sodium saccharin 
• Strawberry flavour (contains propylene glycol) 
• Vanilla flavour (contains propylene glycol) 
• Citric acid monohydrate  
• Purified water 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
Before opening: 3 years. 
After first opening: 2 months.  
 



13 

6.4 Special precautions for storage 
 
Keep the bottle in the outer carton in order to protect from light. 
Do not freeze. 
Store the bottle and the oral syringe in the outer carton between each use.  
 
6.5 Nature and contents of container  
 
120 mL solution, in a type III amber-glass bottle fitted with a low density polyethylene insert and a 
child resistant polypropylene screw cap, provided with a polypropylene oral syringe graduated in mg 
of propranolol base. 
Pack size: carton containing 1 bottle and 1 oral syringe. 
 
6.6 Special precautions for disposal  
 
No special requirements.  
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 

7 MARKETING AUTHORISATION HOLDER 
 
PIERRE FABRE DERMATOLOGIE 
45 place Abel  Gance 
F- 92100 Boulogne 
 
 

8 MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/919/001 
 

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 23 April 2014 
Date of latest renewal: 
 

10 DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE  

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



15 

 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

Farmea 
10, rue Bouché Thomas 
ZAC d'Orgemont 
F-49000 Angers 
France 
 
 
PIERRE FABRE MEDICAMENT PRODUCTION  
Site PROGIPHARM, Rue du Lycée 
45500 GIEN 
France 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

 
• Periodic safety update reports  
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal.  

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
• Risk Management Plan (RMP) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  



16 

 

• Additional risk minimisation measures 
The MAH shall provide an educational pack for the proposed indication, targeting all caregivers 
who are expected to prepare and administer HEMANGIOL to children. This educational pack is 
aimed at increasing awareness about the potential risk of hypotension, bradycardia, and 
bronchospasm, after taking HEMANGIOL, and providing guidance on how to monitor/manage that 
risk. 

It is also aimed to instruct caregivers to correctly feed the children during treatment in order to 
avoid the risk of hypoglycaemia. 

The MAH must agree the content and format of the educational material, together with a 
communication plan, with the national competent authority prior to distribution of the educational 
pack. The educational pack must be available for distribution prior to the launch of the new 
indication (treatment of proliferating infantile haemangioma) in the Member State. 

The educational materials for caregivers treating children with HEMANGIOL should include the 
following key safety elements:  

• Information on the conditions for which HEMANGIOL should not be given 

• Information on the correct procedure of product preparation and administration including: 

- Instructions on how to prepare the solution with HEMANGIOL 

- Advice on how to feed children during treatment 

- Information on how to detect and manage any sign of hypoglycaemia during treatment 
with HEMANGIOL 

- Instructions on when to discontinue the administration of HEMANGIOL 

• The need to monitor and to contact the healthcare professionals if the following signs and 
symptoms occur after treatment:  

- For bradycardia and hypotension: fatigue, coldness, pallor, bluish-coloured skin, and 
fainting. 

- For hypoglycaemia: minor symptoms like pallor, tiredness, sweating, shakiness, 
palpitations, anxiety, hunger, difficulty waking up; major symptoms like excessive sleeping, 
difficulty to get a response, poor feeding, temperature decrease, convulsions (fits), brief 
pauses in breathing, loss of consciousness 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



19 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  
 
CARTON BOX / BOTTLES 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
HEMANGIOL 3.75 mg/mL oral solution  
propranolol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml of solution contains 4.28 mg of propranolol hydrochloride equivent to 3.75 mg of propranolol. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oral solution. 
1 bottle of 120 mL and 1 oral syringe. 
  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Use with oral syringe graduated in mg of propranolol included in the package. Do not use any other 
measuring device.  
Do not shake the bottle before use. 
Read the package leaflet before use. 
Oral use. 

 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
After first opening, the medicine should be used within 2 months. 
 
 



20 

9. SPECIAL STORAGE CONDITIONS 
 
Keep the bottle in the outer carton in order to protect from light.  
Store the bottle and oral syringe in the outer carton between each use. 
Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
PIERRE FABRE DERMATOLOGIE 
45 place Abel  Gance 
F- 92100 Boulogne 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/919/001 
 
 
13. BATCH NUMBER 
 
Batch  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
HEMANGIOL 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number}   
SN: {number}   
NN: {number}   



21 

 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 
 
 
 



22 

Package leaflet: Information for the user 
 

HEMANGIOL 3.75 mg/mL oral solution 
propranolol 

 
 
Read all of this leaflet carefully before your child starts receiving this medicine because it 
contains important information. 
• Keep this leaflet. You may need to read it again.  
• If you have any further questions, ask your doctor, or pharmacist or nurse. 
• This medicine has been prescribed for your child only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as your child’s. 
• If your child get any side effects, talk to your doctor or pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4.  
 
What is in this leaflet 
1. What HEMANGIOL is and what it is used for  
2. What you need to know before your child receives HEMANGIOL 
3. How to give HEMANGIOL to your child 
4. Possible side effects  
5. How to store HEMANGIOL  
6. Contents of the pack and other information 
 
 

1 What HEMANGIOL is and what it is used for 
 
What HEMANGIOL is 
The name of your medicine is HEMANGIOL. The active ingredient is propranolol. 
Propranolol belongs to a group of medicines known as beta-blockers. 
 
What it is used for 
This medicine is used to treat a disease called haemangioma. A haemangioma is a collection of extra 
blood vessels that have formed a lump in or under the skin. Haemangioma can be superficial or deep. 
It is sometimes called ‘strawberry mark’ because the surface of a haemangioma looks a bit like a 
strawberry. 
Hemangiol is started in infants aged 5 weeks to 5 months, when: 

- the localisation and/or extend of the lesions are life- or function threatening (might impair 
vital organs or senses such as vision or hearing); 

- the haemangioma is ulcerated (i.e. with sore on the skin which fails to heal) and painful, 
and/or does not respond to simple wound care measures; 

- there is a risk of permanent scars or disfigurement.  
 
 

2 What you need to know before your child receives HEMANGIOL  
 
Do not give HEMANGIOL 
If your child: 
• is born prematurely and he/she has not reached the corrected age of 5 weeks (the corrected age 

being the age a premature baby would be if he/she had been born on their due date). 
• is allergic to propranolol or any of the other ingredients of this medicine (listed in section 6). An 

allergic reaction can include a rash, itching or shortness of breath. 
• has asthma or history of breathing difficulties. 



23 

• has a slow heart rate for his/her age. Please check with your doctor if you are not sure. 
• has a heart problem (such as disorders of the heart rhythm and heart failure. 
• has very low blood pressure. 
• has circulation problems which make the toes and fingers numb and pale. 
• is prone to low blood sugar level. 
• has a high blood pressure caused by a tumour on the adrenal gland. This is called 

'phaeochromocytoma'. 
 
If you are breastfeeding your child, and if you are taking medicines that must not be used with 
HEMANGIOL (see ‘‘If you are breastfeeding your child’’ and “Other medicines and HEMANGIOL”) 
do not give this medicine to your child. 
 
Warnings and precautions  
Before your child receives HEMANGIOL, tell your doctor: 
• If your child has problems with his/her liver or kidneys. This medicine will not be recommended 

in case of liver or kidneys impairment. 
• If your child has ever had an allergic reaction whatever its origin (e.g. medicine or alimentary 

substance etc.). An allergic reaction can include a rash, itching or shortness of breath. 
• If your child has psoriasis (a skin condition that produces red, dry plaques of thickened skin), as 

this medicine may worsen the symptoms of this condition. 
• If your child has diabetes: in this case, your child’s blood sugar level should be measured more 

frequently. 
• If your child has a PHACE syndrome (a condition combining haemangioma and vascular 

abnormalities including cerebral blood vessels), as this medicine may increase the risk of 
cerebral stroke. 

 
Important signs to look after administration of HEMANGIOL 
 
Risk of hypotension and bradycardia (low heart rate) 
HEMANGIOL can decrease blood pressure (hypotension) and heart rate (bradycardia). This is why 
your child will be kept under close clinical and heart rate monitoring for 2 hours after the first dose or 
after a dose increase. Then, your doctor will regularly examine your child during treatment.  
  

Call your doctor right away if your child has any signs such as tiredness, coldness, pallor, 
bluish-coloured skin, or fainting while taking HEMANGIOL. 

 
Risks of hypoglycaemia 
This medicine can mask the warning signs of hypoglycaemia (also known as low blood sugar level), 
especially if the baby is fasting, vomiting or in case of overdose. These signs may be: 
• Minor: pallor, tiredness, sweating, shaking, palpitations, anxiety, hunger, difficulty waking up. 
• Major: excessive sleeping, difficulty responding, poor feeding, decrease in body temperature, 

convulsions (fits), brief pauses in breathing, loss of consciousness. 
 

To avoid risks of hypoglycaemia, your child must be fed regularly during treatment. If your 
child is not eating, develops another illness or is vomiting, it is recommended to skip the dose. 
DO NOT GIVE HEMANGIOL TO YOUR CHILD UNTIL HE IS BEING CORRECTLY FED 
AGAIN. 
 
If your child has any signs of hypoglycaemia while taking HEMANGIOL, give if possible oral 
liquid containing sugar and, if symptoms persist, call your doctor right away or go directly to 
hospital. 

 



24 

Risks of bronchospasm 
Stop treatment and contact your doctor immediately if after giving HEMANGIOL to your child you 
observe the following symptoms suggestive of a bronchospasm (temporary restriction of the bronchial 
tubes that leads to difficulty breathing): cough, quick or difficult breathing or wheezing, associated or 
not with a bluish-coloured skin.  
 
Risk of hyperkaliemia 
HEMANGIOL may increase potassium blood level (hyperkaliemia). In case of large ulcerated 
haemangioma,, your child’s blood potassium level should be measured. 
 
If your child should undergo a general anaesthesia 
Tell the your doctor that he/she is taking HEMANGIOL. This is because your child can get low blood 
pressure if given certain anaesthetics while taking this medicine (see “Other medicines and 
HEMANGIOL”). HEMANGIOL might need to be discontinued at least 48h before the anaesthesia. 
 
If you are breastfeeding your child 
• Tell your doctor before giving this medicine. 
• Do not give this medicine to your child if you are taking medicines that must not be used with 

HEMANGIOL (see “Other medicines and HEMANGIOL”). 
 
Other medicines and HEMANGIOL 
• Tell your doctor, pharmacist or nurse if you are giving, have recently given or might give any 

other medicines to your child. This is because HEMANGIOL can change the way other 
medicines work, and some medicines can have an effect on the way HEMANGIOL works. 

• Moreover, if you are breastfeeding your child, it is important to tell your doctor, pharmacist or 
nurse which medicines you are yourself taking, as they may pass into your breast-milk and 
interfere with the treatment of your child. Your doctor will advise you on whether you need to 
stop breastfeeding or not. 

 
In particular, in case you are breastfeeding, tell your doctor or pharmacist if you are or if your child is 
taking: 
• Medicines for diabetes, 
• Medicines for heart and blood vessels problems such as uneven heart beats, chest pain or angina, 

high blood pressure, heart failure, 
• Medicines to treat anxiety and depression as well as more serious mental health problems, and 

epilepsy, 
• Medicines to treat tuberculosis, 
• Medicines to treat pain and inflammation, 
• Medicines used to lower lipids in the blood, 
• Medicines used for anaesthesia. 
 
If you have any further questions, ask your doctor or pharmacist. 
 
HEMANGIOL contains sodium and propylene glycol 
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’. 
This medicine contains 2.08 mg of propylene glycol/kg/day. If your baby is less than 4 weeks old, talk 
to your doctor or pharmacist before giving them this medicine, in particular if the baby is given other 
medicines that contain propylene glycol or alcohol. 
 
 



25 

3 How to give HEMANGIOL to your child  
 
The treatment of your child has been initiated by a physician who has expertise in the diagnosis, 
treatment and management of infantile haemangioma. 
Always give this medicine to your child exactly as your doctor or pharmacist has told you. Check with 
your doctor or pharmacist if you are not sure.  
 
Never change the dose you are giving to your child yourself. Every increase in dose or any dose 
adjustment to your baby’s weight must be done by your doctor. 

 
Dose 
• Dosing is based on your baby’s weight following the scheme below: 

 
Weeks  
(daily dose) 

Dose by intake Timing of intakes  

First week  
(1 mg/kg/day) 

0.5 mg/kg • one in the morning  
• one in late afternoon 
• at least 9 hours interval 

between two intakes  
 

Second week  
(2 mg/kg/day) 

1mg/kg 

Third and following weeks 
(3 mg/kg/day) 

1.5 mg/kg 

 
• If necessary, you may mix the medicine with a small quantity of baby-milk or age-adapted apple 

and/or orange fruit juice and give it to your child in a baby bottle. Do not mix the medicine with a 
full bottle of milk or juice. 
For children weighing up to 5 kg you may mix the dose with one teaspoonful of milk 
(approximately 5 mL).  For children weighing more than 5 kg the dose may be mixed with a 
tablespoonful of milk or fruit juice (approximately 15 mL). 
Use the mixture within 2 hours of preparation. 

 
 
How to give HEMANGIOL to your child 
• Hemangiol is for oral use. 
• The medicine is to be given during or straight after a feed. 
• The dose should always be measured using the oral syringe supplied with the bottle. 
• Give HEMANGIOL directly into your child's mouth using the oral syringe supplied with the 

bottle.  
• Feed your child regularly to avoid prolonged fast. 
• If your child is not eating or is vomiting it is recommended to skip the dose.  
• If your child spits up a dose or if you are uncertain whether he/she got all of the medicine, do not 

give another dose, just wait until the next scheduled dose. 
• HEMANGIOL and the feed must be given by the same person in order to avoid the risk of 

hypoglycaemia. If different people are involved, good communication is essential in order to 
ensure the safety of your child. 

 

Instructions for use: 

• Step 1. Remove the items from the box 
The carton contains the following items that you will need to administer the medicine: 
- The glass bottle containing 120 mL propranolol oral solution 
- The oral syringe graduated in mg provided with this medicine 
Remove the bottle and oral syringe from the box and remove the syringe from the plastic bag.  



26 

 
 
• Step 2. Check the dose 
Check the HEMANGIOL dose in milligrams (mg) as prescribed by your doctor. Locate this number 
on the oral syringe. 

 
• Step 3. Open the bottle 
The bottle comes with a child-proof cap. Here is how to open it: push down the plastic cap while 
turning the cap counter-clockwise (to the left). 
Do not shake the bottle before use. 
 

 
 
• Step 4. Insert the syringe 
Insert tip of the oral syringe into the upright bottle and push the plunger all the way down. 
Do not remove the syringe adapter from the neck of the bottle. 
Only use the oral syringe that is supplied with the medicine to measure and administer the dose. Do 
not use a spoon or any other dispensing device. 



27 

 

 
 
• Step 5: Remove the dose  
With the oral syringe in place, turn the bottle upside down.  
Pull the plunger of the syringe up to the number of mg you need. 
 

 
 
• Step 6: Check for air bubbles 
If you see air bubbles in the syringe, hold the syringe upright, push the plunger upwards just far 
enough to completely push out any large air bubbles and then readjust to the dose prescribed by your 
doctor. 
 
 
 

 
 
• Step 7. Remove the syringe 
Turn bottle upright and remove the entire syringe from the bottle. Be careful, do not push the plunger 
in during this step. 
 



28 

 
• Step 8. Close the bottle.  
Replace the plastic cap on the bottle by turning it clock-wise (to the right). 
 

 
 
• Step 9. Give HEMANGIOL to your child 
Insert the syringe into your baby’s mouth and place it against the inside of the cheek.  
Now you can slowly squirt HEMANGIOL from the syringe directly into your baby’s mouth. 
Do not lie the child down immediately after the administration. 
 

 
 
• Step 10: Clean the syringe.  
Do not dismantle the syringe. Rinse the empty syringe after each use into a glass of clean water: 
1- Take a glass of clean water 
2- Pull the plunger in 
3- Discard the water into your sink 
4- Repeat this cleaning process 3 times.  
 



29 

  
Do not use any soap or alcohol based product to clean. Wipe the outside dry. 
Do not put the syringe through a sterilizer or dishwasher. 
Store the bottle and the syringe together in the carton until next use in a safe place where your child 
can’t see or reach it. Discard the syringe once the bottle is finished. 

 

If you give to your child more HEMANGIOL than you should 
If you have given to your child more HEMANGIOL than you should, please consult your doctor 
immediately.  
 
If you forget to give HEMANGIOL to your child 
Skip the missed dose, and do not give a double dose to make up for a forgotten dose. Continue the 
treatment at the usual frequency: one dose in the morning and one in the late afternoon. 
 
If you stop giving HEMANGIOL to your child 
HEMANGIOL may be stopped at once at the end of the treatment as decided by the doctor. 

 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse. 
 
 

4 Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
Important warning signs of potential side effects such as low blood pressure, low heart rate, low blood 
sugar level, and bronchospasm (breathing difficulties) should be looked after following administration 
of HEMANGIOL. Please refer to section 2 of this leaflet. 
 
 
Very common side effects (may affect more than 1 in 10 people) 
• Bronchitis (inflammation of the bronchi), 
• Sleep disorders (insomnia, poor quality of sleep and difficulties to wake-up),  
• Diarrhoea and vomiting.  
 
Common side effects (may affect up to 1 in 10 people) 
• Bronchospasm (breathing difficulties),  
• Bronchiolitis (inflammation of small bronchi with breathing difficulties and wheeze in the chest,  

associated with cough and fever),  
• Decreased blood pressure. 
• Decreased appetite,  
• Agitation, nightmares, irritability,  
• Somnolence,  
• Cold extremities,  



30 

• Constipation, abdominal pain,  
• Erythema (skin redness),  
• Nappy rash. 

 
 Uncommon side effects (may affect up to 1 in 100 people) 
• Heart conduction or rhythm disorders (slow or uneven heart beats), 
• Urticaria (allergic reaction of the skin), alopecia (loss of hair), 
• Decreased blood sugar levels, 
• Reduction of the number of white blood cells. 
 
The frequency of the following side effects is not known (frequency cannot be estimated from the 
available data) 
• Convulsions (fits) linked to hypoglycaemia (abnormally low blood sugar levels), 
• Bradycardia (abnormally low heart rate), 
• Low blood pressure,  
• Very low levels of white blood cells that fight infection 
• Circulation problems which make the toes and fingers numb and pale 
• Elevated level of potassium in the blood 
 
 
Reporting of side effects  
If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 

5 How to store HEMANGIOL 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the outer carton and bottle label. The 
expiry date refers to the last day of that month. 
Keep the bottle in the outer carton in order to protect from light. Store the bottle and the oral syringe in 
the outer carton between each use. Do not freeze.  
After first opening, the medicine should be used within 2 months. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

6 Contents of the pack and other information 
 
What HEMANGIOL contains  
• The active substance is propranolol. Each ml contains 4.28 mg of propranolol hydrochloride 

equivalent to 3.75 mg of propranolol. 
• The other ingredients are hydroxyethylcellulose, sodium saccharin, strawberry flavour (contains 

propylene glycol), vanilla flavour (contains propylene glycol), citric acid monohydrate, purified 
water.  See section 2 under ‘HEMANGIOL contains sodium and propylene glycol’ for further 
information.  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


31 

 
What HEMANGIOL looks like and contents of the pack 
• HEMANGIOL is a clear, colourless to slightly yellow oral solution, with a fruity odour. 
• It is supplied in a 120-mL amber glass bottle, with a child resistant screw-cap. Box of 1 bottle. 
• An oral polypropylene syringe graduated in mg of propranolol, is provided with each bottle. 
 
 
Marketing Authorisation Holder 
PIERRE FABRE DERMATOLOGIE 
45 Place Abel Gance 
92100 BOULOGNE 
FRANCE 
   
Manufacturer 
FARMEA 
10 rue Bouché Thomas 
ZAC Sud d’Orgemont 
49000 ANGERS  
FRANCE  
 
Or  
 
PIERRE FABRE MEDICAMENT PRODUCTION  
Site PROGIPHARM, Rue du Lycée 
45500 GIEN 
FRANCE 
 
For any information about this medicine, please contact the Marketing Authorisation Holder. 
 
This leaflet was last revised in. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
{'Title': '1. what hemangiol is and what it is used for', 'Section_Content': None, 'Entity_Recognition': None}
{'Title': '2. what you need to know before your child receives hemangiol', 'Section_Content': None, 'Entity_Recognition': None}
{'Title': '3. how to give hemangiol to your child', 'Section_Content': None, 'Entity_Recognition': None}
{'Title': '4. possible side effects', 'Section_Content': None, 'Entity_Recognition': None}
{'Title': '5. how to store hemangiol', 'Section_Content': 'keep this medicine out of the sight and reach of children. do not use this medicine after the expiry date which is stated on the outer carton and bottle label. the expiry date refers to the last day of that month. keep the bottle in the outer carton in order to protect from light. store the bottle and the oral syringe in the outer carton between each use. do not freeze. after first opening, the medicine should be used within 2 months. do not throw away any medicines via wastewater or household waste. ask your pharmacist how to throw away medicines you no longer use. these measures will help protect the environment.', 'Entity_Recognition': [{'Text': 'hemangiol', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 70, 'EndOffset': 83}, {'Text': 'the outer carton', 'Type': 'TREATMENT', 'BeginOffset': 233, 'EndOffset': 249}, {'Text': 'the oral syringe', 'Type': 'TREATMENT', 'BeginOffset': 303, 'EndOffset': 319}, {'Text': 'the medicine', 'Type': 'TREATMENT', 'BeginOffset': 394, 'EndOffset': 406}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 429, 'EndOffset': 430}]}
{'Title': '6. contents of the pack and other information', 'Section_Content': "what hemangiol contains the active substance is propranolol. each ml contains 4.28 mg of propranolol hydrochloride equivalent to 3.75 mg of propranolol. the other ingredients are hydroxyethylcellulose, sodium saccharin, strawberry flavour (contains propylene glycol), vanilla flavour (contains propylene glycol), citric acid monohydrate, purified water. see section 2 under 'hemangiol contains sodium and propylene glycol' for further information. what hemangiol looks like and contents of the pack hemangiol is a clear, colourless to slightly yellow oral solution, with a fruity odour. it is supplied in a 120-ml amber glass bottle, with a child resistant screw-cap. box of 1 bottle. an oral polypropylene syringe graduated in mg of propranolol, is provided with each bottle.", 'Entity_Recognition': [{'Text': 'hemangiol', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 48, 'EndOffset': 59, 'Score': 0.9989325404167175, 'Text': 'propranolol', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.8831282258033752, 'RelationshipScore': 0.9598696231842041, 'RelationshipType': 'DOSAGE', 'Id': 3, 'BeginOffset': 129, 'EndOffset': 136, 'Text': '3.75 mg', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': '4.28', 'Type': 'NUMBER', 'BeginOffset': 78, 'EndOffset': 82}, {'Id': 2, 'BeginOffset': 89, 'EndOffset': 114, 'Score': 0.9917974472045898, 'Text': 'propranolol hydrochloride', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.9589545130729675, 'RelationshipScore': 0.9998784065246582, 'RelationshipType': 'DOSAGE', 'Id': 1, 'BeginOffset': 78, 'EndOffset': 85, 'Text': '4.28 mg', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'DOSAGE', 'Score': 0.8831282258033752, 'RelationshipScore': 0.8429086208343506, 'RelationshipType': 'DOSAGE', 'Id': 3, 'BeginOffset': 129, 'EndOffset': 136, 'Text': '3.75 mg', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': '3.75', 'Type': 'NUMBER', 'BeginOffset': 129, 'EndOffset': 133}, {'Id': 4, 'BeginOffset': 140, 'EndOffset': 151, 'Score': 0.9990726709365845, 'Text': 'propranolol', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.9589545130729675, 'RelationshipScore': 0.9581559896469116, 'RelationshipType': 'DOSAGE', 'Id': 1, 'BeginOffset': 78, 'EndOffset': 85, 'Text': '4.28 mg', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'DOSAGE', 'Score': 0.8831282258033752, 'RelationshipScore': 0.9998010993003845, 'RelationshipType': 'DOSAGE', 'Id': 3, 'BeginOffset': 129, 'EndOffset': 136, 'Text': '3.75 mg', 'Category': 'MEDICATION', 'Traits': []}]}, {'Id': 5, 'BeginOffset': 179, 'EndOffset': 200, 'Score': 0.6063234210014343, 'Text': 'hydroxyethylcellulose', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 6, 'BeginOffset': 202, 'EndOffset': 218, 'Score': 0.9361504316329956, 'Text': 'sodium saccharin', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'strawberry flavour', 'Type': 'TREATMENT', 'BeginOffset': 220, 'EndOffset': 238}, {'Text': 'propylene glycol)', 'Type': 'TREATMENT', 'BeginOffset': 249, 'EndOffset': 266}, {'Id': 8, 'BeginOffset': 268, 'EndOffset': 283, 'Score': 0.38362255692481995, 'Text': 'vanilla flavour', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 9, 'BeginOffset': 294, 'EndOffset': 310, 'Score': 0.9808684587478638, 'Text': 'propylene glycol', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 10, 'BeginOffset': 313, 'EndOffset': 336, 'Score': 0.9837090969085693, 'Text': 'citric acid monohydrate', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 11, 'BeginOffset': 338, 'EndOffset': 352, 'Score': 0.9432557225227356, 'Text': 'purified water', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 366, 'EndOffset': 367}, {'Text': "sodium and propylene glycol'", 'Type': 'TREATMENT', 'BeginOffset': 394, 'EndOffset': 422}, {'Text': 'slightly yellow oral solution', 'Type': 'PROBLEM', 'BeginOffset': 535, 'EndOffset': 564}, {'Text': 'a fruity odour', 'Type': 'PROBLEM', 'BeginOffset': 571, 'EndOffset': 585}, {'Text': 'a 120-ml amber glass bottle', 'Type': 'TREATMENT', 'BeginOffset': 605, 'EndOffset': 632}, {'Text': 'a child resistant screw', 'Type': 'TREATMENT', 'BeginOffset': 639, 'EndOffset': 662}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 675, 'EndOffset': 676}, {'Text': 'an oral polypropylene syringe', 'Type': 'TREATMENT', 'BeginOffset': 685, 'EndOffset': 714}, {'Id': 16, 'BeginOffset': 734, 'EndOffset': 745, 'Score': 0.9988162517547607, 'Text': 'propranolol', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'ROUTE_OR_MODE', 'Score': 0.5140015482902527, 'RelationshipScore': 0.9990390539169312, 'RelationshipType': 'ROUTE_OR_MODE', 'Id': 13, 'BeginOffset': 688, 'EndOffset': 692, 'Text': 'oral', 'Category': 'MEDICATION', 'Traits': []}]}]}