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.
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, aggravated respiratory tract infections such as bronchitis and bronchiolitis associated with cough and fever, diarrhoea, and vomiting.
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 two clinical studies, including 424 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 < |
