Initiation and use of Hemangiol®
Immediately after the marketing authorisation published by the EMA in April 2014 (EU/1/14/919/001), our group of experts in proliferative IH, involving plastic surgeons, dermatologists, ear nose and throat (ENT) physicians, and paediatric cardiologists, drafted a single and common institutional protocol on initiation and use of Hemangiol® for IH, adapted from the summary of product characteristics (SPC). This protocol included five consecutive stages:
1) The initial consultation with an expert in the diagnosis, treatment and management of IH (paediatric dermatologist, paediatric plastic surgeon, paediatric ENT physician, or paediatric cardiologist) determined whether Hemangiol® was indicated or not.
2) The paediatric cardiology consultation with clinical examination, electrocardiogram and echocardiography, assessed the absence of contraindications for beta-blocker use: premature infants for whom the corrected age of 5 weeks has not been reached, breastfed infants in mothers treated with medicinal products contraindicated with propranolol, hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SPC, asthma or history of bronchospasm, second- or third-degree atrioventricular blocks, disease of the sinus node (including sinoatrial block), bradycardia (heart rates <100 beats per minute (bpm) in infants 0-3 months old, <90 bpm in infants 3-6 months old, and <80 bpm in infants 6-12 months old), low blood pressure (<65/45 mmHg in infants 0-3 months old, <70/50 mmHg in infants 3-6 months old, and <80/55 mmHg in infants 6-12 months old), cardiogenic shock, heart failure not controlled by treatment, severe peripheral arterial circulatory disturbances, infants prone to hypoglycaemia, and pheochromocytoma.
3) To initiate Hemangiol® treatment, we defined a “conventional” initiation protocol and a “rapid” initiation protocol.
The conventional initiation protocol included a 3-week titration phase, as reported in the SPC: starting dose of 1 mg/kg/day (0.5 mg/kg b.i.d.) of propranolol base for 1 week, then 2 mg/kg/day (1 mg/kg b.i.d.) for 1 week, and finally 3 mg/kg/day (1.5 mg/kg b.i.d.) as a maintenance therapeutic dose. During the titration phase, the child was hospitalised in our ambulatory paediatric day care facility at day 1 (initiation), day 7 (week 1) and day 14 (week 2) with close clinical monitoring for 3 hours after treatment’s administration (hourly monitoring of vital constants, and assessment of side effects). Bradycardia was defined as heart rates <100 bpm in infants 0-3 months old, <90 bpm in infants 3-6 months old, and <80 bpm in infants 6-12 months old. Hypotension was defined as tensions <65/45 mmHg in infants 0-3 months old, <70/50 mmHg in infants 3-6 months old, and <80/55 mmHg in infants 6-12 months old.
Parental education was provided by a specialist nurse, focusing on the three following key messages: i) Hemangiol® is to be given during or right after feeding to avoid the risk of hypoglycaemia, with one dose in the morning and one dose in late afternoon, respecting a time interval of at least 9 hours between two intakes. ii) If the child is not eating or is vomiting it is recommended to skip the dose. iii) In case the child spits up a dose or does not take the entire medicinal product, no other dose should be given before the next scheduled dose. The information booklet provided by the pharmaceutical company (Pierre Fabre) was systematically given to parents, as well as our emergency paediatric cardiology 24/7 phone number.
The rapid initiation protocol was used for severe proliferative IH involving any vital risk, uncontrolled bleeding, ulceration, pain, or infectious risk. Such severe forms were managed in conventional hospitalisation in the paediatric cardiology unit, using a rapid dose escalation scheme: Hemangiol® initiation dose of 0.5 mg/kg (stage 1), then 1 mg/kg 12 hours later (stage 2), then 1.5mg/kg 12 hours later (stage 3), in order to reach the maintenance therapeutic dose of 3 mg/kg/day in two daily intakes at day 2. Analgesics, antibiotics and local skin care were provided when required, upon IH specialist’s recommendation. Continuous clinical monitoring was provided (hourly monitoring of vital constants, cardiac telemetry and assessment of side effects), as well as parental education (cf. previous section). In the absence of adverse effects or need for IH care, patient was discharged after day 2 (rapid initiation protocol in supplementary Figure).
4) The children underwent follow-up examination with the IH specialist 4 to 8 weeks after Hemangiol® initiation in non-severe IH, and 2 weeks after Hemangiol® initiation in severe cases. The IH specialist determined the frequency of the following consultations, as well as the overall treatment duration.
5) The child underwent a paediatric cardiology consultation 3 months after Hemangiol® initiation, or at any time if required by the IH specialist, the patient’s family practitioner, or after any family emergency phone call.