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.