Diagnosis and Management of Infantile Hemangioma

Harms Data for Medications Included in the Analysis
The following sections provide an overview of the common and notable adverse events of
each medication. When possible, adverse event data specific for pediatric patients have been
included. It is important to note that the information provided in this section is not an allinclusive
list of adverse events. Consult the corresponding package insert for complete
information. Many of the adverse events reported are from various clinical trials used in support
of the medication’s FDA approval. As a result, these trials many have been conducted under
varying conditions and the adverse event rates may not reflect what is observed in clinical
practice. In addition, these rates may not necessarily be able to be compared to the rates observed
in the clinical trials of different drugs. Post-marketing adverse events are reported on a voluntary
basis and therefore do not represent complete patient data.
Hemangeol® (propranolol hydrochloride)
Hemangeol® is the only medication included in this review that has an FDA approved
indication for infantile hemangioma. The safety of Hemageol® in pediatric patients has been
reported in the medication package insert. 1 FDA medical review packages were not available for
this medication.
The most common adverse events, occurring in greater than 10% of infants, were sleep
disorders, aggravated respiratory tract infections such as bronchitis and bronchiolitis associated
with cough and fever, diarrhea, and vomiting. 1 In a study of pooled safety data (n=424), infants
(63% aged 91-150 days) were treated with Hemangeol® 1.2 mg/kg/day or 3.4 mg/kg/day for 3 or
6 months. Treatment emergent adverse events occurring in 3% or greater in infants receiving the
Hemangeol® 1.2 mg/kg/day (n=200) or Hemangeol® 3.4 mg/kg/day (n=224) compared to
placebo were provided. Adverse events and frequencies for patients receiving Hemangeol® 1.2
mg/kg/day included: sleep disorders (17.5%), bronchitis (8%), peripheral coldness (8%),
agitation (8.5%), diarrhea (4.5%), somnolence (5.0%), nightmare (2.0%), irritability (5.5%),
decreased appetite (2.5%), and abdominal pain (3.5%). Adverse events and frequencies for
patients receiving Hemangeol® 3.4 mg/kg/day (n=224) included: sleep disorders (16.1%),
bronchitis (13.4%), peripheral coldness (6.7%), agitation (4.5%), diarrhea (6.3%), somnolence
(0.9%), nightmare (6.3%), irritability (1.3%), decreased appetite (3.6%), and abdominal pain
(0.4%). Additional adverse events reported in less than 1% of patients participating in clinical
trials included: second degree atrioventricular heart block (occurring in a patient with underlying
conduction disorder), urticaria, alopecia, decreased blood glucose, and decreased heart rate.
Additional Formulations
The safety and efficacy of the oral tablet, oral capsule, and injectable formulations of
propranolol have not been investigated in pediatric patients. 18-20 The package inserts for these
formulations state that reports of bronchospasm and congestive heart failure have been reported
in pediatric patients receiving propranolol.
Post-marketing Adverse Events
Additional adverse events revealed during post-marketing surveillance include:
agranulocytosis, hallucination and purpura. 1
H-13