Diagnosis and Management of Infantile Hemangioma

Table 24. Adverse effects in case series of propranolol to treat IH (continued)
Number of
Studies (#
Intervention
Harm/Adverse Event
Participants
With Harm/Total
Participants)
††† Oral Propranolol +
Atenolol (dose not clearly
reported)
Cold extremities 188 1 (55/109) 51%
Sleep disturbance 188 1 (47/109) 43%
Gastrointestinal problems 188 1 (27/109) 25%
Fatigue 188 1 (20/109) 18%
Coughing 188 1 (19/109) 17%
Sweating 188 1 (16/109) 15%
Pallor 188 1 (14/109) 13%
Agitation/irritation 188 1 (14/109) 13%
Dyspnea/shortness of breath 188 1 (6/109) 6%
Increased activity 188 1 (5/109) 5%
Skin reaction 188 1 (5/109) 5%
Nausea/vomiting 188 1 (4/109) 4%
Decreased appetite 188 1 (4/109) 4%
Increased appetite 188 1 (3/109) 3%
Hypoglycemia 188 1 (3/109) 3%
Syncope 188 1 (2/109) 2%
Dizziness 188 1 (2/109) 2%
Hair loss 188 1 (2/109) 2%
Seizure 188 1 (1/109) 1%
Dry mouth (xerostomia) 188 1 (1/109) 1%
Hallucinations 188 1 (1/109) 1%
Reported
Rates
Across
Studies
ALT = alanine aminotransferase; AST = aspartate transaminase; IH = infantile hemangioma; kg = kilogram; mg = milligram
*One study of 1.5 mg/kg/day (not included in table) 174 reported that 23 of 109 children had adverse events (N of events not
stated) including hypotension, insomnia, agitation, aggravation of bronchitis, cold extremities gastroesophageal issues, and dry
skin. Four children discontinued propranolol due to aggravation of bronchitis (n=2) or gastroesophageal issues (n=2).
** One study 168 also reported that 50/50 children had at least one low diastolic blood pressure, 38/50 had at least one low systolic
blood pressure, and 7/50 had low diastolic, systolic blood pressure and heart rate (data not factored into table). Some children in
another study 199 were also receiving steroids (n=20/76) or timolol (n=7/76) along with propranolol. In a third study evaluating
propranolol, 190 29 of 250 children were also receiving concurrent steroids.
***One study 168 reported “lethargy, viral illness, and hypoglycemia” in 2/250 children (data not factored into table).
†
One study 164 reported discontinuation of propranolol in 4/35 children because of “insomnia, nightmares, loss of energy.” These
data are not factored into the table.
†† Adverse events in Blatt 2011 were considered serious by the study investigators. 185
††† Raphael 2015 is related to de Graaf 2013, 146-148 but the extent of overlap is unclear. The case series 188 also reports harms in 3
individual case reports: among 45 children receiving 4 mg/kg/day propranolol, 1 had multiple episodes of decreased
consciousness, 1 had nausea, 1 had an epileptic seizure after the first propranolol dose. Among those 64 receiving 3 mg/kg/day of
atenolol, 1 had difficulty waking and hypotonia, 1 had two episodes of loss of consciousness, 1 had three episodes of loss of
consciousness.
Harms Reported in Package Insert Data
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. 206 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. 206 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
64