Diagnosis and Management of Infantile Hemangioma

Table 22. Harms/adverse effects in comparative studies of beta-blockers to treat IH
N Studies Reporting
Intervention
Harm/Adverse Event
Harm (# Participants
With Harm/Total
Participants)
Oral propranolol 2-3
mg/kg/day
Oral propranolol 4
mg/kg/day
Oral propranolol (2.2
mg/kg/day) +
prednisolone (1.6 mg)
Intralesional
propranolol 1 mg
Oral atenolol
3mg/kg/day
Oral nadolol up to 4
mg/kg/day
Bronchial hyperreactivity 147 1 (4/28) 14%
Bronchiolitis 17 1 (4/19) 21%
Bronchospasm 94 1 (1/31) 3%
Cold extremities 17,131,145 3 (13/53) 5%-43%
Constipation or gastrointestinal
complaints 96,145,147
3 (5/60) 5%-11%
Dental caries 17 1 (1/19) 5%
Elevated alkaline 17 1 (1/19) 5%
Hypoglycemia 97,100,147 3 (4/106) 1%-10%
* Hypotension 93,96,147 3 (4/55) 4%-20%
Ulceration 17 1 (1/19) 5%
Sleep disturbance (insomnia,
drowsiness, restless
6 (31/150) 6%-50%
sleep) 17,94,96,100,145,147
Streptococcal infection 17 1 (1/19) 5%
Syncopal attack 93 1 (1/15) 7%
Viral gastroenteritis 17 1 (1/19) 5%
** Viral upper respiratory
2 (2/87) 1%-5%
infection 17,97
Poor feeding 145 1 (2/20) 10%
Fever 97 1 (2/68) 3%
Rash 97 1 (2/68) 3%
Tachycardia 97 1 (1/68) 1%
Hypotonia 132 1 (3/30) 10%
Pulmonary obstruction 132 1 (2/30) 6.7%
Drowsiness 99 1 (1/7) 14%
Gastrointestinal upset 100 1 (4/10) 40%
Infection 100 1 (1/10) 10%
Cushingoid appearance 100 1 (6/10) 60%
Pain/inconvenience of therapy 93 1 (3/15) 20%
Hypotension 147 1 (1/30) 3%
Restless sleep 147 1 (8/30) 27%
Constipation 147 1 (2/30) 7%
Diarrhea 147 1 (2/30) 7%
Cold extremities 101 1 (2/10) 20%
Cold induced wheezing 101 1 (1/10) 10%
Sleep disturbance 101 1 (1/10) 10%
Gastrointestinal symptoms 101 1 (5/10) 50%
Placebo Sleep disturbance 17 1 (2/20) 10%
Ulceration 17 1 (1/20) 5%
Visual compromise 17 1 (1/20) 5%
Bronchiolitis 17 1 (1/20) 5%
IH = infantile hemangioma; kg = kilogram; mg = milligram; n = number
* One study 93 reported hypotension and bradycardia in 3/15 children.
** One study 97 reported upper respiratory infection and reactive airway disease in 1/68 children.
Reported Rates
Across Studies
The safety population in a large RCT 92 included 456 patients in total (Table 23). Thirty-three
serious events occurred in 26 patients, and no significant difference overall or in individual
events between the placebo group and group receiving propranolol at 3 mg/kg/day for 6 months
were noted. One serious adverse event of second-degree atrioventricular heart block (with a
preexisting cardiac condition later documented) occurred after dose administration on day 0, and
60