Diagnosis and Management of Infantile Hemangioma

treatment was discontinued. While hypotension and hypoglycemia were both documented in this
trial, neither was clinically significant enough to lead to treatment discontinuation.
Table 23. Harms/adverse events reported by dose in Leaute-Labreze et al. 2015
1 mg/kg/day X 1 mg/kg/day X 3 mg/kg/day X 3 mg/kg/day X 6
Adverse
3 months 6 months 3 months months
Event
(n=98)
(n=102) (n=100)
(n=101)
N experiencing harm (%)
≥1 Serious
adverse event
5 (5) 3 (3) 9 (9) 6 (6) 3 (5)
≥1 Adverse
event occurred
during
89 (91) 92 (90) 92 (92) 97 (96) 42 (76)
treatment
Hypotension 2 (2) 1 (1) 3 (3) 0 (0) 1 (2)
Bronchospasm 0 (0) 0 (0) 2 (2) 1 (1) 1 (2)
Bradycardia 0 (0) 1 (1) 1 (1) 0 (0) 0 (0)
Hypoglycemia 0 (0) 1 (1) 0 (0) 1 (1) 0 (0)
Diarrhea 16 (16) 14 (14) 17 (17) 28 (28) 4 (7)
Sleep disorder 28 (29) 14 (14) 19 (19) 22 (22) 7 (13)
Bronchitis 5 (5) 7 (7) 11 (11) 17 (17) 1 (2)
Vomiting 16 (16) 13 (13) 10 (10) 13 (13) 3 (5)
Bronchiolitis 6 (6) 7 (7) 6 (6) 10 (10) 3 (5)
Cold hands
8 (8) 10 (10) 1 (1) 10 (10) 1 (2)
and feet
Agitation 12 (12) 18 (18) 8 (8) 7 (7) 6 (11)
Constipation 9 (9) 6 (6) 9 (9) 4 (4) 1 (2)
Decreased
5 (5) 3 (3) 5 (5) 1 (1) 1 (2)
appetite
Somnolence 6 (6) 4 (4) 1 (1) 1 (1) 1 (2)
kg = kilogram; mg = milligram; n = number
Placebo
(n=55)
Table 24 summarizes the incidence and type of adverse effects reported in case series.
Consistent with the pharmacological action of propranolol, decreases in blood pressure and heart
rate were the most frequently reported adverse events and were as high as 100 percent in some
series. 168,171 However, reductions in these parameters were not always clinically significant. In
most prospective case series, clinically important hypotension and bradycardia were not
reported; asymptomatic changes were specifically noted in several series. 16,151-158,169,182,189,194,
199,205
The lack of cardiac events may be due to required cardiovascular evaluation prior to
initiation of propranolol or discontinuation after short-term monitoring. The number of patients
that did not qualify for propranolol therapy was not provided in any of these series. No adverse
effects were reported in several case series, 154,156,157,196 and most studies of topical beta-blockers
reported that no adverse events were observed, though studies typically did not describe methods
for harms monitoring. 159,160,186 Two studies of topical applications reported recurrent itching
associated with topical propranolol 187 in 3 percent of children and sleep disturbances in 1 percent
of children receiving topical timolol. 161 The remaining case series reported few adverse events,
and those reported rarely caused discontinuation of the medication. In total, 51/3810 (1.3%)
children in case series discontinued treatment due to adverse events including sleep disturbances
(n=13), bronchial hyperreactivity, wheezing, or asthma (n=9), and cold extremities (n=7).
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