| Intervention | Harm/Adverse Event | Number of Studies (# Participants With Harm/Total Participants) | Reported Rates Across Studies |
|---|---|---|---|
| *Oral Propranolol 1–1.5 mg/kg/day | Decrease in heart rate and blood pressure171 | 1 (89/89) | 100% |
| Elevation of liver enzymes (ALT, AST) 171 | 1 (5/89) | 6% | |
| Hypoglycemia171 | 1 (4/89) | 4.5% | |
| Anorexia155 | 1 (1/35) | 3% | |
| Diarrhea153,189 | 2 (6/114) | 3%–12% | |
| Asymptomatic hypotension153 | 1 (1/60) | 2% | |
| Nausea171 | 1 (2/89) | 2% | |
| Cold extremities171 | 1 (1/89) | 1% | |
| Restless sleep171 | 1 (1/89) | 1% | |
| Oral Propranolol 2–2.1 mg/kg/day | **Hypotension18,167,168,173,190,191,194,199,200,202,205 | 11 (89/944) | 0.4%–62% |
| ECG changes167 | 1 (7/25) | 28% | |
| Bradycardia151,167,168,173,190,191,199 | 7 (51/577) | 0.8%–38% | |
| Nausea/Vomiting/Diarrhea151,153,162,175,178,179,181,190–193 | 12 (37/1048) | 0.4%–24% | |
| Cold extremities151,163,178,180,193,200,202 | 7 (17/626) | 1%–10% | |
| Sleep disturbance/Light sleep153,162,165,167,179,190–193,203 | 10 (88/729) | 3%–29% | |
| Behavioral changes162,167,175,178,193,200 | 6 (13/531) | 0.5%–10.8% | |
| Respiratory symptoms/Asthma/Dyspnea151,162,163,165,178,180,190,192,194 | 10 (35/725) | 2%–10% | |
| Fatigue/Somnolence165,167,173,176,180,201 | 6 (15/289) | 1%–25.9% | |
| Fever162 | 1 (2/30) | 7% | |
| Gross motor abnormalities175 | 1 (13/188) | 7% | |
| ***Hypoglycemia168,173,191,194,202 | 5 (14/328) | 2%–6.8% | |
| Cutaneous symptoms/Rash153,176,180 | 3 (5/172) | 2%–5% | |
| Gastroesophageal issues180,194 | 2 (3/99) | 2.3%–4% | |
| Sweating18,176 | 2 (2/85) | 2%–4% | |
| Constipation151,202 | 2 (3/186) | 0.8%–3% | |
| Respiratory tract infection162 | 1 (1/30) | 3% | |
| Skin atrophy156 | 1 (2/50) | 3% | |
| Seizure170 | 1 (1/45) | 2% | |
| Agranulocytosis163 | 1 (1/97) | 1% | |
| Cyanotic breath-holding spells183,184 | 1 (1/71) | 1% | |
| Low body temperature163 | 1 (1/97) | 1% | |
| Stridor183,184 | 1 (1/71) | 1% | |
| Bronchospasm168,193,203 | 3 (3/337) | 0.4%–2.7% | |
| Worsening of ulceration190 | 1 (4/250) | 1.6% | |
| Peripheral cyanosis190 | 1 (2/250) | 0.8% | |
| Oral Propranolol 3–3.3 mg/kg/day | †Sleep disturbances/Nightmares158,164,166 | 3 (14/99) | 3%–23% |
| Transient asymptomatic hypotension158,164 | 2 (7/66) | 3%–17% | |
| Daytime drowsiness164 | 1 (6/35) | 17% | |
| Benign infections164 | 1 (4/35) | 11% | |
| Digestive symptoms164 | 1 (3/35) | 9% | |
| Constipation152 | 1 (2/30) | 7% | |
| Tachypnea152 | 1 (2/30) | 7% | |
| Irritability164 | 1 (2/35) | 6% | |
| Cold extremities152,166 | 2 (2/66) | 3% | |
| Esophageal reflux158,166 | 2 (2/64) | 3% | |
| Poor weight gain164 | 1 (1/35) | 3% | |
| Decreased appetite164 | 1 (1/35) | 3% | |
| Bradycardia164 | 1 (1/35) | 3% | |
| Hypoglycemia152 | 1 (1/30) | 3% | |
| Increased appetite164 | 1 (1/35) | 3% | |
| Shortness of breath on activity164 | 1 (1/35) | 3% | |
| Oral Propranolol 2–3 mg/kg/day | Cold extremities16,172 | 2 (64/206) | 3%–36% |
| Nocturnal restlessness172 | 1 (39/174) | 22% | |
| Daytime sleepiness/Inactivity172 | 1 (28/174) | 16% | |
| Gastrointestinal symptoms172 | 1 (12/174) | 7% | |
| Agitation16 | 1 (2/32) | 6% | |
| Insomnia16 | 1 (2/32) | 6% | |
| Restlessness/Increased daytime activity172 | 1 (9/174) | 5% | |
| Hypotension16,172 | 2 (7/206) | 3% | |
| Asthma/Wheezing16,172 | 2 (18/206) | 3% | |
| Nightmares16 | 1 (1/32) | 3% | |
| Sweating16 | 1 (1/32) | 3% | |
| Feeding difficulties172 | 1 (3/174) | 2% | |
| Ulceration (onset/worsening)172 | 1 (4/174) | 2% | |
| Breath holding spells172 | 1 (2/174) | 1% | |
| ††Oral Propranolol 1–4 mg/kg/day | Somnolence185,195 | 2 (5/83) | 6%–6.7% |
| Hypoglycemia185 | 1 (1/53) | 2% | |
| Hypotension185 | 1 (1/53) | 2% | |
| Profound mottling of extremities185 | 1 (1/53) | 2% | |
| Severe bradycardia185 | 1 (1/53) | 2% | |
| Cold extremities195 | 1 (3/30) | 10% | |
| Bronchospasm195 | 1 (3/30) | 10% | |
| Transaminase increase195 | 1 (1/30) | 3.3% | |
| Topical Propranolol 0.5–3% | Skin changes (redness, rash, itching, erosion, eczema)197,198,204 | 2 (9/249) | 1.96%–4% |
| Ulceration204 | 1 (5/148) | 3% | |
| †††Oral Propranolol + Atenolol (dose not clearly reported) | Cold extremities188 | 1 (55/109) | 51% |
| Sleep disturbance188 | 1 (47/109) | 43% | |
| Gastrointestinal problems188 | 1 (27/109) | 25% | |
| Fatigue188 | 1 (20/109) | 18% | |
| Coughing188 | 1 (19/109) | 17% | |
| Sweating188 | 1 (16/109) | 15% | |
| Pallor188 | 1 (14/109) | 13% | |
| Agitation/irritation188 | 1 (14/109) | 13% | |
| Dyspnea/shortness of breath188 | 1 (6/109) | 6% | |
| Increased activity188 | 1 (5/109) | 5% | |
| Skin reaction188 | 1 (5/109) | 5% | |
| Nausea/vomiting188 | 1 (4/109) | 4% | |
| Decreased appetite188 | 1 (4/109) | 4% | |
| Increased appetite188 | 1 (3/109) | 3% | |
| Hypoglycemia188 | 1 (3/109) | 3% | |
| Syncope188 | 1 (2/109) | 2% | |
| Dizziness188 | 1 (2/109) | 2% | |
| Hair loss188 | 1 (2/109) | 2% | |
| Seizure188 | 1 (1/109) | 1% | |
| Dry mouth (xerostomia) 188 | 1 (1/109) | 1% | |
| Hallucinations188 | 1 (1/109) | 1% |
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 study168 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 study199 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 study168 reported “lethargy, viral illness, and hypoglycemia” in 2/250 children (data not factored into table).
One study164 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 series188 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.
From: Results
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