Intolerable side effects, such as bronchial hyperreactivity, associated with propranolol treatment for problematic infantile hemangiomas are rare and most likely to occur in patients who are younger and have lower body weights, according to a recent study in Scientific Reports, an open access journal from the publishers of Nature.
Infantile hemangiomas are estimated to occur in 5 to 10 percent of children. Most resolve safely without treatment, but from 12 to 24 percent of these benign vascular tumors have complications and require treatment.
Propranolol is a first-line treatment for infantile hemangiomas needing systemic therapy. While effective and safe for most patients, propranolol can cross the blood-brain barrier, putting patients at potential risk for central nervous system side effects, including sleep disturbance and agitation. The drug has also been associated with serious side effects, such as bronchospasm/bronchial hyperreactivity and hypoglycemia.
Due to the intolerability of these side effects, some patients have to discontinue propranolol use. The problem with that is stopping treatment results in a higher risk of tumor rebound growth, according to the authors.
To better understand how often intolerable side effects occur and how best to manage and prevent them, the authors looked at intolerable side effect frequency, risk factors and approaches to management.
They retrospectively reviewed data on 1,250 children treated with propranolol for problematic infantile hemangiomas. Nearly 18 percent of the patients studied had been born prematurely. Patients’ median age at the start of propranolol therapy was 96 days and their median weight was 6.4 kg. More than half of the infantile hemangiomas were on the head and neck.
Among those studied, 26 patients, or 2.1 percent of the total, experienced intolerable side effects and had to discontinue the lipophilic nonselective beta blocker. Most stopped the drug due to severe sleep disturbance. Three patients had severe agitation. Four patients had severe respiratory disorders, including bronchial hyperreactivity and bronchospasm. Other intolerable side effects were symptomatic hypoglycemia, severe ulcerated infantile hemangiomas and viral gastroenteritis.
Starting propranolol at younger than 90 days and at up to 10 kg of body weight were independent risk factors for suffering intolerable side effects from propranolol.
Nine of the 26 patients who had to stop taking propranolol due to intolerable side effects experienced rebound growth after discontinuing the drug.
Twenty-three of the 26 patients who were no longer on propranolol started atenolol treatment, while the remaining three received a single daily dose of oral prednisolone. Patients fared well with 24 weeks of atenolol treatment, with more than 65 percent having an excellent response and almost 35 percent having a good or stable response. Two of the three patients on prednisolone had an excellent response and one a good response, after 24 weeks of treatment. Both medications were generally well tolerated, according to the authors.
PUTTING THE INFORMATION TO PRACTICE
“Clinically treatment decision making should be based on the age and tolerance of the patient; the growth potential, location and size of the tumor or tumors; the severity of the complication; and the urgency of therapy,” according to the authors.
A challenge for providers in evaluating the risks of benefits of needed infantile hemangioma treatments is that while guidelines exist, there is no algorithm or formula that easily addresses all factors that go into the decision making.
The authors and others have reported that oral atenolol effectively treats problematic infantile hemangiomas, without crossing the blood-brain barrier. Central nervous system side effects might therefore be less with atenolol than propranolol.
“In the present study, we found that a treatment switch from propranolol to atenolol did not compromise the efficacy of therapy,” they write.
Based on this and other research, atenolol may be a good option for treating patients who stop propranolol due to intolerable side effects. Atenolol might also be an alternative for treatment of infants at high risk for intolerable side effects from propranolol. Among those, preterm neonates and young infants seem to be at higher risk for propranolol-induced hypoglycemia. For example, there is evidence to suggest that providers should use propranolol with caution in children with poor oral intake. In fact, the two patients in this study who developed hypoglycemia had not been feeding normally, according to the authors.
Corticosteroids also remain useful in the treatment of infantile hemangiomas in certain situations, including when patients have contraindications, such as sinus bradycardia and bronchial asthma, to beta-blocker use.
Studies have also shown other beta-blockers, including nadolol and acebutolol, are among the other drug options that effectively treat infantile hemangiomas, but data is limited.
Ji Y, Chen S, Wang Q, Xiang B, et al. “Intolerable side effects during propranolol therapy for infantile hemangioma: frequency, risk factors and management,” Scientific Reports. March 9 2018;8(1):4264. DOI: 10.1038/s41598-018-22787-8.