Nadolol is a β-adrenergic antagonist that has been shown to be efficacious in the treatment of infantile hemangioma. It has been suggested that this drug may have fewer side effects compared with the gold standard therapy, propranolol, because it does not exhibit membrane-stabilizing effects and has little ability to cross the blood-brain barrier. However, the pharmacokinetics and safety of nadolol in infants are not well understood, potentially making this therapy dangerous. β-adrenergic antagonist toxicity causes bradycardia, hypotension, hypoglycemia, and even death. We report a case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity. Pharmacokinetics studies show a large fraction of oral nadolol either remains in the feces unchanged or is excreted into feces via the biliary system, allowing continued absorption over time in infants who stool infrequently. Propranolol may be a safer therapy overall. Not only does it have a shorter half-life, but propranolol is hepatically metabolized and renally eliminated, allowing for less drug accumulation in healthy infants with variable stooling patterns. We suggest that if nadolol is selected for therapy, pediatricians should instruct parents to monitor their infants' bowel movements closely and encourage early intervention in the event of decreased stooling. This intervention may greatly improve the safety of nadolol in this vulnerable patient population.
Copyright © 2020 by the American Academy of Pediatrics.
Conflict of interest statement
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
Nadolol for the Treatment of Infantile HemangiomaAM Villalba-Moreno et al. Am J Health Syst Pharm 72 (1), 44-6. PMID 25511837. - Case ReportsNadolol was an effective alternative to propranolol in three pediatric patients with hemangiomas.
Oral Nadolol for Children With Infantile Hemangiomas and Sleep Disturbances With Oral PropranololJ Bernabeu-Wittel et al. Pediatr Dermatol 32 (6), 853-7. PMID 26447831.The use of oral nadolol in the treatment of IH in our series of 7 patients, resolved the propranolol-related sleep disturbances in 5 (71%), while in one patient the sympt …
Propranolol Therapy for Infantile HemangiomaN Gunturi et al. Indian Pediatr 50 (3), 307-13. PMID 23680605. - ReviewAlthough large-scale randomized controlled trials must be conducted in order to further evaluate the safety and the possible role of propranolol in the treatment of IH, t …
A Randomized, Controlled Trial of Oral Propranolol in Infantile HemangiomaC Léauté-Labrèze et al. N Engl J Med 372 (8), 735-46. PMID 25693013. - Clinical TrialThis trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Der …
Interventions for Infantile Haemangiomas of the SkinM Novoa et al. Cochrane Database Syst Rev 4 (4), CD006545. PMID 29667726. - ReviewWe found there to be a limited evidence base for the treatment of infantile haemangiomas: a large number of interventions and outcomes have not been assessed in RCTs.Our …