NEODOSE

INDICATIONS

• Tachyarrhythmias and hypertension:
  • Preferred therapy for supraventricular tachycardia if associated with Wolff-Parkinson-White syndrome.
  • Palliation of tetralogy of Fallot and hypertrophic obstructive cardiomyopathy.
  • Adjunctive treatment of neonatal thyrotoxicosis.
In 287 infants (median age, 17 days), oral propranolol 3.6 +/- 1 mg/kg/day divided every 6 hours controlled 67.3% of arrhythmias (reentrant arrhythmias or atrial tachycardia) in a retrospective study. The average dose for propranolol monotherapy, which was successful, at discharge was 4 mg/kg/day. One patient discontinued propranolol due to an adverse event (bradycardia)

• Infantile hemangiomas (IH):The first-line agent for IH requiring systemic treatment is oral propranolol. Oral prednisoLONE or predniSONE are alternatives when propranolol is contraindicated or when there is a lack of response to propranolol. For bulky IH during proliferation or when critical anatomic locations are involved, then intralesional injection of triamcinolone and/or betamethasone is recommended. For thin and/or superficial IH, topical timolol is an option. The strength of evidence is high for the effectiveness of propranolol for reducing IH lesion size; although, the optimal dosage, timing, and duration of propranolol therapy, as well as the potential for long-term harm, is not known . The FDA-approved age for initiation of propranolol is 5 weeks to 5 months based on a randomized, double-blind study (n=460) and in retrospectives studies (n=124), the age of initiation of treatment was usually older than 1 month of age; however, neonates have been treated with propranolol for hemangiomas . The mean age of treatment initiation was 9.4 months (2 to 54 months) in a retrospective study (n=99).

FDA APPROVED INDICATION

Indicated for the treatment of proliferating infantile hemangioma requiring systemic therapy. Initiate treatment at age 5 weeks to 5 months. Safety and effectiveness for infantile hemangioma have not been established in pediatric patients older than 1 year

CONTRAINDICATIONS

Contraindicated in patients with cardiogenic shock, decompensated heart failure, sinus bradycardia, sick sinus syndrome, greater than first degree block (unless permanent pacemaker is present), reactive airway disease, or diminished myocardial contractility. When treating infantile hemangioma, Hemangeol™ is contraindicated in premature infants with corrected age younger than 5 weeks, infants weighing less than 2 kg, asthma or history of bronchospasm, heart rate less than 80 bpm, greater than first degree heart block, decompensated heart failure, blood pressure less than 50/30 mmHg, or pheochromocytoma

PRECAUTIONS

Cardiac ischemia may occur with abrupt discontinuation of therapy, gradually taper dose over 1 to 2 weeks and monitor the patient. Beta-blocker therapy may mask tachycardia occurring with hypoglycemia and signs of hyperthyroidism. Concomitant corticosteroids increase the risk of hypoglycemia. Treatment with epinephrine for severe anaphylactic reactions may be less effective in beta-blocker-treated patients; consider alternative medications. Propranolol may precipitate more severe heart failure. The risk of stroke increases in PHACE (posterior fossa, hemangioma, arterial lesions, cardiac abnormalities/aortic coarctation, and eye abnormalities) syndrome patients with severe cerebrovascular anomalies due to the blood pressure reduction

ADVERSE EFFECTS

Adverse effects are related to beta-receptor blockade. Significant reductions in myocardial function and hypotension resulting in cardiac compromise have been reported in association with beta-blockers, especially during IV administration in infants. May cause AV block. Bradycardia, fatigue, headache, dizziness, somnolence, diarrhea, anorexia, insomnia, personality changes, and depression are the most common adverse effects reported in children. Bronchospasm may occur. Case reports of hypoglycemia occurring in children after therapeutic doses, in absence of diabetes. Infantile hemangioma: The most common (10% or more) adverse events in infants treated for infantile hemangioma were sleep disorders, aggravated respiratory tract infections, peripheral coldness, agitation, diarrhea, somnolence, nightmare, irritability, decreased appetite, abdominal pain, and vomiting . Asymptomatic and symptomatic hypoglycemia, requiring hospitalization, have been reported in infants receiving propranolol for the treatment of infantile hemangioma. Infants less than 3 months of age are at increased risk. Hypoglycemia including hypoglycemic seizures were typically associated with poor oral intake or concomitant infection . Concomitant corticosteroids increase the risk of hypoglycemia. Within 2 hours the effect on heart rate and blood pressure were evident .

ADMINISTRATION

• Intravenous: Administer 1 mg/mL at a rate not to exceed 1 mg per minute. Consider diluting to 0.1 mg/mL.
• Oral: Administer during or right after a feeding, skip the dose if the child is not eating or is vomiting.

BLACK BOX WARNING

Following abrupt cessation of therapy with beta-blockers, exacerbations of angina pectoris and myocardial infarction have occurred. Warn against interruption or discontinuation of therapy without physician advice.

MONITORING

Continuous ECG monitoring should be done during acute treatment of arrhythmias and during IV therapy. Measure systemic blood pressure frequently. Monitor vital signs an measure blood glucose during initiation of treatment and after dosage changes. Assess for increased airway resistance. When treating infantile hemangiomas, monitor heart rate and blood pressure for 2 hours after the first or increasing dose . Perform a complete history and physical examination with particular attention to cardiac and pulmonary systems. Electrocardiography may be considered, particularly in younger infants, those with a low heart rate, and those at risk of congenital heart disease (by examination or family history). Before treating large facial infantile hemangioma with propranolol, assess for potential arteriopathy associated with PHACE syndrome