NEODOSE

INDICATIONS

• Hypoglycemia due to Hyperinsulinism: In small for gestational age infants with hyperinsulinemic hypoglycemia during the first 5 days of life, serum glucose concentration normalized sooner with oral diazoxide compared with placebo, in a randomized, double-blind study (N=30). The median time to achieve hypoglycemia control (defined as glucose IV infusion of 4 mg/kg/min or less for a minimum of 6 hours) was 40 hours for the diazoxide group and 72 hours (p = 0.01) for the placebo group. The total duration of intravenous fluids (114 vs 164 hours; p=0.004) and time to achieve euglycemia (30 vs 60 hours, p = 0.001 or less) was less with diazoxide compared with placebo. Diazoxide dosage was 3 mg/kg/dose orally every 8 hours and increased to 4 mg/kg/dose every 8 hours if hypoglycemia persisted after 48 hours; subsequently tapered by 1 mg/kg/dose every 72 hours once the infant was euglycemic for at least 72 hours.

FDA APPROVED INDICATION

Treatment of hypoglycemia due to hyperinsulinism associated with the following conditions:

leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis.

May also be used preoperatively and postoperatively, as a temporary measure for persistent hypoglycemia.

CONTRAINDICATIONS

• Functional hypoglycemia.
• ypersensitivity to diazoxide or to other thiazides.

PRECAUTIONS

• cardiovascular:
  • Fluid retention from diazoxide may result in congestive heart failure for those with compromised cardiac reserve; diuretics may be used.
  • Antihypertensive effects may be enhanced when diazoxide is coadministered with antihypertensive agents.
• Concomitant Use:
  • Thiazides may potentiate the hyperglycemic and hyperuricemic actions of diazoxide.
• Endocrine and Metabolic:
  • Ketoacidosis and nonketotic hyperosmolar coma have been reported, usually during intercurrent illness and at recommended doses; monitoring required.
  • Hyperuricemia or history of gout; monitoring required.
• Hepatic:
  • Newborns with bilirubinemia; bilirubin may be displaced from albumin by diazoxide.
• Musculoskeletal:
  • Abnormal facial features developed in 4 children treated for more than 4 years with diazoxide.
• Ophthalmic:
  • Cataracts (transient) have occurred in association with hyperosmolar coma in an infant; resolved with correction of hyper-osmolarity.
• Pharmacokinetics:
  • Oral suspension may result in higher blood concentrations than oral capsules; dosage adjustment may be necessary when switching between formulations.
• Renal:
  • Renal function, impaired; risk of drug toxicity.
• Respiratory:
  • Pulmonary hypertension has been reported in infants and newborns administered diazoxide for treatment of low blood sugar and may occur within days or a few months of administration. Risk factors for pulmonary hypertension are those with meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea, pneumonia, sepsis, congenital diaphragmatic hernia, or congenital heart disease. Symptoms may include difficulty breathing, flared nostrils, grunting, chest wall retractions, rapid breathing, difficulty feeding, bluish color of the lips or skin. Discontinue use if pulmonary hypertension develops . Symptoms may be reversible upon discontinuation

ADVERSE EFFECTS

Hirsutism and hypertrichosis have been reported commonly in children. Hypotension, chest pain, thrombocytopenia, and neutropenia have been reported rarely. Concurrent treatment with a thiazide diuretic is recommended to prevent associated fluid retention from diazoxide.

ADMINISTRATION

Shake suspension well before administration.

MONITORING

• Laboratory Parameters
  • Careful monitoring of blood glucose concentrations is recommended during therapy, particularly during treatment initiation and until stabilization. Monitoring urine for sugar and ketones is recommended for patients under stress. A dose reduction may be required in patients with hyperglycemia or glucosuria.
  • Evaluate serum electrolyte levels in patients with impaired renal function.
  • Monitor BUN and creatinine clearance.
  • Monitor hematocrit, platelet counts, and leukocytes (total and differential).
  • Monitor AST and serum uric acid level.
• Physical Exam
  • Monitor for respiratory distress, especially in patients with risk factors for pulmonary hypertension.