Diazoxide

INDICATIONS & USAGE Diazoxide oral suspension is indicated for the management of hypoglycemia due to hyperinsulinism associated with the following conditions: Adults: Inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy. Infants and children: Leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis. Diazoxide oral suspension may be used preoperatively as a temporary measure, and postoperatively, if hypoglycemia persists. Diazoxide oral suspension should be used only after a diagnosis of hypoglycemia due to one of the above conditions has been definitely established. When other specific medical therapy or surgical management either has been unsuccessful or is not feasible, treatment with diazoxide oral suspension should be considered.

DOSAGE & ADMINISTRATION Patients should be under close clinical observation when treatment with diazoxide oral suspension is initiated. Carefully monitor the clinical response and blood glucose until the patient’s condition has stabilized satisfactory; in most instances, this may be accomplished in several days. If administration of diazoxide oral suspension is not effective after 2 or 3 weeks, discontinue diazoxide oral suspension. Individualize the dosage of diazoxide oral suspension based on the severity of the hypoglycemic condition and the blood glucose level and clinical response of the patient. Adjust the dosage until the desired clinical and laboratory effects are produced with the least amount of diazoxide oral suspension. Take special care to ensure the accuracy of the dosage in infants and young children. Adults and children : The recommended starting dosage is 3 mg/kg/day, administered orally, divided into 3 equal doses every 8 hours or 2 equal doses every 12 hours. The dosage may be titrated to a maximum of 8 mg/kg/day. Patients with refractory hypoglycemia may require higher dosages. Infants and newborns : The recommended starting dosage is 8 mg/kg/day, administered orally, divided into 3 equal doses every 8 hours or 2 equal doses every 12 hours. The dosage may be titrated to a maximum of 15 mg/kg/day.

ADVERSE REACTIONS Frequent and Serious : Sodium and fluid retention is most common in young infants and in adults and may precipitate congestive heart failure in patients with compromised cardiac reserve. (see DRUG INTERACTIONS ). Infrequent but Serious : Diabetic ketoacidosis and hyperosmolar nonketotic coma may develop very rapidly. Monitor patients for up to 7 days due to the long half-life of diazoxide (see OVERDOSAGE ). Other frequent adverse reactions : Hirsutism of the lanugo type, mainly on the forehead, back and limbs, occurs most commonly in children and women and may be cosmetically unacceptable. It subsides on discontinuation of diazoxide oral suspension. Hyperglycemia or glycosuria may require reduction in dosage in order to avoid progression to ketoacidosis or hyperosmolar coma. Gastrointestinal intolerance may include anorexia, nausea, vomiting, abdominal pain, ileus, diarrhea, transient loss of taste. Tachycardia, palpitations, increased levels of serum uric acid are common. Thrombocytopenia with or without purpura may require discontinuation of diazoxide oral suspension. Neutropenia is transient, is not associated with increased susceptibility to infection, and ordinarily does not require discontinuation of diazoxide oral suspension. Skin rash, headache, weakness, and malaise may also occur. Other adverse reactions : Cardiovascular : Hypotension occurs occasionally, which may be augmented by thiazide diuretics given concurrently. A few cases of transient hypertension, for which no explanation is apparent, have been noted. Chest pain has been reported rarely. Pulmonary hypertension has been reported in neonates and young infants (see WARNINGS ). There have been postmarketing reports of pericardial effusion in patients without structural heart disease; the majority of cases occurred in pediatric patients and infants. Gastrointestinal : There have been postmarketing reports of necrotizing enterocolitis; the majority of cases occurred in infants with underlying co-morbid conditions. Hematologic : eosinophilia; decreased hemoglobin / hematocrit; excessive bleeding, decreased IgG. Hepato-renal : increased AST, alkaline phosphatase; azotemia, decreased creatinine clearance, reversible nephrotic syndrome, decreased urinary output, hematuria, albuminuria. Neurologic: anxiety, dizziness, insomnia, polyneuritis, paresthesia, pruritus, extrapyramidal signs. Ophthalmologic : transient cataracts, subconjunctival hemorrhage, ring scotoma, blurred vision, diplopia, lacrimation. Skeletal, integumentary; monilial dermatitis, herpes, advance in bone age; loss of scalp hair. Systemic: fever, lymphadenopathy. Other; gout acute pancreatitis/pancreatic necrosis, galactorrhea, enlargement of lump in breast.