Proglycem

INDICATIONS AND USAGE PROGLYCEM 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. PROGLYCEM may be used preoperatively as a temporary measure, and postoperatively, if hypoglycemia persists. PROGLYCEM 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 PROGLYCEM should be considered.

DOSAGE AND ADMINISTRATION Patients should be under close clinical observation when treatment with PROGLYCEM 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 PROGLYCEM is not effective after 2 or 3 weeks, discontinue PROGLYCEM. Individualize the dosage of PROGLYCEM 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 PROGLYCEM. 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.

CONTRAINDICATIONS PROGLYCEM is contraindicated in patients with: Functional hypoglycemia Hypersensitivity to diazoxide, any of the excipients in PROGLYCEM, or other thiazides

WARNINGS The antidiuretic property of diazoxide may lead to significant fluid retention. In patients with compromised cardiac reserve, fluid retention may precipitate congestive heart failure. If fluid retention develops, manage according to standards of care. Co-administration of PROGLYCEM with thiazides may potentiate the hyperglycemic and hyperuricemic actions of diazoxide (see DRUG INTERACTIONS and ANIMAL PHARMACOLOGY AND/OR TOXICOLOGY ). Ketoacidosis and nonketotic hyperosmolar coma have been reported in patients treated with PROGLYCEM, usually during intercurrent illness. Prompt recognition and treatment are essential (see OVERDOSAGE ), and prolonged surveillance following the acute episode is necessary because of the long drug half-life of approximately 30 hours. Advise patients to monitor urine glucose and ketones and to promptly report abnormal findings and symptoms of ketoacidosis to their healthcare provider. Transient cataracts occurred in association with hyperosmolar coma in an infant, and subsided on correction of the hyper-osmolarity. Cataracts have been observed in several animals receiving daily dosages of intravenous or oral diazoxide. The development of abnormal facial features in four children treated chronically (>4 years) with PROGLYCEM for hypoglycemia hyperinsulinism in the same clinic has been reported. Pulmonary Hypertension in Neonates and Infants There have been postmarketing reports of pulmonary hypertension occurring in infants and neonates treated with diazoxide. The cases were reversible upon discontinuation of diazoxide. Monitor patients, especially those with risk factors for pulmonary hypertension, for respiratory distress and discontinue PROGLYCEM if pulmonary hypertension is suspected.

Drug Interactions Since diazoxide is highly bound to serum proteins, it may displace other substances which are also bound to protein, such as bilirubin or coumarin and its derivatives, resulting in higher blood levels of these substances. Concomitant administration of PROGLYCEM and diphenylhydantoin may result in a loss of seizure control. Consider these potential interactions when administering PROGLYCEM. The concomitant administration of thiazides or other diuretics may potentiate the hyperglycemic and hyperuricemic effects of PROGLYCEM.

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 PROGLYCEM (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 PROGLYCEM. 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 PROGLYCEM. Neutropenia is transient, is not associated with increased susceptibility to infection, and ordinarily does not require discontinuation of PROGLYCEM. 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.