DailyMed Label: Diazoxide

DailyMed Label: Diazoxide

2023

DailyMed Prescription

Diazoxide

diazoxide

e5 Pharma, LLC

NDC: 13517-100

NDC: 13517-100

Diazoxide is a nondiuretic benzothiadiazine derivative taken orally for the management of symptomatic hypoglycemia. Diazoxide Oral Suspension, USP contains 50 mg of diazoxide, USP in each milliliter and has a chocolate-mint flavor; alcohol content is approximately 7.25%. Other ingredients: Sorbitol solution, chocolate mint flavor, propylene glycol, magnesium aluminum silicate, carboxymethycellulose sodium, sodium benzoate, methylparaben, poloxamer 188, propylparaben, and purified water. Hydrochloric acid or sodium hydroxide may be added to adjust pH. Diazoxide has the following structural formula: Diazoxide is 7-chloro-3-methyl-2 H -1,2,4-benzothiadiazine 1,1-dioxide with the empirical formula C 8 H 7 ClN 2 O 2 S and the molecular weight 230.7. It is a white powder practically insoluble to sparingly soluble in water. Chemical Structure

Diazoxide Oral Suspension is useful in 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 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 should be considered.

Patients should be under close clinical observation when treatment with diazoxide is initiated. The clinical response and blood glucose level should be carefully monitored until the patient's condition has stabilized satisfactory; in most instances, this may be accomplished in several days. If administration of diazoxide is not effective after two or three weeks, the drug should be discontinued. The dosage of diazoxide must be individualized based on the severity of the hypoglycemic condition and the blood glucose level and clinical response of the patient. The dosage should be adjusted until the desired clinical and laboratory effects are produced with the least amount of the drug. Special care should be taken to assure accuracy of dosage in infants and young children. The usual daily dosage is 3 to 8 mg/kg, divided into two or three equal doses every 8 or 12 hours. In certain instances, patients with refractory hypoglycemia may require higher dosages. Ordinarily, an appropriate starting dosage is 3 mg/kg/day, divided into three equal doses every 8 hours. Thus an average adult would receive a starting dosage of approximately 200 mg daily. The usual daily dosage is 8 to 15 mg/kg divided into two or three equal doses every 8 to 12 hours. An appropriate starting dosage is 10 mg/kg/day, divided into three equal doses every 8 hours.

The use of diazoxide for functional hypoglycemia is contraindicated. The drug should not be used in patients hypersensitive to diazoxide or to other thiazides unless the potential benefits outweigh the possible risks.

Treatment with diazoxide should be initiated under close clinical supervision, with careful monitoring of blood glucose and clinical response until the patient's condition has stabilized. This usually requires several days. If not effective in two to three weeks, the drug should be discontinued. Prolonged treatment requires regular monitoring of the urine for sugar and ketones, especially under stress conditions, with prompt reporting of any abnormalities to the physician. Additionally, blood sugar levels should be monitored periodically by the physician to determine the need for dose adjustment. The effects of diazoxide on the hematopoietic system and the level of serum uric acid should be kept in mind; the latter should be considered particularly in patients with hyperuricemia or a history of gout. In some patients, higher blood levels have been observed with the oral suspension than with the capsule formulation of diazoxide. Dosage should be adjusted as necessary in individual patients if changed from one formulation to the other. Since the plasma half-life of diazoxide is prolonged in patients with impaired renal function, a reduced dosage should be considered. Serum electrolyte levels should also be evaluated for such patients. The antihypertensive effect of other drugs may be enhanced by diazoxide, and this should be kept in mind when administering it concomitantly with antihypertensive agents. Because of the protein binding, administration of diazoxide with coumarin or its derivatives may require reduction in the dosage of the anticoagulant, although there has been no reported evidence of excessive anticoagulant effect. In addition, diazoxide may possibly displace bilirubin from albumin; this should be kept in mind particularly when treating newborns with increased bilirubinemia. Pulmonary hypertension has been reported in neonates and young infants treated with diazoxide (see WARNINGS ). During treatment with diazoxide the patient should be advised to consult regularly with the physician and to cooperate in the periodic monitoring of his condition by laboratory tests. In addition, the patient should be advised: to take the drug on a regular schedule as prescribed, not to skip doses, not to take extra doses; not to use this drug with other medications unless this is done with the physician's advice; not to allow anyone else to take this medication; to follow dietary instructions; to report promptly any adverse effects (i.e., increased urinary frequency, increased thirst, fruity breath odor); to report pregnancy or to discuss plans for pregnancy. The following procedures may be especially important in patient monitoring (not necessarily inclusive); blood glucose determinations (recommended at periodic intervals in patients taking diazoxide orally for treatment of hypoglycemia, until stabilized); blood urea nitrogen (BUN) determinations and creatinine clearance determinations; hematocrit determinations; platelet count determinations; total and differential leukocyte counts; serum aspartate aminotransferase (AST) level determinations; serum uric acid level determinations; and urine testing for glucose and ketones (in patients being treated with diazoxide for hypoglycemia, semiquantitative estimation of sugar and ketones in serum performed by the patient and reported to the physician provides frequent and relatively inexpensive monitoring of the condition). 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 oral diazoxide and diphenylhydantoin may result in a loss of seizure control. These potential interactions must be considered when administering Diazoxide Oral Suspension. The concomitant administration of thiazides or other commonly used diuretics may potentiate the hyperglycemic and hyperuricemic effects of diazoxide. The hyperglycemic and hyperuricemic effects of diazoxide preclude proper assessment of these metabolic states. Increased renin secretion, IgG concentrations and decreased cortisol secretions have also been noted. Diazoxide inhibits glucagon-stimulated insulin release and causes a false-negative insulin response to glucagon. No long-term animal dosing study has been done to evaluate the carcinogenic potential of diazoxide. No laboratory study of mutagenic potential or animal study of effects on fertility has been done. Reproduction studies using the oral preparation in rats have revealed increased fetal resorptions and delayed parturition, as well as fetal skeletal anomalies; evidence of skeletal and cardiac teratogenic effects in rabbits has been noted with intravenous administration. The drug has also been demonstrated to cross the placental barrier in animals and to cause degeneration of the fetal pancreatic beta cells (see  ANIMAL PHARMACOLOGY AND/OR TOXICOLOGY ). Since there are no adequate data on fetal effects of this drug when given to pregnant women, safety in pregnancy has not been established. When the use of Diazoxide Oral Suspension is considered, the indications should be limited to those specified above for adults (see  INDICATIONS AND USAGE ), and the potential benefits to the mother must be weighed against possible harmful effects to the fetus. Diazoxide crosses the placental barrier and appears in cord blood. When given to the mother prior to delivery of the infant, the drug may produce fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism, and possibly other side effects that have occurred in adults. Alopecia and hypertrichosis lanuginosa have occurred in infants whose mothers received oral diazoxide during the last 19 to 60 days of pregnancy. Since intravenous administration of the drug during labor may cause cessation of uterine contractions, and administration of oxytocic agents may be required to reinstate labor, caution is advised in administering diazoxide at that time. Information is not available concerning the passage of diazoxide in breast milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions from diazoxide in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. (See INDICATIONS AND USAGE ).

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. It usually responds to diuretic therapy (see

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 oral diazoxide and diphenylhydantoin may result in a loss of seizure control. These potential interactions must be considered when administering Diazoxide Oral Suspension. The concomitant administration of thiazides or other commonly used diuretics may potentiate the hyperglycemic and hyperuricemic effects of diazoxide.

Diazoxide Oral Suspension, USP 50 mg/mL, a chocolate-mint flavored suspension; bottle of 30 mL (NDC 13517-100-30), with dropper calibrated to deliver 10, 20, 30, 40 and 50 mg diazoxide. Shake well before each use. Protect from light. Store in carton until contents are used. Store in light resistant container as defined in the USP. Store Diazoxide Oral Suspension at 25°C (77°F) excursions permitted 15°-30°C (59-86°F). [See USP Controlled Room Temperature]. Rx only Manufactured for: e5 Pharma, LLC Boca Raton, FL 33432 1000001287  Rev. 08/2023

Diazoxide administered orally produces a prompt dose-related increase in blood glucose level, due primarily to an inhibition of insulin release from the pancreas, and also to an extrapancreatic effect. The hyperglycemic effect begins within an hour and generally lasts no more than eight hours in the presence of normal renal function. Diazoxide decreases the excretion of sodium and water, resulting in fluid retention which may be clinically significant. The hypotensive effect of diazoxide on blood pressure is usually not marked with the oral preparation. This contrasts with the intravenous preparation of diazoxide (see ADVERSE REACTIONS ). Other pharmacologic actions of diazoxide include increased pulse rate; increased serum uric acid levels due to decreased excretion; increased serum levels of free fatty acids' decreased chloride excretion; decreased para-aminohippuric acid; (PAH) clearance with no appreciable effect on glomerular filtration rate. The concomitant administration of a benzothiazide diuretic may intensify the hyperglycemic and hyperuricemic effects of diazoxide. In the presence of hypokalemia, hyperglycemic effects are also potentiated. Diazoxide induced hyperglycemia is reversed by the administration of insulin or tolbutamide. The inhibition of insulin release by diazoxide is antagonized by alpha-adrenergic blocking agents. Diazoxide is extensively bound (more than 90%) to serum proteins, and is excreted in the kidneys. The plasma half-life following I.V. administration is 28 ± 8.3 hours. Limited data on oral administration revealed a half-life of 24 and 36 hours in two adults. In four children aged four months to six years, the plasma half-life varied from 9.5 to 24 hours on long-term oral administration. The half-life may be prolonged following overdosage, and in patients with impaired renal function.

Diazoxide Oral Suspension, USP 50 mg/mL, 30 mL Carton 30 mL NDC 13517-100-30 Rx only