Diazoxide

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Diazoxide
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

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Overview

Diazoxide is a potassium channel opener that is FDA approved for the {{{indicationType}}} of hypoglycemia. Common adverse reactions include hypotension, hyperglycemia, nausea, vomiting, asthenia, and dizziness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypoglycemia
  • Dosing Information
  • initial dosage: 3 mg/kg PO tid(approxmately 200 mg q24h for a adult)
  • maitaing dosage: 3—8 mg/kg PO q8—12 h
  • Patients should be under close clinical observation when treatment with proglycem 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 proglycem® is not effective after two or three weeks, the drug should be discontinued.
  • The dosage of proglycem® 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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Diazoxide in adult patients.

Non–Guideline-Supported Use

Myocardial protection in patients undergoing coronary artery bypass grafting
  • Dosing Information
  • 1.5 mg/kg IV (for over 5 minutes) [1]
Hypertension in pregnancy
  • Dosing Information
  • 30—50 mg IV every 1 to 4 minutes or continuously
Congestive heart failure
  • Dosing Information
  • 300 mg IV every 10 minutes (Total doses of DIAZOXIDE ranged from 450 to 900 mg) [2]
Diabetes mellitus
  • Dosing Information
  • 4—6 mg/kg [3]
Obesity
  • Dosing Information
  • 2/3 mg/kg PO (max 200 mg/day) combined with 1260- (women) to 1570- (men) calorie diets[4]
Pulmonary hypertension
  • Dosing Information
  • 600 mg PO q24h
Schizophrenia
  • Dosing Information

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis
  • Dosing Information
  • Initial dosage: 10 mg/kg tid
  • Maintaining dosage; 8—15 mg/kg q8h or q12h
  • Patients should be under close clinical observation when treatment with proglycem® 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 proglycem® is not effective after two or three weeks, the drug should be discontinued.
  • The dosage of proglycem® 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.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Diazoxide in pediatric patients.

Non–Guideline-Supported Use

Persistent hyperinsulinemic hypoglycemia of infancy
  • Dosing Information
  • 10 mg/kg/day [6]

Contraindications

Warnings

  • The antidiuretic property of diazoxide may lead to significant fluid retention, which in patients with compromised cardiac reserve, may precipitate congestive heart failure. The fluid retention will respond to conventional therapy with diuretics.
  • It should be noted that concomitantly administered thiazides may potentiate the hyperglycemic and hyperuricemic actions of diazoxide.
  • Ketoacidosis and nonketotic hyperosmolar coma have been reported in patients treated with recommended doses of proglycem® usually during intercurrent illness. Prompt recognition and treatment are essential, and prolonged surveillance following the acute episode is necessary because of the long drug half-life of approximately 30 hours. The occurrence of these serious events may be reduced by careful education of patients regarding the need for monitoring the urine for sugar and ketones and for prompt reporting of abnormal findings and unusual symptoms to the physician. 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 doses 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.

PRECAUTIONS

General

  • Treatment with proglycem® 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 proglycem®. 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 proglycem®, and this should be kept in mind when administering it concomitantly with antihypertensive agents.
  • Because of the protein binding, administration of proglycem® 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, proglycem® may possibly displace bilirubin from albumin; this should be kept in mind particularly when treating newborns with increased bilirubinemia.

Adverse Reactions

Clinical Trials Experience

There is limited information about the clinical trial experience.

Postmarketing Experience

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. It usually responds to diuretic therapy.
Infrequent but Serious
  • Diabetic ketoacidosis and hyperosmolar nonketotic coma may develop very rapidly. Conventional therapy with insulin and restoration of fluid and electrolyte balance is usually effective if instituted promptly. Prolonged surveillance is essential in view of the long half-life of proglycem®.
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 the drug.
  • Other adverse reactions which have been observed are

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.

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.

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 coumarinand 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 proglycem® Capsules or Suspension.
  • The concomitant administration of thiazides or other commonly used diuretics may potentiate the hyperglycemic and hyperuricemic effects of diazoxide.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • 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. 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 proglycem® is considered, the indications should be limited to those specified above for adults, and the potential benefits to the mother must be weighed against possible harmful effects to the fetus.


Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Diazoxide in women who are pregnant.

Labor and Delivery

  • 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 proglycem® at that time.

Nursing Mothers

  • 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.

Pediatric Use

(See INDICATIONS AND USAGE).

Geriatic Use

There is no FDA guidance on the use of Diazoxide in geriatric settings.

Gender

There is no FDA guidance on the use of Diazoxide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Diazoxide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Diazoxide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Diazoxide in patients with hepatic impairment.

Females of Reproductive Potential and Males

  • 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.

Immunocompromised Patients

There is no FDA guidance one the use of Diazoxide in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Patients should be under close clinical observation when treatment with proglycem® 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 proglycem® is not effective after two or three weeks, the drug should be discontinued.
  • The dosage of proglycem® 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.

Monitoring

  • The occurrence of these serious events may be reduced by careful education of patients regarding the need for monitoring the urine for sugar and ketones and for prompt reporting of abnormal findings and unusual symptoms to the physician.
  • 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 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).

IV Compatibility

There is limited information about the IV Compatibility.

Overdosage

  • An overdosage of proglycem® causes marked hyperglycemia which may be associated with ketoacidosis. It will respond to prompt insulin administration and restoration of fluid and electrolyte balance. Because of the drug's long half-life (approximately 30 hours), the symptoms of overdosage require prolonged surveillance for periods up to seven days until the blood sugar level stabilizes within the normal range. One investigator reported successful lowering of diazoxide blood levels by peritoneal dialysis in one patient and by hemodialysis in another.

Pharmacology

Template:Px
Diazoxide
Systematic (IUPAC) name
7-chloro-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
Identifiers
CAS number 364-98-7
ATC code C02DA01 V03AH01 (WHO)
PubChem 3019
DrugBank DB01119
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 230.672 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ?
Protein binding 90%
Metabolism Hepatic oxidation and sulfate conjugation
Half life 21-45 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

C(AU) C(US)

Legal status

POM(UK) [[Prescription drug|Template:Unicode-only]](US)

Routes Oral, intravenous

Mechanism of Action

  • 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.

Structure

  • Proglycem® (diazoxide) is a nondiuretic benzothiadiazine derivative taken orally for the management of symptomatic hypoglycemia. Proglycem® Capsulescontain 50 mg diazoxide, USP. The Suspension 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 cream flavor, propylene glycol, magnesium aluminum silicate, carboxymethycellulose sodium, mint flavor, 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:
This image is provided by the National Library of Medicine.

Pharmacodynamics

  • The hyperglycemic effect begins within an hour and generally lasts no more than eight hours in the presence of normal renal function.
  • Proglycem® 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.
  • Other pharmacologic actions of proglycem® 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 proglycem®. In the presence of hypokalemia, hyperglycemic effects are also potentiated.
  • Proglycem®-induced hyperglycemia is reversed by the administration of insulin or tolbutamide. The inhibition of insulin release by proglycem® is antagonized by alpha-adrenergic blocking agents.
  • Proglycem® 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.

Pharmacokinetics

There is limited information regarding Diazoxide Pharmacokinetics in the drug label.

Nonclinical Toxicology

  • Oral diazoxide in the mouse, rat, rabbit, dog, pig, and monkey produces a rapid and transient rise in blood glucose levels. In dogs, increased blood glucose is accompanied by increased free fatty acids, lactate, and pyruvate in the serum. In mice, a marked decrease in liver glycogen and an increase in the blood urea nitrogen level occur.
  • In acute toxicity studies the LD50 for oral diazoxide suspension is >5000 mg/kg in the rat, >522 mg/kg in the neonatal rat, between 1900 and 2572 mg/kg in the mouse, and 219 mg/kg in the guinea pig. Although the oral LD50 was not determined in the dog, a dosage of up to 500 mg/kg was well tolerated.
  • In subacute oral toxicity studies, diazoxide at 400 mg/kg in the rat produced growth retardation, edema, increases in liver and kidney weights, and adrenal hypertrophy. Daily dosages up to 1080 mg/kg for three months produced hyperglycemia, an increase in liver weight and an increase in mortality. In dogs given oral diazoxide at approximately 40 mg/kg/day for one month, no biologically significant gross or microscopic abnormalities were observed. Cataracts, attributed to markedly disturbed carbohydrate metabolism, have been observed in a few dogs given repeated daily doses of oral or intravenous diazoxide. The lenticular changes resembled those which occur experimentally in animals with increased blood glucose levels. In chronic toxicity studies, rats given a daily dose of 200 mg/kg diazoxide for 52 weeks had a decrease in weight gain and an increase in heart, liver, adrenal and thyroid weights. Mortality in drug-treated and control groups was not different. Dogs treated with diazoxide at dosages of 50, l00, and 200 mg/kg/day for 82 weeks had higher blood glucose levels than controls. Mild bone marrow stimulation and increased pancreas weights were evident in the drug-treated dogs; several developed inguinal hernias, one had a testicular seminoma, and another had a mass near the penis. Two females had inguinal mammary swellings. The etiology of these changes was not established. There was no difference in mortality between drug-treated and control groups. In a second chronic oral toxicity study, dogs given milled diazoxide at 50, l00, and 200 mg/kg/day had anorexia and sever weight loss, causing death in a few. Hematologic, biochemical, and histologic examination did not indicate any cause of death other than inanition. After one year of treatment, there is no evidence of herniation or tissue swelling in any of the dogs.
  • When diazoxide was administered at high dosages concomitantly with either chlorothiazide to rats or trichlormethiazide to dogs, increased toxicity was observed. In rats, the combination was nephrotoxic; epithelial hyperplasia was observed in the collecting tubules. In dogs, a diabetic syndrome was produced which resulted in ketosis and death. Neither of the drugs given alone produced these effects.
  • Although the data are inconclusive, reproduction and teratology studies in several species of animals indicate that diazoxide, when administered during the critical period of embryo formation, may interfere with normal fetal development, possibly through altered glucose metabolism. Parturition was occasionally prolonged in animals treated at term. Intravenous administration of diazoxide to pregnant sheep, goats, and swine produced in the fetus an appreciable increase in blood glucose level and degeneration of the beta cells of the Islets of Langerhans. The reversibility of these effects was not studied.

Clinical Studies

  • 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.
  • Proglycem® 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.
  • Other pharmacologic actions of proglycem® 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 proglycem®. In the presence of hypokalemia, hyperglycemic effects are also potentiated.
  • Proglycem®-induced hyperglycemia is reversed by the administration of insulin or tolbutamide. The inhibition of insulin release by proglycem® is antagonized by alpha-adrenergic blocking agents.
  • Proglycem® 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.

How Supplied

  • Proglycem® (diazoxide capsules, USP), 50 mg, half opaque orange and half clear capsules, branded in black with BNP 6000: bottle of 100 (NDC 0575-6000-01).
  • Proglycem® suspension, 50 mg/mL, a chocolate-mint flavored suspension; bottle of 30 ml (NDC 0575-6200-30), 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.

Storage

  • Store proglycem® Capsules and Suspension at 25°C (77°F) excursions permitted 15°-30°C (59-86°F).

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

  • During treatment with proglycem® 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.

Precautions with Alcohol

Alcohol-Diazoxide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Diazoxide Brand Names in the drug label.

Look-Alike Drug Names

There is limited information about the Look-Alike Drug Names.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. Wang X, Wei M, Kuukasjärvi P, Laurikka J, Järvinen O, Rinne T et al. (2003) Novel pharmacological preconditioning with diazoxide attenuates myocardial stunning in coronary artery bypass grafting. Eur J Cardiothorac Surg 24 (6):967-73. PMID: 14643816
  2. Massie BM, Stern R, Hanlon JT, Haughom F (1982) Beneficial hemodynamic effects of intravenous diazoxide in refractory congestive heart failure. Am Heart J 104 (3):581-6. PMID: 7113899
  3. Björk E, Berne C, Kämpe O, Wibell L, Oskarsson P, Karlsson FA (1996) Diazoxide treatment at onset preserves residual insulin secretion in adults with autoimmune diabetes. Diabetes 45 (10):1427-30. PMID: 8826981
  4. Alemzadeh R, Langley G, Upchurch L, Smith P, Slonim AE (1998) Beneficial effect of diazoxide in obese hyperinsulinemic adults. J Clin Endocrinol Metab 83 (6):1911-5. DOI:10.1210/jcem.83.6.4852 PMID: 9626118
  5. Akhondzadeh S, Mojtahedzadeh V, Mirsepassi GR, Moin M, Amini-Nooshabadi H, Kamalipour A (2002) Diazoxide in the treatment of schizophrenia: novel application of potassium channel openers in the treatment of schizophrenia. J Clin Pharm Ther 27 (6):453-9. PMID: 12472985
  6. Touati G, Poggi-Travert F, Ogier de Baulny H, Rahier J, Brunelle F, Nihoul-Fekete C et al. (1998) Long-term treatment of persistent hyperinsulinaemic hypoglycaemia of infancy with diazoxide: a retrospective review of 77 cases and analysis of efficacy-predicting criteria. Eur J Pediatr 157 (8):628-33. PMID: 9727845

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