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Diazoxide: Drug information

Diazoxide: Drug information
(For additional information see "Diazoxide: Patient drug information" and see "Diazoxide: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Proglycem
Brand Names: Canada
  • Proglycem
Pharmacologic Category
  • Antidote, Hypoglycemia;
  • Vasodilator, Direct-Acting
Dosing: Adult
Hyperinsulinemic hypoglycemia

Hyperinsulinemic hypoglycemia:

Note: For use when other specific medical therapy or surgical management for hypoglycemia is unsuccessful or is not feasible.

Oral: Initial: 3 mg/kg/day divided into 3 equal doses every 8 hours; dosing range: 3 to 8 mg/kg/day divided into 2 or 3 equal doses every 8 to 12 hours. Adjust dose until the desired clinical and laboratory effects are produced. Note: Patients with refractory hypoglycemia may require higher doses. Discontinue if no effect after 2 to 3 weeks.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; consider a dosage reduction (half-life may be prolonged).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Pediatric

(For additional information see "Diazoxide: Pediatric drug information")

Hyperinsulinemic hypoglycemia

Hyperinsulinemic hypoglycemia: Note: Diazoxide may not be effective for all types of hyperinsulinemic hypoglycemia. Dose should be individualized and may vary based on the cause (eg, genetic mutation, insulinomas) and severity of the hypoglycemic condition, blood glucose concentration, and clinical response of patient. Use the least amount of drug that achieves the desired clinical and laboratory results. For some hyperinsulinemic conditions, onset of action may vary; the manufacturer recommends discontinuation if no effect after 2 to 3 weeks; however, this may vary based on condition being treated and this timeframe. Often used in combination with a thiazide diuretic to ameliorate possible fluid retention that may occur with diazoxide therapy (Shah 2017).

Infants: Oral: Initial: 5 mg/kg/day in divided doses every 8 hours; gradually titrate; due to the long half-life it may take several days (eg, 5 days) to assess dose-response (Eichenwald 2017); usual range: 8 to 15 mg/kg/day in divided doses every 8 to 12 hours; reported range: 5 to 20 mg/kg/day in divided doses every 8 to 12 hours (Demirbilek 2017; Kapoor 2009; Shah 2017). Note: Pulmonary hypertension has been observed in neonates and infants while on diazoxide therapy; most frequently reported at doses ≥10 mg/kg/day; monitor neonates and infants closely while on therapy; consider baseline and periodic echocardiogram (Timlin 2017).

Children and Adolescents: Oral: Initial: 5 mg/kg/day in divided doses every 8 hours; reported range: 5 to 20 mg/kg/day in divided doses every 8 to 12 hours; usual range: 3 to 8 mg/kg/day in divided doses every 8 to 12 hours (Demirbilek 2017; Shah 2017; Sperling 2014).

Dosing: Kidney Impairment: Pediatric

All patients: Half-life may be prolonged with renal impairment; a reduced dose should be considered.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Oral:

Proglycem: 50 mg/mL (30 mL) [chocolate mint flavor]

Generic: 50 mg/mL (30 mL)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Proglycem: 100 mg

Administration: Adult

Shake suspension well before each use.

Administration: Pediatric

Oral: Shake suspension well before each use; suspension comes with calibrated dropper (to deliver dose of 10 to 50 mg, in 10 mg increments).

Use: Labeled Indications

Hyperinsulinemic hypoglycemia: Management of hypoglycemia due to hyperinsulinism due to certain conditions in adults (eg, inoperable islet cell adenoma or carcinoma, extrapancreatic malignancy) and infants and children (eg, leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, adenomatosis; may be used preoperatively as a temporary measure, and postoperatively, if hypoglycemia persists).

Medication Safety Issues
Sound-alike/look-alike issues:

Diazoxide may be confused with diazePAM, Dyazide

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Hypertension (transient), hypotension, palpitations, tachycardia

Dermatologic: Cutaneous candidiasis, loss of scalp hair, pruritus, skin rash

Endocrine & metabolic: Albuminuria, diabetes mellitus with hyperosmolar coma (nonketotic), diabetic ketoacidosis, fluid retention, galactorrhea not associated with childbirth, hirsutism, hyperglycemia, increased uric acid, sodium retention

Gastrointestinal: Abdominal pain, acute pancreatitis, ageusia (transient), anorexia, diarrhea, intestinal obstruction, nausea, pancreatic necrosis, vomiting

Genitourinary: Azotemia, decreased urine output, glycosuria, hematuria, lump in breast (enlargement)

Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, decreased serum immunoglobulins (IgG), eosinophilia, hemorrhage (excessive), lymphadenopathy, neutropenia (transient), thrombocytopenia

Hepatic: Increased serum alkaline phosphatase, increased serum aspartate aminotransferase

Infection: Herpes virus infection

Nervous system: Anxiety, asthenia, dizziness, extrapyramidal reaction, headache, insomnia, malaise, paresthesia, peripheral neuritis (poly)

Neuromuscular & skeletal: Accelerated bone maturation, gout

Ophthalmic: Blurred vision, cataract (transient), diplopia, lacrimation, scotoma (ring), subconjunctival hemorrhage

Renal: Decreased creatinine clearance, nephrotic syndrome (reversible)

Miscellaneous: Fever

Postmarketing:

Cardiovascular: Chest pain, pericardial effusion (Avatapalle 2012)

Dermatologic: Hypertrichosis (Salido 2013)

Hematologic & oncologic: Hemolysis (Best 1975), immune thrombocytopenia (Thus 2019), thrombocytopenia (Adachi 2014)

Respiratory: Pulmonary hypertension (infants and neonates) (Ohnishi 2020)

Contraindications

Hypersensitivity to diazoxide, other thiazides, or any component of the formulation; functional hypoglycemia

Warnings/Precautions

Concerns related to adverse effects:

• Abnormal facial features: Development of abnormal facial features was reported in children treated >4 years for hypoglycemia hyperinsulinism.

• Hyperglycemic crises: Ketoacidosis or hyperosmolar coma may occur during treatment; usually in patients with concomitant illness; prompt recognition and treatment are essential.

Disease-related concerns:

• Heart failure: Use may lead to increased fluid retention due to antidiuretic properties and may precipitate heart failure in patients with compromised cardiac reserve.

• Gout: Use with caution in patients with hyperuricemia or a history of gout.

• Renal impairment: Use with caution in patients with renal impairment.

Special populations:

• Pediatric: May displace bilirubin from albumin; use caution in newborns with hyperbilirubinemia. Pulmonary hypertension has been reported in newborns and young infants and was reversible upon drug discontinuation; monitor patients (especially patients with risk factors for pulmonary hypertension) for respiratory distress and discontinue diazoxide if pulmonary hypertension is suspected.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Warnings: Additional Pediatric Considerations

Initiate treatment with diazoxide under close clinical supervision; carefully monitor blood glucose and clinical response until patient's condition becomes stable (usually several days). Regular monitoring of urine for glucose and ketones (especially under conditions of stress) are required with prolonged therapy; abnormal results should be reported to physician promptly. Periodic monitoring of blood glucose is required for dosage adjustment.

Pulmonary hypertension has been reported in newborns and infants receiving diazoxide for hypoglycemia; since the early 1970’s, eleven cases have been reported either to the FDA or within the literature; in the majority of cases, the neonate/infant had other ongoing serious medical conditions and were at high risk for development of pulmonary hypertension; reported onset was within a day to a few months after diazoxide therapy initiation and in all cases, the pulmonary hypertension resolved or improved with discontinuation of the diazoxide. Pulmonary hypertension may be dose dependent; a review of published cases reported that circulatory effects were observed most frequently at doses ≥10 mg/kg/day. Monitor neonates and infants closely for signs of respiratory distress (tachypnea, flaring nostrils, grunting, chest wall retractions), cyanosis, or feeding intolerance, particularly those neonates and infants with risk factors for pulmonary hypertension (eg, meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, sepsis, congenital diaphragmatic hernia, congenital heart disease); discontinue if pulmonary hypertension is identified (FDA 2015; Timlin 2017).

Transient cataracts have been reported in an infant in association with hyperosmolar coma; cataracts subsided following correction of hyperosmolarity. Abnormal facial features have been reported in 4 children who received diazoxide for >4 years for the treatment of hypoglycemia hyperinsulinism.

The oral suspension contains 7.25% alcohol. Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: Diazoxide may enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: Diazoxide may decrease the serum concentration of Fosphenytoin-Phenytoin. Total phenytoin concentrations may be affected more than free phenytoin concentrations. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the adverse/toxic effect of Diazoxide. Risk C: Monitor therapy

Thiopental: May enhance the hypotensive effect of Diazoxide. Risk C: Monitor therapy

Pregnancy Considerations

Diazoxide crosses the human placenta and appears in cord blood. Altered carbohydrate metabolism, hyperbilirubinemia, and thrombocytopenia have been reported in the fetus or neonate. Alopecia and hypertrichosis lanuginosa have also been reported in infants following maternal use of diazoxide during the last 19 to 60 days of pregnancy.

Breastfeeding Considerations

It is not known if diazoxide is excreted in breast milk. Due to the potential for serious adverse reactions in the breast-feeding infant, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring Parameters

Blood glucose, serum uric acid, BUN, kidney function, CBC with differential, AST; urine glucose and ketones (especially under stress conditions and during prolonged treatment); serum electrolytes and uric acid; respiratory distress (neonates and infants [especially those with risk factors for pulmonary hypertension]).

Mechanism of Action

Opens ATP-dependent potassium channels on pancreatic beta cells in the presence of ATP and Mg2+, resulting in hyperpolarization of the cell and inhibition of insulin release. Diazoxide binds to a different site on the potassium channel than the sulfonylureas (Doyle, 2003).

Pharmacokinetics

Onset of action: Hyperglycemic: Oral: Within 1 hour

Duration: Hyperglycemic: Oral: Normal renal function: ≤8 hours

Protein binding: >90%

Half-life elimination: Oral: Children: 9.5 to 24 hours; Adults: 24 to 36 hours

Excretion: Urine (50% as unchanged drug)

Pharmacokinetics: Additional Considerations

Altered kidney function: Plasma half-life is prolonged.

Pricing: US

Suspension (Diazoxide Oral)

50 mg/mL (per mL): $12.38 - $12.40

Suspension (Proglycem Oral)

50 mg/mL (per mL): $15.07

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Eudemine (GB);
  • Hyperstat (BE, CZ, HR, HU, LU, SE);
  • Hypertonalum (DE);
  • Naxproglycem (KR);
  • Proglicem (AR, CH, DE, FR, IT, NL, NO, SG);
  • Proglycem (BB, GR, KR, TW);
  • Tensuril (BR)


For country code abbreviations (show table)
  1. Adachi J, Mimura M, Minami I, Kakihana K, Watanabe T. Thrombocytopenia induced by diazoxide in a patient with an insulinoma. Intern Med. 2014;53(7):759-762. doi:10.2169/internalmedicine.53.1094 [PubMed 11487763]
  2. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
  3. Avatapalle B, Banerjee I, Malaiya N, Padidela R. Echocardiography monitoring for diazoxide induced pericardial effusion. BMJ Case Rep. 2012;2012:bcr0320126110. doi:10.1136/bcr.03.2012.6110 [PubMed 22761225]
  4. Best RA, Clink HM. Haemolysis associated with diazoxide, used for the control of hypertension. Postgrad Med J. 1975;51(596):402-404. doi:10.1136/pgmj.51.596.402 [PubMed 1215255]
  5. Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  6. Demirbilek H, Rahman SA, Buyukyilmaz GG, Hussain K. Diagnosis and treatment of hyperinsulinaemic hypoglycaemia and its implications for paediatric endocrinology. Int J Pediatr Endocrinol. 2017;2017:9. [PubMed 28855921]
  7. Diazoxide oral suspension [prescribing information]. Boca Raton, FL: e5 Pharma LLC; December 2019.
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  10. FDA Safety Alert. Proglycem (diazoxide). Food and Drug Administration Website. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsfor Human MedicalProducts/ucm455125.htm Accessed July 16, 2015.
  11. Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about a serious lung condition in infants and newborns treated with Proglycem (diazoxide). Available at http://www.fda.gov/Drugs/DrugSafety/ucm454833.htm. Last accessed July 20, 2015.
  12. Hoe FM, Thornton PS, Wanner LA, Steinkrauss L, Simmons RA, Stanley CA. Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism. J Pediatr. 2006;148(2):207-212. [PubMed 16492430]
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  15. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
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  18. Proglycem (diazoxide) [prescribing information]. Parsippany, NJ: Teva Pharmaceuticals USA Inc; December 2020.
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