Dosing and uses of Proglycem (diazoxide)
Adult dosage forms and strengths
oral suspension
- 50mg/mL
Hypoglycemia
Indicated for hypoglycemia due to hyperinsulinism associated with inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy
3 mg/kg/day PO divided q8-12hr initially; typical dose range 3-8 mg/kg/day
Patients with refractory hypoglycemia may require higher doses
Prader-Willi Syndrome (Orphan)
Orphan designation for diazoxide choline for treatment of Prader-Willi Syndrome
Sponsor
- Essentialis, Inc; 7915 Corte Cardo; Carlsbad, CA 92009
Pediatric dosage forms and strengths
oral suspension
- 50mg/mL
Hypoglycemia
Indicated for hypoglycemia due to hyperinsulinism associated with leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis
Newborn/infant: 10 mg/kg/day PO divided q8hr initially; typical dosage range is 8-15 mg/kg/day PO divided q8-12hr (also see Cautions regarding suspected pulmonary hypertension in newborns and infants)
Children: 3 mg/kg/day PO divided q8hr initially; typical dose range is 3-8 mg/kg/day PO divided q8-12hr
Dosing Considerations
May be used preoperatively as a temporary measure, and postoperatively, if hypoglycemia persists
Prader-Willi Syndrome (Orphan)
Orphan designation for diazoxide choline in DDRC (crystalline salt of diazoxide in a controlled-release, once-a-day tablet formulation)
Orphan sponsor
- Essentialis Therapeutics, Inc; 7915 Corte Cardo; Carlsbad, CA 92009
Proglycem (diazoxide) adverse (side) effects
Frequency not defined
Angina
Cardiac arrest
Anxiety
Fever
Polyneuritis
CHF
Hypotension
Palpitation
Tachycardia
Dizziness
Anorexia
Abdominal pain
Constipation
Diarrhea
Loss of taste
Nausea
Vomiting
Diabetic ketoacidosis
Hirsutism
Scalp hair loss
Hyperglycemia
Sodium and fluid retention
Postmarketing reports
Pulmonary hypertension in neonates and young infants
Warnings
Contraindications
Hypersensitivity to diazoxide, thiazides, or sulfonamide derivatives
Cautions
Use caution in coronary or cerebral insufficiency, DM, extravasation, heart failure (may increase fluid retention), cardiovascular insufficiency, gout, hypotension, hypokalemia, liver disease, renal dysfunction
Pregnancy
Compensatory HTN (aortic coarctation, arteriovenous shunt)
Ineffective in pheochromocytoma
Nonketotic hyperosmolar coma may occur during treatment; transient cataracts reported
May displace bilirubin from albumin; use caution in newborns with hyperbilirubinemia
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
Concomitantly administered thiazides may potentiate the hyperglycemic and hyperuricemic actions of diazoxide
Ketoacidosis and nonketotic hyperosmolar coma reported in patients treated with recommended doses usually during intercurrent illness; prompt recognition and treatment essential and prolonged surveillance following the acute episode necessary because of long drug half-life of approximately 30 hours; occurrence of these serious events may be reduced by careful education of patients regarding monitoring urine for sugar and ketones and for prompt reporting of abnormal findings and unusual symptoms to healthcare provider
Effects of diazoxide on the hematopoietic system and the level of serum uric acid kept in mind; the latter should be considered particularly in patients with hyperuricemia or a history of gout
Antihypertensive effect of other drugs may be enhanced by diazoxide; should keep this in mind when administering it concomitantly with antihypertensive agents
Because of protein binding, administration of diazoxide with coumarin or its derivatives may require reduction in dosage of anticoagulants
Pulmonary hypertension in newborns and infants
- July 16, 2015: FDA warns clinicians to watch for signs of pulmonary hypertension in infants treated for hypoglycemia with diazoxide and discontinue the drug if symptoms appear
- There have been 11 cases identified since the drug was approved (1973) and once diazoxide was discontinued, the symptoms resolved
- Signs of respiratory distress include flaring nostrils, grunting, unusual chest movements, rapid breathing, difficulty feeding, or a bluish tint to the lips or skin
- Monitoring is especially important for infants who have other risk factors for pulmonary hypertension (eg, meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, sepsis, congenital diaphragmatic hernia, and congenital heart disease)
Pregnancy and lactation
Pregnancy category: C
Lactation: Excretion in milk unknown; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Proglycem (diazoxide)
Mechanism of action
Inhibits pancreatic insulin release resulting increased blood glucose; activates potassium channels
Relaxes smooth muscle to decrease PVR, increases HR & CO; precise mechanism of hypotensive effect not fully elucidated; antagonism of calcium may be involved
Pharmacokinetics
Half-Life: 9-24 hr (children); 24-36 hr (adults), increases in patients with renal impairment
Duration: varies greatly, may last to 3-12 hr
Protein binding: 90%
Metabolism: In liver by oxidation and sulfate conjugation
Renal Clearance: 4-5 mL/min
Excretion: urine by glomerular filtration as unchanged drug and metabolites
Dialyzable: HD: yes, PD: yes; no supplemental dose is required
Excretion: Urine
