- 1 Chemistry
- 2 Storage – Stability – Compatibility
- 3 Pharmacology
- 4 Uses – Indications
- 5 Pharmacokinetics
- 6 Contraindications/Precautions
- 7 Adverse Effects – Warnings
- 8 Overdosage
- 9 Drug Interactions
- 10 Drug/Laboratory Interactions
- 11 Doses
- 12 Dosage Forms – Preparations – FDA Approval Status – Withholding Times
Related structurally to the thiazide diuretics, diazoxide occurs as an odorless, white to creamy-white, crystalline powder with a melting point of about 330°. It is practically insoluble to sparingly soluble in water and slightly soluble in alcohol.
Storage – Stability – Compatibility
Diazoxide capsules and oral suspensions should be stored at 2-30°C and protected from light. Protect solutions/suspensions from freezing. Do not use darkened solutions/suspensions as they may be subpotent.
Although related structurally to the thiazide diuretics, diazoxide does not possess any appreciable diuretic activity. By directly causing a vasodilatory effect on the smooth muscle in peripheral arterioles, diazoxide reduces peripheral resistance and blood pressure. To treat malignant hypertension, intravenous diazoxide is generally required for maximal response.
Diazoxide also exhibits hyperglycemic activity by directly inhibiting pancreatic insulin secretion. This action may be a result of the drug’s capability to decrease the intracellular release of ionized calcium, thereby preventing the release of insulin from the insulin granules. Diazoxide does not apparently affect the synthesis of insulin, nor does it possess any antineoplastic activity. Diazoxide also enhances hyperglycemia by stimulating the beta-adrenergic system, thereby stimulating epinephrine release and inhibiting the uptake of glucose by cells.
Uses – Indications
Oral diazoxide is used in canine medicine for the treatment of hypoglycemia secondary to hyperinsulin secretion (e.g., insulinoma). Insulinomas are apparently very rare in the cat, and there is little experience with this drug in that species.
The serum half-life of diazoxide has been reported to be about 5 hours in the dog; other pharmacokinetic parameters in the dog appear to be unavailable. In humans, serum diazoxide (at 10 mg/kg PO) levels peaked at about 12 hours after dosing with capsules. It is unknown what blood levels are required to obtain hyperglycemic effects. Highest concentrations of diazoxide are found in the kidneys with high levels also found in the liver and adrenal glands. Approximately 90% of the drug is bound to plasma proteins and it crosses the placenta and into the CNS. It is not known if diazoxideis distributed into milk. Diazoxide is partially metabolized in the liver and is excreted as both metabolites and unchanged drug by the kidneys. Serum half-life of the drug is prolonged in patients with renal impairment.
Diazoxide should not be used in patients with functional hypoglycemia or for treating hypoglycemia secondary to insulin overdosage in diabetic patients. Unless the potential advantages outweigh the risks, do not use in patients hypersensitive to thiazide diuretics.
Because diazoxide can cause sodium and water retention, use cautiously in patients with congestive heart failure or with renal disease.
Adverse Effects – Warnings
When used to treat insulinomas in dogs, most commonly seen adverse reactions include anorexia, vomiting and/or diarrhea. Other effects that may be seen include tachycardia, hematologic abnormalities (agranulocytosis, aplastic anemia, thrombocytopenia), diabetes mellitus, cataracts (secondary to hyperglycemia?), and sodium and water retention.
Administering the drug with meals or temporarily reducing the dose may alleviate the gastrointestinal side effects. Adverse effects may be more readily noted in dogs with concurrent hepatic disease.
Acute overdosage may result in severe hyperglycemia and ketoacidosis. Treatment should include insulin (see previous monograph) and fluid and electrolytes. Intensive and prolonged monitoring is recommended.
Thiazide diuretics may potentiate the hyperglycemic effects of oral diazoxide. Some clinicians have recommended using hydrochlorothiazide (2 – 4 mg/kg/day PO) in combination with diazoxide, if diazoxide is ineffective alone to increase blood glucose levels. Caution: hypotension may occur.
Diazoxide may displace warfarin or bilirubin from plasma proteins. Phenothiazines (e.g., chlorpromazine) may enhance the hyperglycemic effects of diazoxide. Diazoxide may increase the metabolism, or decrease the protein binding of phenytoin.
Alpha-adrenergic agents (e.g., phenoxybenzamine) may decrease the effectiveness of diazoxide in increasing glucose levels.
Diazoxide will cause a false-negative insulin response to glucagon.
Doses for dogs:
For hypoglycemia secondary to insulin secreting islet cell tumors:
a) 10 mg/kg divided twice daily PO with meals; may increase dose up to 60 mg/kg to alleviate signs of hypoglycemia, if tolerated.
b) 10 mg/kg/day initially, may increase gradually up to 40 mg/kg/day if needed.
c) If after frequent feedings (4-6 small meals per day) and glucocorticoids (prednisone 1.1 – 4.4 mg/kg/day) alone fail to control hypoglycemia or dog develops “Cushinoid” appearance, add diazoxide (reduce prednisone dose if “Cushinoid”) initially at 10 mg/kg divided twice a day. May gradually increase dosage to 60 mg/kg/day as tolerated and add hydrochlorothiazide (2 – 4 mg/kg/day).
For adjunctive therapy of hypoglycemia secondary to insulin secreting non-islet cell (extra-pancreatic) tumors:
a) Diazoxide 5-13 mg/kg PO tid (may add hydrochlorothiazide 2 – 4 mg/kg/day)
1) Blood (serum) glucose
2) CBC (at least q3-4 months)
3) Physical exam (monitor for symptoms of other adverse effects — see above)
Clients should be instructed to monitor for symptoms of hyper- or hypoglycemia, abnormal bleeding, GI disturbances, etc.
Dosage Forms – Preparations – FDA Approval Status – Withholding Times
Finding a supply of this medication may be a problem.
Diazoxide Oral Capsules 50 mg; Diazoxide Oral Suspension 50 mg/ml in 30 ml dropper bottles; Proglycem® (Baker Norton); (Rx)
Also available as 50 mg tablets in the U.K. as Eudemine®.