Diazoxide — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	5-10 mg/kg (initial), titrate to effect; typical range 3-30 mg/kg/day	q12h (every 12 hours)	Duration: Long-term, as needed for glycemic control Notes: Start at low end and titrate based on blood glucose monitoring. Administer with food to reduce GI upset.
Cat	PO	5-10 mg/kg (initial), titrate to effect; typical range 3-30 mg/kg/day	q12h (every 12 hours)	Duration: Long-term, as needed for glycemic control Notes: Start at low end and titrate based on blood glucose monitoring. Administer with food to reduce GI upset.
Horse	PO	Not established; experimental use only	Not established	Duration: Not established Notes: Use with caution; monitor blood glucose closely.

Clinical Indications & Species Uses

General Indications

Management of hypoglycemia due to hyperinsulinism (e.g., insulinoma) in dogs and cats

Dog (Canine)

Treatment of insulinoma (insulin-secreting pancreatic beta cell tumors) to manage hypoglycemia
Treatment of hypoglycemia due to other causes (e.g., paraneoplastic, idiopathic)

Cat (Feline)

Treatment of insulinoma (rare) to manage hypoglycemia
Treatment of hypoglycemia due to other causes

Pharmacology & Mechanism of Action

Drug Class: Benzothiadiazine derivative | Pharmacological Group: Antihypertensive, Hyperglycemic agent

Mechanism of Action: Diazoxide is a benzothiadiazine derivative that acts as a potassium channel activator. In vascular smooth muscle, it opens ATP-sensitive potassium channels, leading to membrane hyperpolarization, closure of voltage-gated calcium channels, and subsequent vasodilation. In the pancreas, it opens potassium channels in pancreatic beta cells, hyperpolarizing the cell membrane and inhibiting calcium influx, which suppresses insulin release. This results in increased blood glucose levels. Diazoxide also inhibits phosphodiesterase, increasing cyclic AMP, and may have direct inhibitory effects on insulin secretion.

Pharmacodynamics: Diazoxide produces a rapid and sustained decrease in peripheral vascular resistance, leading to hypotension. It also causes hyperglycemia by inhibiting insulin secretion from pancreatic beta cells. The hyperglycemic effect is dose-dependent and can be reversed by insulin administration. Diazoxide may also cause sodium and water retention, reflex tachycardia, and increased renin release.

⚡ Pharmacokinetics Summary

Absorption: Diazoxide is well absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. The oral bioavailability is approximately 90%.

Distribution: Diazoxide is widely distributed throughout the body. It crosses the placenta and is distributed into breast milk. It is approximately 90% bound to plasma proteins.

Metabolism: Diazoxide is partially metabolized in the liver, primarily by oxidation and sulfate conjugation. The metabolites are less active than the parent compound.

Excretion: Diazoxide is excreted primarily by the kidneys, both as unchanged drug and as metabolites. Approximately 50% of the drug is excreted unchanged in the urine. The elimination half-life is prolonged in patients with renal impairment.

Half-Life: Dogs: 2-4 hours; Cats: 3-5 hours; Humans: 24-36 hours (prolonged due to enterohepatic recirculation).

Bioavailability: Oral: ~90%; IV: 100%.

Protein Binding: Approximately 90% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 50 mg, 100 mg (PO)

Oral Suspension 50 mg/mL (PO)

Injectable Solution (IV) 15 mg/mL (human formulation) (IV)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to diazoxide or other benzothiadiazines
Patients with functional hypoglycemia (e.g., insulinoma) should not be given diazoxide if they have concurrent diabetes mellitus
Use with caution in patients with renal or hepatic impairment
Use with caution in patients with cardiovascular disease, especially those with coronary artery disease or cerebrovascular insufficiency

Warnings & Clinical Precautions:

May cause sodium and fluid retention, leading to edema and congestive heart failure in susceptible patients
May cause hyperglycemia; monitor blood glucose regularly
May cause hypotension, especially after IV administration
May cause reflex tachycardia
Use with caution in pregnant or lactating animals; safety not established
May cause gastrointestinal irritation; administer with food
Abrupt withdrawal may lead to rebound hypoglycemia

Adverse Effects & Reactions

Common:

Hyperglycemia
Sodium and fluid retention
Gastrointestinal upset (vomiting, diarrhea)
Anorexia
Tachycardia

Serious / Severe:

Hypotension
Cardiac arrhythmias
Cerebral ischemia
Diabetic ketoacidosis (in predisposed animals)
Pancreatitis (rare)

Rare:

Bone marrow suppression
Thrombocytopenia
Leukopenia
Hepatotoxicity
Allergic reactions (rash, fever)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Thiazide diuretics	Additive hyperglycemic and hypotensive effects	Moderate
Beta-blockers	May mask signs of hypoglycemia and enhance hyperglycemic effect	Moderate
Corticosteroids	Additive hyperglycemic effect	Moderate
Phenytoin	May decrease diazoxide metabolism, increasing diazoxide levels	Moderate
Sulfonylureas	Antagonistic effect on insulin secretion; diazoxide may reduce sulfonylurea efficacy	Moderate
Antihypertensive agents	Additive hypotensive effects	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe hypotension
Hyperglycemia
Tachycardia
Cardiac arrhythmias
Cerebral ischemia
Seizures
Coma

Emergency Treatment Protocol: Discontinue drug immediately. Provide supportive care: IV fluids for hypotension, administer insulin for severe hyperglycemia, monitor cardiac function, and treat arrhythmias as needed. There is no specific antidote; treatment is symptomatic and supportive.

Food Animal Withdrawal Times

Not approved for food animals; no withdrawal times established. Use in food animals is prohibited or requires extended withdrawal periods under veterinary supervision.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C, 68-77°F). Protect from light and moisture.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Keep container tightly closed. Do not freeze oral suspension.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use (e.g., Proglycem) for hypoglycemia.

Extra-Label (Off-Label) Use: In the US, diazoxide is not FDA-approved for veterinary use; however, it may be used extra-label in accordance with AMDUCA (Animal Medicinal Drug Use Clarification Act) for non-food animals. For food animals, extra-label use is prohibited or requires a very long withdrawal period and is generally not recommended.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Diazoxide is primarily used in veterinary medicine for the management of hypoglycemia caused by insulinoma in dogs and cats. It is not a curative treatment but helps control clinical signs. Therapy should be individualized based on blood glucose monitoring. The drug may take several days to achieve full effect; therefore, initial dosing should be conservative and titrated upward as needed. Common adverse effects include hyperglycemia, GI upset, and fluid retention. In animals with insulinoma, diazoxide may be used in combination with surgical resection or other therapies. Close monitoring of blood glucose, electrolytes, and renal function is recommended. Due to the risk of hypotension, IV administration should be reserved for emergency situations and performed slowly. Always consider the potential for drug interactions and contraindications before initiating therapy.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)