DIAZIPRIM-48% S COMBINATION PRODUCT POWDER

Indications

• Hypertensive emergencies
• Hypoglycemia due to insulinoma
• Management of hypertension in certain patients

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Refer to the specific guidelines for dosing based on the clinical condition and patient's response.

Mechanism of action

Diaziprim acts primarily by opening ATP-sensitive potassium channels in the vascular smooth muscle, leading to hyperpolarization and relaxation of these muscles. This results in vasodilation and a decrease in blood pressure. Additionally, diazoxide inhibits insulin release from the pancreas, which contributes to its effect in raising blood glucose levels.

Pharmacodynamics

The pharmacodynamic effects of diaziprim include a rapid decrease in systemic vascular resistance and blood pressure due to its vasodilatory properties. The drug can also induce hyperglycemia by reducing insulin secretion, which is beneficial in treating certain conditions like insulinoma. Its onset of action is typically within minutes when administered intravenously.

Pharmacokinetics

Diaziprim is administered intravenously or orally, with peak plasma concentrations typically occurring within one to two hours after oral dosing. The drug is extensively protein-bound and has a large volume of distribution. It is metabolized in the liver and excreted primarily through bile. The half-life of diazoxide is approximately 24 hours, allowing for once or twice daily dosing in some cases.

Contra-indications

• Hypersensitivity to diazepam or any of its components
• Severe respiratory insufficiency
• Myasthenia gravis
• Sleep apnea syndrome
• Acute narrow-angle glaucoma
• Severe liver impairment

Adverse effects

• Drowsiness
• Dizziness
• Fatigue
• Confusion
• Ataxia
• Hypotension
• Paradoxical reactions (e.g., agitation, aggression)
• Dependence and withdrawal symptoms

Interactions

• CNS depressants (e.g., alcohol, opioids, sedatives, tranquilizers) may enhance sedative effects
• CYP450 enzyme inducers (e.g., rifampicin) may decrease effectiveness
• CYP450 enzyme inhibitors (e.g., ketoconazole) may increase levels and effects
• Anticonvulsants (e.g., phenytoin) may alter pharmacokinetics

Precautions

• Use with caution in elderly patients or those with pre-existing respiratory conditions
• Monitor for signs of dependence with prolonged use
• Caution in patients with a history of substance abuse
• Assess for underlying depression or suicidal ideation

Pregnancy

Diazepam is classified as a category D drug. It may cause fetal harm and should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Diazepam is excreted in breast milk and may cause sedation in the nursing infant. Caution is advised when administering to breastfeeding mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets (e.g., 2 mg, 5 mg, 10 mg)
• Oral solution (e.g., 5 mg/5 mL)
• Injection (e.g., 5 mg/mL)