Diazoxide (Proglycem) is available as orally supension. It inhibits the release of insulin from the pancreatic beta-cells resulting in hyperglycemia. It is primarily used in the management of patients with insulinoma.

Diazoxide (Proglycem) Uses:

• Hyperinsulinemic hypoglycemia:
  • The following conditions are those for which it is indicated to treat hypoglycemia secondary to hyperinsulinemia.:
    • inoperable pancreatic islet cell adenoma or carcinoma
    • Infants and children with
      • leucine sensitivity
      • Islet cell hyperplasia
      • Nesidioblastosis
      • Extrapancreatic malignancy
      • Islet cell adenoma
    • It may be used preoperatively temporarily, and postoperatively, if hypoglycemia persists.

Diazoxide (Proglycem) Dose in Adults

Note: When alternative particular medical therapies or surgical care for hypoglycemia caused by the aforementioned diseases have either failed or are impractical, diazoxide treatment should be taken into consideration.

Diazoxide (Proglycem) Dose in the treatment of Hyperinsulinemic hypoglycemia:

• Initial dose:
  • Oral administration of 3 evenly spaced doses of 3 mg/kg/day every 8 hours.
  • The dosage ranges from 3 to 8 mg/kg/day delivered in 2 or 3 evenly spaced doses, 8 to 12 hours apart.
  • Once the desired clinical and laboratory outcomes are manifested, adjust the dose.

Note:

• Occasionally, patients may require higher doses as in those with refractory hypoglycemia.
• The treatment may be discontinued if no effects are observed after 2 to 3 weeks.

Diazoxide (Proglycem) Dose in Childrens

Diazoxide (Proglycem) Dose in the treatment of Hyperinsulinemic hypoglycemia:

Note:

• It may not be effective equally in all patients with hypoglycemia secondary to hyperinsulinemia.
• The doses should be individualized and may be variable based on the cause and the genetic mutations, severity of hypoglycemia, blood glucose, and the clinical response of the patient.
• Use the lowest dose necessary to provide the desired clinical and laboratory findings.
• The onset of action may vary. The manufacturer recommends discontinuing it if no clinical response is seen in 2 to 3 weeks' time.
• The drug is often combined with a thiazide diuretic to reduce the chances of fluid retention that may occur during the treatment.
• Infants:
  • Initial:
    • 3 doses of 5 mg/kg/day administered orally in an equally split fashion.;
  • The dose is then titrated gradually. Because of its lengthy half-life, determining the treatment's effectiveness could take up to five days.
  • The typical dosage range is two or three evenly spaced doses of 8 to 15 mg/kg/day.
  • The recommended dosage range is two or three evenly spaced doses of 5 to 20 mg/kg/day.
  • Note:
    • Neonates and infants have been reported to develop pulmonary hypertension while on diazoxide therapy.
    • The most frequent reports of pulmonary hypertension have been at doses more than 10 mg/kg/day.
    • Monitor neonates and infants closely while on therapy.
    • An echocardiogram at baseline and periodically thereafter is recommended.
• Children and Adolescents:
  • Initial:
    • Three equally spaced daily dosages of 5 mg/kg.
    • The recommended dosage range is 2 or 3 evenly spaced doses of 5 to 20 mg/kg/day.
    • The typical dosage range is 2 or 3 evenly spaced doses of 3 to 8 mg/kg/day.

Diazoxide Pregnancy Risk Category: C

• Studies on animal reproduction have demonstrated that negative outcomes are possible.
• It enters the human placenta and manifests in the cord blood.
• It has been shown to cause impaired carbohydrate metabolism, hyperbilirubinemia, thrombocytopenia, and other complications in the neonate or fetus.
• Infants who were exposed to diazoxide by their mothers in the last 19-60 days of pregnancy have also experienced alopecia and hypertrichosis.

Diazoxide use during breastfeeding:

• The drug's potential for excretion into breastmilk is unknown.
• Due to the possibility of serious adverse drug reactions in infants, it is best to stop breastfeeding or to switch to a medicine that weighs the risks and benefits for the mother and infant.

Dose in Kidney Disease:

The manufacturer's labelling does not mention dosage modifications. However, because of the prolonged half-life, a lower dose should be taken into account.

Dose in Liver disease:

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

Side effects of Diazoxide (Proglycem):

• Cardiovascular:
  • Cardiac Failure (Due To Sodium And Water Retention)
  • Hyperosmolar Coma (Nonketotic)
  • Hypertension (Transient)
  • Hypotension
  • Palpitations
  • Tachycardia
• Central Nervous System:
  • Anxiety
  • Dizziness
  • Extrapyramidal Reaction
  • Headache
  • Insomnia
  • Malaise
  • Paresthesia
  • Peripheral Neuritis (Poly)
• Dermatologic:
  • Cutaneous Candidiasis
  • Loss Of Scalp Hair
  • Pruritus
  • Purpura
  • Skin Rash
• Endocrine & Metabolic:
  • Albuminuria
  • Diabetic Ketoacidosis
  • Fluid Retention
  • Galactorrhea
  • Glycosuria
  • Gout
  • Hirsutism
  • Hyperglycemia
  • Sodium Retention
• Gastrointestinal:
  • Abdominal Pain
  • Acute Pancreatitis
  • Ageusia (Transient)
  • Anorexia
  • Diarrhea
  • Intestinal Obstruction
  • Nausea
  • Pancreatic Necrosis
  • Vomiting
• Genitourinary:
  • Azotemia
  • Decreased Urine Output
  • Hematuria
  • Lump In Breast (Enlargement)
  • Nephrotic Syndrome (Reversible)
  • Uricosuria
• Hematologic & Oncologic:
  • Decreased Hematocrit
  • Decreased Hemoglobin
  • Decreased Serum Immunoglobulins (Igg)
  • Eosinophilia
  • Hemorrhage (Excessive)
  • Lymphadenopathy
  • Neutropenia (Transient)
  • Thrombocytopenia
• Hepatic:
  • Increased Serum Alkaline Phosphatase
  • Increased Serum AST
• Infection:
  • Herpes Virus Infection
• Neuromuscular & Skeletal:
  • Accelerated Bone Maturation
  • Craniofacial Abnormality (Children With Chronic Use)
  • Weakness
• Ophthalmic:
  • Blurred Vision
  • Cataract (Transient)
  • Diplopia
  • Lacrimation
  • Scotoma (Ring)
  • Subconjunctival Hemorrhage
• Renal:
  • Decreased Creatinine Clearance
• Miscellaneous:
  • Fever

Contraindications to Diazoxide (Proglycem):

• Hypersensitivity to diazoxide or other thiazides or any component of this formulation
• Functional hypoglycemia

Warnings and precautions

• Facial abnormalities
  • Children who were treated for hypoglycemia hyperinsulinism for over 4 years had abnormal facial features.
• Hyperosmolar coma:
  • Patients are at greater risk for nonketotic hyperosmolar compa. Concomitant diseases increase the risk. It is important to monitor patients and get early diagnosis.
  • Transient cataracts are also associated with hyperosmolarity. These usually resolve after correction of the hyperosmolar condition.
• Ketoacidosis:
  • Ketoacidosis is more common in patients who are on treatment. Concomitant diseases can increase the risk.
• Heart failure:
  • It can cause antidiuretic-like effects, fluid retention, and possibly heart failure in people with impaired cardiac reserve.
• Gout
  • It should be used with caution for patients with hyperuricemia or those who have had gout in the past.
• Renal impairment
  • Patients with impaired renal function should be cautious and take lower doses.

Diazoxide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Clinical response,
• blood glucose,
• Serum electrolytes, serum uric acid, BUN, and creatinine clearance,
• CBC with differential,
• AST,
• urine glucose and ketones (especially under stress and during prolonged therapy);
• Breathing difficulties in newborns and babies (especially those with risk factors for pulmonary hypertension).

How to administer Diazoxide (Proglycem)?

Shake the suspension well before each use.   

Mechanism of action of Diazoxide (Proglycem):

• Diazoxide hyperpolarizes pancreatic beta cells and inhibits insulin release. 
• In the presence of ATP or Magnesium, it opens the ATP-dependent potassium channel on pancreatic beta cell.
• It binds to a different spot on the potassium channel than the other sulfonylureas.

The 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)

International Brand Names of Diazoxide:

• Proglycem
• Aroglycem
• Eudemine
• Hyperstat
• Hypertonalum
• Naxproglycem
• Proglicem
• Proglycem
• Tensuril

Diazoxide Brand Names in Pakistan:

No Brands Available in Pakistan.