Diazoxide

This is not a complete list of Diazoxidedrug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Diazoxide falls into category C:

In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans, though. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

OR

There are no well-controlled studies that have been done in pregnant women. Diazoxide should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

OR

No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Diazoxide should be given to a pregnant woman only if clearly needed.

You should not take this medicine if you are allergic to diazoxide or to certain heart or blood pressure medicines such as hydrochlorothiazide (HCTZ), HydroDiuril, Hyzaar, Lopressor HCT, Vaseretic, Zestoretic, and others.

You should not take diazoxide to treat occasional low blood sugar caused by diet.

To make sure diazoxide is safe for you, tell your doctor if you have:

• congestive heart failure;

• high blood pressure;

• kidney disease;

• gout; or

• low levels of potassium in your blood (hypokalemia).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether diazoxide passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• blurred vision, tunnel vision, eye pain, or seeing halos around lights;

• breathing problems in an infant or newborn treated with diazoxide;

• shortness of breath (even with mild exertion), swelling, rapid weight gain;

• a light-headed feeling, like you might pass out; or

• signs of high blood sugar (hyperglycemia) such as increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss.

Common side effects may include:

• pounding heartbeats or fluttering in your chest;

• swelling in your hands, ankles, or feet;

• fine hair growth on the face, arms, and back (especially in women or children);

• nausea, vomiting, stomach pain, loss of appetite;

• diarrhea, constipation; or

• decreased sense of taste.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Contraindications

• Hypersensitivity to the drug, other thiazide derivatives, or other sulfonamide-derived agents.c

• Functional hypoglycemia.c

Warnings/Precautions

Warnings

Pulmonary hypertension reported in neonates and infants.600 601 602

Monitor infants and neonates for manifestations of respiratory distress (e.g., tachypnea, flaring nostrils, grunting, chest wall retractions, feeding intolerance, cyanosis), particularly in those with risk factors for pulmonary hypertension (e.g., meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, sepsis, congenital diaphragmatic hernia, congenital heart disease).600 (See Advice to Patients.) Discontinue therapy if pulmonary hypertension occurs.600

Sodium and water retention occurs frequently in patients (adults and young infants), and may result in edema, weight gain, and CHF (especially in uremic patients).a b c (See Renal Impairment under Cautions.)

Monitor blood glucose concentrations.a c In patients receiving oral therapy for the treatment of hypoglycemia, monitor blood glucose concentrations carefully until the patient’s condition has stabilized.c

Usually mild and subsides without treatment.b May require administration of oral hypoglycemic agents or insulin, especially in diabetic patients or those receiving repeated doses of diazoxide.b

Ketoacidosis and nonketotic hyperosmolar coma reported with recommended oral dosage, usually during intercurrent illness.c

If ketoacidosis occurs, administer insulin and restore fluid and electrolyte balance immediately.c

Sensitivity Reactions

Rash, leukopenia, fever.a c

General Precautions

Repeated administration may cause sodium and fluid retention.a c (See Cardiovascular Effects under Cautions.)

Administer a diuretic to patients receiving multiple doses of diazoxide.a c Consider the possibility of potentiation of hypotensive, hyperglycemic, and hyperuricemic effects in patients receiving concomitant diuretic therapy.a b

Administer with caution to patients in whom retention of sodium and water may be hazardous (e.g., those with impaired cardiac reserve).a b c

Exercise caution when administering to uremic patients, since these patients may experience a greater hypotensive effect.b Hematologic monitoring may be advisable in patients who receive the drug for longer than a few days; monitor serum uric acid concentration in patients with hyperuricemia or a history of gout.b

Specific Populations

Category C.a c May produce fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism.a b c

IV diazoxide may cause cessation of uterine contractions during labor; administration of oxytocic agents may be required.a Caution advised if oral diazoxide administered during labor and delivery.c

Not known whether diazoxide is distributed into milk.a c Discontinue nursing or the drug.a c

Nondiabetic hypertensive patients with impaired renal function may develop diabetic ketoacidosis following multiple doses of diazoxide.b Observe patients carefully for possible development of severe hyperglycemia.b

Avoid prolonged hypotension since it may aggravate preexisting renal failure.a b

Monitor serum electrolyte concentrations in patients with renal impairment.c Such patients may require potent diuretics such as furosemide or ethacrynic acid rather than thiazide diuretics to manage sodium and fluid retention.a

Common Adverse Effects

Sodium and fluid retention, tachycardia, palpitations, increased uric acid concentrations, hyperglycemia or glycosuria, GI intolerance, hirsutism, thrombocytopenia.c d j

Absorption

Bioavailability

Peak blood concentrations attained in 4 hours.b

Duration

Glycemic effect begins within 1 hour and lasts approximately ≤8 hours in patients with normal renal function.c

Plasma Concentrations

Minimum blood diazoxide concentrations of 10 mcg/mL appear to be necessary for initial hypotensive effects.b i

Distribution

Extent

In animals, distributes into kidneys with relatively high concentrations in liver and adrenal glands.b

Crosses placenta and blood-brain barrier.a b c Not known whether the drug is distributed into milk.a

Plasma Protein Binding

>90% bound.c

May displace bilirubin from albumin; may produce neonatal hyperbilirubinemia.b c

Special Populations

Diazoxide is less bound to cord plasma proteins than to adult plasma proteins.b

In patients with chronic uremia, there is a substantial reduction of plasma protein binding, probably resulting from decreased serum albumin in these patients.b

Elimination

Metabolism

Partially metabolized by oxidation and sulfate conjugation and excreted slowly in urine by glomerular filtration as unchanged drug and metabolites.b

Elimination Route

In one patient, 2% of an orally administered dose of diazoxide was recovered in feces.b

Half-life

21–48 hours in adults with normal renal function.b i The high degree of protein binding is responsible for the prolonged half-life.b

Special Populations

In pediatric patients, terminal elimination half-life may be somewhat shorter than in adults.b

In patients with renal impairment, half-life is prolonged in proportion to decreases in Clcr.b c Diazoxide and its metabolites are removed by hemodialysis and peritoneal dialysis, but dialysance is relatively low because of extensive protein binding.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Oral:

Proglycem: 50 mg/mL (30 mL) [chocolate mint flavor]

• Antidote, Hypoglycemia
• Vasodilator, Direct-Acting

Hyperinsulinemic hypoglycemia: Oral: Initial dose: 3 mg/kg/day divided into 3 equal doses every 8 hours; dosing range: 3 to 8 mg/kg/day divided into 2 or 3 equal doses every 8 to 12 hours. Adjust dose until the desired clinical and laboratory effects are produced. Note: In certain instances, patients with refractory hypoglycemia may require higher doses. Discontinue if no effect after 2 to 3 weeks.

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Blood Pressure Lowering Agents: Diazoxide may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Fosphenytoin: Diazoxide may decrease the serum concentration of Fosphenytoin. Total phenytoin concentrations may be affected more than free phenytoin concentrations. Monitor therapy

Phenytoin: Diazoxide may decrease the serum concentration of Phenytoin. Total phenytoin concentrations may be affected more than free phenytoin concentrations. Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the adverse/toxic effect of Diazoxide. Monitor therapy

Thiopental: May enhance the hypotensive effect of Diazoxide. Monitor therapy

Concerns related to adverse effects:

• Abnormal facial features: Development of abnormal facial features was reported in children treated >4 years for hypoglycemia hyperinsulinism.

• Hyperosmolar coma: Nonketotic hyperosmolar coma may occur during treatment; usually in patients with concomitant illness; prompt recognition and treatment are essential. Transient cataracts have been reported which subside following correction of hyperosmolarity.

• Ketoacidosis: Ketoacidosis may occur during treatment, usually in patients with concomitant illness.

Disease-related concerns:

• Heart failure: Use may lead to increased fluid retention due to antidiuretic properties and may precipitate heart failure in patients with compromised cardiac reserve.

• Gout: Use with caution in patients with hyperuricemia or a history of gout.

• Renal impairment: Use with caution in patients with renal impairment; a reduced dose should be considered.

Special populations:

• Pediatric: May displace bilirubin from albumin; use caution in newborns with hyperbilirubinemia. Pulmonary hypertension has been reported in newborns and young infants and was reversible upon drug discontinuation; monitor patients (especially patients with risk factors for pulmonary hypertension) for respiratory distress and discontinue diazoxide if pulmonary hypertension is suspected.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

1 to 5 mg/kg IV up to a maximum of 150 mg every 5 to 15 minutes, then every 4 to 24 hours. The dose should be administered in less than 30 seconds into a peripheral vein. Alternatively, 3 to 5 mg/kg infused over 30 minutes may result in less hypotension and hyperglycemia.