Diazoxide (Capsules) Instructions for Use

Marketing Authorization Holder

LIFE SCIENCES OHFK, LLC (Russia)

Manufactured By

OHFK, JSC (Russia)

ATC Code

V03AH01 (Diazoxide)

Active Substance

Diazoxide (Rec.INN registered by WHO)

Dosage Forms

	Diazoxide	Capsules 25 mg: 10, 20, 30, 40, 50, 60, 80 or 100 pcs.
		Capsules 100 mg: 10, 20, 30, 40, 50, 60, 80 or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin opaque No. 3, white body and cap; capsule contents – white or almost white powder.

Excipients : anhydrous lactose, magnesium stearate.

Composition of the capsule body and cap titanium dioxide gelatin.

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
20 pcs. – blister packs (1) – cardboard packs.
20 pcs. – blister packs (2) – cardboard packs.
20 pcs. – blister packs (3) – cardboard packs.
20 pcs. – blister packs (4) – cardboard packs.
20 pcs. – blister packs (5) – cardboard packs.

Capsules hard gelatin opaque No. 2, white body and cap; capsule contents – white or almost white powder.

Excipients : anhydrous lactose, magnesium stearate.

Composition of the capsule body and cap titanium dioxide gelatin.

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
20 pcs. – blister packs (1) – cardboard packs.
20 pcs. – blister packs (2) – cardboard packs.
20 pcs. – blister packs (3) – cardboard packs.
20 pcs. – blister packs (4) – cardboard packs.
20 pcs. – blister packs (5) – cardboard packs.

Clinical-Pharmacological Group

Drug affecting carbohydrate metabolism

Pharmacotherapeutic Group

Hypoglycemia treatment agent

Pharmacological Action

Diazoxide is a hypoglycemia treatment agent, a benzothiadiazine derivative. When taken orally, Diazoxide causes a rapid dose-dependent increase in blood glucose levels, both by suppressing insulin release from the pancreas and through a direct extrapancreatic effect.

The hyperglycemic effect develops within the first hour after oral administration and in persons with normal renal function usually lasts no more than 8 hours.

Diazoxide reduces the excretion of sodium ions, which leads to fluid retention that may be clinically significant.

Indications

Treatment of hypoglycemia in patients with hyperinsulinemia that has developed in adults with inoperable extrapancreatic tumor or tumor of pancreatic cells (both malignant and benign) in which insulin synthesis occurs; in children aged 0 to 18 years with pancreatic cell hyperplasia sensitive to leucine, with nesidioblastosis (neonatal hypoglycemic syndrome caused by total transformation of the ductal epithelium of pancreatic islet cells), extrapancreatic location of insulin-producing cells, tumor of pancreatic islet cells.

In the preoperative period as a temporary measure and in the postoperative period, if hypoglycemia persists.

ICD codes

Dosage Regimen

For oral administration.

The dose is determined individually and depends on the clinical condition of the patient and the blood glucose concentration.

The recommended daily dose is 3-8 mg/kg, divided into 2-3 doses (every 8-12 hours). The usual initial dose is 3 mg/kg/day, divided into 3 doses (every 8 hours). The recommended initial dose is 200 mg.

Children aged 0 to 7 years: the recommended daily dose is 8-15 mg/kg, divided into 2-3 doses (every 8-12 hours). The recommended initial dose is 10 mg/kg/day, divided into 3 doses (every 8 hours).

Children aged 8 to 18 years: the recommended daily dose is 3-8 mg/kg, divided into 2-3 doses (every 8-12 hours). The usual initial dose is 3 mg/kg/day, divided into 3 doses (every 8 hours). The recommended initial dose is 200 mg.

Treatment should be started under careful clinical supervision with mandatory monitoring of blood glucose concentration and clinical response until the patient’s condition stabilizes. This usually takes several days. If after 2-3 weeks the therapeutic effect is insufficient, Diazoxide should be discontinued. The duration of therapy will be determined by the attending physician.

Adverse Reactions

Most often: nausea, in some cases requiring the prescription of antiemetic drugs and even discontinuation of treatment.

Metabolism and nutrition disorders : often – fluid and salt retention (such retention may lead to the development or worsening of congestive heart failure in patients with impaired ability of the heart to increase cardiac output); rarely – diabetic ketoacidosis, hyperosmolar nonketoacidotic coma, azotemia, hyperglycemia, glucosuria, hyperuricemia, gout.

Blood and lymphatic system disorders often – thrombocytopenia, transient neutropenia; infrequently – eosinophilia, lymphadenopathy, decreased hemoglobin/hematocrit level, spontaneous bleeding,

Immune system disorders infrequently – hypogammaglobulinemia (decreased immunoglobulin G level, especially in children).

Skin and subcutaneous tissue disorders often – lanugo-type hypertrichosis in women and children (excessive growth of vellus hair on the upper part of the face, back and limbs; usually resolves after discontinuation of treatment; the appearance of hypertrichosis should not lead to discontinuation of therapy when the therapeutic effects of the drug are vital), skin itching; infrequently – herpes, monilial dermatitis (fungal skin infection usually caused by fungi of the genus Candida), dermatitis.

Nervous system disorders often – headache, decreased libido; infrequently – dizziness, anxiety, insomnia, polyneuritis, paresthesia, extrapyramidal disorders (muscle rigidity, parkinsonism, tremor).

Cardiac and vascular disorders often – tachycardia, palpitations, decreased BP; infrequently – arterial hypotension, chest pain, cardialgia, angina pectoris, cardiomegaly, worsening of heart failure, arrhythmias, pulmonary hypertension, dyspnea.

Eye disorders often – transient cataract; infrequently – subconjunctival hemorrhage, annular scotoma, visual impairment, diplopia, lacrimation.

Gastrointestinal disorders often – anorexia (absence or decreased appetite), nausea, vomiting, abdominal pain, diarrhea, temporary loss of taste, intestinal obstruction; infrequently – acute pancreatitis (inflammation of the pancreas), pancreatic necrosis, increased activity of AST and ALP.

Endocrine disorders infrequently – galactorrhea.

Musculoskeletal and connective tissue disorders infrequently – premature closure of bone growth zones in children.

Renal and urinary disorders infrequently – decreased CC, reversible nephrotic syndrome, urinary retention, hematuria, albuminuria.

General disorders and administration site conditions often – malaise, weakness.

Contraindications

Hypersensitivity to diazoxide, other thiazides;
Acute cerebrovascular accident; acute stage of myocardial infarction; functional hypoglycemia (for example, low blood sugar due to improper diet); pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

Use with caution in children strictly in accordance with the indications and recommended dosage regimen.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Diazoxide should be used only after the diagnosis of hypoglycemia due to the causes listed in the “Indications” section has been accurately established.

Use with caution in patients with impaired cardiac or cerebral circulation, as well as in patients with coarctation of the aorta, aortic stenosis, arteriovenous shunt, heart failure or other cardiovascular diseases in whom sodium and water retention may worsen or accelerate congestive heart failure, or an increase in cardiac output may worsen the patient’s condition.

In such patients, the water-electrolyte balance of the blood serum should also be monitored. The antidiuretic property of diazoxide can lead to significant fluid retention and to the development/worsening of manifestations of chronic heart failure. Sodium and water retention will likely require therapy with oral diuretics, such as furosemide or ethacrynic acid (up to 1 g/day). It should be borne in mind that when using diuretics, both the hypotensive and hyperglycemic activity of diazoxide will be enhanced, and a reduction in the dose of diazoxide will likely be required.

During treatment, it is necessary to regularly monitor BP; the hypotensive effect of other drugs may be enhanced by diazoxide.

In patients with severe renal failure, it is advisable to maintain, against the background of diuretic therapy, a diuresis exceeding 1 liter per day.

The development of hypokalemia should be avoided by adequate potassium replacement. Diazoxide should be used with caution in patients with a history of hyperuricemia or gout – an increase in serum uric acid concentration is possible.

During diazoxide administration, the following are possible: tachycardia, palpitations, thrombocytopenic purpura, thrombocytopenia and neutropenia. At-risk patients should be monitored for these conditions, and blood tests should be performed periodically to detect possible disorders.

Intensive, almost complete binding of diazoxide to proteins requires careful dosing in patients whose blood plasma protein levels may be below normal. Monitoring of the diazoxide concentration is necessary for timely correction of the drug dose.

Long-term therapy requires regular monitoring of urine glucose and ketone body content (especially under stress conditions) – this is necessary to prevent the development of ketoacidosis and hyperosmolar nonketoacidotic coma. Rapid recognition and treatment of these conditions, as well as sufficiently long observation after relief of acute episodes (due to the long half-life of the active substance, which reaches 30 hours), is vital.
In patients with impaired renal function, the plasma half-life of diazoxide increases, and a reduction in the diazoxide dose should be considered.

In the presence of hypokalemia, the hyperglycemic effects of diazoxide are enhanced.

Use in pediatrics

In newborns, infants and children, the development of pulmonary hypertension is possible when using diazoxide. Newborns receiving Diazoxide should be under careful supervision, especially in the presence of risk factors for the development of pulmonary hypertension.

In children, regular assessment of growth, bone mass and psychological maturation should be carried out.

Diazoxide can displace bilirubin from its binding to albumin; this must be taken into account, especially when treating newborns with increased bilirubinemia.

Effect on ability to drive vehicles and operate machinery

Patients in whom Diazoxide causes such adverse reactions as drowsiness and/or orthostatic hypotension should exercise caution when engaging in activities requiring increased concentration and speed of psychomotor reactions.

Drug Interactions

Diuretics – the hyperglycemic and hyperuricemic effect of diazoxide may be enhanced by the simultaneous administration of thiazides or other widely used diuretics.

Coumarin derivative anticoagulants – administration of diazoxide to patients taking coumarin and its derivatives may lead to an enhancement of the anticoagulant effect and require a reduction in the dose of the anticoagulant.

Diphenylhydantoin – administration of diazoxide to patients taking diphenylhydantoin may cause loss of seizure control.

Chlorpromazine – the hyperglycemic effect of diazoxide may be enhanced.

Insulins block the hyperglycemic effect of diazoxide. In addition, Diazoxide, by suppressing glucagon-induced insulin release, may cause a false-negative glucagon test.

Alpha-blockers (dilate blood vessels and reduce their tone, most often used in the treatment of arterial hypertension and benign prostatic hyperplasia) – reduce the severity of the hyperglycemic effect of diazoxide.

Diazoxide may enhance the effect of antihypertensive drugs.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.