Proglycem

PROGLYCEM® (diazoxide capsules, USP), 50 mg, half opaque orange and half clear capsules, branded in black with BNP 6000: bottle of 100 (NDC 0575-6000-01).

PROGLYCEM® suspension, 50 mg/mL, a chocolate-mint flavored suspension; bottle of 30 ml (NDC 0575-6200-30), with dropper calibrated to deliver 10, 20, 30, 40 and 50 mg diazoxide. Shake well before each use. Protect from light. Store in carton until contents are used. Store in light resistant container as defined in the USP. Store PROGLYCEM® Capsules and Suspension at 25°C (77°F) excursions permitted 15°-30°C (59-86°F). [See USP Controlled Room Temperature].

Distributed by: Teva Pharmaceuticals USA, Inc. North Wales, PA 19454. Revised: Sep 2015

Proglycem is part of the drug classes:

• Drugs for treatment of hypoglycemia

• Thiazide derivatives

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Shake the oral suspension (liquid) well just before you measure a dose. Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Diazoxide is usually taken every 8 to 12 hours. Take the medicine at the same time intervals each day.

Diazoxide usually begins to work within 1 hour, and its effects can last up to 8 hours.

Your blood sugar will need to be checked often, and your urine may also need to be tested for ketones. Call your doctor at once if you have abnormal test results. You may need other blood tests at your doctor's office.

Diazoxide is only part of a treatment program that may also include diet. Follow your doctor's instructions very closely.

Do not share this medicine with another person, even if they have the same symptoms you have.

Store at room temperature away from moisture, heat, and light.

If your condition does not improve after taking diazoxide for 2 to 3 weeks, stop taking diazoxide and talk to your doctor.

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

Storage

Oral

25°C (may be exposed to 15–30°C); protect from light.c Should not use darkened oral suspensions since they may be subpotent.b

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• Proglycem

Available Dosage Forms:

• Capsule
• Suspension

Therapeutic Class: Glucose Regulation, Antihypoglycemic

Chemical Class: Thiazide Related

Diazoxide is used to manage symptoms of hypoglycemia (low blood sugar) that is caused by pancreas cancer, surgery, or other conditions. Diazoxide works by preventing release of insulin from the pancreas.

This medicine is available only with your doctor's prescription.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Chest pain

• Abdominal or stomach pain
• black, tarry stools
• blood in the urine
• bloody nose
• blurred vision
• confusion
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• extreme thirst
• fast, irregular, pounding, or racing heartbeat or pulse
• fever
• flushed, dry skin
• fruit-like breath odor
• heavier menstrual periods
• increased hunger
• increased thirst
• increased urination
• loss of consciousness
• nausea
• pinpoint red spots on the skin
• seizures
• skin rash
• stomachache
• sweating
• troubled breathing
• unexplained weight loss
• unusual bleeding or bruising
• unusual tiredness or weakness
• urinating large amounts or urinating very little
• vomiting
• weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Increased hair growth, especially on the forehead, back, arms, and legs

• Loss of appetite
• loss of taste
• weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

General:

Treatment with Proglycem® should be initiated under close clinical supervision, with careful monitoring of blood glucose and clinical response until the patient's condition has stabilized. This usually requires several days. If not effective in two to three weeks, the drug should be discontinued.

Prolonged treatment requires regular monitoring of the urine for sugar and ketones, especially under stress conditions, with prompt reporting of any abnormalities to the physician. Additionally, blood sugar levels should be monitored periodically by the physician to determine the need for dose adjustment.

The effects of diazoxide on the hematopoietic system and the level of serum uric acid should be kept in mind; the latter should be considered particularly in patients with hyperuricemia or a history of gout.

In some patients, higher blood levels have been observed with the oral suspension than with the capsule formulation of Proglycem®. Dosage should be adjusted as necessary in individual patients if changed from one formulation to the other.

Since the plasma half-life of diazoxide is prolonged in patients with impaired renal function, a reduced dosage should be considered. Serum electrolyte levels should also be evaluated for such patients.

The antihypertensive effect of other drugs may be enhanced by Proglycem®, and this should be kept in mind when administering it concomitantly with antihypertensive agents.

Because of the protein binding, administration of Proglycem® with coumarin or its derivatives may require reduction in the dosage of the anticoagulant, although there has been no reported evidence of excessive anticoagulant effect. In addition, Proglycem® may possibly displace bilirubin from albumin; this should be kept in mind particularly when treating newborns with increased bilirubinemia.

Pulmonary hypertension has been reported in neonates and young infants treated with diazoxide. (see WARNINGS)

Information for Patients:

During treatment with Proglycem® the patient should be advised to consult regularly with the physician and to cooperate in the periodic monitoring of his condition by laboratory tests. In addition, the patient should be advised:

Laboratory tests:

The following procedures may be especially important in patient monitoring (not necessarily inclusive); blood glucose determinations (recommended at periodic intervals in patients taking diazoxide orally for treatment of hypoglycemia, until stabilized); blood urea nitrogen (BUN) determinations and creatinine clearance determinations; hematocrit determinations; platelet count determinations; total and differential leukocyte counts; serum aspartate aminotransferase (AST) level determinations; serum uric acid level determinations; and urine testing for glucose and ketones (in patients being treated with diazoxide for hypoglycemia, semiquantitative estimation of sugar and ketones in serum performed by the patient and reported to the physician provides frequent and relatively inexpensive monitoring of the condition).

Drug Interactions:

Since diazoxide is highly bound to serum proteins, it may displace other substances which are also bound to protein, such as bilirubin or coumarin and its derivatives, resulting in higher blood levels of these substances. Concomitant administration of oral diazoxide and diphenylhydantoin may result in a loss of seizure control. These potential interactions must be considered when administering Proglycem® Capsules or Suspension.

The concomitant administration of thiazides or other commonly used diuretics may potentiate the hyperglycemic and hyperuricemic effects of diazoxide.

Drug/Laboratory Test Interactions:

The hyperglycemic and hyperuricemic effects of diazoxide preclude proper assessment of these metabolic states. Increased renin secretion, IgG concentrations and decreased cortisol secretions have also been noted. Diazoxide inhibits glucagon-stimulated insulin release and causes a false-negative insulin response to glucagon.

Carcinogenesis, mutagenesis, impairment of fertility:

No long-term animal dosing study has been done to evaluate the carcinogenic potential of diazoxide. No laboratory study of mutagenic potential or animal study of effects on fertility has been done.

Pregnancy Category C:

Reproduction studies using the oral preparation in rats have revealed increased fetal resorptions and delayed parturition, as well as fetal skeletal anomalies; evidence of skeletal and cardiac teratogenic effects in rabbits has been noted with intravenous administration. The drug has also been demonstrated to cross the placental barrier in animals and to cause degeneration of the fetal pancreatic beta cells (See ANIMAL PHARMACOLOGY AND/OR TOXICOLOGY). Since there are no adequate data on fetal effects of this drug when given to pregnant women, safety in pregnancy has not been established. When the use of Proglycem® is considered, the indications should be limited to those specified above for adults (See INDICATIONS AND USAGE), and the potential benefits to the mother must be weighed against possible harmful effects to the fetus.

Non-teratogenic effects:

Diazoxide crosses the placental barrier and appears in cord blood. When given to the mother prior to delivery of the infant, the drug may produce fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism, and possibly other side effects that have occurred in adults.

Alopecia and hypertrichosis lanuginosa have occurred in infants whose mothers received oral diazoxide during the last 19 to 60 days of pregnancy.

Labor and delivery:

Since intravenous administration of the drug during labor may cause cessation of uterine contractions, and administration of oxytocic agents may be required to reinstate labor, caution is advised in administering Proglycem® at that time.

Nursing mothers:

Information is not available concerning the passage of diazoxide in breast milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions from diazoxide in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use:

(See INDICATIONS AND USAGE).

Proglycem® (diazoxide capsules, USP), 50 mg, half opaque orange and half clear capsules, branded in black with BNP 6000: bottle of 100 (NDC 0575-6000-01).

Proglycem® suspension, 50 mg/mL, a chocolate-mint flavored suspension; bottle of 30 ml (NDC 0575-6200-30), with dropper calibrated to deliver 10, 20, 30, 40 and 50 mg diazoxide.
Shake well before each use. Protect from light. Store in carton until contents are used. Store in light resistant container as defined in the USP. Store Proglycem® Capsules and Suspension at 25°C (77°F) excursions permitted 15°-30°C (59-86°F). [See USP Controlled Room Temperature].

Rx only

Distributed by:

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. 9/2015