英文药名: Proglycem(diazoxide capsules)

中文药名: 二氮嗪胶囊,降压嗪,氯苯甲噻二嗪,氯甲苯噻嗪

此药品需要处方

品牌药生产厂家: Schering

药品名称

中文通用名称：二氮嗪
英文通用名称：Diazoxide
其 它 名 称：舒压嗪, 氯甲苯噻嗪, 氯甲哌噻嗪, 氯苯甲噻二嗪, 降压嗪, 低压唑, Proglycem, Mutabase, Hyperstat, Diazoxidum, 二氮嗪注射液, Diazoxide Injection
产 品 分 类: 心血管系统用药\降血压药\血管扩张类降压药
适应症

1.用于高血压危象、恶性高血压的紧急降压，但对单胺氧化酶抑制药或嗜铬细胞瘤所致高血压无效。
2.还可用于幼儿特发性低血糖症及由胰岛细胞瘤引起的严重低血糖。
用法用量

成人
•常规剂量
•静脉注射
1.恶性高血压：一次150mg或1-3mg/kg，隔5-15分钟重复注射1次，以后根据疗效每4-24小时给药1次，一日总量不超过1200mg。症状缓解后以口服降压药维持。
2.高血压危象：一次200-400mg，15-20秒钟内注射完。可在0.5-3小时内再注射1次，一日总量不超过1200mg。症状缓解后改用口服降压药维持。
•静脉滴注
一次50-150mg，以15-30mg/min的滴速给药。
•肾功能不全时剂量
肾功能减退患者应减量。
•老年人剂量
老年患者应减量。
儿童
•常规剂量
•静脉注射
按1-3mg/kg或30-90mg/m☆2☆给药。隔5-15分钟重复注射一次，以后根据疗效每4-24小时给药一次，一日总量不超过1200mg。症状缓解后以口服降压药维持。
[国外用法用量参考]
成人
•常规剂量
•静脉注射
1.恶性高血压：1-3mg/kg(最大量150mg)静脉快速注射，每隔5-15分钟重复给药一次，至舒张压降至13.33kPa(100mmHg)以下。此法既可有效降低血压又可减少低血压发生。不可用300mg的剂量静脉快速注射。也有学者推荐在非急症情况下应缓慢静脉滴注本药。
2.妊娠高血压：30-60秒内静脉快速注射30mg，每隔1-2分钟重复一次，至舒张压低于12kPa(90mmHg)。
•口服给药
1.恶性高血压：有报道，可采用一日600-800mg，疗程1-20个月不等，用于长期治疗顽固性恶性高血压。
2.低血糖：首剂为3mg/kg，分3次(每隔8小时1次)服用。通常用量为一日3-8mg/kg，分2-3次(每隔8-12小时1次)服用。如2-3周后仍无效，应停药。用量须个体化，应以患者临床情况和对药物的反应为依据。
•肾功能不全时剂量
虽然肾功能不全时本药半衰期延长，但不需调整用量。
•透析时剂量
血液透析或腹膜透析时不需加量。
儿童
•常规剂量
•静脉注射
1.一般用量：本药小剂量静脉快速注射(1-3mg/kg，每隔5-15分钟一次，单次最大量为150mg)至舒张压低于13.33kPa(100mmHg)，这样既可改善用药的安全性，又保证了相当的疗效。不应用300mg的剂量静脉快速注射。
2.高血压危象：可用1-5mg/kg静脉快速注射，或以0.25-5mg/(kg•min)的速度静脉滴注。
•口服给药
低血糖症：一日3-8mg/kg，分2-3次(每隔8-12小时一次)服用。
•肾功能不全时剂量
虽然肾功能不全时本药半衰期延长，但不需调整用量。
•透析时剂量
血液透析或腹膜透析时不需加量。
任何疑问，请遵医嘱！
给药说明

1.本药不宜与其它药物配伍。
2.本药须溶于专用溶剂内静脉注射。患者应取卧位快速静脉注射。
3.应取周围静脉注射，而不宜作肌内、心腔内或皮下注射。注射局部可有疼痛，须注意药液不要外漏，以免引起局部组织炎症及疼痛，如有外漏应立即局部冷湿敷。
4.本药与利尿药合用可加强降压效果，防止由水钠潴留引起的心力衰竭。推荐注射本药前30-60分钟静脉注射呋塞米40-80mg；若未事先给予利尿药防止血容量增加，本药的降压作用可出现耐药性。
5.对糖尿病患者或多次注射本药的患者，为防止血糖上升，可用胰岛素或口服降血糖药以控制血糖。
6.缓慢注射本药可因与蛋白结合多而使疗效减弱及作用时间缩短。但近来发现本药滴注可产生较缓慢的降压作用，降压幅度较小，可避免因血压骤降引起的重要器官血液灌注不足。
7.本药过量可引起高血糖及低血压(甚至导致休克)。
8.药物过量处理：高血糖可用降血糖药治疗，且须监测血糖7日以上，直至血糖稳定；低血压可用缩血管药物(如去甲肾上腺素)纠正。
9.本药不适用于原发性高血压的长期治疗。
不良反应

1.心血管系统
常见水肿，甚至有导致充血性心力衰竭的可能；也可见直立性低血压、心动过速或心律失常；少见心肌缺血、心绞痛、心肌梗死；静脉注射可引起静脉炎，表现为注射部位静脉灼痛。
2.消化系统
可有味觉改变、食欲减退、恶心、呕吐、胃痛、便秘等，并可使碱性磷酸酶、游离脂肪酸、天门冬氨酸氨基转移酶浓度增高。
3.精神神经系统
可出现脑缺血或血栓形成，表现为神志模糊、手麻、失眠、锥体外系症状等。
4.代谢/内分泌系统
(1)较少见血糖过高引起的倦怠、排尿增多、口渴，偶可发展为酮症酸中毒及高渗性昏迷。一次静脉给药后引起的高血糖常较短暂(持续24-48小时)，但24小时谧⑸?次以上，则高血糖持续时间较长。此外，血钾过低时本药的升高血糖作用增强。
(2)可出现高尿酸血症及诱发痛风。
(3)可使血钠、尿酸等浓度增高。
5.血液
少见白细胞及血小板减少。可使血细胞比容、血红蛋白减少。
6.泌尿生殖系统
可使尿素氮浓度增高、肌酐清除率及尿钾、氯、碳酸氢盐排泄减少。
7.其它
可有发热、皮疹、出血、颜面潮红、头痛、乏力、耳鸣、听觉异常及免疫球蛋白(IgG)减少。
注意事项

1.交叉过敏
对噻嗪类利尿药、袢利尿药、碳酸酐酶抑制药过敏者，对本药也可能过敏。
2.禁忌症
(1)充血性心力衰竭、糖尿病、肾功能不全的重型高血压。
(2)孕妇。
(3)哺乳妇女。
(4)功能性低血糖症(国外资料)。
(5)伴主动脉瓣狭窄或动静脉分流的高血压(国外资料)。
(6)对本药、噻嗪类利尿药或磺胺类药过敏(国外资料)。
3.慎用
(1)急性主动脉夹层分离。
(2)冠状动脉或脑动脉供血不足。
(3)痛风。
(4)肝功能障碍。
(5)低钾血症。
4.药物对儿童的影响
儿童急性严重高血压可用本药作暂时紧急降压，但不能久用。
5.药物对妊娠的影响
本药可透过胎盘，可使胎儿血糖过高、血胆红素过高、脱发或毛发过度增生、血小板减少等。动物中曾发现本药有致畸作用，也能抑制分娩，故孕妇应尽量避免应用。美国药品和食品管理局(FDA)对本药的妊娠安全性分级为C级。
6.药物对哺乳的影响
尚不明确本药是否排入乳汁。
7.药物对检验值或诊断的影响
本药可改变胰岛素对胰高糖素的反应，出现假阴性。
8.用药前后及用药时应当检查或监测
(1)国外资料推荐，在注射本药前及开始注射后5分钟内，每隔1分钟监测血压。以后可每隔5分钟监测一次，至血压平稳后可改为每小时监测一次。
(2)糖尿病或肝、肾功能不全者应定时检查血糖。
 
规格

二氮嗪胶囊 100mg*100 胶囊
 
二氮嗪片   50mg  100片(UCB Pharma.生产)

FOR ORAL ADMINISTRATION

Rx only

DESCRIPTION

PROGLYCEM® (diazoxide) is a nondiuretic benzothiadiazine derivative taken orally for the management of symptomatic hypoglycemia. PROGLYCEM® Capsules contain 50 mg diazoxide, USP. The Suspension contains 50 mg of diazoxide, USP in each milliliter and has a chocolate-mint flavor; alcohol content is approximately 7.25%. Other ingredients: Sorbitol solution, chocolate cream flavor, propylene glycol, magnesium aluminum silicate, carboxymethycellulose sodium, mint flavor, sodium benzoate, methylparaben, hydrochloric acid to adjust pH, poloxamer 188, propylparaben, purified water.

Diazoxide has the following structural formula:

Diazoxide is 7-chloro-3-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide with the empirical formula C8H7ClN2O2S and the molecular weight 230.7. It is a white powder practically insoluble to sparingly soluble in water.

CLINICAL PHARMACOLOGY

Diazoxide administered orally produces a prompt dose-related increase in blood glucose level, due primarily to an inhibition of insulin release from the pancreas, and also to an extrapancreatic effect.

The hyperglycemic effect begins within an hour and generally lasts no more than eight hours in the presence of normal renal function.

PROGLYCEM® decreases the excretion of sodium and water, resulting in fluid retention which may be clinically significant.

The hypotensive effect of diazoxide on blood pressure is usually not marked with the oral preparation. This contrasts with the intravenous preparation of diazoxide (see ADVERSE REACTIONS).

Other pharmacologic actions of PROGLYCEM® include increased pulse rate; increased serum uric acid levels due to decreased excretion; increased serum levels of free fatty acids' decreased chloride excretion; decreased para-aminohippuric acid; (PAH) clearance with no appreciable effect on glomerular filtration rate.

The concomitant administration of a benzothiazide diuretic may intensify the hyperglycemic and hyperuricemic effects of PROGLYCEM®. In the presence of hypokalemia, hyperglycemic effects are also potentiated.

PROGLYCEM®-induced hyperglycemia is reversed by the administration of insulin or tolbutamide. The inhibition of insulin release by PROGLYCEM® is antagonized by alpha-adrenergic blocking agents.

PROGLYCEM® is extensively bound (more than 90%) to serum proteins, and is excreted in the kidneys. The plasma half-life following I.V. administration is 28 ± 8.3 hours. Limited data on oral administration revealed a half-life of 24 and 36 hours in two adults. In four children aged four months to six years, the plasma half-life varied from 9.5 to 24 hours on long-term oral administration. The half-life may be prolonged following overdosage, and in patients with impaired renal function.

INDICATIONS AND USAGE

PROGLYCEM® (ORAL DIAZOXIDE) is useful in the management of hypoglycemia due to hyperinsulinism associated with the following conditions:

Adults: Inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy.

Infants and Children: Leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis. PROGLYCEM® may be used preoperatively as a temporary measure, and postoperatively, if hypoglycemia persists.

PROGLYCEM® should be used only after a diagnosis of hypoglycemia due to one of the above conditions has been definitely established. When other specific medical therapy or surgical management either has been unsuccessful or is not feasible, treatment with PROGLYCEM® should be considered.

CONTRAINDICATIONS

The use of PROGLYCEM® for functional hypoglycemia is contraindicated. The drug should not be used in patients hypersensitive to diazoxide or to other thiazides unless the potential benefits outweigh the possible risks.

WARNINGS

The antidiuretic property of diazoxide may lead to significant fluid retention, which in patients with compromised cardiac reserve, may precipitate congestive heart failure. The fluid retention will respond to conventional therapy with diuretics.

It should be noted that concomitantly administered thiazides may potentiate the hyperglycemic and hyperuricemic actions of diazoxide (See DRUG INTERACTIONS and ANIMAL PHARMACOLOGY AND/OR TOXICOLOGY).

Ketoacidosis and nonketotic hyperosmolar coma have been reported in patients treated with recommended doses of PROGLYCEM® usually during intercurrent illness. Prompt recognition and treatment are essential (See OVERDOSAGE), and prolonged surveillance following the acute episode is necessary because of the long drug half-life of approximately 30 hours. The occurrence of these serious events may be reduced by careful education of patients regarding the need for monitoring the urine for sugar and ketones and for prompt reporting of abnormal findings and unusual symptoms to the physician. Transient cataracts occurred in association with hyperosmolar coma in an infant, and subsided on correction of the hyper-osmolarity. Cataracts have been observed in several animals receiving daily doses of intravenous or oral diazoxide.

The development of abnormal facial features in four children treated chronically (>4 years) with PROGLYCEM® for hypoglycemia hyperinsulinism in the same clinic has been reported.

PRECAUTIONS

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.

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:

to take the drug on a regular schedule as prescribed, not to skip doses, not to take extra doses;

not to use this drug with other medications unless this is done with the physician's advice;

not to allow anyone else to take this medication;

to follow dietary instructions;

to report promptly any adverse effects (i.e., increased urinary frequency, increased thirst, fruity breath odor);

to report pregnancy or to discuss plans for pregnancy.

 

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).

ADVERSE REACTIONS

Frequent and Serious

Sodium and fluid retention is most common in young infants and in adults and may precipitate congestive heart failure in patients with compromised cardiac reserve. It usually responds to diuretic therapy (See DRUG INTERACTIONS).

Infrequent but Serious

Diabetic ketoacidosis and hyperosmolar nonketotic coma may develop very rapidly. Conventional therapy with insulin and restoration of fluid and electrolyte balance is usually effective if instituted promptly. Prolonged surveillance is essential in view of the long half-life of PROGLYCEM® (See OVERDOSAGE).

Other frequent adverse reactions

Hirsutism of the lanugo type, mainly on the forehead, back and limbs, occurs most commonly in children and women and may be cosmetically unacceptable. It subsides on discontinuation of the drug.

Hyperglycemia or glycosuria may require reduction in dosage in order to avoid progression to ketoacidosis or hyperosmolar coma.

Gastrointestinal intolerance may include anorexia, nausea, vomiting, abdominal pain, ileus, diarrhea, transient loss of taste.

Tachycardia, palpitations, increased levels of serum uric acid are common.

Thrombocytopenia with or without purpura may require discontinuation of the drug. Neutropenia is transient, is not associated with increased susceptibility to infection, and ordinarily does not require discontinuation of the drug. Skin rash, headache, weakness, and malaise may also occur.

Other adverse reactions which have been observed are

Cardiovascular: hypotension occurs occasionally, which may be augmented by thiazide diuretics given concurrently. A few cases of transient hypertension, for which no explanation is apparent, have been noted. Chest pain has been reported rarely.

Hematologic: eosinophilia; decreased hemoglobin / hematocrit; excessive bleeding, decreased IgG.

Hepato-renal: increased AST, alkaline phosphatase; azotemia, decreased creatinine clearance, reversible nephrotic syndrome, decreased urinary output, hematuria, albuminuria. Neurologic: anxiety, dizziness, insomnia, polyneuritis, paresthesia, pruritus, extrapyramidal signs. Ophthalmologic: transient cataracts, subconjunctival hemorrhage, ring scotoma, blurred vision, diplopia, lacrimation. Skeletal, integumentary; monilial dermatitis, herpes, advance in bone age; loss of scalp hair. Systemic: fever, lymphadenopathy. Other; gout acute pancreatitis/pancreatic necrosis, galactorrhea, enlargement of lump in breast.

OVERDOSAGE

An overdosage of PROGLYCEM® causes marked hyperglycemia which may be associated with ketoacidosis. It will respond to prompt insulin administration and restoration of fluid and electrolyte balance. Because of the drug's long half-life (approximately 30 hours), the symptoms of overdosage require prolonged surveillance for periods up to seven days until the blood sugar level stabilizes within the normal range. One investigator reported successful lowering of diazoxide blood levels by peritoneal dialysis in one patient and by hemodialysis in another.

DOSAGE AND ADMINISTRATION

Patients should be under close clinical observation when treatment with PROGLYCEM® is initiated. The clinical response and blood glucose level should be carefully monitored until the patient's condition has stabilized satisfactory; in most instances, this may be accomplished in several days. If administration of PROGLYCEM® is not effective after two or three weeks, the drug should be discontinued.

The dosage of PROGLYCEM® must be individualized based on the severity of the hypoglycemic condition and the blood glucose level and clinical response of the patient. The dosage should be adjusted until the desired clinical and laboratory effects are produced with the least amount of the drug. Special care should be taken to assure accuracy of dosage in infants and young children.

Adults and children

The usual daily dosage is 3 to 8 mg/kg, divided into two or three equal doses every 8 or 12 hours. In certain instances, patients with refractory hypoglycemia may require higher dosages. Ordinarily, an appropriate starting dosage is 3 mg/kg/day, divided into three equal doses every 8 hours. Thus an average adult would receive a starting dosage of approximately 200 mg daily.

Infants and newborns

The usual daily dosage is 8 to 15 mg/kg divided into two or three equal doses every 8 to 12 hours. An appropriate starting dosage is 10 mg/kg/day, divided into three equal doses every 8 hours.

ANIMAL PHARMACOLOGY AND/OR TOXICOLOGY

Oral diazoxide in the mouse, rat, rabbit, dog, pig, and monkey produces a rapid and transient rise in blood glucose levels. In dogs, increased blood glucose is accompanied by increased free fatty acids, lactate, and pyruvate in the serum. In mice, a marked decrease in liver glycogen and an increase in the blood urea nitrogen level occur.

In acute toxicity studies the LD50 for oral diazoxide suspension is >5000 mg/kg in the rat, >522 mg/kg in the neonatal rat, between 1900 and 2572 mg/kg in the mouse, and 219 mg/kg in the guinea pig. Although the oral LD50 was not determined in the dog, a dosage of up to 500 mg/kg was well tolerated.

In subacute oral toxicity studies, diazoxide at 400 mg/kg in the rat produced growth retardation, edema, increases in liver and kidney weights, and adrenal hypertrophy. Daily dosages up to 1080 mg/kg for three months produced hyperglycemia, an increase in liver weight and an increase in mortality. In dogs given oral diazoxide at approximately 40 mg/kg/day for one month, no biologically significant gross or microscopic abnormalities were observed. Cataracts, attributed to markedly disturbed carbohydrate metabolism, have been observed in a few dogs given repeated daily doses of oral or intravenous diazoxide. The lenticular changes resembled those which occur experimentally in animals with increased blood glucose levels. In chronic toxicity studies, rats given a daily dose of 200 mg/kg diazoxide for 52 weeks had a decrease in weight gain and an increase in heart, liver, adrenal and thyroid weights. Mortality in drug-treated and control groups was not different. Dogs treated with diazoxide at dosages of 50, l00, and 200 mg/kg/day for 82 weeks had higher blood glucose levels than controls. Mild bone marrow stimulation and increased pancreas weights were evident in the drug-treated dogs; several developed inguinal hernias, one had a testicular seminoma, and another had a mass near the penis. Two females had inguinal mammary swellings. The etiology of these changes was not established. There was no difference in mortality between drug-treated and control groups. In a second chronic oral toxicity study, dogs given milled diazoxide at 50, l00, and 200 mg/kg/day had anorexia and sever weight loss, causing death in a few. Hematologic, biochemical, and histologic examination did not indicate any cause of death other than inanition. After one year of treatment, there is no evidence of herniation or tissue swelling in any of the dogs.

When diazoxide was administered at high dosages concomitantly with either chlorothiazide to rats or trichlormethiazide to dogs, increased toxicity was observed. In rats, the combination was nephrotoxic; epithelial hyperplasia was observed in the collecting tubules. In dogs, a diabetic syndrome was produced which resulted in ketosis and death. Neither of the drugs given alone produced these effects.

Although the data are inconclusive, reproduction and teratology studies in several species of animals indicate that diazoxide, when administered during the critical period of embryo formation, may interfere with normal fetal development, possibly through altered glucose metabolism. Parturition was occasionally prolonged in animals treated at term. Intravenous administration of diazoxide to pregnant sheep, goats, and swine produced in the fetus an appreciable increase in blood glucose level and degeneration of the beta cells of the Islets of Langerhans. The reversibility of these effects was not studied.

HOW SUPPLIED

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].

PROGLYCEM® (diazoxide capsules, USP), manufactured by IVAX Pharmaceuticals, Inc., Miami, Florida 33137

PROGLYCEM® (diazoxide USP), Oral Suspension, manufactured by TEVA PHARMACEUTICALS USA, Sellersville, PA 18960

Rx only

Capsules Manufactured by:
IVAX Pharmaceuticals, Inc.
Miami, Fl 33137

Suspension Manufactured for:
GATE PHARMACEUTICALS
Div. of Teva Pharmaceuticals USA
Sellersville, PA 18960

Suspension Manufactured by:
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960