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 

品牌药生产厂家: Schering

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  

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 

•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。 

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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]

Opens ATP-dependent potassium channels on pancreatic beta cells in the presence of ATP and Mg2+, resulting in hyperpolarization of the cell and inhibition of insulin release. Diazoxide binds to a different site on the potassium channel than the sulfonylureas (Doyle, 2003).

Urine (50% as unchanged drug)

Hyperglycemic: Oral: Within 1 hour

Hyperglycemic: Oral: Normal renal function: ≤8 hours

Oral: Children: 9.5 to 24 hours; Adults: 24 to 36 hours

>90%

Plasma half-life is prolonged.

Hyperinsulinemic hypoglycemia: Management of hypoglycemia due to hyperinsulinism due to the following conditions in adults (ie, inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy) and infants and children (ie, leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis; may be used preoperatively as a temporary measure, and postoperatively, if hypoglycemia persists).

Note: Consider treatment with diazoxide when other specific medical therapy or surgical management for hypoglycemia due to the above conditions either has been unsuccessful or is not feasible.

Hypersensitivity to diazoxide, other thiazides, or any component of the formulation; functional hypoglycemia

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.

Refer to adult dosing.

Hyperinsulinemic hypoglycemia: Oral:

Neonates and Infants: Initial dose: 10 mg/kg/day divided into 3 equal doses every 8 hours; dosing range: 8 to 15 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. Discontinue if no effect after 2 to 3 weeks.

Children and Adolescents: Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling; a reduced dose should be considered (half-life may be prolonged).

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

Shake suspension well before each use. Assure accuracy of dosage in infants and young children.

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Store in carton until contents are used.

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

Serum renin concentrations and IgG concentrations may be increased. Serum cortisol concentrations may be decreased. May cause a false-negative insulin response to glucagon.

Frequency not defined.

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

<1% (Limited to important or life-threatening): Chest pain, pulmonary hypertension (infants and neonates)

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).

Clinical response, blood glucose, serum uric acid, BUN, creatinine clearance, CBC with differential, AST; urine glucose and ketones (especially under stress conditions and during prolonged treatment); serum electrolytes and uric acid; respiratory distress (neonates and infants [especially those with risk factors for pulmonary hypertension]).

C

Adverse events have been observed in animal studies. Diazoxide crosses the human placenta and appears in cord blood. Altered carbohydrate metabolism, hyperbilirubinemia, and thrombocytopenia have been reported in the fetus or neonate. Alopecia and hypertrichosis lanuginosa have also been reported in infants following maternal use of diazoxide during the last 19 to 60 days of pregnancy.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, lack of appetite, diarrhea, change in taste, or loss of strength and energy. Have patient report immediately to prescriber signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), shortness of breath, excessive weight gain, swelling of arms or legs, severe constipation, severe abdominal pain, tachycardia, abnormal heartbeat, bruising, bleeding, severe dizziness, passing out, severe headache, angina, urinary retention, change in amount of urine passed, vision changes, tremors, difficulty moving, hair growth on forehead, back, arms, and legs, or stiffness (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.