--------------------------------------------------------------
详细处方信息以本药内容附件PDF文件（2009101307190418.PDF）的“原文     Priscribing Information”为准
---------------------------------------------------------------

General
HYPERSTAT (diazoxide) I.V. Injection is an effective antihypertensive agent requiring close monitoring of the patient's blood pressure at frequent intervals. Its administration may occasionally cause hypotension requiring treatment with sympathomimetic drugs. Therefore, HYPERSTAT I.V. Injection should be used primarily in the hospital or where adequate facilities exist to treat such untoward responses.

HYPERSTAT I.V. Injection should be administered only into a peripheral vein. Because the alkalinity of the solution is irritating to tissue, avoid extravascular injection or leakage. Subcutaneous administration has produced inflammation and pain without subsequent necrosis. If leakage into subcutaneous tissue occurs, the area should be treated with warm compresses and rest.

HYPERSTAT I.V. Injection should be used with care in patients who have impaired cerebral or cardiac circulation, that is, patients in whom abrupt reduction in blood pressure might be detrimental or those in whom mild tachycardia or decreased blood perfusion may be deleterious (see [#section-7 WARNINGS]). Prolonged hypotension should be avoided so as not to aggravate preexisting renal failure.

Information for Patients
During and immediately following intravenous injection of HYPERSTAT I.V. Injection, the patient should remain supine.

Laboratory Tests
Diagnostic laboratory tests necessary to establish the patient's condition and status should be carried out prior to treatment with HYPERSTAT I.V. Injection. During and following treatment with HYPERSTAT I.V. Injection, laboratory tests to monitor the effects of treatment with this drug and the patient's condition should be done. Among the tests (not necessarily inclusive) are: hematologic (hematocrit, hemoglobin, white blood cell and platelet counts); metabolic (glucose, uric acid, total protein, albumin); electrolyte (sodium, potassium) and osmolality; renal function (creatinine, urine-protein); electrocardiogram.

Drug Interactions
Diazoxide is highly bound to serum protein. It can be expected to 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.

An undesirable hypotension may result when diazoxide is administered to patients who have received other antihypertensive medication within 6 hours.

One patient in a clinical study exhibited excessive hypotension after concomitant administration of HYPERSTAT with hydralazine and methyldopa. An episode of maternal hypotension and fetal bradycardia occurred in a patient in labor who received both reserpine and hydralazine prior to administration of diazoxide. Neonatal hyperglycemia following intrapartum administration of HYPERSTAT I.V. Injection has also been reported.

HYPERSTAT I.V. Injection should not be administered within 6 hours of the administration of: hydralazine, reserpine, alphaprodine, methyldopa, beta-blockers, prazosin, minoxidil, the nitrites and other papaverine-like compounds.

Concomitant administration with thiazides or other commonly used diuretics may be expected to potentiate the hyperuricemic and antihypertensive 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 secretion have also been noted. Diazoxide inhibits glucagon-stimulated insulin release and will cause a false-negative insulin response to glucagon. In the rat, dog, and monkey, diazoxide increased serum free fatty acids and decreased plasma insulin levels.

Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term animal dosing study has been done to evaluate the carcinogenic potential of diazoxide. No laboratory studies of mutagenic potential or animal studies of effects on fertility have been done.

Pregnancy Category C
Diazoxide has been shown to reduce fetal and/or pup survival; and to reduce fetal growth in rats, rabbits, and dogs at daily doses of 30, 21, or 10 mg/kg, respectively. In rats treated at term, diazoxide, at doses of 10 mg/kg and above, prolonged parturition.

The safety of HYPERSTAT I.V. Injection in pregnancy has not been established.

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

Labor and Delivery
HYPERSTAT I.V. Injection is not indicated for use in pregnancy. Intravenous administration of the drug during labor may cause cessation of uterine contractions, requiring administration of an oxytocic agent.

Nursing Mothers
Information is not available concerning the passage of HYPERSTAT in breast milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from diazoxide, 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 [#section-5 INDICATIONS AND USAGE].

ADVERSE REACTIONS
It is reasonable to speculate that the currently recommended minibolus dosing regimen, which has replaced the 300-mg bolus dose in clinical practice, will result in adverse effects which are of similar character but of lesser frequency and severity.

In clinical experience with the rapid bolus administration of 300 mg, the most common adverse reactions reported were: hypotension (7%); nausea and vomiting (4%); dizziness and weakness (2%). Additional adverse reactions reported with bolus administration of 300 mg were as follows:

Cardiovascular: sodium and water retention after repeated injections, especially important in patients with impaired cardiac reserve; hypotension to shock levels; myocardial ischemia, usually transient and manifested by angina, atrial and ventricular arrhythmias, and marked electrocardiographic changes, but occasionally leading to myocardial infarction; optic nerve infarction following too rapid decrease in severely elevated blood pressure; supraventricular tachycardia and palpitation; bradycardia; chest discomfort or nonanginal "tightness in the chest."

Central Nervous System: cerebral ischemia, usually transient but occasionally leading to infarction and manifested by unconsciousness, convulsions, paralysis, confusion, or focal neurological deficit such as numbness of the hands; vasodilative phenomena, such as orthostatic hypotension, sweating, flushing, and generalized or localized sensations of warmth; various transient neurological findings secondary to alteration in regional blood flow to brain, such as headache (sometimes throbbing), dizziness, lightheadedness, sleepiness (also reported as lethargy, somnolence or drowsiness), euphoria or "funny feeling," ringing in the ears and momentary hearing loss, and weakness of short duration; apprehension or anxiety.

Gastrointestinal: rarely, acute pancreatitis; nausea, vomiting and/or abdominal discomfort; anorexia; alteration in taste; parotid swelling; salivation; dry mouth; lacrimation; ileus; constipation and diarrhea.

Other: hyperglycemia in diabetic patients, especially after repeated injections; hyperosmolar coma in an infant; transient hyperglycemia in nondiabetic patients; transient retention of nitrogenous wastes; various respiratory finding secondary to the relaxation of smooth muscle, such as dyspnea, cough and choking sensation; warmth or pain along the injected vein; cellulitis without sloughing and/or phlebitis at the injection site of extravasation; back pain and increased nocturia; hypersensitivity reactions, such as rash, leukopenia and fever; papilledema induced by plasma volume expansion secondary to the administration of diazoxide reported in a patient who had received eleven injections (300 mg/dose) over a 22-day period; malaise and blurred vision; transient cataract in an infant; hirsutism, and decreased libido.

OVERDOSAGE
Overdosage of HYPERSTAT I.V. Injection may cause undesirable hypotension. Usually, this can be controlled with the Trendelenberg maneuver. If necessary, sympathomimetic agents, such as dopamine or norepinephrine, may be administered. Failure of blood pressure to rise in response to such agents suggests that the hypotension may have been caused by something other than diazoxide. Excessive hyperglycemia resulting from overdosage will respond to conventional therapy of hyperglycemia.

DOSAGE AND ADMINISTRATION
HYPERSTAT I.V. Injection was originally recommended for use by bolus administration of 300 mg. Recent studies have shown that minibolus administration of HYPERSTAT I.V. Injection, ie, doses of 1 to 3 mg/kg repeated at intervals of 5 to 15 minutes is as effective in reducing blood pressure. Minibolus administration usually provides a more gradual reduction in blood pressure and thus may be expected to reduce the circulatory and neurological risks associated with acute hypotension.

HYPERSTAT I.V. Injection is administered undiluted and rapidly by intravenous injections of 1 to 3 mg/kg up to a maximum of 150 mg in a single injection. This dose may be repeated at intervals of 5 to 15 minutes until a satisfactory reduction in blood pressure (diastolic pressure below 100 mmHg) has been achieved.

With the patient recumbent, the calculated dose of HYPERSTAT I.V. Injection is administered intravenously in 30 seconds or less.

HYPERSTAT I.V. Injection should only be given into a peripheral vein. Do not administer it intramuscularly, subcutaneously, or into body cavities. Avoid extravasation of the drug into subcutaneous tissues.

Following the use of HYPERSTAT I.V. Injection, the blood pressure should be monitored closely until it has stabilized. Thereafter, measurements taken hourly during the balance of the effect should indicate any unusual response. A further decrease in blood pressure 30 minutes or more after injection should be investigated for causes other than the action of HYPERSTAT I.V. Injection. It is preferable that the patient remain supine for at least 1 hour after injection. In ambulatory patients, the blood pressure should also be measured with the patient standing before surveillance is ended.

Repeated administration of HYPERSTAT I.V. Injection at intervals of 4 to 24 hours usually will maintain the blood pressure below pretreatment levels until a regimen of oral antihypertensive medication can be instituted. The interval between injections may be adjusted by the duration of the response to each injection. It is usually unnecessary to continue treatment with HYPERSTAT I.V. Injection for more than 4 to 5 days.

Since repeated administration of HYPERSTAT I.V. Injection can lead to sodium and water retention, administration of a diuretic may be necessary both for maximal blood pressure reduction and to avoid congestive heart failure. (See [#section-4 CLINICAL PHARMACOLOGY].)

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED
HYPERSTAT I.V. Injection is supplied in a 20-mL ampule, containing 300 mg diazoxide, in a clear, sterile, colorless, aqueous solution; box of one ampule (NDC 0085-0201-05).

Protect from light and freezing. Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].

                          --------------------------------------------------------------- 

二氮嗪　Diazoxide（降压嗪，氯甲苯噻嗪，HYPERSTAT）
　　【药理及应用】能松弛血管平滑肌，降低周围血管阻力，使血压急剧下降。一次快速静注本品300mg，可在5分钟内出现降压高峰，使血压降至正常水平，并可维持2～18小时或更长一些。在降压的同时，并不降低心输出量，故脑、肾、冠脉的血流量不变。适用于高血压危象的急救。

　　还能抑制胰脏β细胞分泌胰岛素，可用作升血糖药，用于幼儿特发性低血糖症、由于胰岛细胞瘤引起的严重低血糖。

　　【用法】临用时将本品溶于专用溶剂内，患者取卧位快速静注。症状缓解后再改以口服降压药维持。快速静注，1次200～400mg，在15～20秒钟内注完。抢救高血压危象时，可在0.5～3小时内再注射1次，1日总量不超过1200mg。儿童剂量：5mg／kg。

　　【注意】

　　（1）可引起水钠潴留，多次重复使用可能引起水肿、充血性心力衰竭，过量可引起低血压症甚至导致休克，均应及时予以处理。

　　（2）对糖尿病患者或多次注射本品的患者，为防止血糖上升，可用胰岛素或口服降血糖药以控制血糖。

　　（3）用药后可能出现一时性脑或心肌缺血、发热感、头痛、恶心、失眠、便秘、腹部不适感、听觉异常、静脉灼痛感等。

　　（4）充血性心力衰竭、糖尿病、肾功能不全的重型高血压患者及乳妇忌用。

　　（5）本品不宜与其他药物及输液配伍。

　　【制剂】注射用二氮嗪：每支300mg，附专用溶剂20ml。

---------------------------------------------------------------
详细处方信息以本药内容附件PDF文件（2009101307190418.PDF）的“原文     Priscribing Information”为准
---------------------------------------------------------------

更新于2010年11月11日