英文药名:Bumex(Bumetanide Tablets)

中文药名:布美他尼片

生产厂家:Leo
药品名称
通用名称：布美他尼
英文名：Bumetanide
其它中文名：便多、丁胺速尿、丁苯氧酸、丁尿胺
其它英文名：Aquazone、Bonures、Bumex、Burine、Butinat、Cambiex、Diurama、Fontego、Fordiuran、Lunetoron、Segurex
药品类别: 利尿药
药理毒理
对水和电解质排泄的作用基本同呋塞米，其利尿作用为呋塞米20～60倍。主要抑制肾小管髓袢升支厚壁段对NaCl的主动重吸收，对近端小管重吸收Na＋也有抑制作用，但对远端肾小管无作用，故排钾作用小于呋塞米。能抑制前列腺素分解酶的活性，使前列腺素E2含量升高，从而具有扩张血管作用。扩张肾血管，降低肾血管阻力，使肾血流量尤其是肾皮质深部血流量增加，在布美他尼的利尿作用中具有重要意义，也是其用于预防急性肾功能衰竭的理论基础。另外，与其他利尿药不同，袢利尿药在肾小管液流量增加的同时肾小球滤过率不下降，可能与流经致密斑的氯减少，从而减弱或阻断了球-管平衡有关。布美他尼能扩张肺部容量静脉，降低肺毛细血管通透性，加上其利尿作用，使回心血量减少，左心室舒张末期压力降低，有助于急性左心衰竭的治疗。由于布美他尼可降低肺毛细血管通透性，为其治疗成人呼吸窘迫综合征提供了理论依据。
药代动力学
口服吸收较呋塞米完全，几乎全部迅速被吸收，充血性心力衰竭和肾病综合征等水肿性疾病时，由于肠道黏膜水肿，口服吸收率下降，血浆蛋白结合率为94%~96%，口服和静脉注射的作用开始时间分别为30~60分钟和数分钟，作用达峰时间为1~2小时和15~30分钟。作用持续时间为4小时（应用1～2mg时，大剂量时为4～6小时）和3.5～4 小时。T1／2β为60~90分钟，略长于呋塞米，肝肾功能受损时延长。本药不被透析清除。77～85％经尿排泄，其中45％为原形，15～23％由胆汁和粪便排泄。本药经肝脏代谢者较少。
适应症
1.水肿性疾病包括充血性心力衰竭、肝硬化、肾脏疾病(肾炎、肾病及各种原因所致的急、慢性肾功能衰竭)，尤其是应用其他利尿药效果不佳时，应用本类药物仍可能有效。与其他药物合用治疗急性肺水肿和急性脑水肿等。
2.高血压 在高血压的阶梯疗法中，不作为治疗原发性高血压的首选药物，但当噻嗪类药物疗效不佳。尤其当伴有肾功能不全或出现高血压危象时，本类药物尤为适用。
3.预防急性肾功能衰竭用于各种原因导致肾脏血流灌注不足，例如失水、休克、中毒、麻醉意外以及循环功能不全等，在纠正血容量不足的同时及时应用，可减少急性肾小管坏死的机会。
4.高钾血症及高钙血症。
5.稀释性低血症尤其是当血钠浓度低于120mmol/L时。
6.抗利尿激素分泌过多症（SIADH）。
7.急性药物毒物中毒 如巴比妥类药物中毒等。
8.对某些呋塞米无效的病例仍可能有效。
用法用量
1.成人
治疗水肿性疾病或高血压，口服起始每日 0.5~2mg，必要时每隔4～5小时重复，最大剂量每日可达10～20mg。也可间隔用药，即隔1～2日用药1日。
2.小儿
口服一次按体重0.01～0.02mg/kg，必要时4～6小时1次。
任何疑问，请遵医嘱！
不良反应
常见者与水、电解质紊乱有关、尤其是大剂量或长期应用时，如体位性低血压、休克、低钾血症、低氯血症、低氯性碱中毒、低钠血症、低钙血症以及与此有关的口渴、乏力、肌肉酸痛、心律失常等。少见者有过敏反应(包括皮疹、甚至心脏骤停)、头晕、头痛、纳差、恶心、呕吐、腹痛、腹泻、胰腺炎、肌肉强直等，骨髓抑制导致粒细胞减少，血小板减少性紫癫和再生障碍性贫血，肝功能损害，指（趾）感觉异常，高糖血症，尿糖阳性，原有糖尿病加重，高尿酸血症。耳鸣、听力障碍多见于大剂量静脉快速注射时（每分钟剂量大于4~15mg），多为暂时性，少数为不可逆性，尤其当与其他有耳毒性的药物同时应用时。在高钙血症时，可引起肾结石。尚有报道本药可加重特发性水肿。偶见未婚男性遗精和阴茎勃起困难。大剂量时可发生肌肉酸痛、胸痛。对糖代谢的影响可能小于呋塞米。
注意事项
（1）交叉过敏。对磺胺药和噻嗪类利尿药过敏者，对本药可能亦过敏。
（2）对诊断的干扰:可致血糖升高、尿糖阳性，尤其是糖尿病或糖尿病前期患者,过度脱水可使血尿酸和尿素氮水平暂时性升高。血Na＋、Cl－、K+、 Ca2+和Mg2+浓度下降。
(3)下列情况慎用：
①无尿或严重肾功能损害者，后者因需加大剂量，故用药间隔时间应延长，以免出现耳毒性等副作用;
②糖尿病;
③高尿酸血症或有痛风病史者;
④严重肝功能损害者，因水电解质紊乱可诱发肝昏迷;
⑤急性心肌梗死，过度利尿可促发休克;
⑥胰腺炎或有此病史者；
⑦有低钾血症倾向者，尤其是应用洋地黄类药物或有室性心律失常者;
⑧前列腺肥大。
（4）随访检查:
①血电解质，尤其是合用洋地黄类药物或皮质激素类药物、肝肾功能损害者;
②血压，尤其是用于降压，大剂量应用或用于老年人;
③肾功能;
④肝功能;
⑤血糖;
⑥血尿酸;
⑦酸碱平衡情况;
⑧听力。
（5）动物实验提示本药能延缓胎儿生长和骨化。对新生儿和乳母的情况尚不清楚。能增加尿磷的排泄量，可干扰尿磷的测定。
孕妇及哺乳期妇女用药
（1）本药可通过胎盘屏障，孕妇尤其是妊娠前3个月应尽量避免应用。对妊娠高血压综合征无预防作用。动物实验表明本品可致胎仔肾孟积水，延缓胎儿生长和骨化，流产和胎仔死亡率升高。
（2）本药可经乳汁分泌，哺乳期妇女应慎用。
儿童用药
本药在新生儿的半衰期明显延长，故新生儿用药间隔应延长。
老年患者用药
老年人应用本药时发生低血压、电解质紊乱，血栓形成和肾功能损害的机会增多。
药物相互作用
（1）肾上腺糖、盐皮质激素，促肾上腺皮质激素及雌激素能降低本药的利尿作用，并增加电解质紊乱尤其是低钾血症的发生机会。
（2）非甾体类消炎镇痛药能降低本药的利尿作用，肾损害机会也增加，与前者抑制前列腺素合成，减少肾血流量有关。
（3）与拟交感神经药物及抗惊厥药物合用，利尿作用减弱。
（4）与氯贝丁酯（安妥明）合用，两药的作用均增强，并可出现肌肉酸痛、强直。
（5）与多巴胺合用，利尿作用加强。
（6）饮酒及含酒精制剂和可引起血压下降的药物能增强本药的利尿和降压作用；与巴比妥类药物、麻醉药合用，易引起体位性低血压。
（7）本药可使尿酸排泄减少，血尿酸升高，故与治疗痛风的药物合用时，后者的剂量应作适当调整。
（8）降低降血糖药的疗效。
（9）降低抗凝药物和抗纤溶药物的作用，主要是利尿后血容量下降，致血中凝血因子浓度升高，以及利尿使肝血液供应改善、肝脏合成凝血因子增多有关。
（10）本药加强非去极化肌松药的作用，与血钾下降有关。
（11）与两性霉素、头孢霉素、氨基糖苷类等抗生素合用，肾毒性和耳毒性增加，尤其是原有肾损害时。
（12）与抗组胺药物合用时耳毒性增加，易出现耳鸣、头晕、眩晕。
（13）与锂合用肾毒性明显增加，应尽量避免。
（14）服用水合氯醛后静注本药可致出汗、面色潮红和血压升高，此与甲状腺素由结合状态转为游离状态增多，导致分解代谢加强有关。
（15）与碳酸氢钠合用发生低氯性碱中毒机会增加。
规格
片剂：1mg, 5mg/片
WARNING
Bumex (bumetanide) is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required, and dose and dosage schedule have to be adjusted to the individual patient's needs (see DOSAGE AND ADMINISTRATION).
DESCRIPTION

Bumex® (bumetanide) is a loop diuretic, available as scored tablets, 0.5 mg (light green), 1 mg (yellow) and 2 mg (peach) for oral administration; each tablet also contains lactose, magnesium stearate, microcrystalline cellulose, cornstarch and talc, with the following dye systems: 0.5 mg—D&C Yellow No. 10 and FD&C Blue No. 1; 1 mg—D&C Yellow No. 10; 2 mg—red iron oxide.
Chemically, bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid. It is a practically white powder having a calculated molecular weight of 364.41, and the following structural formula:
CLINICAL PHARMACOLOGY
Bumex is a loop diuretic with a rapid onset and short duration of action. Pharmacological and clinical studies have shown that 1 mg Bumex has a diuretic potency equivalent to approximately 40 mg furosemide. The major site of Bumex action is the ascending limb of the loop of Henle.
The mode of action has been determined through various clearance studies in both humans and experimental animals. Bumex inhibits sodium reabsorption in the ascending limb of the loop of Henle, as shown by marked reduction of free-water clearance (CH2O) during hydration and tubular free-water reabsorption (TCH2O) during hydropenia. Reabsorption of chloride in the ascending limb is also blocked by Bumex, and Bumex is somewhat more chloruretic than natriuretic.
Potassium excretion is also increased by Bumex, in a dose-related fashion.
Bumex may have an additional action in the proximal tubule. Since phosphate reabsorption takes place largely in the proximal tubule, phosphaturia during Bumex induced diuresis is indicative of this additional action. This is further supported by the reduction in the renal clearance of Bumex by probenecid, associated with diminution in the natriuretic response. This proximal tubular activity does not seem to be related to an inhibition of carbonic anhydrase. Bumex does not appear to have a noticeable action on the distal tubule.
Bumex decreases uric acid excretion and increases serum uric acid. Following oral administration of Bumex the onset of diuresis occurs in 30 to 60 minutes. Peak activity is reached between 1 and 2 hours. At usual doses (1 mg to 2 mg) diuresis is largely complete within 4 hours; with higher doses, the diuretic action lasts for 4 to 6 hours. Diuresis starts within minutes following an intravenous injection and reaches maximum levels within 15 to 30 minutes.
Several pharmacokinetic studies have shown that bumetanide, administered orally or parenterally, is eliminated rapidly in humans, with a half-life of between 1 and 1½ hours. Plasma protein-binding is in the range of 94% to 96%.
Oral administration of carbon-14 labeled Bumex to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Urinary and biliary metabolites identified in this study were formed by oxidation of the N-butyl side chain. Biliary excretion of Bumex amounted to only 2% of the administered dose.
Pediatric Pharmacology
Elimination of bumetanide appears to be considerably slower in neonatal patients compared with adults, possibly because of immature renal and hepatobiliary function in this population. Small pharmacokinetic studies of intravenous bumetanide in preterm and full-term neonates with respiratory disorders have reported an apparent half-life of approximately 6 hours, with a range up to 15 hours and a serum clearance ranging from 0.2 to 1.1 mL/min/kg. In a population of neonates receiving bumetanide for volume overload, mean serum clearance rates were 2.17 mL/min/kg in patients less than 2 months of age and 3.8 mL/min/kg in patients aged 2 to 6 months. Mean serum half-life of bumetanide was 2.5 hours and 1.5 hours in patients aged less than 2 months and those aged 2 to 6 months, respectively. Elimination half-life decreased considerably during the first month of life, from a mean of approximately 6 hours at birth to approximately 2.4 hours at 1 month of age.
In preterm neonates, mean serum concentrations following a single 0.05 mg/kg dose ranged from 126 mcg/L at 1 hour to 57 mcg/L at 8 hours. In another study, mean serum concentrations following a single 0.05 mg/kg dose were 338 ng/mL at 30 minutes and 176 ng/mL after 4 hours. A single dose of 0.1 mg/kg produced mean serum levels of 314 ng/mL at 1 hour, and 195 ng/mL at 6 hours. Mean volume of distribution in neonates and infants has been reported to range from 0.26 L/kg to 0.39 L/kg.
The degree of protein binding of bumetanide in cord sera from healthy neonates was approximately 97%, suggesting the potential for bilirubin displacement. A study using pooled sera from critically ill neonates found that bumetanide at concentrations of 0.5 to 50 mcg/mL, but not 0.25 mcg/mL, caused a linear increase in unbound bilirubin concentrations.
In 56 infants aged 4 days to 6 months, bumetanide doses ranging from 0.005 mg/kg to 0.1 mg/kg were studied for pharmacodynamic effect. Peak bumetanide excretion rates increased linearly with increasing doses of drug. Maximal diuretic effect was observed at a bumetanide excretion rate of about 7 mcg/kg/hr, corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produced a higher bumetanide excretion rate but no increase in diuretic effect. Urine flow rate peaked during the first hour after drug administration in 80% of patients and by 3 hours in all patients.
Geriatric Pharmacology
In a group of ten geriatric subjects between the ages of 65 and 73 years, total bumetanide clearance was significantly lower (1.8 ± 0.3 mL/min∙kg) compared with younger subjects (2.9 ± 0.2 mL/min∙kg) after a single oral bumetanide 0.5 mg dose. Maximum plasma concentrations were higher in geriatric subjects (16.9 ± 1.8 ng/mL) compared with younger subjects (10.3 ± 1.5 ng/mL). Urine flow rate and total excretion of sodium and potassium were increased less in the geriatric subjects compared with younger subjects, although potassium excretion and fractional sodium excretion were similar between the two age groups. Nonrenal clearance, bioavailability, and volume of distribution were not significantly different between the two groups.
INDICATIONS AND USAGE
Bumex is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome.
Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route.
Successful treatment with Bumex following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity.
CONTRAINDICATIONS
Bumex is contraindicated in anuria. Although Bumex can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with Bumex. Bumex is also contraindicated in patients in hepatic coma or in states of severe electrolyte depletion until the condition is improved or corrected. Bumex is contraindicated in patients hypersensitive to this drug.
WARNINGS
Volume and Electrolyte Depletion
The dose of Bumex should be adjusted to the patient's need. Excessive doses or too frequent administration can lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume and circulatory collapse with the possibility of vascular thrombosis and embolism, particularly in elderly patients.
Hypokalemia
Hypokalemia can occur as a consequence of Bumex administration. Prevention of hypokalemia requires particular attention in the following conditions: patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis and ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, certain diarrheal states, or other states where hypokalemia is thought to represent particular added risks to the patient, ie, history of ventricular arrhythmias.
In patients with hepatic cirrhosis and ascites, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient's clinical status and electrolyte balance. Supplemental potassium and/or spironolactone may prevent hypokalemia and metabolic alkalosis in these patients.
Ototoxicity
In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity. In these test animals bumetanide was 5 to 6 times more potent than furosemide and, since the diuretic potency of bumetanide is about 40 to 60 times furosemide, it is anticipated that blood levels necessary to produce ototoxicity will rarely be achieved. The potential exists, however, and must be considered a risk of intravenous therapy, especially at high doses, repeated frequently in the face of renal excretory function impairment. Potentiation of aminoglycoside ototoxicity has not been tested for bumetanide. Like other members of this class of diuretics, bumetanide probably shares this risk.
Allergy to Sulfonamides
Patients allergic to sulfonamides may show hypersensitivity to Bumex.
Thrombocytopenia
Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia.
PRECAUTIONS
General
Serum potassium should be measured periodically and potassium supplements or potassium-sparing diuretics added if necessary. Periodic determinations of other electrolytes are advised in patients treated with high doses or for prolonged periods, particularly in those on low-salt diets.
Hyperuricemia may occur; it has been asymptomatic in cases reported to date. Reversible elevations of the BUN and creatinine may also occur, especially in association with dehydration and particularly in patients with renal insufficiency. Bumex may increase urinary calcium excretion with resultant hypocalcemia.
Diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Laboratory Tests
Studies in normal subjects receiving Bumex revealed no adverse effects on glucose tolerance, plasma insulin, glucagon and growth hormone levels, but the possibility of an effect on glucose metabolism exists. Periodic determinations of blood sugar should be done, particularly in patients with diabetes or suspected latent diabetes.
Patients under treatment should be observed regularly for possible occurrence of blood dyscrasias, liver damage or idiosyncratic reactions, which have been reported occasionally in foreign marketing experience. The relationship of these occurrences to Bumex use is not certain.
Drug Interactions
Drugs With Ototoxic Potential (see WARNINGS)
Especially in the presence of impaired renal function, the use of parenterally administered bumetanide in patients to whom aminoglycoside antibiotics are also being given should be avoided, except in life-threatening conditions.
Drugs With Nephrotoxic Potential
There has been no experience with the concurrent use of Bumex with drugs known to have a nephrotoxic potential. Therefore, the simultaneous administration of these drugs should be avoided.
Lithium
Lithium should generally not be given with diuretics (such as Bumex) because they reduce its renal clearance and add a high risk of lithium toxicity.
Probenecid
Pretreatment with probenecid reduces both the natriuresis and hyperreninemia produced by Bumex. This antagonistic effect of probenecid on Bumex natriuresis is not due to a direct action on sodium excretion but is probably secondary to its inhibitory effect on renal tubular secretion of bumetanide. Thus, probenecid should not be administered concurrently with Bumex.
Indomethacin
Indomethacin blunts the increases in urine volume and sodium excretion seen during Bumex treatment and inhibits the bumetanide-induced increase in plasma renin activity. Concurrent therapy with Bumex is thus not recommended.
Antihypertensives
Bumex may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs.
Digoxin
Interaction studies in humans have shown no effect on digoxin blood levels.
Anticoagulants
Interaction studies in humans have shown Bumex to have no effect on warfarin metabolism or on plasma prothrombin activity.
Carcinogenesis, Mutagenesis and Impairment of Fertility
Bumex was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitro metabolic activation system. An 18-month study showed an increase in mammary adenomas of questionable significance in female rats receiving oral doses of 60 mg/kg/day (2000 times a 2-mg human dose). A repeat study at the same doses failed to duplicate this finding.
Reproduction studies were performed to evaluate general reproductive performance and fertility in rats at oral dose levels of 10, 30, 60 or 100 mg/kg/day. The pregnancy rate was slightly decreased in the treated animals; however, the differences were small and not statistically significant.
Pregnancy
Teratogenic Effects
Pregnancy Category C. Bumex is neither teratogenic nor embryocidal in mice when given in doses up to 3400 times the maximum human therapeutic dose.
Bumex has been shown to be nonteratogenic, but it has a slight embryocidal effect in rats when given in doses of 3400 times the maximum human therapeutic dose and in rabbits at doses of 3.4 times the maximum human therapeutic dose. In one study, moderate growth retardation and increased incidence of delayed ossification of sternebrae were observed in rats at oral doses of 100 mg/kg/day, 3400 times the maximum human therapeutic dose. These effects were associated with maternal weight reductions noted during dosing. No such adverse effects were observed at 30 mg/kg/day (1000 times the maximum human therapeutic dose). No fetotoxicity was observed at 1000 to 2000 times the human therapeutic dose.
In rabbits, a dose-related decrease in litter size and an increase in resorption rate were noted at oral doses of 0.1 and 0.3 mg/kg/day (3.4 and 10 times the maximum human therapeutic dose). A slightly increased incidence of delayed ossification of sternebrae occurred at 0.3 mg/kg/day; however, no such adverse effects were observed at the dose of 0.03 mg/kg/day. The sensitivity of the rabbit to Bumex parallels the marked pharmacologic and toxicologic effects of the drug in this species.
Bumex was not teratogenic in the hamster at an oral dose of 0.5 mg/kg/day (17 times the maximum human therapeutic dose). Bumetanide was not teratogenic when given intravenously to mice and rats at doses up to 140 times the maximum human therapeutic dose.
There are no adequate and well-controlled studies in pregnant women. A small investigational experience in the United States and marketing experience in other countries to date have not indicated any evidence of adverse effects on the fetus, but these data do not rule out the possibility of harmful effects. Bumex should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while the patient is on Bumex since it may be excreted in human milk.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 18 have not been established.
In vitro studies using pooled sera from critically ill neonates have shown bumetanide to be a potent displacer of bilirubin (see CLINICAL PHARMACOLOGY: Pediatric Pharmacology). The administration of bumetanide could present a particular concern if given to critically ill or jaundiced neonates at risk for kernicterus.
Geriatric Use
Clinical studies of Bumex did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
ADVERSE REACTIONS
The most frequent clinical adverse reactions considered probably or possibly related to Bumex are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%) and encephalopathy (in patients with preexisting liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with Bumex.
Less frequent clinical adverse reactions to Bumex are impaired hearing (0.5%), pruritus (0.4%), electrocardiogram changes (0.4%), weakness (0.2%), hives (0.2%), abdominal pain (0.2%), arthritic pain (0.2%), musculoskeletal pain (0.2%), rash (0.2%) and vomiting (0.2%). One or more of these adverse reactions have been reported in approximately 2.9% of patients treated with Bumex.
Other clinical adverse reactions, which have each occurred in approximately 0.1% of patients, are vertigo, chest pain, ear discomfort, fatigue, dehydration, sweating, hyperventilation, dry mouth, upset stomach, renal failure, asterixis, itching, nipple tenderness, diarrhea, premature ejaculation and difficulty maintaining an erection.
Laboratory abnormalities reported have included hyperuricemia (in 18.4% of patients tested), hypochloremia (14.9%), hypokalemia (14.7%), azotemia (10.6%), hyponatremia (9.2%), increased serum creatinine (7.4%), hyperglycemia (6.6%), and variations in phosphorus (4.5%), CO2 content (4.3%), bicarbonate (3.1%) and calcium (2.4%). Although manifestations of the pharmacologic action of Bumex, these conditions may become more pronounced by intensive therapy.
Also reported have been thrombocytopenia (0.2%) and deviations in hemoglobin (0.8%), prothrombin time (0.8%), hematocrit (0.6%), WBC (0.3%) and differential counts (0.1%). There have been rare spontaneous reports of thrombocytopenia from postmarketing experience.
Diuresis induced by Bumex may also rarely be accompanied by changes in LDH (1.0%), total serum bilirubin (0.8%), serum proteins (0.7%), SGOT (0.6%), SGPT (0.5%), alkaline phosphatase (0.4%), cholesterol (0.4%) and creatinine clearance (0.3%). Increases in urinary glucose (0.7%) and urinary protein (0.3%) have also been seen.
OVERDOSAGE
Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.
DOSAGE AND ADMINISTRATION
Dosage should be individualized with careful monitoring of patient response.
Oral Administration
The usual total daily dosage of Bumex is 0.5 mg to 2 mg and in most patients is given as a single dose.
If the diuretic response to an initial dose of Bumex is not adequate, in view of its rapid onset and short duration of action, a second or third dose may be given at 4- to 5-hour intervals up to a maximum daily dose of 10 mg. An intermittent dose schedule, whereby Bumex is given on alternate days or for 3 to 4 days with rest periods of 1 to 2 days in between, is recommended as the safest and most effective method for the continued control of edema. In patients with hepatic failure, the dosage should be kept to a minimum and, if necessary, dosage increased very carefully.
Because cross-sensitivity with furosemide has rarely been observed, Bumex can be substituted at approximately a 1:40 ratio of Bumex to furosemide in patients allergic to furosemide.
Parenteral Administration
Bumetanide injection may be administered parenterally (IV or IM) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical.
Parenteral treatment should be terminated and oral treatment instituted as soon as possible.
HOW SUPPLIED
Tablets, 0.5 mg (light green), bottles of 100 (NDC 0004-0125-01) and 5000 (NDC 0004-0125-11); 1 mg (yellow), bottles of 100 (NDC 0004-0121-01), 500 (NDC 0004-0121-14) and 5000 (NDC 0004-0121-11); 2 mg (peach), bottles of 100 (NDC 0004-0162-01) and 5000 (NDC 0004-0162-11).
Imprint on tablets: 0.5 mg–ROCHE BUMEX 0.5; 1 mg–ROCHE BUMEX 1; 2 mg–ROCHE BUMEX 2.
Store tablets at 59° to 86°F (15° to 30°C).