应用硝普钠注意事项.doc

注射用硝普钠硝普钠为鲜红色透明粉末状结晶，易溶于水，液体呈褐色性质不稳定，放置后或遇光时易分解，使高铁离子(Fe3+) 变为低铁离子(Fe2+)，液体变为蓝色。由于其作用迅速，而且消失也快，是治疗高血压急症及急性左心衰竭的常用药物。应用硝普钠注意事项(1)肾功能不全而本品应用超过4872小时者，每天须测定血浆中氰化物或硫氰酸盐，保持硫氰酸盐不超过100g/ml；氰化物不超过3mol/ml。(2) 下列情况慎用：脑血管或冠状动脉供血不足；麻醉中控制性降压时，应先纠正贫血或低血容量；脑病或其他颅内压增高；肝、肾功能不全；甲状腺功能过低；肺功能不全；维生素B12缺乏。(3) 老年人用本品须注意增龄时肾功能减退对本品排泄的影响，老年人对降压反应也比较敏感，故用量宜酌减。(4) 本品不可静脉注射，应缓慢点滴或使用微量输液泵。(5) 在用药期间，应经常监测血压，急性心肌梗死患者使用本品时须监测肺动脉舒张压或嵌压。(6) 药液有局部刺激性，谨防外渗。(7) 如静脉滴注已达每分钟10g/kg，经10分钟降压仍不满意，应考虑停用本品。(8) 左心衰竭伴低血压时，应用本品须同时加用心肌正性肌力药如多巴胺或多巴酚丁胺。 (9)偶尔出现耐药性，视为氰化物中毒先兆，减慢滴速即可消失。硫氰酸盐中毒或逾量时，可出现运动失调、视力模糊、谵妄、眩晕、头痛、意识丧失、恶心、呕吐、耳鸣、气短；氰化物中毒或超极量时，可出现反射消失、昏迷、心音遥远、低血压、脉搏消失、皮肤粉红色、呼吸浅、瞳孔散大。恶心、呕吐、头痛、食欲不振、皮疹、出汗、药热、剂量过大出现血压下降，可引起重要器官供血不足。长期使用有硫氰酸盐中毒症状，严重过量可致昏迷、死亡。过量则出现严重的低血压并可引起冠状动脉或脑血管灌注减低而产生严重后果。 因此，在不能连续监测心脏的情况下，尽量避免应用硝普钠。其他不良反应与此药降解为氰化物有关。假若剂量大或长期高速滴入，则氰化物蓄积可导致组织缺氧、代谢性酸中毒及死亡，特别是肾功能减退的患者。如同时输入维生素B12，则可防止这些不良反应。小剂量长期用硝普钠几天后，可导致硫氰酸盐中毒，表现为甲状腺功能低下、头痛、 食欲不振、恶心、呕吐及无力，并发展为昏迷及死亡。正铁血红蛋白血症是很少见的并发病。 硝普钠所含的亚铁离子与红细胞内的巯基化合物迅速结合成氰化物，在血液中停留时间很短，在肝脏内迅速代谢成硫氰酸盐，血浆硫氰酸盐浓度大于10mg/L，为硝普钠中毒的指标。硫氰酸盐中毒多见于老人、肾功能不全或长期（超过3天）较大剂量给药时，在这些情况下，临床应注意观察硫氰酸盐中毒的症状，并监测血硫氰酸盐浓度。临床症状：出现神经系统抑制、代谢性酸中毒及心血管系统不稳定等应考虑为氰化物或硫氰酸盐中毒，须立即停药，给予支持治疗以及解毒剂。常用解毒荆有：亚硝酸钠、亚甲蓝、硫代硫酸钠及羟钴胺等。硝普钠应用3d应监测硫氰酸盐血浓度，也应监测氰化物血浓度。硫代硫酸钠与硝普钠联用可预防氰化物毒性反应。伴有肾损害的患者可用非诺多泮代替硝普钠。 硫氰酸钠检测-分子式：NaSCN 硫氰酸钠中毒病理分析硫氰酸钠(NaSCN) 是白色斜方晶系结晶或粉末,毒害品。易溶于水、乙醇和丙酮。硫氰酸钠的毒性主要由其在体内释放的氰根离子而引起。氰根离子在体内能很快与细胞色素氧化酶中的三价铁离子结合, 抑制该酶活性, 使组织不能利用氧。氰根离子所致的急性中毒分为轻、中、重三级。轻度中毒表现为眼及上呼吸道刺激症状, 有苦杏仁味, 口唇及咽部麻木, 继而可出现恶心、呕吐、震颤等；中度中毒表现为叹息样呼吸, 皮肤、黏膜常呈鲜红色,其他症状加重；重度中毒表现为意识丧失, 出现强直性和阵发性抽搐, 直至角弓反张, 血压下降, 尿、便失禁, 常伴发脑水肿和呼吸衰竭。原料乳或奶粉中掺入硫氰酸钠后可有效的抑菌、保鲜, 是不法奶户的掺假物质之一。但硫氰酸钠是毒害品, 少量的食入就会对人体造成极大伤害。卫生部发布的食品中可能违法添加的非食用物质和易滥用的食品添加剂品种名单（第一批）中明确规定乳及乳制品中硫氰酸钠属于违法添加物质。甲磺酸非诺多泮及注射剂 项目简介 : 【药理作用】 非诺多泮是一快速作用的血管扩张剂，是 DA1 受体激动剂，与 2- 肾上腺素受体有中度结合力，与 DA2 、 1 和 肾上腺素受体、 5HT1 和 5HT2 受体或毒覃碱受体没有明显亲和力。非诺多泮是一种消旋混合物， R 异构体具有生物活性。 R- 异构体与 DA1 受体的亲和力较 S- 异构体高 250 倍。非诺多泮研究中，本品对突触前 DA2 受体、 或 - 肾上腺素受体没有亲和力，对血管紧张素转化酶也无活性。非诺多泮可以增加去甲肾上腺素的血浆浓度。 本品主要刺激 DA1 受体诱导小动脉扩张。既可降低动脉压，又可扩张肾血管致肾血流增加。此外，本品作用于肾小细胞，具有直接的促尿钠排泄和利尿特性，特别是对高血压病人此作用更为明显。 本品静脉注射起效时间约为 5 分钟，约 20 分钟达到稳态血药浓度，经肝脏迅速代谢为无活性代谢产物，而后大部分由尿排泄，血浆清除半衰期约为 5 分钟。 【适应症】 严重高血压的紧急短期处理。 项目概述： 一项随机双盲、安慰剂 对照研究中， 32 名轻中度原发性高血压患者（舒张期血压在 95-119mmHg 之间）分为 5 组，患者的平均基础血压 154/98mmHg ，心率为 75 下 / 分钟，以恒定的速率静脉滴注非诺多泮，收缩期和舒张期血压产生剂量相关性减少。以固定速率滴注 48 小时。所有滴速均快速产生反应，所有试验组中 15 分钟产生的效应是 1 小时时产生效应的 50 100 。在两个高剂量组中 48 小时时产生部分耐受，但是实质性影响持续至 48 小时。当滴注停止后血压渐渐恢复至治疗前水平，并未出现反跳现象。这一研究表明以 0.8g/kg/min 的速率滴注并不比 0.4g/kg/min 速率滴注反应强。 一项多中心、随机、双盲比较试验中， 94 名高血压急症患者（定义为舒张压 120mmHg ，伴有末端器官损害，包括心血管、肾脏、大脑和视网膜系统）以 4 种速率（ 0.01 、 0.03 、 0.1 、 0.3g/kg/min ）静脉滴注非诺多泮 24 小时。如果临床允许，在滴注后 1 小时滴速可加倍。结果显示收缩压和舒张压出现剂量依赖性快速降低，心率增加。 一项有 153 例严重高血压（舒张压 16kPa ）病人参与的随机开放性多中心研究发现，本品与硝普钠疗效相仿。本品灌注引起的剂量相关性动脉压降低可达 24 小时，未见耐受性方面的不良反应，也未见停药反跳现象和明显的心率变化。对某些严重高血压伴肾功能损害的病人，本品可改善其肾功能。本品还可降低接受心脏或非心脏外科手术病人的术后高血压，能维持或增加排尿量。 市场分析: 近些年，严重高血压的治疗在临床上越来越受到关注和重视，成为心血管科医生和新药开发机构研究的重要目标。目前，国内临床上常用的此类药物主要是硝普钠。但是，硝普钠在临床使用过程中存在很多问题，给患者和医生带来极大的不方便。如在使用硝普钠过程中可出现不同程度的恶心、呕吐、精神不安、肌肉痉挛、头痛、厌食、皮疹、出汗、发热等。长期或大量使用，特别是在肾功能衰竭病人中，可能引起硫氰化物蓄积而导致甲状腺功能减退，甚至出现险峻的低血压症。突然停药可出现反跳现象。再加上硝普钠性质不稳定，使用过程中见光易变质，这些缺点在很大程度上限制了它的使用。而非诺多泮由于性质稳定、疗效可靠，安全性高、不良反应甚微等优势在上市后的短短两年间就被收载进了美国药典（ USP ） 24 版（ 2000 年）增补版。总之，随着严重高血压的发病人群不断扩增，随着人们对严重高血压的认识不断加深，非诺多泮必将作为治疗该病的一线药物取代硝普钠的市场。知识产权情况 : 与该产品化合物有关的专利最早由 Smithkline 公司于 1981 年 1 月在欧洲申请，专利号为 EP22330 ，优先权国为美国。此后在欧美等多个国家申请专利。但是，该产品化合物没有在中国申请专利。同时，也不存在行政保护问题。 甲磺酸非诺多泮注射液(FENOLDOPAM MESYLATE)关键字：甲磺酸非诺多泮注射液中文名称：甲磺酸非诺多泮中文别名：6-氯-2,3,4,5-四氢-1-(4-羟苯基)-1H-3-苯并氮杂卓-7,8-二醇甲磺酸盐英文名称：Fenoldopam mesylate英文别名：8-Chloro-2-(4-hydroxyphenyl)-4-azabicyclo5.4.0undeca-7,9,11-triene-9,10-diol methanesulphonate用途：非诺多泮可以增加去甲肾上腺素的血浆浓度。主要刺激DA1受体诱导小动脉扩张。既可降低动脉压，又可扩张肾血管致肾血流增加。药理作用：非诺多泮是一快速作用的血管扩张剂，是 DA1 受体激动剂，与 2- 肾上腺素受体有中度结合力，与 DA2 、 1 和 肾上腺素受体、 5HT1 和 5HT2 受体或毒覃碱受体没有明显亲和力。非诺多泮是一种消旋混合物， R 异构体具有生物活性。 R- 异构体与 DA1 受体的亲和力较 S- 异构体高 250 倍。非诺多泮研究中，本品对突触前 DA2 受体、 或 - 肾上腺素受体没有亲和力，对血管紧张素转化酶也无活性。非诺多泮可以增加去甲肾上腺素的血浆浓度。本品主要刺激 DA1 受体诱导小动脉扩张。既可降低动脉压，又可扩张肾血管致肾血流增加。此外，本品作用于肾小细胞，具有直接的促尿钠排泄和利尿特性，特别是对高血压病人此作用更为明显。本品静脉注射起效时间约为 5 分钟，约 20 分钟达到稳态血药浓度，经肝脏迅速代谢为无活性代谢产物，而后大部分由尿排泄，血浆清除半衰期约为 5 分钟。适应症：严重高血压的紧急短期处理。项目概述：一项随机双盲、安慰剂 对照研究中， 32 名轻中度原发性高血压患者（舒张期血压在 95-119mmHg 之间）分为 5 组，患者的平均基础血压 154/98mmHg ，心率为 75 下 / 分钟，以恒定的速率静脉滴注非诺多泮，收缩期和舒张期血压产生剂量相关性减少。以固定速率滴注 48 小时。所有滴速均快速产生反应，所有试验组中 15 分钟产生的效应是 1 小时时产生效应的 50 100 。在两个高剂量组中 48 小时时产生部分耐受，但是实质性影响持续至 48 小时。当滴注停止后血压渐渐恢复至治疗前水平，并未出现反跳现象。这一研究表明以 0.8g/kg/min 的速率滴注并不比 0.4g/kg/min 速率滴注反应强。一项多中心、随机、双盲比较试验中， 94 名高血压急症患者（定义为舒张压 120mmHg ，伴有末端器官损害，包括心血管、肾脏、大脑和视网膜系统）以 4 种速率（ 0.01 、 0.03 、 0.1 、 0.3g/kg/min ）静脉滴注非诺多泮 24 小时。如果临床允许，在滴注后 1 小时滴速可加倍。结果显示收缩压和舒张压出现剂量依赖性快速降低，心率增加。一项有 153 例严重高血压（舒张压 16kPa ）病人参与的随机开放性多中心研究发现，本品与硝普钠疗效相仿。本品灌注引起的剂量相关性动脉压降低可达 24 小时，未见耐受性方面的不良反应，也未见停药反跳现象和明显的心率变化。对某些严重高血压伴肾功能损害的病人，本品可改善其肾功能。本品还可降低接受心脏或非心脏外科手术病人的术后高血压，能维持或增加排尿量。市场分析：近些年，严重高血压的治疗在临床上越来越受到关注和重视，成为心血管科医生和新药开发机构研究的重要目标。目前，国内临床上常用的此类药物主要是硝普钠。但是，硝普钠在临床使用过程中存在很多问题，给患者和医生带来极大的不方便。如在使用硝普钠过程中可出现不同程度的恶心、呕吐、精神不安、肌肉痉挛、头痛、厌食、皮疹、出汗、发热等。长期或大量使用，特别是在肾功能衰竭病人中，可能引起硫氰化物蓄积而导致甲状腺功能减退，甚至出现险峻的低血压症。突然停药可出现反跳现象。再加上硝普钠性质不稳定，使用过程中见光易变质，这些缺点在很大程度上限制了它的使用。而非诺多泮由于性质稳定、疗效可靠，安全性高、不良反应甚微等优势在上市后的短短两年间就被收载进了美国药典（ USP ） 24 版（ 2000 年）增补版。总之，随着严重高血压的发病人群不断扩增，随着人们对严重高血压的认识不断加深，非诺多泮必将作为治疗该病的一线药物取代硝普钠的市场。原产地英文商品名:FENOLDOPAM(Corlopam GENERIC)10mg/ml/ampule原产地英文药品名:FENOLDOPAM MESYLATE原产地英文化合物名称:8-Chloro-2-(4-hydroxyphenyl)-4-azabicyclo5.4.0undeca-7,9,11-triene-9,10-diol methanesulphonate中文参考商品译名:非诺多泮(Corlopam仿制药)10毫克/毫升/安醅中文参考药品译名:甲磺酸非诺多泮中文参考化合物名称:6-氯-2,3,4,5-四氢-1-(4-羟苯基)-1H-3-苯并氮杂卓-7,8-二醇甲磺酸盐FenoldopamGeneric Name: Fenoldopam mesylateDosage Form: injectionFenoldopam MESYLATE INJECTION USPRx ONLYFenoldopam Description Fenoldopam Mesylate Injection USP is a dopamine D1-like receptor agonist. The product is formulated as a solution to be diluted for intravenous infusion. Chemically it is 6-chloro-2,3,4,5-tetrahydro-1-(p-hydroxy-phenyl)-1H-3-benzazepine-7,8-diol methanesulfonate (salt) with the following structure:Fenoldopam mesylate is a white to off-white powder with a molecular weight of 401.87 and a molecular formula of C17H20CINO6S. It is sparingly soluble in water, ethanol and methanol, and is soluble in propylene glycol.Each mL contains, in sterile aqueous solution, citric acid 3.44 mg; Fenoldopam mesylate equivalent to Fenoldopam 10 mg; propylene glycol 518 mg; sodium citrate dihydrate 0.61 mg; sodium metabisulfite 1 mg. The pH range is 2.8 to 3.8.Fenoldopam - Clinical PharmacologyMechanism of ActionFenoldopam is a rapid-acting vasodilator. It is an agonist for D1-like dopamine receptors and binds with moderate affinity to 2-adrenoceptors. It has no significant affinity for D2-like receptors, 1 and adrenoceptors, 5HT1 and 5HT2 receptors, or muscarinic receptors. Fenoldopam is a racemic mixture with the R-isomer responsible for the biological activity. The R-isomer has approximately 250-fold higher affinity for D1-like receptors than does the S-isomer. In non-clinical studies, Fenoldopam had no agonist effect on presynaptic D2-like dopamine receptors, or - or -adrenoceptors, nor did it affect angiotensin-converting enzyme activity. Fenoldopam may increase norepinephrine plasma concentration.In animals, Fenoldopam has vasodilating effects in coronary, renal, mesenteric and peripheral arteries. All vascular beds, however, do not respond uniformly to Fenoldopam. Vasodilating effects have been demonstrated in renal efferent and afferent arterioles.PharmacokineticsAdult Patients: Fenoldopam, administered as a constant infusion at dosages of 0.01 to 1.6 mcg/kg/min, produced steady-state plasma concentrations that were proportional to infusion rates. The elimination half-life was about 5 minutes in mild to moderate hypertensives, with little difference between the R (active) and S isomers. Steady state concentrations are attained in about 20 minutes (4 half-lives). The steady state plasma concentrations of Fenoldopam, at comparable infusion rates, were similar in normotensive subjects and in patients with mild to moderate hypertension or hypertensive emergencies.The pharmacokinetics of Fenoldopam were not influenced by age, gender, or race in adult patients with a hypertensive emergency. There have been no formal drug-drug interaction studies using intravenous Fenoldopam. Clearance of parent (active) Fenoldopam is not altered in adult patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD) and is not altered in adult patients with severe hepatic failure. The effects of hemodialysis on the pharmacokinetics of Fenoldopam have not been evaluated.Pediatric Patients: Information related to the pharmacokinetics of Fenoldopam injection in pediatric patients is approved for Abbott Laboratories Fenoldopam drug products. However, due to Abbotts marketing exclusivity rights, this drug product is not labeled for pediatric use.In radiolabeled studies in rats, no more than 0.005% of Fenoldopam crossed the blood-brain barrier.Excretion and MetabolismRadiolabeled studies show that about 90% of infused Fenoldopam is eliminated in urine, 10% in feces. Elimination is largely by conjugation, without participation of cytochrome P-450 enzymes. The principal routes of conjugation are methylation, glucuronidation, and sulfation. Only 4% of the administered dose is excreted unchanged. Animal data indicate that the metabolites are inactive.Pharmacodynamics and Clinical StudiesAdult Patients: In a randomized double-blind, placebo-controlled, 5-group study in 32 patients with mild to moderate essential hypertension (diastolic blood pressure between 95 and 119 mm Hg), and a mean baseline pressure of about 154/98 mm Hg, and heart rate of about 75 bpm, fixed-rate IV infusions of Fenoldopam mesylate produced dose-related reductions in systolic and diastolic blood pressure. Infusions were maintained at a fixed rate for 48 hours. Table 1 shows the results of the study. The onset of response was rapid at all infusion rates, with the 15-minute response representing 50 to 100% of the one-hour response in all groups. There was some suggestion of partial tolerance at 48 hours in the two higher dose infusions, but a substantial effect persisted through 48 hours. When infusions were stopped, blood pressure gradually returned to pretreatment values with no evidence of rebound. This study suggests that there is no greater response to 0.8 mcg/kg/min than to 0.4 mcg/kg/min.Table 1 PHARMACODYNAMIC EFFECTS OF Fenoldopam IN MILD TO MODERATE ADULT HYPERTENSIVE PATIENTSMean change from time zero SETime Point and MeanChange From Time Zero SEDrug Dosage (mcg/kg/min)Placebon=70.04n=70.1n=70.4n=50.8n=615 Minutes of InfusionSystolic BP06-156-198-144-246Diastolic BP02-53-124-153204Heart rate+22+32+51+163+19330 Minutes of InfusionSystolic BP-65-176-186-148-266Diastolic BP-63-73-164-143-202Heart rate+22+32+102+183+2331 Hour of InfusionSystolic BP-154-227-227-269-229Diastolic BP-53-92-184-194-211Heart rate+13+52+123+194+2544 Hours of InfusionSystolic BP-145-169-3115-2211-257Diastolic BP-148-84-199-253-201Heart rate+53+63+104+212+27724 Hours of InfusionSystolic BP-206-238-357-226-2311Diastolic BP-116-115-2310-225-133Heart rate+63+53+132+174+15348 Hours of InfusionSystolic BP-128-316-228-96-1410Diastolic BP-95-106-97-92-93Heart rate+1204+14+123+83 In a multicenter, randomized, double-blind comparison of four infusion rates, Fenoldopam mesylate was administered as constant rate infusions of 0.01, 0.03, 0.1 and 0.3 mcg/kg/min for up to 24 hours to 94 adult patients experiencing hypertensive emergencies (defined as diastolic blood pressure 120 mm Hg with evidence of compromise of end-organ function involving the cardiovascular, renal, cerebral or retinal systems). Infusion rates could be doubled after one hour if clinically indicated. There were dose-related, rapid-onset, decreases in systolic and diastolic blood pressures and increases in heart rate (Table 2).Table 2 PHARMACODYNAMIC EFFECTS OF Fenoldopam IN ADULT HYPERTENSIVE EMERGENCY PATIENTSMean change from baseline SETime Point and PharmacodynamicParametersDrug Dosage (mcg/kg/min)0.01n=250.03n=240.1n=220.3n=23Pre-Infusion BaselineSystolic BP- meanSE21021208262052421117Diastolic BP- meanSE13616135111331413615Heart rate- meanSE872084148119801415 Minutes of InfusionSystolic BP-54-74-164-194Diastolic BP-53-83-122-212Heart rate-23+11+21+11230 Minutes of InfusionSystolic BP-64-114-213-164Diastolic BP-103-123-173-202Heart rate-23-11+32+1231 Hour of Infusio nSystolic BP-53-94-194-224Diastolic BP-83-133-182-232Heart rate-1302+32+1134 Hours of Infusio nSystolic BP-144-205-234-374Diastolic BP-123-183-213-293Heart rate-2402+42+112Two hundred and thirty six severely hypertensive adult patients (DBP 120 mm Hg), with or without end-organ compromise, were randomized to receive in two open-label studies either Fenoldopam or nitroprusside. The response rate was 79% (92/117) in the Fenoldopam group and 77% (90/119) in the nitroprusside group. Response required a decline in supine diastolic blood pressure to less than 110 mm Hg if the baseline were between 120 and 150 mm Hg, inclusive, or by 40 mm Hg if the baseline were 150 mm Hg. Patients were titrated to the desired effect. For Fenoldopam, the dose ranged from 0.1 to 1.5 mcg/kg/min; for nitroprusside, the dose ranged from 1.0 to 8.0 mcg/kg/min. As in the study in mild to moderate hypertensives, most of the effect seen at one hour is present at 15 minutes. The additional effect seen after 1 hour occurs in all groups and may not be drug-related (there was no placebo group for evaluation).Pediatric Patients: Information related to the pharmacodynamics of Fenoldopam injection in pediatric patients is approved for Abbott Laboratories Fenoldopam drug products. However, due to Abbotts marketing exclusivity rights, this drug product is not labeled for pediatric use.Indications and Usage for FenoldopamAdult Patients: Fenoldopam is indicated for the in-hospital, short-term (up to 48 hours) management of severe hypertension when rapid, but quickly reversible, emergency reduction of blood pressure is clinically indicated, including malignant hypertension with deteriorating end-organ function. Transition to oral therapy with another agent can begin at anytime after blood pressure is stable during Fenoldopam mesylate infusion.Pediatric Patients: Information related to the indicated use of Fenoldopam injection in pediatric patients is approved for Abbott Laboratories Fenoldopam drug products. However, due to Abbotts marketing exclusivity rights, this drug product is not labeled for pediatric use.ContraindicationsNone known.WarningsContains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.PrecautionsIntraocular PressureIn a clinical study of 12 patients with open-angle glaucoma or ocular hypertension (mean baseline intraocular pressure was 29.2 mm Hg with a range of 22 to 33 mm Hg), infusion of Fenoldopam mesylate at escalating doses ranging from 0.05 to 0.5 mcg/kg/min over a 3.5 hour period caused a dose-dependent increase in intraocular pressure (IOP). At the peak effect, the intraocular pressure was raised by a mean of 6.5 mm Hg (range -2 to +8.5 mm Hg, corrected for placebo effect). Upon discontinuation of the Fenoldopam mesylate infusion, the IOP returned to baseline values within 2 hours. Fenoldopam mesylate administration to patients with glaucoma or intraocular hypertension should be undertaken with caution.TachycardiaFenoldopam mesylate causes a dose-related tachycardia (Table 2), particularly with infusion rates above 0.1 mcg/kg/min. Tachycardia in adults diminishes over time but remains substantial at higher doses. Tachycardia in pediatric patients at doses 0.8 mcg/kg/min persists at least for 4 hours.HypotensionFenoldopam mesylate may occasionally produce symptomatic hypotension and close monitoring of blood pressure during administration is essential. (See ADVERSE REACTIONS.) It is particularly important to avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or hemorrhage. In pediatric patients, Fenoldopam mesylate was only administered to patients with an indwelling intraarterial line.Hypokalemia Decreases in serum potassium occasionally to values below 3 mEq/L were observed after less than 6 hours of Fenoldopam infusion. It is not clear if the hypokalemia reflects a pressure natriuresis with enhanced potassium-sodium exchange or a direct drug effect. During clinical trials, electrolytes were monitored at intervals of 6 hours. Hypokalemia was treated with either oral or intravenous potassium supplementation. Patient management should include appropriate attention to serum electrolytes.Intracranial PressureThe effect of Fenoldopam in the presence of increased intracranial pressure has not been studied.Drug Interactions with Beta-BlockersConcomi