奈西立肽

中文名称：奈西立肽 

中文别名：醋酸人脑利钠肽；醋酸奈西立肽；利钠肽；脑促尿钠排泄肽

英文名称：Nesiritide acetate

奈西立肽是一类抗心功能不全的药物。是利用重组DNA技术合成的B型利钠肽。通过与利钠钛受体结合。奈西立肽具有明确的扩血管和排钠利尿作用。临床研究表明，这是一个疗效显著、起效快、不良反应少的治疗急性心衰的新药，可改善心衰病人的血流动力学和临床症状。 [1] 

药理作用

奈西立肽为人工合成的基因重组人B型利钠肽（recombined human B-type natriuretic peptide，rhBNP），与心室肌分泌的天然利钠肽具有相同的32个氨基酸序列。奈西立肽能与血管平滑肌和内皮细胞上的鸟苷酸环化酶受体结合，增加细胞内的cGMP的含量，cGMP作为第二信使使动静脉扩张。研究显示，奈西立肽能使内皮素Ⅰ或α-肾上腺素受体激动剂处理的离体人动脉和静脉舒张。在人体，奈西立肽能剂量依赖性降低心衰患者肺毛细血管嵌楔压（pulmonary capillarywedge pressure，PCWP）和动脉压力。

药代动力学

与细胞表面的消除受体结合，被细胞溶酶体酶分解；被肽类内肽酶（如血管表面的中性肽链内切酶）溶蛋白性分解；经肾脏滤过。

适应证

奈西立肽用于急性代偿失调性充血性心力衰竭伴休息时或轻微活动时呼吸困难的患者，降低肺毛细血管嵌楔压，改善呼吸困难症状。

禁忌证

1．对奈西立肽及其中任何成分过敏的患者禁用。

2．收缩压≤90mmHg的患者禁用。

3．心源性休克的患者禁用。

4．奈西立肽不适宜心脏瓣膜狭窄、限制或阻塞性心肌病、缩窄性心包炎、心包填塞等患者。

5．已知或怀疑心脏充盈压低的患者避免使用。

注意事项

1．奈西立肽可引起低血压，舒张压低于100mmHg的患者慎用。孕妇用药安全性尚未确立，孕妇慎用。奈西立肽是否通过乳汁分泌尚不清楚，哺乳期妇女慎用。

2．尚无儿童应用奈西立肽安全性和有效性的研究资料。

3．肾功能不足的患者不需调整剂量。

4．奈西立肽对肺毛细血管嵌楔压、心排血指数、收缩压的影响与肾功能不足（基线血清肌酐的范围2～4.3mg/dl）及正常肾功能的患者没有明显差异。

5．奈西立肽的清除与患者的体重成正比，应根据患者的千克体重调整剂量。

6．奈西立肽应新鲜配制，配制的药液2～8℃可保存24h。

7．室温保存。 [3] 

不良反应

奈西立肽不良反应为低血压、心动过速、房颤、窦房结传导阻滞、注射部位反应、发热、感觉异常、嗜睡、咳嗽、咯血、出汗、腿痛性痉挛、皮疹、皮肤瘙痒、弱视、贫血等。 [4] 

用法用量

初始剂量为2mg/kg静注，然后以0.01mg/（kg·min）静滴。初始剂量不能超过推荐剂量。将奈西立肽1.5mg用5%葡萄糖注射液或0.9%氯化钠注射液或5%葡萄糖氯化氯化氯化钠注射液5ml溶解后，加入到250ml上述液体中静滴。 [3] 

药物的相互作用

1．奈西立肽与肝素、胰岛素、利尿酸钠、布美他尼、依那普利、肼屈嗪、呋塞米等混合可产生理化反应，静滴时不能用同一输液管。

2．奈西立肽可与肝素钠结合，使用含肝素的注射器可降低奈西立肽的作用。

3．奈西立肽与血管紧张素转化酶抑制剂合用，易导致症状性低血压。

4．奈西立肽与亚硫酸钠存在配伍禁忌，含亚硫酸钠作为防腐剂的注射剂不能与奈西立肽同时输注。

5．对于难治性心力衰竭，联合用药奈西立肽和托伐普坦可显著改善患者症状 [5] 

剂型与规格

注射剂：1.5mg(含奈西立肽1.58mg，枸橼酸2.1mg，枸橼酸钠二水合物294mg)。

Generic Name: Nesiritide  

Brand Name: Natrecor

Medically reviewed on May 2, 2018

Index Terms

· B-type Natriuretic Peptide (Human)

· hBNP

· Natriuretic Peptide

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Natrecor: 1.5 mg (1 ea)

Brand Names: U.S.

· Natrecor

Pharmacologic Category

· Natriuretic Peptide, B-Type, Human

Pharmacology

Binds to guanylate cyclase receptor on vascular smooth muscle and endothelial cells, increasing intracellular cyclic GMP, resulting in smooth muscle cell relaxation. Has been shown to produce dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure.

Distribution

Vss: 0.19 L/kg

Metabolism

Proteolytic cleavage by vascular endopeptidases and proteolysis following binding to the membrane bound natriuretic peptide (NPR-C) and cellular internalization

Excretion

Primarily eliminated by metabolism; also excreted in the urine

Onset of Action

PCWP reduction: 15 minutes (60% of 3-hour effect achieved within this time period); Peak effect: Within 1 hour

Duration of Action

>60 minutes (up to several hours) for systolic blood pressure; hemodynamic effects persist longer than serum half-life would predict

Half-Life Elimination

Initial (distribution) ~2 minutes; Terminal: ~18 minutes

Use: Labeled Indications

Acutely decompensated heart failure (HF): Treatment of acutely decompensated heart failure (HF) with dyspnea at rest or with minimal activity

Contraindications

Hypersensitivity to natriuretic peptide or any component of the formulation; cardiogenic shock (when used as primary therapy); hypotension (persistent systolic blood pressure <100 mm Hg) prior to therapy

Dosing: Adult

Acute decompensated heart failure: IV: Initial: 2 mcg/kg (bolus optional); followed by continuous infusion at 0.01 mcg/kg/minute. Note: Should not be initiated at a dosage higher than initial recommended dose. There is limited experience with increasing the dose >0.01 mcg/kg/minute; in one trial, a limited number of patients received higher doses that were increased no faster than every 3 hours by 0.005 mcg/kg/minute (preceded by a bolus of 1 mcg/kg), up to a maximum of 0.03 mcg/kg/minute. Increases beyond the initial infusion rate should be limited to selected patients and accompanied by close hemodynamic and renal function monitoring.

Patients experiencing hypotension during the infusion: Infusion dose should be reduced or discontinued. Other measures to support blood pressure should be initiated (eg, IV fluids, Trendelenburg position). Hypotension may be prolonged (up to hours); once patient is stabilized, may attempt to restart at a lower dose (reduce previous infusion dose by 30% and omit bolus).

Maximum dosing weight: According to the manufacturer, the PRECEDENT Trial capped dosing weight at 160 kg and the VMAC Trial capped dosing weight at 175 kg. There are no specific guidelines on maximum dosing weight and clinical judgment should be used.

Dosing: Geriatric

Refer to adult dosing. Older individuals may be more sensitive to the effect of nesiritide than younger patients.

Dosing: Renal Impairment

No dosage adjustment necessary. Use cautiously in patients with renal impairment or those patients who rely on the renin-angiotensin-aldosterone system for renal perfusion. Monitor renal function closely.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

Reconstitution

Reconstitute 1.5 mg vial with 5 mL of diluent removed from a prefilled 250 mL plastic IV bag (compatible with D5W, D51/2NS, D51/4NS, NS). Do not shake vial to dissolve (roll gently). Withdraw entire contents of vial and add to 250 mL IV bag. Invert several times to mix. Resultant concentration of solution is ∼6 mcg/mL.

Administration

IV: Do not administer through a heparin-coated catheter (concurrent administration of heparin via a separate catheter is acceptable, per manufacturer).

Prime IV tubing with 5 mL of infusion prior to connection with vascular access port and prior to administering bolus or starting the infusion. Withdraw bolus from the prepared infusion bag and administer over 60 seconds. Begin infusion immediately following administration of the bolus.

Storage

Vials may be stored below 25°C (77°F); do not freeze. Protect from light. Following reconstitution, vials are stable at 2°C to 25°C (36°F to 77°F) for up to 24 hours. Use reconstituted solution within 24 hours.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents.Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion.Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents.Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Adverse Reactions

Note: Incidences of adverse reactions include unapproved dosing regimens as well as combination therapy data.

>10%:

Cardiovascular: Hypotension (4% to 12%)

Renal: Increased serum creatinine (28% with >0.5 mg/dL above baseline; 5% with 50% greater serum creatinine levels than at baseline), renal insufficiency (>25% decrease in glomerular filtration rate: 31%)

1% to 10%:

Central nervous system: Headache (7%)

Endocrine & metabolic: Hypoglycemia (≥2%)

Gastrointestinal: Nausea (3%)

Neuromuscular & skeletal: Back pain (3%)

<1%, postmarketing and/or case reports: Extravasation, hypersensitivity reactions, pruritus, skin rash

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic/hypersensitivity reactions: Serious anaphylactic or hypersensitivity reactions may occur following administration; obtain careful history and use caution in patients with previous hypersensitivity to other recombinant peptides; nesiritide prepared through recombinant technology using E. coli.

• Hypotension: May cause hypotension; administer in clinical situations when blood pressure may be closely monitored. Effects may be additive with other agents capable of causing hypotension. Hypotensive effects may last for several hours.

• Renal effects: May be associated with development of azotemia; use caution in patients with renal impairment or in patients where renal perfusion is dependent on renin-angiotensin-aldosterone system (eg, severe heart failure); avoid initiation at doses higher than recommended; increases in serum creatinine may occur at an elevated rate.

Disease-related concerns:

• Cardiovascular disease: Should not be used in patients with low cardiac filling pressures, or in patients with conditions which depend on venous return including significant valvular stenosis, restrictive or obstructive cardiomyopathy, constrictive pericarditis, and pericardial tamponade.

• Renal impairment: Use with caution in patients with renal impairment.

Other warnings/precautions:

• Prolonged infusions: Use caution with prolonged infusions; limited experience with infusions >96 hours.

Monitoring Parameters

Blood pressure, hemodynamic responses (PCWP, RAP, CI), BUN, creatinine; urine output; consult individual institutional policies and procedures

Pregnancy Considerations

Adverse events were not observed in an animal reproduction study. Nesiritide is a recombinant B-type natriuretic peptide (rhBNP). BNP and NT-proBNP (which has been used as a marker of BNP), are endogenous peptides and NT-proBNP is measurable in the umbilical cord serum of normal pregnancies. Information related to the administration of nesiritide during pregnancy has not been located.

Patient Education

• 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 headache, nausea, or back pain. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), severe dizziness, or passing out (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.