Mechanism of effect
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.
Pharmacodynamic
Natriuretic Peptide, B-Type, Human
Pharmacokinetics
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
Drug indications
Acutely decompensated heart failure (HF): Treatment of acutely decompensated heart failure (HF) with dyspnea at rest or with minimal activity
Dosage
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).
Dosing: Geriatric
Refer to adult dosing. Older individuals may be more sensitive to the effect of nesiritide than younger patients.
dose by 30% and omit bolus).
Dosing: Geriatric
Refer to adult dosing. Older individuals may be more sensitive to the effect of nesiritide than younger patients.
Drug 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
Side effects
General
The most frequently reported side effects were hypotension, headache, nausea, renal impairment, and back pain.
Cardiovascular
Very common (10% or more): Hypotension (12%)
Renal
Very common (10% or more): GFR decreased (up to 31.4%), serum creatinine increased (up to 28%)
Nervous system
Common (1% to 10%): Headache, dizziness
Dermatologic
Postmarketing reports: Pruritus, rash
Musculoskeletal
Common (1% to 10%): Back pain
Metabolic
Common (1% to 10%): Hypoglycemia
Gastrointestinal
Common (1% to 10%): Nausea
Local
Postmarketing reports: Infusion site extravasation
Hypersensitivity
Postmarketing reports: Hypersensitivity reaction
Interactions
Enalapril , isosorbide dinitrate , Isoxsuprine , Brimonidine , Papaverine , Procarbazine , quinapril , ozanimod , Verteporfin , Ertugliflozin , Avanafil , Treprostinil , Moexipril , riociguat , Amyl Nitrite , Sapropterin , Glycyrrhiza glabra , Benazepril , Dapagliflozin , Empagliflozin , Tolazoline , Fosinopril , Ramipril , Trandolapril , Perindopril , Canagliflozin , Nefazodone , isosorbide mononitrate , selexipag , Fenoldopam , Amifostine , Epoprostenol , Vardenafil , Nitroprusside sodium , Linezolid , isocarboxazid , safinamide , rasagiline , Sildenafil , Furazolidone , Lisinopril , Minoxidil , Nitroglycerin , Hydralazine , pentoxifylline , Tranylcypromine , Diazoxide , Dipyridamole , Selegiline , Garlic
amifostine
amyl nitrite
apomorphine
apraclonidine ophthalmic
avanafil
benazepril
brimonidine ophthalmic
brimonidine topical
canagliflozin
captopril
dapagliflozin
diazoxide
dipyridamole
empagliflozin
enalapril
enalaprilat
epoprostenol
ertugliflozin
fenoldopam
fosinopril
furazolidone
garlic
hydralazine
iloprost
isocarboxazid
isosorbide dinitrate
isosorbide mononitrate
isoxsuprine
licorice
linezolid
lisinopril
maraviroc
minoxidil
minoxidil topical
moexipril
nefazodone
nimodipine
nitroglycerin
nitroprusside
ozanimod
papaverine
pentoxifylline
perindopril
phenelzine
procarbazine
quinapril
ramipril
rasagiline
riociguat
safinamide
sapropterin
selegiline
selexipag
sildenafil
sodium nitrite
tadalafil
tizanidine
tolazoline
trandolapril
tranylcypromine
treprostinil
trimethaphan camsylate
vardenafil
amyl nitrite
apomorphine
apraclonidine ophthalmic
avanafil
benazepril
brimonidine ophthalmic
brimonidine topical
canagliflozin
captopril
dapagliflozin
diazoxide
dipyridamole
empagliflozin
enalapril
enalaprilat
epoprostenol
ertugliflozin
fenoldopam
fosinopril
furazolidone
garlic
hydralazine
iloprost
isocarboxazid
isosorbide dinitrate
isosorbide mononitrate
isoxsuprine
licorice
linezolid
lisinopril
maraviroc
minoxidil
minoxidil topical
moexipril
nefazodone
nimodipine
nitroglycerin
nitroprusside
ozanimod
papaverine
pentoxifylline
perindopril
phenelzine
procarbazine
quinapril
ramipril
rasagiline
riociguat
safinamide
sapropterin
selegiline
selexipag
sildenafil
sodium nitrite
tadalafil
tizanidine
tolazoline
trandolapril
tranylcypromine
treprostinil
trimethaphan camsylate
vardenafil
verteporfin
Alerts
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.
Points of recommendation
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.
Pregnancy level
Adverse events were not observed in an animal reproduction study.
Data in humans are inadequate to make recommendations for use in pregnancy
Breast feeding warning
no dataTags
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