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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(nye troe PRUS ide)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Management of hypertensive crises; acute decompensated heart failure (HF); used for controlled hypotension to reduce bleeding during surgery
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal studies have shown that nitroprusside may cross the placental barrier and result in fetal cyanide levels that are dose-related to maternal nitroprusside levels. However, information related to use in pregnancy is limited.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Treatment of compensatory hypertension (aortic coarctation, arteriovenous shunting); to produce controlled hypotension during surgery in patients with known inadequate cerebral circulation or in moribund patients requiring emergency surgery; high output heart failure associated with reduced systemic vascular resistance (eg, septic shock); congenital optic atrophy or tobacco amblyopia
Warnings/Precautions
Boxed warnings:
• Appropriate administration: See “Other warnings/precautions” below.
• Cyanide toxicity: See “Concerns related to adverse effects” below.
• Hypotension: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Cyanide toxicity: [U.S. Boxed Warning]: Except when used briefly or at low (<2 mcg/kg/minute) infusion rates, nitroprusside gives rise to large cyanide quantities. Do not use the maximum dose for more than 10 minutes; if blood pressure is not controlled by the maximum rate after 10 minutes, discontinue infusion. Monitor for cyanide toxicity via acid-base balance and venous oxygen concentration; however, clinicians should note that these indicators may not always reliably indicate cyanide toxicity.
• Hypotension: [U.S. Boxed Warning]: Excessive hypotension resulting in compromised perfusion of vital organs may occur; continuous blood pressure monitoring by experienced personnel is required.
• Thiocyanate toxicity: Can occur in patients with renal impairment or those on prolonged infusions (ie, >3 mcg/kg/minute for >72 hours).
Disease-related concerns:
• Anemia: When nitroprusside is used for controlled hypotension during surgery, correct pre-existing anemia prior to use when possible.
• Increased intracranial pressure: Use with extreme caution in patients with elevated intracranial pressure.
• Hepatic impairment: Use with extreme caution in patients with hepatic impairment.
• Hypovolemia: When nitroprusside is used for controlled hypotension during surgery, correct pre-existing hypovolemia prior to use when possible.
• Renal impairment: Use with extreme caution in patients with renal impairment; use the lowest end of the dosage range; monitor thiocyanate concentrations closely.
Other warnings/precautions:
• Appropriate administration: [U.S. Boxed Warning]: Solution must be further diluted with 5% dextrose in water. Do not administer by direct injection.
Adverse Reactions
Frequency not defined.
Cardiovascular: Bradycardia, ECG changes, flushing, hypotension (excessive), palpitation, substernal distress, tachycardia
Central nervous system: Apprehension, dizziness, headache, intracranial pressure increased, restlessness
Dermatologic: Rash
Endocrine & metabolic: Metabolic acidosis (secondary to cyanide toxicity), hypothyroidism
Gastrointestinal: Abdominal pain, ileus, nausea, retching, vomiting
Hematologic: Methemoglobinemia, platelet aggregation decreased
Local: Injection site irritation
Neuromuscular & skeletal: Hyperreflexia (secondary to thiocyanate toxicity), muscle twitching
Ocular: Miosis (secondary to thiocyanate toxicity)
Otic: Tinnitus (secondary to thiocyanate toxicity)
Respiratory: Hyperoxemia (secondary to cyanide toxicity)
Miscellaneous: Cyanide toxicity, diaphoresis, thiocyanate toxicity
Metabolism/Transport Effects
None known.
Drug Interactions
Alfuzosin: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Calcium Channel Blockers: May enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Storage
Store the intact vial at 20°C to 25°C (68°F to 77°F). Protect from light.
Stability of parenteral admixture at room temperature (25°C) and at refrigeration temperature (4°C) is 24 hours.
Reconstitution
Prior to administration, nitroprusside sodium should be further diluted by diluting 50 mg in 250-1000 mL of D5W.
Use only clear solutions; solutions of nitroprusside exhibit a color described as brownish, brown, brownish-pink, light orange, and straw. Solutions are highly sensitive to light. Exposure to light causes decomposition, resulting in a highly colored solution of orange, dark brown or blue. A blue color indicates almost complete decomposition. Do not use discolored solutions (eg, blue, green, red) or solutions in which particulate matter is visible.
Prepared solutions should be wrapped with aluminum foil or other opaque material to protect from light (do as soon as possible).
Compatibility
Stable in D5W (preferred), LR, NS; Note: Exposure to light causes decompensation regardless of the diluent
Y-site administration: Compatible: Alprostadil, argatroban, atracurium, bivalirudin, caffeine citrate, calcium chloride, calcium gluconate, dexmedetomidine, diltiazem, dobutamine, dobutamine with dopamine, dobutamine with lidocaine, dobutamine with nitroglycerin, dopamine, dopamine with lidocaine, dopamine with nitroglycerin, enalaprilat, epinephrine, esmolol, famotidine, furosemide, heparin, hetastarch in lactate electrolyte injection (Hextend®), inamrinone, indomethacin, insulin (regular), isoproterenol, labetalol, lidocaine, lidocaine with nitroglycerin, magnesium sulfate, micafungin, midazolam, milrinone, morphine, nesiritide, norepinephrine, nitroglycerin, pancuronium, potassium chloride, potassium phosphate, procainamide, propofol, tacrolimus, theophylline, vecuronium. Incompatible: Drotrecogin alfa, levofloxacin, pantoprazole. Variable (consult detailed reference): Amiodarone, cisatracurium, haloperidol, metoprolol.
Compatibility in syringe: Compatible: Caffeine citrate, heparin. Incompatible: Pantoprazole.
Mechanism of Action
Causes peripheral vasodilation by direct action on venous and arteriolar smooth muscle, thus reducing peripheral resistance; will increase cardiac output by decreasing afterload; reduces aortal and left ventricular impedance
Pharmacodynamics/Kinetics
Onset of action: Hypotensive effect: <2 minutes
Duration: Hypotensive effect: 1-10 minutes
Metabolism: Nitroprusside combines with hemoglobin to produce cyanide and cyanmethemoglobin. Cyanide detoxification occurs via rhodanase-mediated conversion of cyanide to thiocyanate; rhodanase couples cyanide molecules to sulfane sulfur groups from a sulfur donor (eg, thiosulfate, cystine, cysteine). This process has limited capacity and may become overwhelmed with large exposures once sulfur donor supplies are exhausted resulting in toxicity.
Half-life elimination: Nitroprusside, circulatory: ~2 minutes; Thiocyanate, elimination: ~3 days (may be doubled or tripled in renal failure)
Excretion: Urine (as thiocyanate)
Dosage
I.V.:
Children: Acute hypertension: Initial: 0.3-0.5 mcg/kg/minute; may be titrated every few minutes to achieve desired hemodynamic effect; maximum dose: 10 mcg/kg/minute (Hegenbarth, 2008; NHBPEP, 2005). Doses ≥1.8 mcg/kg/minute are associated with increased cyanide concentration in pediatric patients (Moffett, 2008); monitor cyanide levels with prolonged use (eg, >72 hours) (NHBPEP, 2005).
Adults:
Acute hypertension: Initial: 0.25-0.3 mcg/kg/minute; may be titrated by 0.5 mcg/kg/minute every few minutes to achieve desired hemodynamic effect (JNC 7; Rhoney, 2009); usual dose: 3 mcg/kg/minute; maximum dose: 10 mcg/kg/minute. When administered in doses >3 mcg/kg/minute for prolonged periods of time (eg, 3-4 days), thiocyanate levels should be monitored daily.
Acute decompensated heart failure: Initial: 5-10 mcg/minute; may be titrated rapidly (eg, up to every 5 minutes) to achieve desired hemodynamic effect; usual dosage range: 5-300 mcg/minute. Doses >400 mcg/minute are not recommended due to minimal added benefit and increased risk for thiocyanate toxicity (HFSA, 2010).
Dosage adjustment in renal impairment: There are no dosage adjustments provided in manufacturer's labeling. However, use in patients with renal impairment may lead to the accumulation of thiocyanate and subsequent toxicity; limit use.
Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in manufacturer's labeling; due to the risk of cyanide toxicity, use with caution.
Administration: I.V.
I.V. infusion only; infusion pump required. Must be diluted with D5W (preferred), LR, or NS prior to administration; not for direct injection. Due to potential for excessive hypotension, continuously monitor patient's blood pressure during therapy.
Administration: I.V. Detail
pH: 3.5-6.0
Monitoring Parameters
Blood pressure, heart rate; monitor for cyanide and thiocyanate toxicity; monitor acid-base status as acidosis can be the earliest sign of cyanide toxicity; monitor thiocyanate levels if requiring prolonged infusion (>3 days) or dose >3 mcg/kg/minute or patient has renal dysfunction; monitor cyanide blood levels in patients with decreased hepatic function; cardiac monitor and blood pressure monitor required
Reference Range
Serum thiocyanate levels are not helpful in detecting toxicity. A level may be confirmatory if a patient is exhibiting signs and symptoms of thiocyanate toxicity. Initial signs of toxicity (eg, tinnitus) may be observed at levels >35 mcg/mL (manufacturer suggests 60 mcg/mL), but serious toxicity typically may not occur with levels <100 mcg/mL.
Patient Education
This drug can only be given I.V. You will be monitored at all times during infusion. Promptly report any pain/burning at site of infusion.
Geriatric Considerations
Elderly patients may have an increased sensitivity to nitroprusside possibly due to a decreased baroreceptor reflex, altered sensitivity to vasodilating effects or a resistance of cardiac adrenergic receptors to stimulation by catecholamines.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Elderly patients may have an increased sensitivity to nitroprusside possibly due to a decreased baroreceptor reflex, altered sensitivity to vasodilating effects or a resistance of cardiac adrenergic receptors to stimulation by catecholamines.
Blood Pressure Management of Intracerebral Hemorrhage (ICH): In addition to standard management of ICH, blood pressure (BP) management while maintaining cerebral perfusion pressure in patients who are hypertensive is also of paramount importance when treating ICH. The primary rationale for lowering BP is to prevent further progression of the bleed. This can be accomplished using a number of different pharmacologic treatments (eg, nicardipine, labetalol, nitroprusside). Nitroprusside may increase ICP due to the pronounced vasodilatory actions and therefore may be less preferable. Specific BP targets are not supported by available evidence. The 2007 AHA/ASA guidelines for the management of spontaneous intracerebral hemorrhage in adults recommend initiating antihypertensive therapy if the SBP >180 mm Hg or if MAP >130 mm Hg (Broderick, 2007).
Cardiovascular Considerations
Thiocyanate levels should be monitored if high doses are used for more than 24 hours, particularly in patients with renal dysfunction and hepatic dysfunction. Nitroprusside is a very effective agent for controlled blood pressure lowering because of the very short half-life. Reasonably accurate titrations, based on target blood pressure, can be achieved. Because of restricted cardiac output conditions, nitroprusside should be avoided in patients with aortic stenosis or coarctation. Nitroprusside should also be used cautiously in patients with acute myocardial infarction because of hemodynamic effects and possible coronary steal.
Acute Decompensated Heart Failure: Nitroprusside may also be useful for short-term afterload reduction in patients with acute decompensated heart failure. Patients with refractory end-stage heart failure, once stabilized, should be switched to an oral regimen that can maintain symptomatic improvement and reduce the risk of subsequent deterioration if possible.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause restlessness, disorientation, or psychosis
Mental Health: Effects on Psychiatric Treatment
None reported, but monitor for hypotension if receiving a psychotropic
Nursing: Physical Assessment/Monitoring
Infusion site must be monitored closely to prevent extravasation. Continuous blood pressure monitoring is needed. Assess acid/base balance (metabolic acidosis is early sign of cyanide toxicity). Monitor for disorientation, hypoxia, and muscular twitching.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sodium:
Nitropress®: 25 mg/mL (2 mL)
References
Berlin CM, “The Treatment of Cyanide Poisoning in Children,” Pediatrics, 1970, 46(5):793-6.
Broderick J, Connolly S, Feldmann E, et al, “Guidelines for the Management of Spontaneous Intracerebral Hemorrhage in Adults: 2007 Update: A Guideline From the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group,” Stroke, 2007, 38(6):2001-23.
Erstad BL and Barletta JF, “Treatment of Hypertension in the Perioperative Patient,” Ann Pharmacother, 2000, 34(1):66-79.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-90.
Ihlen H, Myhre E, and Opstad P, “Evaluation of Potential Adverse Effects of Sodium Nitroprusside During Pacing-Induced Myocardial Ischaemia in Man,” Eur Heart J, 1984, 5(10):834-41.
Lindenfeld J, Albert NM, Boehmer JP, et al, “HFSA 2010 Comprehensive Heart Failure Practice Guideline,” J Card Fail, 2010, 16(6):e1-194.
Moffett BS and Price JF, "Evaluation of Sodium Nitroprusside Toxicity in Pediatric Cardiac Surgical Patients," Ann Pharmacother, 2008, 42(11):1600-4.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
Palmer RF and Lasseter KC, “Drug Therapy: Sodium Nitroprusside,” N Engl J Med, 1975, 292(6):294-7.
Rhoney D and Peacock WF, “Intravenous Therapy for Hypertensive Emergencies, Part 1”, Am J Health-Syst Pharm, 2009, 66(15):1343-52.
Vesey CJ and Cole PV, “Blood Cyanide and Thiocyanate Concentrations Produced by Long-Term Therapy With Sodium Nitroprusside,” Br J Anaesth, 1985, 57(2):148-55.
Wesson DE, Foley R, Sabatini S, et al, “Treatment of Acute Cyanide Intoxication With Hemodialysis,” Am J Nephrol, 1985, 5(2):121-6.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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