Nitropress: After reconstitution, nitroprusside is not suitable for direct injection. The reconstituted solution must be further diluted in dextrose 5% injection before infusion.
Nitroprusside can cause precipitous decreases in blood pressure. In patients not properly monitored, these decreases can lead to irreversible ischemic injuries or death. Use only when available equipment and personnel allow blood pressure to be continuously monitored.
Except when used briefly or at low (less than 2 mcg/kg/min) infusion rates, nitroprusside injection gives rise to important quantities of cyanide ion, which can reach toxic, potentially lethal levels. The usual dose rate is 0.5 to 10 mcg/kg/min, but infusion at the maximum dose rates should never last more than 10 minutes. If blood pressure has not been adequately controlled after 10 minutes of infusion at the maximum rate, terminate administration immediately. Although acid-base balance and venous oxygen concentration should be monitored and may indicate cyanide toxicity, these laboratory tests provide imperfect guidance.
Note: Safety: Use may be limited due to risk for cyanide and thiocyanate toxicity, which is increased with higher doses (eg, >2 mcg/kg/minute) and/or prolonged duration of use, especially in patients with kidney or hepatic impairment. Invasive blood pressure monitoring, preferably via arterial line in a critical care unit, is recommended for appropriate dose titration.
Acute aortic syndromes/acute aortic dissection (adjunctive agent) (off-label use):
Note: Manage patients on an emergency basis (including operative assessment) by first controlling pain with IV opioids and heart rate (target 60 to 80 beats per minute) with a parenteral beta blocker (eg, esmolol) while targeting systolic BP of <120 mm Hg (or lowest tolerated pressure without compromising perfusion). If systolic BP remains elevated after heart rate is controlled at 60 to 80 beats per minute with beta-blockade, may consider adding a vasodilator (eg, nitroprusside) (Ref).
Continuous infusion: IV: Initial: 0.25 to 0.5 mcg/kg/minute; titrate as needed by 0.5 mcg/kg/minute every 5 minutes to achieve desired hemodynamic effect; maximum dose: 10 mcg/kg/minute. Higher doses (eg, 8 to 10 mcg/kg/minute) should only be used for a maximum of 10 minutes; use for the shortest duration possible to avoid toxicity (Ref).
Acute decompensated heart failure (adjunctive agent):
Note: May consider in patients with volume overload in the absence of symptomatic hypotension to help relieve congestion and dyspnea as an adjunct to IV diuretics (Ref).
Continuous infusion: IV: Initial: 0.1 to 0.3 mcg/kg/minute; titrate as needed every 5 to 15 minutes to achieve desired hemodynamic effect; usual dosage range: 1 to 3 mcg/kg/minute; maximum dose: 5 mcg/kg/minute for an 80 kg patient (Ref).
Acute ischemic stroke, BP management with reperfusion therapy (off-label use):
Note: During and 24 hours after reperfusion therapy, maintain a target BP of ≤180/105 mm Hg; reserve nitroprusside for hypertension that is refractory to first-line agents or diastolic BP >140 mm Hg (Ref).
Continuous infusion: IV: Initial: 0.25 to 0.5 mcg/kg/minute; titrate by 0.5 mcg/kg/minute every 5 minutes. Maximum dose: 10 mcg/kg/minute (for a maximum of 10 minutes); consider a maximum dose of 2 mcg/kg/minute to avoid toxicity (Ref).
Hypertensive emergency:
Note: Consider for use when preferred agents with less toxicity are unavailable. In general, reduce mean arterial blood pressure gradually by ~10% to 20% over the first hour, then by an additional 5% to 15% over the next 23 hours, unless there is a compelling indication for more rapid blood pressure and heart rate control (eg, acute aortic dissection) (Ref).
Continuous infusion: IV: Initial: 0.25 to 0.5 mcg/kg/minute; titrate as needed by 0.5 mcg/kg/minute every 5 minutes to achieve the target blood pressure; to avoid toxicity, limit dose to ≤2 mcg/kg/minute if possible; maximum dose: 10 mcg/kg/minute. Higher doses (eg, 8 to 10 mcg/kg/minute) should only be used for a maximum of 10 minutes; use for the shortest duration possible to avoid toxicity (Ref).
Use in patients with kidney impairment may lead to the accumulation of thiocyanate and subsequent toxicity; limit use.
eGFR <30 mL/minute/1.73 m2: Limit mean infusion rate to <3 mcg/kg/minute.
Anuric patients: Limit mean infusion rate to 1 mcg/kg/minute.
No dosage adjustment provided in manufacturer's labeling; due to the risk of cyanide toxicity, use with caution.
Refer to adult dosing.
(For additional information see "Nitroprusside: Pediatric drug information")
Note: Increased infusion rates and prolonged use have been associated with increased cyanide concentrations and cyanide toxicity; monitor cyanide levels with prolonged use (eg, >72 hours); coadministration with sodium thiosulfate is recommended (Ref):
Hypertension, acute including hypertensive crisis: Infants, Children, and Adolescents: Continuous IV infusion: Initial: 0.3 to 0.5 mcg/kg/minute; titrate every 5 minutes to desired effect; usual dose: 3 mcg/kg/minute; maximum dose: 10 mcg/kg/minute (Ref).
Cardiac output maintenance/stabilization, post resuscitation: Limited data available:
Infants, Children, and Adolescents: Continuous IV infusion: Initial: 0.3 to 1 mcg/kg/minute; titrate to desired effect; maximum dose: 8 mcg/kg/minute (Ref).
Infants, Children, and Adolescents: Use in patients with renal impairment may lead to the accumulation of thiocyanate and subsequent toxicity; limit use and monitor thiocyanate blood concentrations:
eGFR <30 mL/minute/1.73 m2: Limit mean infusion rate to <3 mcg/kg/minute.
Anuric patients: Limit mean infusion rate to 1 mcg/kg/minute.
There are no dosage adjustments provided in the manufacturer's labeling; due to the risk of cyanide toxicity, use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Bradycardia, ECG changes, flushing, palpitations, severe hypotension, substernal pain, tachycardia
Central nervous system: Apprehension, dizziness, headache, increased intracranial pressure, restlessness
Dermatologic: Diaphoresis, localized erythematous streaking, skin rash
Endocrine & metabolic: Hypothyroidism
Gastrointestinal: Abdominal pain, intestinal obstruction, nausea, retching
Hematologic & oncologic: Decreased platelet aggregation, methemoglobinemia
Local: Irritation at injection site
Neuromuscular & skeletal: Muscle twitching
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 (A.S.A. Class 5E) requiring emergency surgery; acute heart failure associated with reduced systemic vascular resistance (eg, septic shock); congenital (Leber's) optic atrophy or tobacco amblyopia; concomitant use with avanafil, sildenafil, tadalafil, vardenafil, or riociguat
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindication (not in US labeling): Hypersensitivity to nitroprusside or any component of the formulation; uncorrected anemia or hypovolemia; hepatic disease; severe kidney disease; disease states associated with vitamin B12 deficiency
Concerns related to adverse effects:
• Cyanide toxicity: [US 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 (ie, 10 mcg/kg/minute) 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. Patients at risk of cyanide toxicity include those who are malnourished, have hepatic impairment, or those undergoing cardiopulmonary bypass, or therapeutic hypothermia (Rindone 1992). Discontinue use of nitroprusside if signs and/or symptoms of cyanide toxicity (eg, metabolic acidosis, decreased oxygen saturation, bradycardia, confusion, convulsions) occur. Although not routinely done, sodium thiosulfate has been co-administered with nitroprusside using a 10:1 ratio of sodium thiosulfate to nitroprusside when higher doses of nitroprusside are used (eg, 4 to 10 mcg/kg/minute) for extended periods of time in order to prevent cyanide toxicity (Shulz 2010; Varon 2008); thiocyanate toxicity may still occur with this approach (Rindone 1992). The use of other agents (eg, clevidipine, labetalol, nicardipine) should be considered if blood pressure is not controlled with nitroprusside.
• Hypotension: [US Boxed Warning]: Excessive hypotension resulting in compromised perfusion of vital organs may occur; continuous blood pressure monitoring by experienced personnel is required.
• Increased intracranial pressure: Use may elevate intracranial pressure; in patients whose intracranial pressure is already elevated, use only with extreme caution.
Methemoglobinemia: Nitroprusside can cause a dose-dependent conversion of hemoglobin to methemoglobin. Methemoglobinemia should be suspected in any patient receiving >10 mg/kg of nitroprusside and exhibiting signs of impaired oxygen delivery despite adequate cardiac output and arterial pO2. Symptomatic patients, regardless of methemoglobin level should be treated with methylene blue (first-line). Treatment is suggested if level is ≥30% even if asymptomatic unless patient has a preexisting condition (eg, coronary artery disease) and are incapable of tolerating reductions in oxygen carrying capacity then treatment is suggested if level reaches 10% (Cortazzo 2013).
• Thiocyanate toxicity: Can occur in patients with kidney 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.
• 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.
• Kidney impairment: Use with extreme caution in patients with kidney impairment; use the lowest end of the dosage range; monitor thiocyanate concentrations closely.
• Myocardial infarction: Use caution in patients with acute myocardial infarction because of hemodynamic effects and possible coronary steal.
Other warnings/precautions:
• Appropriate administration: Nitropress: [US Boxed Warning]: Solution must be further diluted with 5% dextrose in water. Do not administer by direct injection.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as sodium:
Nipride RTU: 20 mg/100 mL in NaCl 0.9% (100 mL)
Generic: 25 mg/mL (2 mL); 50 mg/2 mL (2 mL)
Solution, Intravenous, as sodium [preservative free]:
Nipride RTU: 50 mg/100 mL in NaCl 0.9% (100 mL)
Generic: 25 mg/mL (2 mL); 20 mg/100 mL in NaCl 0.9% (100 mL); 50 mg/100 mL in NaCl 0.9% (100 mL)
Yes
Solution (Nipride RTU Intravenous)
20 mg/100 mL 0.9% (per mL): $0.54
50 mg/100 mL 0.9% (per mL): $0.66
Solution (Nitroprusside Sodium Intravenous)
25 mg/mL (per mL): $9.75 - $161.82
Solution (Nitroprusside Sodium-NaCl Intravenous)
20 mg/100 mL 0.9% (per mL): $0.43
50 mg/100 mL 0.9% (per mL): $0.53
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as sodium:
Nipride: 25 mg/mL (2 mL)
Generic: 25 mg/mL (2 mL)
IV: IV infusion only; infusion pump required. Due to potential for excessive hypotension, continuously monitor patient’s blood pressure during therapy. Product should always be protected from light, even during administration.
Parenteral: Administer as a continuous IV infusion via infusion pump. Solution should be protected from light, but not necessary to wrap administration set or IV tubing.
Concentrated solution (25 mg/mL): Not for direct injection; must dilute prior to administration.
Premixed solutions (200 mcg/mL, 500 mcg/mL): No further dilution required.
IV infusion: 50 mg in 250 mL (concentration: 200 mcg/mL) or 100 mg in 250 mL (concentration: 400 mcg/mL) of D5W
Note: Premixed solutions available.
IV infusion: 100 mcg/mL or 200 mcg/mL.
Acute decompensated heart failure: Management of acute decompensated heart failure.
Hypertensive emergency: Management of hypertensive crises; used for controlled hypotension to reduce bleeding during surgery.
Acute aortic syndromes/acute aortic dissection; Acute ischemic stroke, BP management with reperfusion therapy
Nitroprusside may be confused with nitroglycerin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Blood Pressure Lowering Agents: May increase hypotensive effects of Nitroprusside. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Dapsone (Topical): May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Risk C: Monitor
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Local Anesthetics: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor
Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitric Oxide: May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects 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. Risk D: Consider Therapy Modification
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Nitroprusside. Risk X: Avoid
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Prilocaine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor
Primaquine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Primaquine. Specifically, the risk for methemoglobinemia may be increased. Management: Avoid concomitant use of primaquine and other drugs that are associated with methemoglobinemia when possible. If combined, monitor methemoglobin levels closely. Risk D: Consider Therapy Modification
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Riociguat: May increase hypotensive effects of Nitroprusside. Risk X: Avoid
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sodium Nitrite: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor
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.
It is not known if nitroprusside is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
Blood pressure via arterial line and heart rate (cardiac monitor and blood pressure monitor required) (Friedrich 1995); monitor for cyanide and thiocyanate toxicity; monitor venous oxygen saturation; 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 kidney dysfunction; monitor cyanide blood levels (if available with appropriate turnaround time) in patients with decreased hepatic function
Consult individual institutional policies and procedures.
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 (SI: >602 micromole/L) (manufacturer suggests 60 mcg/mL [SI: 1,032 micromole/L]), but serious toxicity typically may not occur with levels <100 mcg/mL (SI: <1,720 micromole/L).
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
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)