Prescription Drug Information: Sodium Nitroprusside (Page 2 of 4)


Sodium nitroprusside is indicated for the immediate reduction of blood pressure of adult and pediatric patients in hypertensive crises. Concomitant longer-acting antihypertensive medication should be administered so that the duration of treatment with sodium nitroprusside can be minimized.

Sodium nitroprusside is also indicated for producing controlled hypotension in order to reduce bleeding during surgery.

Sodium nitroprusside is also indicated for the treatment of acute congestive heart failure.


Sodium nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or arteriovenous shunting.

Sodium nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation, or in moribund patients (A.S.A. Class 5E) coming to emergency surgery.

Patients with congenital (Leber’s) optic atrophy or with tobacco amblyopia have unusually high cyanide/thiocyanate ratios. These rare conditions are probably associated with defective or absent rhodanase, and sodium nitroprusside should be avoided in these patients.

Sodium nitroprusside should not be used for the treatment of acute congestive heart failure associated with reduced peripheral vascular resistance such as high-output heart failure that may be seen in endotoxic sepsis.


(See also the boxed warning at the beginning of this insert.)

The principal hazards of Sodium Nitroprusside Injection administration are excessive hypotension and excessive accumulation of cyanide (see also OVERDOSAGE and DOSAGE AND ADMINISTRATION).

Excessive Hypotension: Small transient excesses in the infusion rate of sodium nitroprusside can result in excessive hypotension, sometimes to levels so low as to compromise the perfusion of vital organs. These hemodynamic changes may lead to a variety of associated symptoms; see ADVERSE REACTIONS. Nitroprusside induced hypotension will be self-limited within 1 to 10 minutes after discontinuation of the nitroprusside infusion; during these few minutes, it may be helpful to put the patient into a head-down (Trendelenburg) position to maximize venous return. If hypotension persists more than a few minutes after discontinuation of the infusion of Sodium Nitroprusside Injection, Sodium Nitroprusside Injection is not the cause, and the true cause must be sought.

Cyanide Toxicity: As described in CLINICAL PHARMACOLOGY above, sodium nitroprusside infusions at rates above 2 mcg/kg/min generate cyanide ion (CN ) faster than the body can normally dispose of it. (When sodium thiosulfate is given, as described under DOSAGE AND ADMINISTRATION, the body’s capacity for CN elimination is greatly increased.) Methemoglobin normally present in the body can buffer a certain amount of CN , but the capacity of this system is exhausted by the CN produced from about 500 mcg/kg of sodium nitroprusside. This amount of sodium nitroprusside is administered in less than an hour when the drug is administered at 10 mcg/kg/min (the maximum recommended rate). Thereafter, the toxic effects of CN may be rapid, serious, and even lethal.

The true rates of clinically important cyanide toxicity cannot be assessed from spontaneous reports or published data. Most patients reported to have experienced such toxicity have received relatively prolonged infusions, and the only patients whose deaths have been unequivocally attributed to nitroprusside-induced cyanide toxicity have been patients who had received nitroprusside infusions at rates (30 to 120 mcg/kg/min) much greater than those now recommended. Elevated cyanide levels, metabolic acidosis, and marked clinical deterioration, however, have occasionally been reported in patients who received infusions at recommended rates for only a few hours and even, in one case, for only 35 minutes. In some of these cases, infusion of sodium thiosulfate caused dramatic clinical improvement, supporting the diagnosis of cyanide toxicity.

Cyanide toxicity may manifest itself as venous hyperoxemia with bright red venous blood, as cells become unable to extract the oxygen delivered to them; metabolic (lactic) acidosis; air hunger; confusion; and death. Cyanide toxicity due to causes other than nitroprusside has been associated with angina pectoris and myocardial infarction; ataxia, seizures, and stroke; and other diffuse ischemic damage.

Hypertensive patients, and patients concomitantly receiving other antihypertensive medications, may be more sensitive to the effects of sodium nitroprusside than normal subjects.


General: Like other vasodilators, sodium nitroprusside can cause increases in intracranial pressure. In patients whose intracranial pressure is already elevated, sodium nitroprusside should be used only with extreme caution.

Hepatic: Use caution when administering nitroprusside to patients with hepatic insufficiency.

Use in Anesthesia: When sodium nitroprusside (or any other vasodilator) is used for controlled hypotension during anesthesia, the patient’s capacity to compensate for anemia and hypovolemia may be diminished. If possible, pre-existing anemia and hypovolemia should be corrected prior to administration of Sodium Nitroprusside Injection.

Hypotensive anesthetic techniques may also cause abnormalities of the pulmonary ventilation/perfusion ratio. Patients intolerant of these abnormalities may require a higher fraction of inspired oxygen.

Extreme caution should be exercised in patients who are especially poor surgical risks (A.S.A. Class 4 and 4E).

Laboratory Tests: The cyanide-level assay is technically difficult, and cyanide levels in body fluids other than packed red blood cells are difficult to interpret. Cyanide toxicity will lead to lactic acidosis and venous hyperoxemia, but these findings may not be present until an hour or more after the cyanide capacity of the body’s red-cell mass has been exhausted.

Drug Interactions: The hypotensive effect of sodium nitroprusside is augmented by that of most other hypotensive drugs, including ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Animal studies assessing sodium nitroprusside’s carcinogenicity and mutagenicity have not been conducted. Similarly, sodium nitroprusside has not been tested for effects on fertility.

Pregnancy: Teratogenic effects. There are no adequate, well-controlled studies of Sodium Nitroprusside Injection in either laboratory animals or pregnant women. It is not known whether Sodium Nitroprusside Injection can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Sodium Nitroprusside Injection should be given to a pregnant woman only if clearly needed.

Nonteratogenic Effects: In three studies in pregnant ewes, nitroprusside was shown to cross the placental barrier. Fetal cyanide levels were shown to be dose-related to maternal levels of nitroprusside. The metabolic transformation of sodium nitroprusside given to pregnant ewes led to fatal levels of cyanide in the fetuses. The infusion of 25 mcg/kg/min of sodium nitroprusside for one hour in pregnant ewes resulted in the death of all fetuses. Pregnant ewes infused with 1 mcg/kg/min of sodium nitroprusside for one hour delivered normal lambs.

According to one investigator, a pregnant woman at 24 weeks gestation was given sodium nitroprusside to control gestational hypertension secondary to mitral valve disease. Sodium nitroprusside was infused at 3.9 mcg/kg/min for a total of 3.5 mg/kg over 15 hours prior to delivery of a 478 gram stillborn infant without any obvious anomalies. Cyanide levels in the fetal liver were less than 10 mcg/mL. Toxic levels have been reported to be more than 30 to 40 mcg/mL. The mother demonstrated no cyanide toxicity.

The effects of administering sodium thiosulfate in pregnancy, either by itself or as a co-infusion with sodium nitroprusside, are completely unknown.

Nursing Mothers: It is not known whether sodium nitroprusside and its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from sodium nitroprusside, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Efficacy in the pediatric population was established based on adult trials and supported by the dose-ranging trial (Study 1) and an open label trial of at least 12 hour infusion at a rate that achieved adequate MAP control (Study 2) with pediatric patients on sodium nitroprusside. No novel safety issues were seen in these studies in pediatric patients. See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.


The most important adverse reactions to sodium nitroprusside are the avoidable ones of excessive hypotension and cyanide toxicity, described above under WARNINGS. The adverse reactions described in this section develop less rapidly and, as it happens, less commonly.

Methemoglobinemia: As described in CLINICAL PHARMACOLOGY above, sodium nitroprusside infusions can cause sequestration of hemoglobin as methemoglobin. The back-conversion process is normally rapid, and clinically significant methemoglobinemia (>10%) is seen only rarely in patients receiving Sodium Nitroprusside Injection. Even patients congenitally incapable of back-converting methemoglobin should demonstrate 10% methemoglobinemia only after they have received about 10 mg/kg of sodium nitroprusside, and a patient receiving sodium nitroprusside at the maximum recommended rate (10 mcg/kg/min) would take over 16 hours to reach this total accumulated dose.

Methemoglobin levels can be measured by most clinical laboratories. The diagnosis should be suspected in patients who have received >10 mg/kg of sodium nitroprusside and who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

When methemoglobinemia is diagnosed, the treatment of choice is 1 to 2 mg/kg of methylene blue, administered intravenously over several minutes. In patients likely to have substantial amounts of cyanide bound to methemoglobin as cyanmethemoglobin, treatment of methemoglobinemia with methylene blue must be undertaken with extreme caution.

Thiocyanate Toxicity: As described in CLINICAL PHARMACOLOGY above, most of the cyanide produced during metabolism of sodium nitroprusside is eliminated in the form of thiocyanate. When cyanide elimination is accelerated by the co-infusion of thiosulfate, thiocyanate production is increased.

Thiocyanate is mildly neurotoxic (tinnitus, miosis, hyperreflexia) at serum levels of 1 mmol/L (60 mg/L). Thiocyanate toxicity is life-threatening when levels are 3 or 4 times higher (200 mg/L).

The steady-state thiocyanate level after prolonged infusions of sodium nitroprusside is increased with increased infusion rate, and the half-time of accumulation is 3 to 4 days. To keep the steady-state thiocyanate level below 1 mmol/L, a prolonged infusion of sodium nitroprusside should not be more rapid than 3 mcg/kg/min; in anuric patients, the corresponding limit is just 1 mcg/kg/min. When prolonged infusions are more rapid than these, thiocyanate levels should be measured daily.

Physiologic maneuvers (e.g., those that alter the pH of the urine) are not known to increase the elimination of thiocyanate. Thiocyanate clearance rates during dialysis, on the other hand, can approach the blood flow rate of the dialyzer.

Thiocyanate interferes with iodine uptake by the thyroid.

Abdominal pain, apprehension, diaphoresis, “dizziness,” headache, muscle twitching, nausea, palpitations, restlessness, retching, and retrosternal discomfort have been noted when the blood pressure was too rapidly reduced. These symptoms quickly disappeared when the infusion was slowed or discontinued, and they did not reappear with a continued (or resumed) slower infusion.

Other adverse reactions reported are:

Cardiovascular: Bradycardia, electrocardiographic changes, tachycardia.

Dermatologic: Rash.

Endocrine: Hypothyroidism.

Gastrointestinal: Ileus.

Hematologic: Decreased platelet aggregation.

Neurologic: Increased intracranial pressure.

Miscellaneous: Flushing, venous streaking, irritation at the infusion site.

To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 or FDA at 1-800-FDA-1088 or provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

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