Nipride Rtu
Sodium Nitroprusside · Injection, Solution · Intravenous
Uses
Sodium nitroprusside is a direct acting vasodilator indicated for:
• Immediate reduction of blood pressure ( 1.1 )
• Producing controlled hypotension to reduce bleeding during surgery. ( 1.2 )
• Treatment of acute heart failure to reduce left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, peripheral vascular resistance and mean arterial blood pressure. ( 1.3 ) 1.1 Immediate Reduction of Blood Pressure Sodium nitroprusside is indicated for the immediate reduction of blood pressure of adult and pediatric patients in hypertensive crises. 1.2 Induction and Maintenance of Controlled Hypotension Sodium nitroprusside indicated for induction and maintenance of controlled hypotension in adults and children during surgery, to reduce bleeding. 1.3 Treatment of Acute Heart Failure Sodium nitroprusside is indicated for the treatment of acute heart failure to reduce, left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, peripheral vascular resistance and mean arterial blood pressure.
Dosage and administration
Initiate infusion of sodium nitroprusside at a rate of 0.3 mcg/kg/min, and titrate every few minutes until the desired effect is achieved OR the maximum recommended infusion rate of 10 mcg/kg/min has been reached ( 2.2 ). 2.1 Inspection Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Sodium nitroprusside should be a clear colorless to red/brown color; do not use if solution is blue, green, or bright red. 2.2 Dosing Continuously monitor blood pressure in patients receiving sodium nitroprusside. Start infusion of sodium nitroprusside at a rate of 0.3 mcg/kg/min. Evaluate blood pressure for at least 5 minutes before titrating to a higher or lower dose to achieve the desired blood pressure. The dose may be titrated upward until:
• the desired effect is achieved,
• systemic blood pressure cannot be further reduced without compromising the perfusion of vital organs, or
• the maximum recommended infusion rate of 10 mcg/kg/min has been reached, whichever occurs first. In patients with eGFR <30 mL/min/1.73 m 2 , limit the mean infusion rate to less than 3 mcg/kg/min. In anuric patients, limit the mean infusion rate to 1 mcg/kg/min. 2.3 Administration Do not administer other drugs in the same solution with sodium nitroprusside. Sodium nitroprusside must be delivered by a volumetric infusion pump because small variations in infusion rate can lead to wide, undesirable variations in blood pressure [see Clinical Pharmacology ( 12.2 )] .
Dosage forms and strengths
Injection: 50 mg/100 mL of 0.9% sodium chloride (0.5 mg/mL), 20 mg/100 mL of 0.9% sodium chloride (0.2 mg/mL), and 10 mg/50 mL of 0.9% sodium chloride (0.2 mg/mL). NIPRIDE ® RTU is supplied as a sterile, unpreserved, colorless to red-brown solution available in a single-use vial. Injection: 50 mg of sodium nitroprusside in 100 mL of 0.9% sodium chloride (0.5 mg/mL) in 100 mL single-use vials, 20 mg of sodium nitroprusside in 100 mL of 0.9% sodium chloride (0.2 mg/mL) in 100 mL single-use vials and 10 mg of sodium nitroprusside in 50 mL of 0.9% sodium chloride (0.2 mg/mL) in 50 mL single-use vials ( 3 ).
Contraindications
• Diseases with compensatory hypertension (e.g., coarctation of the aorta, arteriovenous shunting).
• 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.
• Acute heart failure associated with reduced peripheral vascular resistance.
• Concomitant use with sildenafil, tadalafil, vardenifil, or riociguat.
• Diseases with compensatory hypertension (e.g. coarctation of the aorta, arteriovenous shunting) ( 4 ).
• Inadequate cerebral circulation or moribund patients (A.S.A. Class 5E) coming to emergency surgery ( 4 ).
• Congenital (Leber’s) optic atrophy or tobacco amblyopia ( 4 ).
• Acute heart failure with reduced peripheral vascular resistance ( 4 ).
• Concomitant use with sildenafil, tadalafil, vardenifil, or riociguat ( 4 )
Warnings and precautions
• Thiocynate toxicity ( 5.3 )
• Methemoglobinemia ( 5.4 )
• Increases in intracranial pressure ( 5.5 )
• Diminished capacity to compensate for anemia and hypovolemia with anesthesia during surgery ( 5.6 ) 5.1 Excessive Hypotension Sodium nitroprusside, can cause excessive hypotension leading to hypoperfusion of vital organs. Hypotension should resolve within 1-10 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, consider other causes. Elderly patients may be more sensitive to the hypotensive effects of the drug. 5.2 Cyanide Toxicity Sodium nitroprusside infusions above 2 mcg/kg/min generate cyanide ion (CN¯) faster than the body can normally dispose of it. At the maximum recommended infusion rate of 10 mcg/kg/min, the patient’s ability to buffer CN¯ will be exceeded in less than one hour [see Overdose ( 10 )] . Patients with hepatic dysfunction are more susceptible to cyanide toxicity. An early manifestation of cyanide toxicity is increasing dosage requirements to maintain blood pressure control. Metabolic acidosis may not be evident for more than an hour after toxic cyanide levels accumulate. If cyanide toxicity develops, discontinue sodium nitroprusside, and consider specific treatment of cyanide toxicity [see Overdosage ( 10 )] . 5.3 Thiocyanate Toxicity Most of the cyanide produced during metabolism of sodium nitroprusside is eliminated in the form of thiocyanate. Thiocyanate is mildly neurotoxic (tinnitus, miosis, hyperreflexia) at serum levels of 1 mmol/L (60 mg/L). Thiocyanate is life-threatening when levels reach ~200 mg/L. Therefore, routine monitoring of plasma thiocyanate levels is recommended in patients with normal renal function when cumulative sodium nitroprusside doses exceed 7 mg/kg/day. In patients with eGFR <30 mL/min/1.73 m2, limit the mean infusion rate to less than 3 mcg/kg/min. In anuric patients, limit the mean infusion rate to 1 mcg/kg/min. Renal hemodialysis may be used to eliminate thiocyanate in cases of severe toxicity. 5.4 Methemoglobinemia Sodium nitroprusside infusions cause conversion of hemoglobin to methemoglobin in a dose-dependent manner. Methemoglobin binds oxygen more strongly than does hemoglobin, and when methemoglobin levels are elevated, oxygen release from red blood cells in tissue capillaries may be impaired. However, conversion of methemoglobin back to hemoglobin is normally rapid, and clinically significant methemoglobinemia is infrequent. Suspect methemoglobinemia 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. Methemoglobinemic blood is chocolate brown, without the expected color change on exposure to air. Methemoglobin levels >10% are considered clinically significant. When methemoglobinemia is diagnosed, the treatment of choice is 1-2 mg/kg of methylene blue, administered intravenously over several minutes. 5.5 Increased Intracranial Pressure Like other vasodilators, sodium nitroprusside can cause increases in intracranial pressure. 5.6 Anemia and Hypovolemia with 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, correct pre-existing anemia and hypovolemia prior to administration.
Side effects
The following adverse reactions are described, or described in greater detail, in other sections:
• Hypotension [see Warnings and Precautions ( 5.1 )]
• Cyanide Toxicity [see Warnings and Precautions ( 5.2 )]
• Thiocyanate Toxicity [see Warnings and Precautions ( 5.3 )]
• Methemoglobinemia [see Warnings and Precautions ( 5.4 )]
• Increased Intracranial Pressure [see Warnings and Precautions ( 5.5 )]
• Anemia and Hypovolemia [see Warnings and Precautions ( 5.6 )] Less common adverse reactions include: Cardiovascular: Bradycardia, electrocardiographic changes, tachycardia, palpitations, retrosternal discomfort Dermatologic: Rash Endocrine: Hypothyroidism Gastrointestinal: Ileus, nausea, abdominal pain Hematologic: Decreased platelet aggregation Musculoskelatal: Muscle twitching Neurologic: Increased intracranial pressure, dizziness, headache Miscellaneous: Flushing, diaphoresis, venous streaking, irritation at the infusion site Most common adverse reactions are hypotension and cyanide toxicity ( 6 ). To report SUSPECTED ADVERSE REACTIONS, Contact Exela Pharma Sciences, LLC at 1-888-451-4321 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Use in specific populations
8.1 Pregnancy Risk Summary Based on animal data and mechanism of action, sodium nitroprusside may lead to cyanide exposure and potential adverse effects in the fetus [see Clinical Pharmacology ( 12.3 ) and Clinical Considerations] . Published post-marketing reports with sodium nitroprusside use in pregnant women are insufficient to inform a drug-associated risk of adverse pregnancy related outcomes [see Data] . There were no animal reproduction studies conducted with sodium nitroprusside during pregnancy. However, there are published studies in pregnant sheep that demonstrate that nitroprusside crosses the placenta and that fetal cyanide levels were dose-related to maternal levels of sodium nitroprusside [see Data]. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use and large doses of sodium nitroprusside during pregnancy may result in cyanide toxicity that may be fatal to the fetus. In the unusual case that there is no appropriate alternative to therapy with sodium nitroprusside for a particular patient, apprise the mother of the potential risk to the fetus [see Warnings and Precautions ( 5.2 )] . Data Human Data A small number of cases have reported adverse events, including stillbirths, in pregnant women with severe pregnancy-induced hypertension who were treated with sodium nitroprusside. However, methodological limitations, including small sample size and limited information on sodium nitroprusside dosage and duration of treatment, as well as the cyanide concentration in maternal blood or fetal tissue, preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of sodium nitroprusside during pregnancy. Animal Data 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. 8.2 Lactation Risk Summary There is no information about the presence of sodium nitroprusside in human milk, the effects on the breastfed infant, or the effects on milk production. Thiocyanate, one of sodium nitroprusside’s metabolites, is present in human milk. It is unclear how long, if ever, levels of thiocyanate in milk are clinically relevant. 8.4 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 Studies ( 14 )].
Overdosage
Overdosage of nitroprusside can be manifested as excessive hypotension or cyanide toxicity [see Warnings and Precaution ( 5.1 , 5.2 )] or as thiocyanate toxicity [see Warnings and Precautions ( 5.3 )] . Cyanide toxicity causes venous hyperoxemia with bright red venous blood. Cells become unable to extract the oxygen delivered to them, leading to air hunger, confusion and death. Lactic acidosis may occur, but its emergence may lag other life-threatening manifestations of cyanide toxicity. Cyanide levels can be measured by many laboratories, and blood-gas studies that can detect venous hyperoxemia or acidosis are widely available. Acidosis may not appear until more than an hour after the appearance of dangerous cyanide levels. Suspicion of cyanide toxicity is adequate grounds for initiation of treatment. Treatment of cyanide toxicity consists of:
• discontinuing sodium nitroprusside;
• administration of sodium nitrite to convert as much hemoglobin into methemoglobin as the patient can safely tolerate; and then
• infusing sodium thiosulfate to convert the cyanide into thiocyanate. Hemodialysis is ineffective in removal of cyanide, but it will eliminate most thiocyanate. Sodium nitrite is available in a 3% solution, and 4-6 mg/kg (about 0.2 mL/kg) should be injected over 2-4 minutes. This dose can be expected to convert about 10% of the patient’s hemoglobin into methemoglobin; this level of methemoglobinemia is not associated with any important hazard of its own. Immediately after infusion of the sodium nitrite, sodium thiosulfate should be infused. This agent is available in 10% and 25% solutions, and the recommended dose is 150-200 mg/kg; a typical adult dose is 50 mL of the 25% solution. Thiosulfate treatment of an acutely cyanide-toxic patient will raise thiocyanate levels, but not to a dangerous degree. The nitrite/thiosulfate regimen may be repeated, at half the original doses, after two hours. Cyanide antidote kits are available.
Description
Sodium nitroprusside is disodium pentacyanonitrosylferrate(2-) dihydrate, a hypotensive agent whose structural formula is Sodium Nitroprusside has molecular formula Na 2 [Fe(CN) 5 NO]
• 2H 2 O and molecular weight of 297.95. Dry sodium nitroprusside is a reddish-brown powder, soluble in water. Sodium nitroprusside solution is rapidly degraded by trace contaminants, often with resulting color changes [see Dosage and Administration ( 2.1 )] . NIPRIDE ® RTU is supplied as a sterile, unpreserved, colorless to red-brown solution packaged in a single-use 100-mL vial. Each 100 mL of solution in vial contains 50 mg of sodium nitroprusside (0.5 mg/mL), 900 mg of sodium chloride, USP (9 mg/mL), in sterile water for injection, USP. NIPRIDE ® RTU is also supplied as a sterile, unpreserved, colorless to red-brown solution packaged in a single-use 100-mL vial. Each 100 mL of solution in vial contains 20 mg of sodium nitroprusside (0.2 mg/mL), 900 mg of sodium chloride, USP (9 mg/mL), in sterile water for injection, USP. NIPRIDE ® RTU is also supplied as a sterile, unpreserved, colorless to red-brown solution packaged in a single-use 50-mL vial. Each 50 mL of solution in vial contains 10 mg of sodium nitroprusside (0.2 mg/mL), 450 mg of sodium chloride, USP (9 mg/mL), in sterile water for injection, USP. structure
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING NIPRIDE ® RTU is supplied in amber-colored, single-dose, 50 mg/100 mL (0.5 mg/mL) Fliptop Vials (NDC 51754-1006-1), 20 mg/100 mL (0.2 mg/mL) Fliptop Vials (NDC 51754-1029-1) and 10 mg/50 mL (0.2 mg/mL) Fliptop Vials (NDC 51754-1018-1). Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. To protect NIPRIDE ® RTU from light, vial should be stored in its carton until used.
Patient information
Pregnancy Inform female patients of reproductive potential that Sodium Nitroprusside Injection may cause fetal harm and to inform their prescriber of a known or suspected pregnancy [see Use in Specific Population ( 8.1 )].
Label text from the FDA structured product label by EXELA PHARMA SCIENCES, LLC (revised Jul 20, 2018). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Sodium Nitroprusside in 2 products
Nipride Rtu NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 51754-1006 | Sodium Nitroprusside .5 mg/mL Injection, Solution | EXELA PHARMA SCIENCES, LLC | NDA |
| 51754-1029 | Sodium Nitroprusside .2 mg/mL Injection, Solution | EXELA PHARMA SCIENCES, LLC | NDA |
Frequently asked questions
What is Nipride Rtu used for?
Sodium nitroprusside is a direct acting vasodilator indicated for: • Immediate reduction of blood pressure ( 1.1 ) • Producing controlled hypotension to reduce bleeding during surgery. ( 1.2 ) • Treatment of acute heart failure to reduce left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, peripheral vascular resistance and mean arterial blood pressure. ( 1.3 ) 1.1…
What are the side effects of Nipride Rtu?
The following adverse reactions are described, or described in greater detail, in other sections: • Hypotension [see Warnings and Precautions ( 5.1 )] • Cyanide Toxicity [see Warnings and Precautions ( 5.2 )] • Thiocyanate Toxicity [see Warnings and Precautions ( 5.3 )] • Methemoglobinemia [see Warnings and Precautions ( 5.4 )] • Increased Intracranial Pressure [see Warnings and Precautions ( 5.5… See the full label for the complete list.
Who makes Nipride Rtu?
Nipride Rtu is listed by 1 labeler in the FDA NDC directory, including EXELA PHARMA SCIENCES, LLC.