NIPRIDE RTU Solution for injection Ref.[10893] Active ingredients: Nitroprusside

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 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.

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)].

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.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].