DBL SODIUM NITROPRUSSIDE Solution for injection Ref.[8344] Active ingredients: Nitroprusside

Dose

SODIUM NITROPRUSSIDE IS ONLY TO BE USED AS AN INFUSION WITH STERILE 5% GLUCOSE IN WATER. IT SHOULD NOT BE ADMINISTERED BY DIRECT INJECTION.

Product is for single use in one patient only. Discard any residue.

Dilution to proper strength for infusion

Depending on the desired concentration, DBL Sodium Nitroprusside concentrated injection containing 50 mg/2 mL sodium nitroprusside must be further diluted in 500-1000 mL of sterile 5% glucose injection. The diluted solution should be protected from light, using the supplied opaque sleeve, aluminium foil, or other opaque material. It is not necessary to cover the infusion drip chamber or the tubing.

Verification of the chemical integrity of the product

Sodium nitroprusside solution can be inactivated by reactions with trace contaminants. The products of these reactions are often blue, green, or red, much brighter than the faint brownish colour of unreacted DBL Sodium Nitroprusside concentrated injection. Discoloured solutions, or solutions in which particulate matter is visible, should not be used. To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 2°C-8°C for not more than 24 hours, protected from light

No other drugs should be administered in the same solution with sodium nitroprusside.

Avoidance of excessive hypotension

While the average effective rate in adults and children is about 3 mcg/kg/min, some patients will become dangerously hypotensive when they receive DBL Sodium Nitroprusside concentrated injection at this rate. Infusion of sodium nitroprusside should therefore be started at a very low rate (0.3 mcg/kg/min), with upward titration every few minutes until the desired effect is achieved or the maximum recommended infusion rate (10 mcg/kg/min) has been reached. Because sodium nitroprusside’s hypotensive effect is very rapid in onset and in dissipation, small variations in infusion rate can lead to wide, undesirable variations in blood pressure, Sodium nitroprusside should not be infused through ordinary I.V. apparatus, regulated only by gravity and mechanical clamps. Only an infusion pump, preferably a volumetric pump, should be used.

Because sodium nitroprusside can induce essentially unlimited blood-pressure reduction, the blood pressure of a patient receiving this drug must be continuously monitored, using either a continually reinflated sphygmomanometer or (preferably) an intra-arterial pressure sensor. Special caution should be used in elderly patients, since they may be more sensitive to the hypotensive effects of the drug.

When sodium nitroprusside is used in the treatment of acute congestive heart failure, titration of the infusion rate must be guided by the results of invasive haemodynamic monitoring with simultaneous monitoring of urine output. Sodium nitroprusside can be titrated by increasing the infusion rate until:

• measured cardiac output is no longer increasing,
• systemic blood pressure cannot be further reduced without compromising the perfusion of vital organs, or
• the maximum recommended infusion rate has been reached, whichever comes earliest. Specific haemodynamic goals must be tailored to the clinical situation, but improvements in cardiac output and left ventricular filling pressure must not be purchased at the price of undue hypotension and consequent hypoperfusion.The table below shows the infusion rates corresponding to the recommended initial and maximal doses (0.3 mcg/kg/min and 10 mcg/kg/min, respectively) for both adults and children of various weights. Some of the listed infusion rates are so slow or so rapid as to be impractical, and these practicalities must be considered when the concentration to be used is selected.

Note that when the concentration used in a given patient is changed, the tubing is still filled with a solution at the previous concentration.

Avoidance of cyanide toxicity

As described in section 5.2 above, when more than 500 mcg/kg of sodium nitroprusside is administered faster than 2 mcg/kg/min, cyanide is generated faster than the unaided patient can eliminate it. Administration of sodium thiosulfate has been shown to increase the rate of cyanide processing, reducing the hazard of cyanide toxicity. Although toxic reactions to sodium thiosulfate have not been reported, the co-infusion regimen has not been extensively studied, and it cannot be recommended without reservation. In one study, sodium thiosulfate appeared to potentiate the hypotensive effects of sodium nitroprusside.

Co-infusions of sodium thiosulfate have been administered at rates of 5-10 times that of sodium nitroprusside. Care must be taken to avoid the indiscriminate use of prolonged or high doses of sodium nitroprusside with sodium thiosulfate as this may result in thiocyanate toxicity and hypovolemia. Incautious administration of sodium nitroprusside must still be avoided, and all of the precautions concerning sodium nitroprusside administration must still be observed.

Infusion rates (mL/hour) to Achieve Initial (0.3 mcg/kg/min) and Maximal (10 mcg/kg/min) dosing of DBL™ SODIUM NITROPRUSSIDE concentrated injection:

Consideration of methaemoglobinemia and thiocyanate toxicity

Rare patients receiving more than 10 mg/kg of sodium nitroprusside will develop methaemoglobinaemia; other patients, especially those with impaired renal function, will predictably develop thiocyanate toxicity after prolonged, rapid infusions. In accordance with the descriptions in Section 4.8 above, patients with suggestive findings should be tested for these toxicities.

WARNING: Do not use flexible container in series connections.

Paediatric

Sodium nitroprusside can safely be used in children, provided that a satisfactory hypotensive response is obtained using doses calculated on a microgram/kg basis with adjustments as recommended for the adult.

Geriatric

Commence therapy with low doses since geriatric patients appear to be more sensitive to the hypotensive effects of the medicine. Induced hypotension in elderly patients, especially those with hypertension, carries a significant morbidity and mortality. Therefore, the medicine should be administered with caution in this age group.

Impaired liver function

Caution should be observed in patients with severe liver impairment as the medicine is largely metabolised by the hepatic enzyme rhodanase (transsulphurase), the enzyme responsible for the conversion of cyanide ions to thiocyanate. Patients with liver disease are therefore more susceptible to toxic effects associated with accumulation of cyanide.

Impaired renal function

Caution should be observed in patients with impaired renal function since thiocyanate, a major metabolite of the medicine, is excreted by the kidney. Toxicity from thiocyanate accumulation has occurred in patients with renal failure who have received prolonged nitroprusside infusion for hypertensive crises. Blood levels of thiocyanate should be determined if the medicine is used in patients suffering severe renal dysfunction.

Overdosage of nitroprusside can be manifested as excessive hypotension or cyanide toxicity (see section 4.4) or as thiocyanate toxicity (see section 4.8).

The acute intravenous mean lethal doses (LD50) of nitroprusside in rabbits, dogs, mice, and rats are 2.8, 5.0, 8.4, and 11.2 mg/kg, respectively.

Treatment of cyanide toxicity

Cyanide levels can be measured by many laboratories, and blood-gas studies that can detect venous hyperoxaemia or acidosis are widely available. Acidosis may not appear until more than an hour after the appearance of dangerous cyanide levels, and laboratory tests should not be awaited. Reasonable suspicion of cyanide toxicity is adequate grounds for initiation of treatment.

Treatment of cyanide toxicity consists of:

• discontinuing the administration of sodium nitroprusside;
• providing a buffer for cyanide by using sodium nitrite to convert as much haemoglobin into methaemoglobin as the patient can safely tolerate; and then
• infusing sodium thiosulfate in sufficient quantity to convert the cyanide into thiocyanate.

Haemodialysis is ineffective in removal of cyanide, but it will eliminate most thiocyanate.

Amyl nitrate via inhalation may be administered in environments where intravenous administration of sodium nitrite may be delayed. In a patient who already has a patent intravenous line, use of amyl nitrite confers no benefit that is not provided by infusion of sodium nitrite. 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 haemoglobin into methaemoglobin; this level of methaemoglobinaemia is not associated with any important hazard of its own. The nitrite infusion may cause transient vasodilatation and hypotension, and this hypotension must, if it occurs, be routinely managed.

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 to 200 milligram/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.

For advice on the management of overdose please contact the National Poisons Centre on 0800 POISON (0800 764766).

Shelf life:

• 18 months.
• 24 hours reconstituted stored at 2° to 8°C (Refrigerate, do not freeze) protect from light.

Store below 25°C. Protect from light. Retain in carton until time of use.

DBL Sodium Nitroprusside concentrated injection is a clear solution available in amber glass vials containing the equivalent of 50 mg sodium nitroprusside dihydrate in 2 mL solution..

Any unused medicine or waste material should be disposed of in accordance with local requirements.