Nipride RTU

Immediate Reduction Of Blood Pressure

Sodium nitroprusside is indicated for the immediate reduction of blood pressure of adult and pediatric patients in hypertensive crises.

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.

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.

Included as part of the "PRECAUTIONS" Section

• Aldomet
• Apresoline
• Avapro
• Cardura
• Cardura XL
• Cozaar

• Danocrine
• Desoxyn
• Didrex
• Hyzaar
• Intuniv
• Tenex

© Nipride RTU Patient Information is supplied by Cerner Multum, Inc. and Nipride RTU Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

In the U.S.

• Nipride RTU
• Nitropress

Available Dosage Forms:

• Solution
• Powder for Solution

Therapeutic Class: Peripheral Vasodilator

Your doctor will check your progress closely while you or your child are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using this medicine, tell your doctor right away.

Do not use this medicine together with riociguat (Adempas®), sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®). Using these medicines together may cause unwanted effects.

This medicine could lower your blood pressure too much and cause you to feel dizzy or lightheaded. Stand or sit up slowly if you are dizzy.

Tell your doctor right away if you or your child have bluish-colored lips, fingernails, or palms, dark urine, trouble breathing, unusual bleeding, bruising, or weakness while using this medicine.

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

Mechanism of Action

Sodium nitroprusside interacts with oxyhemoglobin to produce methemoglobin, cyanide, and nitric oxide (NO). NO then reacts with guanylate cyclase in vascular smooth muscle to produce cGMP that reduces intracellular calcium concentrations resulting in relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins. Other smooth muscle (e.g., uterus, duodenum) is not affected. Sodium nitroprusside is more active on veins than on arteries, but this selectivity is much less marked than that of nitroglycerin. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilatation of the coronary arteries also occurs.

Pharmacodynamics

In association with the decrease in blood pressure, sodium nitroprusside administered intravenously to hypertensive and normotensive patients produces slight increases in heart rate and a variable effect on cardiac output. In hypertensive patients, moderate doses induce renal vasodilatation roughly proportional to the decrease in systemic blood pressure, so there is no appreciable change in renal blood flow or glomerular filtration rate.

The hypotensive effect of sodium nitroprusside is seen within a minute or two after the start of an adequate infusion, and it dissipates almost as rapidly after an infusion is discontinued. The effect is augmented by ganglionic blocking agents and inhaled anesthetics.

Pharmacokinetics

Infused sodium nitroprusside is rapidly distributed to a volume that is approximately coextensive with the extracellular space. The drug is cleared by intraerythrocytic reaction with hemoglobin (Hgb), and sodium nitroprusside’s resulting circulatory half-life is about 2 minutes.

The products of the nitroprusside/hemoglobin reaction are cyanmethemoglobin (cyanmetHgb) and cyanide ion (CN¯).

Metabolism

As shown in the diagram below, the essential features of nitroprusside metabolism are:

• one molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN¯ ions;
• methemoglobin, obtained from hemoglobin, can sequester cyanide as cyanmethemoglobin;
• thiosulfate reacts with cyanide to produce thiocyanate;
• thiocyanate is eliminated in the urine;
• cyanide not otherwise removed binds to cytochromes; and
• cyanide is much more toxic than methemoglobin or thiocyanate.

Cyanide ion is normally found in serum; it is derived from dietary substrates and from tobacco smoke. CN¯ levels in packed erythrocytes are typically less than 1 μmol/L (less than 25 mcg/L); levels are roughly doubled in heavy smokers.

At healthy steady state, most people have less than 1% of their hemoglobin in the form of methemoglobin. Nitroprusside metabolism can lead to methemoglobin formation. Relatively large quantities of sodium nitroprusside, however, are required to produce significant methemoglobinemia.

At physiologic methemoglobin levels, the CN¯ binding capacity of packed red cells is a little less than 200 μmol/L (5 mg/L). Cytochrome toxicity is seen at levels only slightly higher, and death has been reported at levels from 300 to 3000 μmol/L (8–80 mg/L). A patient with a normal redcell mass (35 mL/kg) and normal methemoglobin levels can buffer about 175 mcg/kg of CN¯, corresponding to a little less than 500 mcg/kg of infused sodium nitroprusside.

Thiocyanate (SCN¯) is a normal physiological constituent of serum, with normal levels typically in the range of 50-250 μmol/L (3-15 mg/L). Clearance of SCN¯ is primarily renal. In renal failure, the half-life can be doubled or tripled.

When thiosulfate is being supplied only by normal physiologic mechanisms, conversion of CN¯ to SCN¯ generally proceeds at about 1 mcg/kg/min. This rate of CN¯ clearance corresponds to steady-state processing of a sodium nitroprusside infusion of slightly more than 2 mcg/kg/min. CN¯ begins to accumulate when sodium nitroprusside infusions exceed this rate.

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)].

Manufactured and Distributed by:

Exela Pharma Sciences, LLC
Lenoir, NC 28645

Rx Only         NDC 51754-1006-1

Nipride RTU

SODIUM NITROPRUSSIDE

in 0.9% Sodium Chloride Injection

(Ready to Use)

50 mg/100mL (0.5 mg/mL)

For Intravenous Infusion Only

100 mL Single Dose Vial. Discard unused portion.

Rx Only NDC 51754-1006-1

Nipride RTU

SODIUM NITROPRUSSIDE

in 0.9% Sodium Chloride Injection

(Ready to Use)

50 mg/100mL (0.5 mg/mL)

For Intravenous Infusion Only

100 mL Single Dose Vial. 

There are no data on the excretion of nitroprusside into human milk. The manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.