Naniprus (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Inter-S Group, LLC (Russia)

Manufactured By

Sopharma, JSC (Bulgaria)

ATC Code

C02DD01 (Sodium nitroprusside)

Active Substance

Sodium nitroprusside (USP United States Pharmacopeia)

Dosage Form

Naniprus

Lyophilisate for preparation of solution for infusions 30 mg: amp. 1 pc. in set with solvent

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for infusions in the form of an unformed tablet with a coarse mesh structure or a coarse-grained powder from light orange with a brownish tint to orange in color; solvent – colorless transparent liquid; lyophilisate solution – transparent light brown liquid.

Excipients : sodium citrate dihydrate – 61.7 mg (calculated as anhydrous sodium citrate – 54.15 mg).

Solvent water for injections – 5 ml.

30 mg – dark glass ampoules with a capacity of 10 ml (1) in a set with a solvent (amp. 5 ml 1 pc.) – black polyethylene bags (1) – cardboard packs.

Clinical-Pharmacological Group

Peripheral vasodilator

Pharmacotherapeutic Group

Vasodilating agent

Pharmacological Action

A rapid-acting and short-acting peripheral vasodilator. It reduces the tone of arteries and veins due to a direct myotropic effect. By dilating peripheral arterial vessels, sodium nitroprusside reduces afterload, decreases left ventricular tension, and lowers blood pressure. By dilating peripheral veins, it reduces cardiac preload, which leads to an improvement in systemic and intracardiac hemodynamics and a decrease in pressure in the pulmonary circulation.

In some cases, it causes reflex tachycardia. The hypotensive effect after intravenous administration develops within the first 2-5 minutes, and 5-15 minutes after the end of administration, blood pressure returns to the initial level.

Pharmacokinetics

In the body, Sodium nitroprusside is metabolized by erythrocyte enzymes into cyanides, which, with the participation of hepatic rhodanase, are converted into thiocyanate.

T_1/2 – 4 hours. It is excreted by the kidneys (20% unchanged) and with bile. It penetrates the blood-brain barrier and the placental barrier, and is excreted in small amounts in breast milk.

Indications

Hypertensive crisis; acute left ventricular failure with pulmonary edema; controlled arterial hypotension during surgical interventions to reduce operative blood loss; acute heart failure when rapid reduction of left ventricular afterload is necessary, to reduce left ventricular filling pressure.

ICD codes

Dosage Regimen

Administer intravenously as a continuous infusion only. Do not administer by direct intravenous injection. Initiate therapy in a setting with continuous blood pressure monitoring and intensive care facilities.

Reconstitute the 30 mg lyophilisate with the provided 5 ml Water for Injections. The resulting solution contains 6 mg/ml of sodium nitroprusside. Further dilute this reconstituted solution in 250 ml to 1000 ml of 5% Dextrose Injection, USP. Do not use any other diluent. Protect the prepared infusion solution from light by wrapping the container in aluminum foil or another opaque material. Use the prepared solution immediately; discard any unused portion after 24 hours.

The initial infusion rate is 0.25-0.3 mcg/kg/min. Increase the infusion rate gradually, by increments of 0.5 mcg/kg/min every 5 minutes, until the desired therapeutic effect is achieved. The average effective dose is 3 mcg/kg/min. Do not exceed the maximum recommended infusion rate of 10 mcg/kg/min.

Infusion at the maximum rate for more than 10 minutes is not recommended. If adequate blood pressure control is not achieved at the maximum rate, discontinue the infusion immediately. The total cumulative dose should not exceed 1.5 mg/kg of body weight to minimize the risk of cyanide toxicity.

Monitor for signs of cyanide intoxication, including metabolic acidosis, tachycardia, air hunger, and altered consciousness, particularly with high-dose or prolonged infusion. Monitor plasma thiocyanate concentrations if infusion continues for more than 72 hours, or in patients with renal impairment; do not exceed 100 mcg/ml.

To terminate the infusion, reduce the rate gradually to avoid a precipitous rebound increase in blood pressure. Closely monitor the patient’s hemodynamic status for several hours after discontinuation.

Adverse Reactions

From the nervous system headache, anxiety, dizziness, muscle spasms, hyperreflexia.

From the cardiovascular system rapid decrease in blood pressure, tachycardia, bradycardia, chest discomfort.

From the digestive system: nausea, vomiting, abdominal pain.

Dermatological reactions rarely – skin rash, itching, erythema.

Local reactions redness, swelling, acute phlebitis at the injection site.

Other increased sweating; rarely – decreased platelet count, hypothyroidism; when used in excessively high doses – development of cyanide intoxication (vomiting, loss of consciousness, tissue hypoxia), with rapid discontinuation of infusion – “rebound” syndrome.

Contraindications

Hypersensitivity to sodium nitroprusside; symptomatic (compensatory) arterial hypertension (with arteriovenous shunting or coarctation of the aorta); acute cerebrovascular accident, increased intracranial pressure, arterial hypotension, chronic heart failure associated with reduced peripheral vascular resistance, aortic stenosis, hypovolemia, hypothyroidism, vitamin B₁₂ deficiency; sulfotransferase (rhodanase) deficiency in patients with Leber’s optic atrophy, optic nerve atrophy, glaucoma; severe hepatic and/or renal failure; pregnancy, lactation (breastfeeding). In emergency situations (for vital indications), these contraindications are relative.

With caution in patients with hypothermia, hyponatremia, coronary artery disease, and in elderly patients.

Use in Pregnancy and Lactation

Sodium nitroprusside is contraindicated for use during pregnancy and lactation (breastfeeding). In emergency situations (for vital indications), these contraindications are relative.

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency. In emergency situations (for vital indications), this contraindication is relative.

Use in Renal Impairment

Contraindicated in severe renal insufficiency. In emergency situations (for vital indications), this contraindication is relative.

Pediatric Use

Experience of use in children is limited. It should be used with caution – according to indications, in recommended doses.

Geriatric Use

Should be used with caution in elderly patients (more rapid development of the antihypertensive effect).

Special Precautions

The development of a hypertensive crisis with concomitant cerebrovascular phenomena is not an indication for treatment with sodium nitroprusside. The decision is made in the presence of visceral complications with an immediate threat to life.

In patients with hyponatremia and impaired renal function, prolonged treatment with sodium nitroprusside can lead to higher plasma concentrations of the main metabolite, thiocyanate. Since the latter suppresses the uptake of iodine by the thyroid gland, symptoms of hypothyroidism may appear.

In young patients, to prevent a pronounced compensatory reaction associated with a sharp increase in catecholamine and renin levels, the dose increase and decrease should be carried out gradually.

Drug Interactions

Ganglioblockers, general anesthetics, beta-blockers, diuretics, “slow” calcium channel blockers (diltiazem), ACE inhibitors (captopril) can enhance the antihypertensive effect of sodium nitroprusside.

Since Sodium nitroprusside is a nitric oxide donor, it should not be used simultaneously with phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil).

When used concomitantly with estrogens or sympathomimetics, the antihypertensive effect of sodium nitroprusside is reduced.

Mixing the infusion solution of sodium nitroprusside with other medicinal products is not allowed.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.