INSTRUCTIONS FOR USE

NIRFOL

Trade name: NIRFOL

International nonproprietary name : Propofol

Dosage form: Emulsion for injection

Composition per 1 ml:
Propofol Br.F 10 mg

Soybean oil F.USA

Glycerin Br.F.

Egg lecithin

Water for injection Br.F QS

Description:

white homogeneous emulsion

Pharmacotherapeutic group:

means for non-inhalation general anesthesia.

ATX code

N01AX10

Pharmacological properties

Pharmacodynamics

«NIRFOL» is a fast-acting intravenous anesthetic for induction and maintenance of general anesthesia, as well as for sedation of patients during intensive care. The general consensus is that this anesthetic causes a nonspecific effect at the level of lipid membranes. In most patients, general anesthesia occurs within 30-60 seconds. The duration of anesthesia, depending on the dose and concomitant medications, ranges from 10 minutes to 1 hour. The patient awakens from anesthesia quickly and with a clear consciousness. The opportunity to open your eyes appears after 10 minutes. Specific sites of specific adsorption have not been established.

When using NIRFOL for induction of anesthesia and for its maintenance, a decrease in average blood pressure and slight changes in heart rate are observed. However, hemodynamic parameters usually remain relatively stable during maintenance of general anesthesia and the incidence of adverse hemodynamic changes is low.

Although respiratory depression may occur following administration of Propofol, any effects are qualitatively similar to those experienced with other intravenous anesthetics and are easily controlled in a clinical setting.

«NIRFOL» reduces cerebral blood flow, intracranial pressure and reduces cerebral metabolism. The reduction in intracranial pressure was significant in patients with elevated baseline intracranial pressure.

Pharmacokinetics:

Propofol is 97% bound to plasma proteins. Drug kinetics following intravenous bolus injection can be represented by a three-part model: rapid distribution phase (half-life 2-4 minutes), β-phase (half-life 30-60 minutes) and γ-phase (half-life 200-300 minutes). ). During the γ-phase, the decrease in drug concentration in the blood occurs slowly due to slow redistribution from poorly perfused, probably fatty tissues. In a clinical setting, this phase does not affect the time of awakening. Propofol is metabolized primarily by conjugation in the liver with a clearance of about 2 l/min, but metabolism also occurs outside the liver. Clearance in children is higher than in adults. The half-life after intravenous infusion ranged from 277 to 403 minutes. Inactive metabolites are excreted mostly by the kidneys (about 88%). When anesthesia was maintained as usual, no significant accumulation of Propofol was observed after surgical procedures lasting at least 5 hours. Within the recommended infusion rates, pharmacokinetics are linear.

Indications for use

«NIRFOL» is used:

in adults and children over 1 month for general intravenous anesthesia, which has a short-term effect;
in adults and children over 1 month for induction of anesthesia and for its maintenance;
in adults and children over 16 years of age to provide sedation, receiving intensive care and on mechanical ventilation;
in conscious adults, in order to provide a sedative effect during surgical and diagnostic procedures.

Contraindications

Hypersensitivity to one of the components of the drug, pregnancy, children under 1 month of age. Propofol is contraindicated for sedation of patients under 16 years of age during intensive care.

Carefully

Elderly patients, patients with impaired cardiac, respiratory, renal or liver function, as well as patients with hypovolemia and epilepsy, Propofol should be administered with caution and at a reduced rate.

If there is cardiac, circulatory or respiratory failure, it should be compensated before Propofol is administered.

Use with caution in patients with severe heart failure and other severe heart disease unless extreme caution and intensive monitoring of the patient is provided.

Particular caution should be exercised in patients with high intracranial pressure and low mean arterial pressure, who are at increased risk of a significant fall in intracranial perfusion pressure.

Propofol is not recommended for use in patients undergoing electroconvulsive therapy.

Pregnancy and lactation

Propofol crosses the placental barrier and may have a depressant effect on the fetus. For this reason, the drug is contraindicated during pregnancy, as well as in high doses for anesthesia during childbirth, with the exception of operations to terminate pregnancy.

A small amount of propofol passes into breast milk. It is not considered to pose a risk to the infant if the mother begins breastfeeding within a few hours of propofol administration.

Directions for use and doses

For intravenous use only. When administering propofol, the physician should have at his disposal the equipment usually used during anesthesia, including means of monitoring the functioning of the cardiovascular system (ECG, pulse, oximetry) and resuscitation equipment.

The dose of Propofol is selected individually depending on the patient’s response to premedication. As a rule, when using the drug, additional administration of analgesic drugs is required.

General anesthesia in adults.

Induction anesthesia.

To induce anesthesia, NIRFOL is administered fractionally (approximately 20-40 mg every 10 seconds) until clinical signs of anesthesia appear. The usual dose for adults under 55 years of age is 1.5-2.5 mg/kg body weight. During continuous infusion, 0.3-4.0 mg/kg body weight/hour is administered. It is not recommended to exceed the infusion rate of 4.0 mg/kg body weight/hour.

At older ages, the required dose generally decreases. In patients corresponding to American Society of Anesthesiologists (ASA) classes III and IV, induction of anesthesia develops more slowly, which requires slower administration of NIRFOL : approximately 2 ml (20 mg) every 10 seconds.

Maintenance of anesthesia:

When using Propofol, maintenance of anesthesia is achieved either by continuous infusion or by repeated bolus injections.

To maintain anesthesia by continuous infusion, the dose and rate of administration are selected individually, usually 4-12 mg/kg body weight/hour of propofol is administered. For minor operations, such as minimally invasive procedures, a lower maintenance dose of approximately 4 mg/kg body weight/hour may be sufficient.

A reduction in the dose of Propofol to 4 mg/kg body weight/hour is also recommended for elderly patients, patients with hypovolemia and patients with grade III-IV severity of the condition according to the ASA classification.

To maintain anesthesia through repeated bolus injections, Propofol should be administered in a dose of 25 to 50 mg, which corresponds to 2.5 to 5 ml of the drug.

In elderly patients, rapid bolus administration is not indicated due to the possibility of cardiopulmonary depression.

General anesthesia in children older than 1 month.

Due to lack of experience with use, Propofol should not be used in children under 1 month of age.

Induction anesthesia:

When used for induction purposes, it is recommended to titrate the dose until clinical signs of the onset of anesthesia appear. The dose should be adjusted based on the patient’s age and/or weight. When inducing anesthesia in children over 8 years of age, approximately 2.5 mg/kg body weight of propofol is usually required. It is necessary to administer the drug slowly in repeated fractional doses until clinical signs of anesthesia appear. Younger children may require a higher dose. The initial dose of propofol should be 3 mg/kg body weight, and if necessary, an additional dose of 1 mg/kg body weight can be administered.

Due to the lack of experience with clinical use, lower doses are recommended for young children at high risk (ASA grade III–IV).

Maintaining anesthesia.

To maintain anesthesia in children by continuous infusion, recommended doses of propofol are 9-15 mg/kg body weight per hour. Children under 3 years of age may require a higher dose within the recommended dose range than older children. The dose should be selected individually and special attention should be paid to the adequacy of pain relief. The maximum duration of use should not exceed approximately 60 minutes, except in specific indications for longer use, such as malignant hyperthermia, when inhalational anesthetics cannot be used.

The use of «NIRFOL» as a sedative during intensive care in adults.

The dose is selected depending on the required depth of sedation. When maintaining anesthesia through continuous infusion, a dose of propofol is used from 0.3 to 4.0 mg/kg body weight per hour. Administration rates higher than 4.0 mg/kg body weight per hour are not recommended. When administering fat emulsions to a patient, it must be taken into account that 1 ml of Propofol contains 0.1 g of fat.

Propofol should not be used as a sedative in children under 16 years of age.

Methods of administration.

Infusion of Propofol undiluted is allowed. Dilution of «NIRFOL» is recommended only with a 5% glucose solution for intravenous administration or a 0.9% sodium chloride solution for intravenous administration in glass bottles.

Shake before administration!

Use only homogeneous emulsion from an intact container.

Before use, the rubber membrane of the container or the neck of the ampoule is sprayed with an alcohol aerosol or wiped with a swab soaked in alcohol.

Since NIRFOL is a fat emulsion that does not contain preservatives and does not have antimicrobial activity, the drug can serve as a favorable environment for the rapid growth of microorganisms. When opening a bottle or ampoule containing NIRFOL , it is necessary to strictly follow the rules of asepsis. Administration of the drug must be started without delay.

During the entire period of propofol administration, the rules for aseptic handling of the drug and the parenteral infusion system must be observed. When injecting NIRFOL together with other drugs and solutions in the same system, it is recommended that the latter be administered closer to the cannula. Propofol should not be administered through a microbiological filter.

Propofol and other infusion systems containing propofol are intended for single injection or infusion into only one patient individually.

Infusion of undiluted NIRFOL .

When infusing undiluted Propofol, it is recommended to always use devices to control the volume of the drug administered, such as a drop counter, syringe pumps or volumetric infusion pumps.

When administering fat emulsions, including Propofol, it is recommended to use the same infusion system for no more than 12 hours. After 12 hours of use, the system containing propofol or the container with the drug should be replaced.

Infusion of diluted NIRFOL .

To administer diluted propofol, it is possible to use various options for intravenous infusion systems. However, the use of standard systems does not guarantee against accidental uncontrolled administration of large volumes of diluted NIRFOL . The IV system should include devices to control the volume of drug administered, such as a drop counter, burette, or volumetric infusion pump. When determining the maximum burette dilution, the risk of administering large doses of propofol should be taken into account.

The recommended dilution of propofol is 1 part of Propofol and 4 parts of 5% glucose solution for intravenous administration or 0.9% sodium chloride solution for intravenous administration (the content of the active substance in the diluted solution should not be less than 2 mg/ml). The dilution is prepared under aseptic conditions immediately before administration of the drug; the infusion should be completed no later than 6 hours after preparing the dilution. Propofol should not be diluted with other solutions for infusion or injection. Co-administration of a 5% glucose solution, 0.9% sodium chloride solution with Propofol is allowed through a tee with a valve in close proximity to the injection site.

To reduce pain at the injection site of Propofol, it is permissible to mix it immediately before administration with a preservative-free 1% solution of lidocaine hydrochloride for injection (20 parts of Propofol + 1 part of 1% solution of lidocaine hydrochloride for injection).

Muscle relaxant drugs such as atracurium and mivacurium can be administered at the injection site of Propofol only after jet rinsing.

Propofol should not be used after the expiration date.

Administration of the NIRFOL emulsion should begin immediately after opening the ampoule or bottle.

The system for administering undiluted Propofol must be replaced at the end of the 12-hour period after opening the ampoule or vial. Dilutions of propofol with 5% glucose solution for intravenous administration or 0.9% sodium chloride solution for intravenous administration must be prepared under aseptic conditions immediately before infusion, their administration must be completed within 6 hours after preparation of the dilution.

Any remaining contents of ampoules or vials after use must be destroyed.

Side effects.

Are common

During induction of anesthesia, a decrease in pressure and temporary cessation of breathing may develop, which can be severe, especially in patients with a general deterioration in condition. Less commonly, epileptoform movements, convulsions and opisthotonus were observed, sometimes several hours or days after drug administration. Cases of pulmonary edema have also been reported. Sometimes upon awakening, consciousness deteriorates again for a short time. In some cases, allergic reactions have been observed in the presence of anaphylactic symptoms, such as severe hypotension, bronchospasm, facial edema or erythema. Bradycardia and, in some cases, cardiac arrest (asystole) have occurred during the use of propofol. In very rare cases, when propofol was used for sedation during intensive care at doses above 4 mg/kg/h, rhabdomyolysis, metabolic acidosis, hyperkalemia or heart failure have been observed. Very rarely, pancreatitis developed after the administration of propofol; but the cause-and-effect relationship has not been clearly confirmed. Postoperative chills, fever, cold sensation, and euphoria were also noted. With long-term use of propofol, green or reddish-brown coloration of urine may occur, which is caused by quinol metabolites of propofol and is not dangerous. Changes in sexual behavior may occur, as with the use of other anesthetics. Mild thrombopenia was observed after repeated administration of propofol.

Local

Propofol is usually well tolerated. There is often pain at the injection site, which can be relieved by mixing the drug with lidocaine or by injecting the drug into one of the large veins in the forearm or in the cubital fossa. Phlebitis and venous thrombosis are rarely observed. In isolated cases, severe tissue reactions have occurred following intravenous administration of propofol.

Overdose

An overdose can cause depression of the cardiovascular and respiratory systems. If the respiratory system is depressed, artificial ventilation with oxygen is recommended, and if the cardiovascular system is depressed, the patient’s position should be changed so that his head is higher and his legs lower. If necessary, vasopressors, plasma replacement agents, or electrolyte solutions such as Ringer’s solutions can be used.

Interaction with other drugs.

Propofol can be used in conjunction with other drugs usually used for premedication, inhalation anesthesia, muscle relaxants or local anesthetics. Cases of pharmacological incompatibility have not yet been reported. A reduction in the dose of the drug is required if general anesthesia is accompanied by local anesthesia.

The use of benzodiazepines, parasympatholytics or inhalational anesthetics in combination with propofol prolongs the anesthetic effect and reduces the respiratory rate.

After joint premedication with opiates, the frequency and duration of apnea may increase.

During the administration of suxamethonium or neostigmine, bradycardia and cardiac arrest may occur.

Propofol in combination with these drugs that have a hypotensive effect and affect breathing may enhance these phenomena.

It should be taken into account that the use of Propofol during premedication simultaneously with inhalation or other analgesics may potentiate anesthesia and side effects from the cardiovascular system. The combined use of drugs that depress the central nervous system, for example, alcohol, general anesthetics or narcotic analgesics, leads to a pronounced manifestation of their sedative effect. If the administration of Propofol is combined with parenterally administered drugs that depress the central nervous system, severe respiratory and cardiac depression is possible.

After administration of fentanyl, the blood level of Propofol temporarily increases. There is evidence that the administration of fat emulsions, such as Propofol, to patients receiving cyclosporine causes leukoencephalopathy.

special instructions

Propofol does not reduce the tone of the vagus nerve, and its use in some cases is accompanied by bradycardia (sometimes pronounced), as well as asystole. Before induction or during maintenance of anesthesia with Propofol, the possibility of intravenous administration of anticholinergics should be considered, especially in cases of suspected increased vagal tone or when Propofol is used in conjunction with other drugs that can cause bradycardia.

To relieve pain at the injection site during induction of anesthesia with Propofol, lidocaine can be administered before administering the drug emulsion. When using lidocaine, it should be taken into account that it should not be used in patients with hereditary porphyria.

Propofol should only be administered by physicians trained in anesthesia or intensive care.

The effectiveness and safety of Propofol for (background) relaxation in children under 16 years of age has not been studied. Serious side effects, including death, have been reported when the drug is used unlicensed for (background) relaxation in children under 16 years of age, although a causal relationship has not been established. In particular, cases of metabolic acidosis, hyperlipidemia, rhabdomyolysis and/or heart failure have been reported. These effects were most often observed in children with respiratory tract infections receiving doses of the drug in intensive care units that exceeded adult doses. Similarly, rare cases of metabolic acidosis, rhabdomyolysis, hyperkalemia, and/or rapidly progressive heart failure (in some cases fatal) have been reported in adults treated for longer than 58 hours at rates greater than 5 mg/kg/hour. This rate exceeds the maximum rate of 4 mg/kg/hour recommended for use of the drug for the purpose of relaxation of patients in intensive care units. Heart failure in such cases is usually not responsive to maintenance therapy with inotropes.

Once again, we remind doctors, if possible, not to exceed the dosage of 4 mg/kg/hour, which is usually sufficient for relaxation of patients on mechanical ventilation in intensive care units (for treatment durations of more than 1 day). Physicians should be alert for these side effects and reduce the dose or switch to other sedatives at the first sign of their occurrence.

In some cases, after the use of Propofol, a period of postoperative unconsciousness of the patient was observed, accompanied by increased muscle tone. Although consciousness returned spontaneously, patients who are unconscious require careful monitoring.

Propofol contains soybean oil, which in rare cases can cause severe allergic reactions.

Before discharging the patient from the clinic, you should ensure that he has fully recovered from anesthesia.

During the entire infusion period, the principles of asepsis should be observed both in relation to the drug Propofol and in relation to the infusion equipment. Parallel administration of other substances through the infusion system for Propofol should be carried out as close to the cannula as possible. The drug should not be administered through an antibacterial filter.

Propofol and all infusion equipment for its administration can be used only once and only for one patient.

The rate of administration of Propofol should be reduced in patients with congenital dementia, patients with epilepsy, with impaired function of the heart, lungs, liver and kidneys, and with hypovolemic conditions.

Special precautions should be taken in patients with lipid metabolism disorders, as well as in other conditions that require caution when infusing fat emulsion, since 1 ml of Propofol contains 0.1 g of fat.

If it is necessary to administer an increased dose of the drug to overweight patients, the increased risk of hemodynamic disturbances and adverse effects on the cardiovascular system should be taken into account.

After 3 days of using Propofol in the intensive care unit, lipid levels should be checked. After 3 days of using Propofol in the intensive care unit, lipid levels should be checked.

Due to the increased dose of the drug required for patients with severe obesity, the risk of changes in hemodynamics and effects on the cardiovascular system should be taken into account.

The use of Propofol as a sedative in adults can be carried out

only by doctors with special training in anesthesiology and intensive care.

Propofol should not be administered by personnel performing diagnostic or surgical procedures.

Although a cause-and-effect relationship has not been established, the use of Propofol as a sedative in children has caused serious complications, including death in some cases. Such cases were most often observed with unauthorized use in children with respiratory tract infections, and the dose exceeded the recommended dose for adults.

Driving a car and working with machinery

After the administration of Propofol, the patient should be under medical supervision for an appropriate period of time. The patient should be informed that he should not drive vehicles or machinery, should avoid drinking alcohol and working in potentially hazardous conditions. The patient can be sent home only with an accompanying person.

Storage conditions.

Store at a temperature not exceeding 30° C. Do not freeze!
Shake before use!
Use only if the emulsion is homogeneous and the packaging is not damaged.

Best before date.

24 months

Release form

Glass bottles containing 10, 20 and 50 ml of the drug, each in a box with instructions for use.

Conditions for dispensing from pharmacies :

Dispensed with a doctor’s prescription

Manufacturer

Aculife Healthcare Pvt. Ltd. India

NIRFOL

Price on Request

NIRFOL

Price on Request