Remifentanil (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Moscow Endocrine Plant FSUE (Russia)

ATC Code

N01AH06 (Remifentanil)

Active Substance

Remifentanil (Rec.INN registered by WHO)

Dosage Forms

	Remifentanil	Lyophilisate for the preparation of a concentrate for the preparation of a solution for intravenous administration 2 mg
		Lyophilisate for the preparation of a concentrate for the preparation of a solution for intravenous administration 5 mg

Dosage Form, Packaging, and Composition

Lyophilisate for the preparation of a concentrate for the preparation of a solution for intravenous administration

2.194 mg – vials – cardboard packs – By prescription
2.194 mg – vials (5 pcs.) – cardboard packs – By prescription

Lyophilisate for the preparation of a concentrate for the preparation of a solution for intravenous administration

5.485 mg – vials – cardboard packs – By prescription
5.485 mg – vials (5 pcs.) – cardboard packs – By prescription

Clinical-Pharmacological Group

Pure opioid receptor agonist. Analgesic

Pharmacotherapeutic Group

Anesthetics; general anesthetics; opioid analgesics

Pharmacological Action

Opioid analgesic, selective agonist of mu-opioid receptors. It is characterized by a rapid onset of effect and a short duration of action.

Antagonists of remifentanil at mu-opioid receptors are drugs that inhibit the action of narcotic drugs, including naloxone.

Indications

For general anesthesia during induction of anesthesia; for maintenance of general anesthesia during various surgical interventions (including cardiac surgery); for the purpose of prolonged analgesia in the early postoperative period (conducted under strict medical supervision) when transitioning to analgesia with long-acting drugs.

ICD codes

Dosage Regimen

Administer intravenously as a continuous infusion; an initial bolus dose may be used at induction. Titrate all doses to the individual patient’s response, age, weight, and clinical status.

For induction of anesthesia in adults, administer a dose of 0.5 to 1 mcg/kg/min. Simultaneously, reduce doses of concomitant anesthetic agents. A bolus dose of 0.5 to 1 mcg/kg over at least 30 seconds may be administered at the start of the infusion.

For maintenance of anesthesia in adults, use infusion rates of 0.1 to 2 mcg/kg/min. Adjust the rate within this range based on surgical stimulus. Reduce infusion rate to 0.05 mcg/kg/min in the absence of surgical stimulus. Continuously administer a hypnotic or sedative agent.

For analgesia in the postoperative period, initiate an infusion at 0.025 to 0.1 mcg/kg/min. Titrate to achieve adequate analgesia. Monitor patients closely for respiratory depression in a fully equipped setting.

For geriatric patients (over 65 years), reduce the initial dose by 50%. Titrate carefully due to increased sensitivity to cardiovascular effects.

For obese patients, calculate the dosage based on ideal body weight, not actual body weight.

For pediatric patients (1 to 12 years), adjust regimen based on approved pediatric dosing schedules; safety and efficacy in neonates are not established.

For patients with severe hepatic impairment, initiate therapy at reduced doses and titrate cautiously due to increased risk of respiratory depression.

Reconstitute the lyophilisate with the specified diluent. Further dilute the resulting concentrate to a final concentration of 20, 25, 50, or 250 mcg/mL in an appropriate IV fluid. Administer using a controlled infusion device.

Adverse Reactions

From the digestive system often – nausea, vomiting, rarely – constipation.

From the cardiovascular system often – arterial hypotension, possible – bradycardia, postoperative increase in blood pressure.

From the respiratory system possible – acute respiratory depression, apnea.

Allergic reactions when remifentanil is combined with one or more general anesthetics, allergic reactions and anaphylactic reactions were rarely observed.

Other often – skeletal muscle rigidity, postoperative chills; rarely – sedative effect (during recovery from general anesthesia), hypoxia, postoperative pain.

Side effects resolved within a few minutes after discontinuation of administration or after reducing the rate of remifentanil infusion.

Contraindications

Hypersensitivity to remifentanil and other fentanyl analogues.

The dosage form of remifentanil contains glycine, therefore its use for epidural and spinal blockade is contraindicated.

Use in Pregnancy and Lactation

Adequate and strictly controlled clinical studies on the safety of the drug during pregnancy have not been conducted. Remifentanil can be used during pregnancy only if the intended benefit to the mother outweighs the potential risk to the fetus.

The safety of remifentanil during labor and delivery has not been established.

Available data are insufficient to recommend the use of remifentanil during labor or cesarean section.

Remifentanil crosses the placental barrier, and fentanyl analogues can cause respiratory depression in the child.

It is not known whether Remifentanil is excreted in breast milk. Use with caution during lactation.

It should be borne in mind that fentanyl analogues are excreted in breast milk.

In experimental studies, after administration of remifentanil, its metabolites were detected in the breast milk of rats.

Use in Hepatic Impairment

Patients with severe hepatic impairment may be more sensitive to the respiratory depressant effect of remifentanil. Such patients require careful monitoring and individual selection of the remifentanil dose.

Geriatric Use

Elderly patients may be more sensitive to the cardiovascular effects of remifentanil.

Special Precautions

Remifentanil should be used only by anesthesiologists in departments fully equipped with monitoring and support equipment for the respiratory and cardiovascular systems.

The incidence of muscle rigidity depends on the dose and rate of administration of remifentanil. Treatment of muscle rigidity should be carried out taking into account the patient’s clinical condition. Rigidity usually disappears within a few minutes after stopping the remifentanil infusion.

Debilitated or elderly patients, as well as patients with hypovolemia, may be more sensitive to the cardiovascular effects of remifentanil.

In obese patients, it is recommended to reduce the dose of remifentanil and calculate it based on ideal body weight, because the clearance and V_d of remifentanil correlate more with ideal rather than actual body weight.

Patients with severe hepatic impairment may be more sensitive to the respiratory depressant effect of remifentanil. Such patients require careful monitoring and individual selection of the remifentanil dose.

In patients of ASA classes III/IV (high physical status risk) during general anesthesia, the effect of potent opioids on hemodynamics may be more pronounced, so Remifentanil should be administered to such patients with caution. Like other opioid analgesics, Remifentanil can cause drug dependence.

When administering remifentanil, the doses of inhalational and intravenous anesthetics, as well as benzodiazepines used in general anesthesia, should be reduced.

Effect on the ability to drive vehicles and operate machinery

In case of early discharge from the hospital after general anesthesia, patients should not drive a car or perform work that requires high concentration and quick psychomotor reactions.

Drug Interactions

With the simultaneous use of remifentanil with drugs that have a depressant effect on the central nervous system (including inhalational and intravenous anesthetics, as well as benzodiazepines used in general anesthesia), without reducing the dose of the latter, an increase in the frequency of side effects of these drugs is possible.

With the simultaneous use of remifentanil with drugs that reduce myocardial contractility (including beta-blockers, calcium channel blockers), an increase in arterial hypotension and bradycardia is possible.

Nonspecific esterases contained in blood products can cause hydrolysis of remifentanil with the formation of an inactive metabolite.

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.