Naloxone instructions for use analogues. International non-proprietary name

Naloxone is a competitive opioid receptor antagonist.

Release form and composition

Dosage form - solution for injection: colorless clear liquid(1 ml each: in colorless glass ampoules, 5 pcs in PVC trays, 2 trays in a carton box; in ampoules, 5 pcs in plastic holders, in a carton box 2 holders or 10 pcs in a carton box ; each pack also contains instructions for the use of Naloxone).

The active substance of Naloxone is naloxone hydrochloride (in the form of naloxone hydrochloride dihydrate), in 1 ml - 0.4 mg.

Auxiliary components: hydrochloric acid (up to pH 3-5), sodium chloride, water for injection.

Pharmacological properties

Pharmacodynamics

Naloxone is a specific opioid receptor antagonist. The mechanism of its action is due to the ability to competitively bind to the main types of opioid receptors and eliminate or prevent the peripheral and central (including respiratory depression) effects of endogenous opioid peptides and exogenous opioids (narcotic analgesics and their surrogates).

Naloxone also affects the dopaminergic and GABAergic systems of the brain. When drug addiction causes the development of withdrawal symptoms. Non addictive and drug addiction.

Clinically significant effects of naloxone: weakening of the hypotensive effect, reduction of sedative and euphoric effects, restoration of breathing.

The drug does not have a pronounced effect on dystrophy and psychomimetic effects caused by narcotic analgesics of the agonist-antagonist group (for example, pentazocine or butofanol). It is not able to completely eliminate the effects of buprenorphine and is ineffective as an antagonist of tramadol.

In patients with drug dependence on opioids, naloxone causes the development of a withdrawal syndrome.

Pharmacokinetics

After intravenous administration of the drug, the effect develops in the first 2 minutes, after intramuscular and subcutaneous injections - within 2-5 minutes. Maximum Action observed after 5-15 minutes, its duration is 20-45 minutes - with intravenous administration and 2.5-3 hours - with intramuscular / subcutaneous administration.

Naloxone crosses the blood-brain and placental barriers.

It is metabolized in the liver with the predominant formation of glucuronides. It is excreted by the kidneys, with 70% of the administered dose excreted from the body within 72 hours.

The half-life (T 1/2) from blood plasma averages 1 hour (30 to 80 minutes). T 1/2 in adults - 64 ± 12 minutes, in newborns (after injection into umbilical vein) - 3.1±0.5 h, in premature babies - 51.8±9.2 min.

Indications for use

• Acute poisoning, including against the background of an overdose of opioid analgesics (fentanyl, trimeperidine, morphine) and other drugs, toxic effect which are due to the presence of an opioid component (methadone, opioid surrogates, pentazocine, butorphanol, buprenorphine, nalbuphine) as part of complex resuscitation measures;
• Postoperative use (only if narcotic analgesics are used during the operation) - to speed up the recovery from general anesthesia, before the completion of controlled breathing;
• Restoration of breathing in newborns, in the case of the introduction of the mother of opioid analgesics during childbirth;
• Diagnostic tool for opioid dependence (naloxone test).

Contraindications

Naloxone is contraindicated in case of hypersensitivity to the components of the drug.

The drug should be used with caution in patients with impaired liver and / or kidney function, in childhood and in newborns.

Appointment during pregnancy and breastfeeding is possible only if absolutely necessary.

Naloxone, instructions for use: method and dosage

Naloxone is intended for intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration.

The rate of administration is selected individually, taking into account the patient's response to the drug and previous single doses.

For infusion use, dilute the Naloxone solution in 5% dextrose solution or 0.9% sodium chloride solution, observing the proportion - 1 ampoule of the drug per 100 ml of infusion medium. Prepare the solution before direct use.

The dose and method of administration is prescribed by the doctor, taking into account the patient's condition, the type and amount of opioid taken by him.

• Adults: the initial single dose is 0.4-2 mg. At life threatening conditions, the drug should be administered intravenously slowly, over 2-3 minutes. For achievement clinical effect re-introduction is indicated after 2-3 minutes, the procedure is repeated until the restoration of uniform breathing and consciousness. If recovery of consciousness and breathing has not occurred after a total dose of 10 mg, a non-opioid cause of poisoning should be considered. Can be used in / m or s / c;
• Children: the initial single dose - at the rate of 0.01 mg per 1 kg of the child's weight, preferably in / in the introduction for 2-3 minutes. If necessary, repeated administration of a dose of 0.1 mg per 1 kg of weight is shown after 2-3 minutes. If intravenous administration is not possible, the drug is administered in divided doses intramuscularly or s / c with an interval of 2-3 minutes, in which case the effect appears more slowly. To obtain a longer action, a single intramuscular or s / c administration is recommended at a dose of about 0.2 mg or 0.06 mg per 1 kg of the child's weight.

Postoperative use of Naloxone:

• Adults: IV at 0.1-0.2 mg with an interval of 2-3 minutes until normal pulmonary ventilation appears and the patient wakes up, but in the absence of distinct sensations of discomfort and pain. Minimal excess symptoms required dose could be an increase blood pressure(AD), cessation of analgesia, sweating, nausea, vomiting, dyscirculatory crisis. Sometimes, especially in cases of the use of opioid analgesics with a long-acting effect, additional intramuscular administration of naloxone is necessary within 1-2 hours. The drug can also be administered by intravenous infusion;
• Children: intravenously at 0.01 mg per 1 kg of weight, in the absence of the desired effect, you can additionally enter a dose corresponding to 0.1 mg per 1 kg of the child's weight. In the absence of the possibility of intravenous administration, fractional intramuscular or s / c administration is shown every 2-3 minutes. single dose should not exceed 0.2 mg of the drug. In addition, infusion administration is indicated.

In the case of the use of opioid analgesics during childbirth, to restore breathing in newborns, intravenous, intramuscular, or subcutaneous administration of Naloxone is indicated. Before insertion, it is necessary to verify the patency respiratory tract baby. The recommended dose is 0.01 mg per 1 kg of body weight, it is possible to repeat the dose after 2-3 minutes. In order to prevent a newborn, you can enter 0.2 mg or 0.06 mg per 1 kg of body weight once intramuscularly.

As a diagnostic tool for drug (opioid) dependence, the drug is used by intravenous administration of a dose of 0.0005 mg per 1 kg of the patient's weight. This dose allows you to establish whether or not difficulty urinating and respiratory depression are caused by opioids. After that, the dose can be slightly increased, but not up to large doses, since high doses completely remove the effect of the opioid, including the analgesic effect, cause excitation of the circulatory system and the sympathetic system.

Side effects

The use of Naloxone in the postoperative period can cause the following side effects: suffocation, increase or decrease in blood pressure, ventricular tachycardia and ventricular fibrillation, pulmonary edema, cardiac arrest (mentioned effects in rare cases can lead to coma and encephalopathy, up to lethal outcome). Doses higher than those recommended may cause psychomotor agitation and loss of analgesia.

Sudden withdrawal of the drug can lead to sweating, nausea, vomiting, pulmonary edema, increased blood pressure, tachycardia, ventricular tachycardia, ventricular fibrillation, cause tremors and convulsions of the body, cardiac arrest, including death.

Symptoms of withdrawal syndrome in opioid dependence: weakness, nausea, vomiting, fever, sweating, cramps in epigastric region, diarrhea, increased blood pressure, tachycardia, rhinitis, sneezing, piloerection, nervousness, irritability, yawning, anxiety, trembling, pain unknown localization; in newborns - unrestrained crying, convulsions, hyperreflexia.

Overdose

Case reports acute overdose did not act.

When naloxone is administered to high doses(from 4 mg/kg) possible the following symptoms: chills, nausea, vomiting, marked decrease or increase in blood pressure, bradycardia, hyperventilation, convulsions. Shown holding conservative treatment in intensive care settings.

At a dose of 2 mg/kg, the drug can cause cognitive and behavioral disorders, including lack of appetite, tension, anxiety, depression, suspicion, irritability, difficulty concentrating. behavioral symptoms may continue for 2-3 days.

It is also possible to develop somatic signs such as stomach pain, feeling of heaviness, nausea, sweating, dizziness.

Treatment is symptomatic.

special instructions

Naloxone is used in stationary conditions provided with the possibility of resuscitation (including cardiopulmonary) and oxygen therapy.

Caution should be used when treating newborns with a history of maternal dependence on opioids, since the complete sudden withdrawal of the drug may potentiate the development acute syndrome cancellation.

Patients with pathology of the lungs, heart, impaired renal and / or liver function, suspected or established physical dependence on opioids, during pregnancy, breastfeeding, in childhood, it is recommended to use the drug under close medical supervision.

Since the response to the use of Naloxone in the treatment of respiratory depression while taking buprenorphine may be incomplete and there is a risk of reduced respiratory activity, the patient may need mechanical ventilation.

Influence on the ability to drive vehicles and complex mechanisms

During the period of use of naloxone, the patient is prohibited from any activity related to the management of vehicles and mechanisms.

Use during pregnancy and lactation

During pregnancy and lactation, Naloxone may be prescribed in case of urgent need.

Application in childhood

In pediatrics, the use of Naloxone is allowed if indicated. Care should be taken to prescribe the drug in doses based on the age of the child.

Caution should be exercised when treating neonates whose mothers have a history of dependence on opioids, as complete and abrupt discontinuation narcotic substance may cause an acute withdrawal syndrome.

For impaired renal function

Naloxone should be used with caution in patients with impaired renal function.

For impaired liver function

Naloxone should be used with caution in patients with hepatic impairment.

drug interaction

When administered intravenously, Naloxone must not be mixed with other agents, and the drug is also incompatible with solutions containing bisulfites.

The drug reduces hypotensive effect clonidine, the action of opioid analgesics (nalbuphine, butorphanol, pentazocine, remifentanil, fentanyl), which contributes to the acceleration of the withdrawal syndrome.

Simultaneous use of methohexital blocks acute period withdrawal symptoms that occurred during the use of naloxone in patients with drug addiction.

Compatible with dextrose solution 5%, sodium chloride solution 0.9% and sterile water for injection.

Analogues

Analogues of Naloxone are Antakson, Vivitrol, Naltrexone, Naltrexone FV, Prodetoxon, Relistor, etc.

Terms and conditions of storage

Keep away from children.

Store in a dark place at temperatures up to 25°C.

Shelf life - 4 years.

Drug: NALOXONE
Active ingredient: naloxone
ATX code: V03AB15
KFG: Competitive opioid receptor antagonist
Reg. number: P No. 011962/01
Date of registration: 31.03.06
The owner of the reg. acc.: WARSAW PHARMACEUTICAL WORK POLFA S.A. (Poland)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Excipients: sodium chloride, hydrochloric acid, water for injection.

1 ml - ampoules (10) - packs of cardboard.

The description of the drug is based on the officially approved instructions for use.

PHARMACHOLOGIC EFFECT

Competitive opioid receptor antagonist. Blocks predominantly mu-receptors, to a lesser extent affects other opioid receptors and eliminates the effect of both endogenous opioid peptides and exogenous opioid analgesics.

The introduction of Naloxone prevents, weakens or eliminates (depending on the dose and time of administration) the effects of opioid analgesics, restores breathing, reduces sedative action and euphoria, weakens the hypotensive effect.

Naloxone has no pronounced effect on psychomimetic effects and dysphoria caused by opioid analgesics of the agonist-antagonist group (pentazocine, butorphanol). Not very effective as an antagonist of tramadol. Does not completely eliminate the effects of buprenorphine.

Naloxone provokes a withdrawal syndrome in patients with opioid dependence.

With intravenous administration, the effect of the drug begins within the first 2 minutes, with intramuscular and s / c administration - after a few minutes. The duration of action is 20-45 minutes after intravenous administration and 2.5-3 hours after intramuscular or s / c administration.

PHARMACOKINETICS

Metabolism and excretion

Naloxone is biotransformed in the liver to form glucuronides. T 1/2 is about 1 hour. Excreted by the kidneys.

INDICATIONS

Acute poisoning with opioid analgesics (morphine, promedol, fentanyl) and other drugs, in the mechanism toxic action which have an opioid component (methadone, pentazocine, buprenorphine, butorphanol, nalbuphine) in combination with other resuscitation measures;

In anesthesiology, to stop the action of morphine-like analgesics during surgery under special circumstances;

To restore breathing in newborns after the introduction of opioid analgesics to a woman in labor;

As a diagnostic tool in patients with suspected opioid dependence (naloxone test).

DOSING MODE

The dose of the drug and the route of administration depend on the condition of the patient and the amount of opioid agonist present in the body.

At poisoning with opioid analgesics The initial dose of Naloxone is 0.4-2 mg IV slowly (over 2-3 minutes), IM or s/C. In life-threatening conditions, the intravenous route of administration is preferred. Repeated doses can be administered after 2-5 minutes before the onset of consciousness and the restoration of spontaneous breathing. If, after administration of a total dose of Naloxone 10 mg, recovery of consciousness and respiration does not occur, another (non-opioid) cause of poisoning should be considered.

Starting dose for children is 5-10 mcg/kg of body weight. Possible if necessary repeated injections drug.

For acceleration of recovery from surgical anesthesia Naloxone is prescribed in smaller doses - from 100 to 200 mcg (1.5-3 mcg / kg) every 2-3 minutes until adequate pulmonary ventilation appears and the patient wakes up, but without distinct pain and discomfort. A dose greater than the minimum required may cause the cessation of analgesia and an increase in blood pressure, as well as other symptoms - nausea, vomiting, increased sweating, dyscirculatory crisis.

Initial dose of Naloxone for children is 1-2 mcg / kg of body weight in / in. If there is no desired effect, the drug is re-introduced at doses up to 100 mcg / kg of body weight every 2 minutes until spontaneous breathing occurs and consciousness is restored. If it is impossible to carry out an intravenous injection, the drug is administered intramuscularly or s / c in fractional doses.

For newborns the initial dose makes 10 mcg/kg of body weight. The introduction can be repeated in accordance with the principles of use in adults with postoperative depression respiration during the use of opioid analgesics.

At respiratory depression caused by the administration of opioid analgesics to the mother during perinatal anesthesia, Naloxone is administered to newborns at an initial dose of 1-2 μg/kg body weight IM, SC or IV. If there is no desired effect, the drug is re-introduced at a dose of up to 100 mcg / kg of body weight every 2 minutes until spontaneous breathing occurs and consciousness is restored. Before the introduction of the drug, it is necessary to verify the patency of the respiratory tract in the newborn. Possible prophylactic intramuscular administration of 200 mcg (60 mcg/kg of body weight) Naloxone.

With the aim of diagnosing opioid addiction 800 mcg of Naloxone is injected intravenously and the patient's condition is monitored in order to identify signs of a withdrawal syndrome.

SIDE EFFECT

Rapid reverse development Narcotic oppression when using Naloxone may be accompanied by various reactions.

From the side digestive system: nausea, vomiting.

From the side of the cardiovascular system: tachycardia, arterial hypertension, cardiac arrest.

From the side of the central nervous system: trembling, convulsions.

Others: increased sweating.

When used in therapeutic doses in patients who do not contain opioids, Naloxone usually does not cause side effects.

When using Naloxone in the postoperative period in doses exceeding the minimum required, the disappearance of analgesia and excitation are possible, arterial hypotension, arterial hypertension, ventricular tachycardia, fibrillation, pulmonary edema.

Withdrawal syndrome in patients with opioid dependence: pain of unspecified localization, diarrhea, hyperthermia, rhinorrhea, sneezing, " goose pimples", sweating, nausea, vomiting, fatigue, tremor, spasms in the epigastric region; in newborns - convulsions, diarrhea, hyperthermia, uncontrollable crying, hyperreflexia, sneezing, tremor, severe irritability, vomiting.

CONTRAINDICATIONS

Hypersensitivity to the drug.

PREGNANCY AND LACTATION

Use Naloxone with caution during pregnancy.

It is not known whether naloxone is excreted from breast milk. The use of the drug during lactation (breastfeeding) is possible according to absolute indications.

SPECIAL INSTRUCTIONS

The duration of action of some opioid analgesics may exceed the duration of action of naloxone, so patients must be under constant medical supervision and in conditions that allow for mechanical ventilation and other resuscitation.

Naloxone is ineffective for respiratory depression caused by non-opioid drugs.

The drug does not cause the development of addiction and the formation of drug dependence.

OVERDOSE

Currently, there are no data on overdose of the drug Naloxone.

DRUG INTERACTIONS

Reduces the effect of opioid analgesics (including butorphanol, fentanyl, pentazocine, nalbuphine, remifentanil) and accelerates the onset of withdrawal.

At simultaneous application Naloxone may reduce the antihypertensive effect of clonidine.

Not compatible with solutions medicines containing bisulfites.

TERMS AND CONDITIONS OF DISCOUNT FROM PHARMACIES

The drug is dispensed by prescription.

TERMS AND CONDITIONS OF STORAGE

Release form, composition and packaging

pharmachologic effect

Pharmacokinetics

Penetrates through the blood-brain and placental barrier. Metabolized in the liver. T 1/2 naloxone - 30-80 min. It is excreted by the kidneys (70% of the administered dose is excreted within 72 hours).

Dosage

The drug is administered intravenously, intramuscularly, subcutaneously.

With an overdose of narcotic analgesics adults- at a dose of 0.4-2 mg, children- 5-10 mcg/kg. If the use at the indicated dose does not bring the expected effect, the administration at the same dose is repeated after 2-3 minutes. The maximum total dose is 10 mg / day. If recovery of consciousness and breathing does not occur, another (non-opioid) cause of poisoning should be considered.

Postoperative administration is carried out in / in, at a dose of 0.1-0.2 mg, after 2-3 minutes the introduction of the same dose is repeated until the patient's satisfactory breathing is restored. Then, if necessary, intramuscular administration is continued for several hours.

At children in / in the initial dose - 1-2 mcg / kg. If there is no desired effect, re-introduce at doses up to 0.1 mg / kg every 2 minutes, until spontaneous breathing occurs and consciousness is restored. If intravenous administration is not possible, it can be administered intramuscularly or subcutaneously in divided doses.

At newborns initial dose - 0.01 mg / kg. The introduction can be repeated in accordance with the principles of use in adults.

With respiratory depression caused by the introduction of opioid analgesics to the mother during childbirth, newborns are administered 0.1 mg/kg IM, subcutaneously or intravenously. Before the introduction, it is necessary to ensure the patency of the respiratory tract in the newborn. Possible prophylactic intramuscular injection of 0.2 mg (0.06 mg/kg).

Diagnosis of opioid dependence - in / in 0.08 mg.

drug interaction

Reduces hypotensive action clonidine.

Reduces the effect of narcotic analgesics (including butorphanol, nalbuphine, pentazocine, fentanyl, remifentanil) and accelerates the appearance of the "withdrawal" syndrome.

Incompatible with solutions of drugs containing hydrosulfates. Pharmaceutically compatible with 0.9% sodium chloride solution, 5% dextrose solution, sterile water for injection.

Pregnancy and lactation

Use during pregnancy is acceptable if the benefit to the mother outweighs the risk to the fetus. It is not known whether naloxone is excreted in breast milk. The use of the drug during breastfeeding is possible according to absolute indications.

Side effects

From the digestive system: nausea, vomiting.

From the side of the cardiovascular system: tachycardia, arrhythmia, increase or decrease in blood pressure.

After administration in doses exceeding the therapeutic one (especially in the postoperative period in patients with diseases of the cardiovascular system): the disappearance of analgesia and excitation, a decrease / increase in blood pressure, ventricular paroxysmal tachycardia, ventricular fibrillation, pulmonary edema, cardiac arrest.

From the side of the central nervous system: tremor, nervousness, agitation, irritability, fatigue, convulsions, behavioral disorder.

Others: increased sweating, allergic reactions, pulmonary edema.

Withdrawal syndrome in patients with opioid dependence: vague pains, diarrhea, hyperthermia, rhinorrhea, sneezing, goosebumps, sweating, nausea, vomiting, nervousness, fatigue, irritability, tremor, spasms in the epigastric region, tachycardia, weakness; in newborns - convulsions, diarrhea, hyperthermia, unrestrained crying, hyperreflexia, sneezing, tremor, unusual irritability, vomiting.

Terms and conditions of storage

Store the drug in a place protected from light, at a temperature not exceeding 25°C. Keep out of the reach of children.

Best before date - 4 years. Do not use after the expiry date stated on the packaging.

Indications

Overdose of narcotic analgesics.

Postoperative use: Accelerating the recovery from general anesthesia, before the end of controlled breathing. Postoperatively, the drug is used only if narcotic analgesics were used during anesthesia. Naloxone is not effective for the treatment of respiratory depression caused by substances other than opioids.