Naloxonum

General characteristics. Structure:

Active ingredient: 400 mkg of Naloxonum of a hydrochloride a dihydrate (in terms of Naloxonum a hydrochloride).

Excipients: sodium chloride,  Acidum hydrochloricum divorced (to рН 3 - 5), water for injections.

Pharmacological properties:

Pharmacodynamics. Naloxonum is a specific antagonist of opioid receptors. Competitively communicates from an osnovnma types of opioid receptors and warns or eliminates central (including respiratory depression) and peripheral effect of both endogenous opioid peptides, and exogenous opioids - narcotic analgetics and their substitutes. Influences also dofaminergichesky and GAMK-ergichesky systems of a brain. Does not cause  tolerance  and  medicinal dependence. At persons with  drug addiction provokes development of an abstinence syndrome.

At intravenous administration the effect develops within the first 2 minutes, at intramuscular and hypodermic introduction - in 2-5 min. and reaches a maximum in 5-15 minutes. Duration of action makes of 20-45 minutes after intravenous administration and 2,5-3 hours after intramuscular and hypodermic introduction. Practical value have ability to recover breath, to reduce sedative and eyforiziruyushchy action, to weaken hypotensive effect.               (Pentazocine, бутофанол) Naloxonum has no the expressed effect on the psychotomimetic effects and dystrophy caused by narcotic analgetics of group of agonists antagonists. It is a little effective as the antagonist of a tramadol. Completely does not eliminate effects of buprenorphine.

Naloxonum provokes a syndrome of "cancellation" at patients with medicinal dependence to opioids. Naloxonum does not cause accustoming and medicinal dependence.

Pharmacokinetics. Gets through hematoencephalic and placental barriers. Plasma elimination half-life of blood (T Ѕ) - about 1 hour (30-80 minutes). At adult T Ѕ - about 64 +/-12 minutes; at newborns (after an injection in an umbilical vein) - about 3,1 +/-0,5 hours; at premature children of T Ѕ - about 51,8 +/-9,2 minutes. Naloxonum is exposed to metabolism in a liver with formation preferential of glucuronides and is removed through kidneys (within 72 hours 70% of the entered dose are removed).

Indications to use:

- acute poisoning (overdose) with narcotic analgetics (morphine, тримперидин, fentanyl) and other medicines in which mechanism of toxic action there is an opioid component (opioid substitutes, methadone, pentazocine, buprenorphine, буторфанол, налбуфин, etc.) in combination with other resuscitation actions;

- postoperative use: acceleration of an exit from the general anesthesia, before the end of the managed breath (drug is used only if during operation narcotic analgetics were used);

- recovery of breath at newborns after introduction to the woman in labor of opioid analgetics;

- as diagnostic means at patients with suspicion on drug (opioid) addiction - naloksonovy test.

Route of administration and doses:

  Rate of administering of medicine should  be selected individually,  depending on reaction of the patient to use of Naloxonum and the entered earlier single doses. Naloxonum is applied intravenously, intramusculary or subcutaneously. In case of infusional use solution of Naloxonum is diluted in 0,9% solution of sodium of chloride or in 5% dextrose solution as follows: 2000 mkg (5 ml of the solution containing 400 mkg/ml of Naloxonum) add to 500 ml of the infusional environment. The solution received after dilution contains 4 mkg of Naloxonum in 1 ml. Solution is prepared just before use.

The dose of Naloxonum and route of administration depend on a condition of the patient, a look and amount of the opioid accepted by it.

At acute poisoning (overdose) with narcotic analgetics. Adults. The initial single dose makes 400-2000 mkg intravenously slowly (within 2-3 minutes). If necessary the dose can be repeated through 2-3 minuga, up to recovery of consciousness and uniform breath. If after introduction of a total dose of Naloxonum of 10 mg there was no recovery of consciousness and breath, it is necessary to assume other (not opioid) reason of poisoning.

It is also possible to apply Naloxonum intramusculary or subcutaneously. At the threatening ostoyaniye to life the intravenous way of introduction is preferable.

Children. The initial single dose makes 10 mkg/kg intravenously slowly (within 2-3 minutes). In case of need in 2-3 minutes it is possible to enter an additional dose of 100 mkg/kg.

If it is impossible to apply Naloxonum intravenously, enter it intramusculary or subcutaneously fractional doses with an interval of 2-3 minutes. At intramuscular introduction the effect of drug is shown more slowly. It is once possible to enter a dose about 200 mkg (i.e. about 60 mkg/kg), receiving more long action.

Postoperative use: for acceleration of an exit from sheathe anesthesia (if during operation narcotic analgetics were used)

Adults. Intravenously 100-200 mkg (1,5-3 mkg/kg) of Naloxonum solution every 2-3 minute before emergence of adequate lung ventilation and awakening of the patient, but without clear pain and discomfort. The dose exceeding minimum necessary can cause the termination of an analgesia and increase in arterial pressure, and also other symptoms: nausea, vomiting, increase in sweating, distsirkulyatorny crisis. In certain cases, especially after reception of opioid analgetics with long time of action, intramuscular introduction of an additional dose of Naloxonum within 1 - 2 hours is necessary.

The drug is also administered by means of intravenous infusion.

Children. Intravenously 10 mkg/kg of solution of Naloxonum. If necessary it is possible to enter an additional dose of 100 mkg/kg.

If it is impossible to apply Naloxonum intravenously, enter it intramusculary or subcutaneously fractional doses with an interval of 2-3 minutes. At intramuscular introduction the effect of drug  is shown  more slowly. It is once possible  to enter a dose about 200 mkg (i.e. about 60 mkg/kg), receiving more long action.

The drug is also administered by means of intravenous infusion. Recovery of breath  at  newborns  after  introduction  to the woman in labor  of opioid analgetics.

Newborns. Before administration of medicine it is necessary to make sure of passability of respiratory tracts of the newborn.

Intravenously, intramusculary or subcutaneously 10 mkg/kg. If necessary the dose can be repeated in 2-3 min.

After the child's birth it can enter one-time for prevention intramusculary 200 mkg (i.e. about 60 mkg/kg) Naloxonum.

As diagnostic means at patients with suspicion on drug (opioid) addiction.

Intravenous administration of a dose of 0,5 mkg/kg allows to solve whether respiratory depression or difficulty of an urination is caused by opioids. Then the dose of Naloxonum can be raised, avoiding too high doses. High doses remove any effect of opioid including they anesthetic, and also lead to excitement of systems of sympathetic system and the blood circulatory system.

Features of use:

Use at pregnancy and during breastfeeding. At pregnancy and during breastfeeding of the child drug should be used only in cases of urgent need.

Influence on ability to manage vehicles, mechanisms. At use of drug it is forbidden to manage vehicles and other moving mechanical devices.

Side effects:

When using drug during the postoperative period: lowering of arterial pressure, increase in arterial pressure, ventricular tachycardia and fibrillation of ventricles, suffocation, fluid lungs, cardiac standstill. The specified effects sometimes lead to a lethal outcome, a coma and encephalopathy. When using the doses of drug exceeding minimum necessary disappearance of an analgesia and psychomotor excitement is possible.

In case of sudden cancellation of opioids there can be nausea, vomiting, perspiration, tachycardia, increase in arterial pressure, a shiver, spasms, ventricular tachycardia and fibrillation of ventricles, a fluid lungs and a stop of cordial activity that can lead to a lethal outcome.

Syndrome of "cancellation" at patients with opioid dependence: nausea, vomiting, diarrhea, weakness, tachycardia, increase in arterial pressure, fever, cold, sneezing, "goose-pimples" (piloerektion), perspiration, yawning, nervousness, concern, irritability, a shiver, spasms in epigastric area, pain of not clear localization. Newborns have spasms, impetuous crying, a hyperreflexia.

If any of the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Naloxonum should not be applied intravenously together with other drugs. 

Drug reduces hypotensive action of a clonidine; reduces effect of opioid analgetics (including a butorfanola, the nalbufina, pentazocine, fentanyl, remifentanit) and accelerates emergence of a syndrome of "cancellation". It is incompatible with solutions of the medicines containing bisulphites. Pharmaceutical we will combine with chloride sodium solution 0,9%, solution of a dextrose of 5%, sterile water for injections.

Metogeksital (derivative barbituric acid of short action) blocks the acute beginning of the abstinence caused by Naloxonum in persons with drug addiction.

Contraindications:

Hypersensitivity to Naloxonum in the anamnesis of patients.

With care. At use of Naloxonum it is necessary to provide a possibility of oxygen therapy and resuscitation actions, and also access to the equipment allowing to carry out cardiopulmonary resuscitation.

It is necessary   to be careful at use of Naloxonum for patients with heart diseases, lungs, abnormal liver functions and/or kidneys, during pregnancy, a lactation, at children's age, at persons with the established or suspected physical dependence on opioids, and also at newborns whose mothers specified dependence on opioids in the anamnesis (sudden and full cancellation of narcotic action can cause an acute syndrome of "cancellation").

It is careful to apply Naloxonum at treatment of the respiratory depression caused  by buprenorphine use  as the response to use  of Naloxonum can be incomplete. In that case it is necessary to apply artificial ventilation of the lungs.

As duration of action of Naloxonum is shorter than duration of effect of opioids, there is a risk of decrease in respiratory activity.

Sudden cancellation of effect of opioids after surgical intervention  can make sick, vomiting, sweating, a shiver, tachycardia and other symptoms. Undesirable effects are possible.

Overdose:

Cases of acute overdose at reception of Naloxonum are noted.

However at administration of drug in high doses (4 mg/kg and above) nausea, vomiting, a fever, a hyperventilation, spasms, the expressed increase or a lowering of arterial pressure and/or bradycardia can be observed.

At emergence of these symptoms conservative treatment is recommended (in the conditions of an intensive care). Doses of 2 mg/kg can cause cognitive disturbances and behavioural symptoms, including irritability, concern, tension, suspiciousness, depression, difficulties with concentration of attention and lack of appetite. Behavioural symptoms can proceed 2-3 days. Also can be observed somatic symptoms, such as dizziness, perspiration, nausea and stomach aches, heavy feeling. Patients with overdose of Naloxonum should be treated symptomatic, under strict observation.

Storage conditions:

Period of validity - 4 years. Not to apply after the period of validity specified on packaging. To store in the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Solution for injections of 400 mkg/ml. On 1 ml in ampoules from colourless glass. Over the place of a break of an ampoule there is a point of white or red color, and also a strip in the form of ringlets: an upper ringlet - yellow, and lower - pink-violet. 5 ampoules place in the pallet for ampoules from PVC. In a cardboard pack there are two pallets (10 ampoules) with the application instruction.