Active substanceNaltrexoneNaltrexone
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  • Dosage form: & nbspcapsules
    Composition:

    One capsule contains:

    Active substance:

    naltrexone hydrochloride in terms of 100% substance - 50.0 mg.

    Excipients:

    lactose monohydrate - 98.5 mg, magnesium stearate - 1.5 mg.

    Capsule hard gelatin № 4 - 38.0 mg.

    Capsule Casing:

    titanium dioxide (E 171) - 2%, gelatin to 100%.

    Capsule cap:

    ferric oxide, yellow (E 172) - 1.7143%, titanium dioxide (E 171) -1%, dye indigo carmine (E 132) 0.3%, gelatin up to 100%.

    Description:

    Hard gelatin capsules No. 4, the capsule body is white, the lid is dark green. Contents of capsules: powder white or almost white.

    Pharmacotherapeutic group:Opioid receptor antagonist
    ATX: & nbsp

    N.07.B.B.04   Naltrexone

    Pharmacodynamics:

    Naltrexone is a pure antagonist of opioid receptors. Competitively binds to opioid receptors of all types and prevents or eliminates the effect of both endogenous opioids,and exogenous opioids - opioid analgesics and their surrogates. The greatest affinity for μ- and kreceptors. Reduces the effect of opioid analgesics (analgesic, antidiarrheal, antitussive); eliminates the side effects of opioids (including endogenous), except for the symptoms caused by the histamine reaction. In comparison with naloxone acts more strongly and for a long time. May cause miosis (mechanism unknown). The combination with opioids in large doses leads to an increase in the release of histamine with a characteristic clinical picture (facial hyperemia, pruritus, rash). In patients with opioid dependence causes an attack of abstinence.

    Naltrexone does not cause disulfiram-like reactions, as a result of the use of opioids and ethanol. When alcoholism is associated with opioid receptors and blocks the effects of endorphins. Reduces the need for alcohol and prevents relapse within 6 months after a 12-week course of therapy (the success of treatment depends on the patient's consent). Long-term appointment does not cause tolerance and dependence.

    With simultaneous long-term administration, it prevents the development of physical dependence on morphine, heroin and other opioids.In a dose of 50 mg blocks the pharmacological effects of 25 mg intravenously injected heroin for 24 hours, a double dose (100 mg) for 48 hours, and 150 mg for 3 days. The competitive blockade of opioid receptors can be overcome by the administration of a higher dose of opioid analgesic.

    Pharmacokinetics:

    - Suction: Absorption after oral administration is rapid and almost complete (96%), is subjected to intestinal-hepatic circulation. The maximum concentration (Cmax), half-life and the total amount of renal excretion for both naltrexone and 6-beta-naltrexol, increase in proportion to the increase in the prescribed dose of naltrexone from 50 to 200 mg. The beginning of the action - after 1 -2 hours. TCmax naltrexone and its active metabolite 6-beta-naltrexol in plasma - 1 hour, after a single administration of 50 mg Cmax naltrexone - 8.6 ng / ml, Cmax - 6-beta-naltrexol - 99.3 ng / ml.

    - distribution: The connection with plasma proteins is low (21%). Well penetrates through the histohematological barriers. The volume of distribution is 1350 liters. Bioavailability of 5-40%.

    With long-term use at a dose of 100 mg / day naltrexone does not cumulate (the concentration of 6-beta-naltrexol in plasma reaches 40%).

    - metabolism: Metabolized in the liver by 98% with the formation of pharmacologically active metabolites, the main of which - 6-beta-naltrexol is also an antagonist of opioids. Other metabolites are - 2-hydroxy-3-methoxy-6-beta-naltrexol and 2-hydroxy-3-methoxy-naltrexone. Enzymes of the cytochrome P450 system do not participate in the metabolism of naltrexone. Naltrexone and its metabolites form conjugates with glucuronidin.

    - excretion: T/1/2 naltrexone -4 h, 6-beta-naltrexol -13 h, which explains its ability to cumulate. Naltrexone and its metabolites are excreted mainly (53-79%) by the kidneys (naltrexone - less than 2%, 6-beta-naltrexol, including in conjugate form - 43%) and with the feces (in small amounts). The total ground clearance is 1.5 l / min.

    Liver failure. Pharmacokinetics of the drug naltrexone does not change in patients with mild or moderate liver dysfunction (Child-Pugh classes A and B), such patients do not need dose adjustment.

    Renal insufficiency. Light renal failure (C1 creatinine 50-80 ml / min) almost does not affect the pharmacokinetics of the drug naltrexone and there is no need to adjust the dose of the drug. Due to naltrexone and its primary metabolite are excreted from the body mainly with urine, prescribe naltrexone patients with moderate to severe renal failure should be cautious.

    The effectiveness of naltrexone in alcoholism and opioid dependence has been confirmed by clinical studies.

    Indications:

    • Treatment of alcohol dependence and blockade of the effects of exogenously introduced opioids.
    • Complex therapy of opioid dependence in order to maintain the patient's state in which opioids can not have a characteristic effect.
    • The drug is indicated to prevent the recurrence of opioid dependence after opioid detoxification.
    • Complex therapy of alcoholism, including with maintenance therapy, in the same dosages as with heroin dependence on the background of psychotherapy.

    Contraindications:

    Patients who are dependent on opioids, including those on treatment with opioid agonists or partial agonists. Positive naloxone test. Use of opioid analgesics or a positive analysis for the urinary content of opioids. Positive test for the presence of opioids in the urine. Opioid withdrawal syndrome. Hypersensitivity to the components of the drug. Acute hepatitis or liver failure. Deficiency of lactase, lactose intolerance. Glucose-galactose malabsorption.

    Carefully:

    Impaired liver and / or kidney function.

    Pregnancy and lactation:

    The drug is classified in category C.

    In experiments on rats (intake in doses 30 times higher than recommended for people immediately before pregnancy and during pregnancy) and in rabbits (taking in doses 60 times higher than recommended for humans), a teratogenic effect was established.

    The use of the drug during pregnancy is possible only if the potential benefit from its use exceeds the potential risk to the fetus.

    When naltrexone was orally taken, naltrexone and 6-beta-naltrexol were excreted in breast milk. Due to the potential carcinogenicity and the likelihood of serious side effects in infants, a decision should be made to discontinue therapy with the drug during breastfeeding or stop breastfeeding during treatment, depending on the importance of therapy for the mother.
    Dosing and Administration:

    Treatment of opioid dependence.

    The phase of introduction to the course of therapy with naltrexone.

    Treatment with naltrexone begins after the patient refrains from taking opioids for 7-10 days (in the absence of manifestations of withdrawal syndrome). Abstinence from the use of opioids is identified by the indicators of laboratory urine tests for the content of opioids.

    Treatment begins with a negative provocative trial with 0.5 mg of naloxone.

    Description of the naloxone test: the patient needs to administer 0.2-0.4 mg of naloxone intravenously for 5 minutes or as an injection subcutaneously or intramuscularly. If there is no response to the administration of naloxone for 15-30 minutes, a second dose of 0.4 mg intravenously or 0.4-0.8 mg is injected subcutaneously and observed. The sample is considered positive with pronounced mydriasis, a change in affect from complacently drowsy to dysphoric, behavioral disorders, and the appearance of signs of opium withdrawal.

    A naloxone sample is not given to patients with symptoms of withdrawal and when opioids are detected in the urine. The naloxone sample can be repeated after 24 hours.

    Treatment with naltrexone begins with caution, gradually increasing the dose. The contents of the capsule are dissolved in 50 ml of water.Initially, 25 mg of naltrexone is administered orally (contained in 25 ml of the stock solution). The doctor should monitor the act of swallowing the drug solution.

    Supportive therapy with naltrexone.

    The day after the introduction of the initial dose naltrexone begin to appoint 50 mg every 24 hours (the use of naltrexone in this dose is sufficient to block the effects of opioids administered parenterally, for example, 25 mg of heroin administered intravenously).

    Naltrexone 100 mg is given every 2 days or 150 mg every 3 days.

    Treatment of alcoholism.

    In the combination therapy.

    Daily intake of 50 mg of naltrexone, the minimum course - 3 months. Treatment should be part of the appropriate program to eliminate alcohol dependence. During the course of treatment, it is necessary to monitor adherence to all components of alcohol treatment that affect the favorable outcome. Drug treatment is recommended to accompany the course of psychotherapy.

    Side effects:

    Classification of WHO adverse adverse reactions according to the frequency of development: Often - >1/10; often - from 1/100 to 1/10; infrequently - from 1/1000 to 1/100; rarely - from 1/10000 to 1/1000; rarely - <1/10000, including individual messages.

    In therapeutic doses, patients who do not have opioids in their bodies, naltrexone usually does not cause serious side effects.

    From the digestive system: very often - nausea and / or vomiting, abdominal pain; often - abdominal pain, decreased or increased appetite, anorexia, diarrhea or constipation, dryness of the oral mucosa, flatulence, increased activity of "liver" enzymes, rarely - aggravation of hemorrhoid symptoms, erosive and ulcerative lesions of the gastrointestinal tract.

    From the nervous system and sense organs: very often - anxiety, nervousness, unusual fatigue, general weakness, restless sleep, "nightmarish" dreams, headache; often - dizziness, blurred vision, confusion, hallucinations, depression of the central nervous system, rarely - depression, delirium, ringing and feeling of stuffiness in the ears, pain and burning sensation in the eyes, photophobia, irritability, drowsiness, disorientation in time and space, Migraine, fainting, asthenia, lethargy, anxiety.

    From the respiratory system: not often - cough, hoarseness, nasal congestion (hyperemia of the vessels of the nasal cavity), difficulty breathing, itching in the nose, rhinorrhea, sneezing, bronchial obstruction, shortness of breath, shortness of breath, epistaxis, dryness in the throat, increased separation of mucous sputum, infections of the upper respiratory tract, sinusitis, laryngitis, pharyngitis (including streptococcal), nasopharyngitis, sinusitis.

    From the side of the cardiovascular system: not often - chest pain, increased blood pressure, tachycardia, palpitations, nonspecific changes in the electrocardiogram, phlebitis.

    From the side of the organs of sight: rarely - conjunctivitis.

    From the genitourinary system: often - sexual disorders in men (delay ejaculation, decreased potency), increased or decreased libido, not often - discomfort with urination, increased frequency of urination, edematous syndrome (swelling of the face, fingers, feet, legs).

    Allergic reactions: often - skin rash, skin hyperemia (including face hyperemia), hyperthermia, skin itching, increased secretion of sebaceous glands, chills.

    From the side of the musculoskeletal system: very often - back pain, joint stiffness, pain in the extremities, spasm, twitching or stiffness of muscles; often - arthralgia, myalgia; arthritis.

    From the skin: papular rash, sweating, acne, alopecia. Other: dry mouth or thirst, sore throat, increased or loss of body weight, pain in the inguinal region, enlarged lymph nodes, lymphocytosis; In one case, the development of idiopathic thrombocytopenic purpura is described against a background of preliminary sensitization to the drug.

    The syndrome of "withdrawal" of opioids: abdominal pain, spasm in the epigastric region, anxiety, nervousness, fatigue, irritability, diarrhea, tachycardia, hyperthermia, rhinorrhea, sneezing, goosebumpter, sweating, yawning, arthralgia, nausea and / or vomiting, tremor, general weakness.

    If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

    Post-registration application experience

    According to the literature, a single case of idiopathic thrombocytopenic purpura is described in a patient who may have been sensitized to naltrexone during the previous treatment. Recovery occurred after the drug was discontinued and a course of corticosteroid therapy was administered.
    Overdose:

    Naltrexone is a moderately safe drug. According to studies, even large doses do not cause serious symptoms. If suspected of intoxication, symptomatic treatment should be prescribed.

    At the stage of preclinical research, when naltrexone was re-administered at a dose of 100 mg / kg, exceeding the maximum daily dose for a person by about 35 times, no significant changes were observed in the hematologic and biochemical parameters of the blood, as well as in the structure of internal organs. Local irritant effect naltrexone also does not render.

    Interaction:

    Reduces the effectiveness of drugs containing opioids (anti-cough medicines, opioid analgesics, anti-cold medications). Where possible, alternative drugs should be used.

    Hepatotoxic drugs increase (mutually) the risk of liver damage.

    Disulfiram inhibits microsomal oxidation in the liver, which can cause an increase in the concentration of drugs in the blood plasma metabolized in the liver (naltrexone), which increases the risk of intoxication.

    Possible lethargy or increased drowsiness when combined with thioridazine. Accelerates the appearance of symptoms of the "cancellation" syndrome on the background of opioid dependence, characterized by persistence and difficulty of their elimination.
    Special instructions:

    Naltrexone is effective only as a part of complex dependence therapy. Prior to use, subclinical hepatic insufficiency must be excluded, during transplantation transient increase in transaminase activity should be periodically monitored.

    Naltrexone has a hepatotoxic effect. Therefore, with prolonged use, it is necessary to monitor liver function.

    Naltrexone is prescribed only after relief of the withdrawal syndrome.

    The drug begins to take only in specialized institutions under the supervision of a doctor. It should be closely monitored for signs of depression or suicidal thoughts in patients with alcohol and / or opioid dependence, including patients receiving naltrexone treatment. Family members and caregivers should be warned about the need to closely monitor the occurrence of symptoms of depression or suicidal behavior and immediately report the occurrence of such symptoms to the treating physician.To ensure the effectiveness of treatment requires complex therapy, including psychological support.

    Naltrexone blocks the effects of opioids. Blockade can be overcome by increasing the dose of opioids.

    A patient who receives naltrexone treatment should be warned that an uncontrolled intake of opioids during this period can lead to a severe withdrawal syndrome up to the development of coma. There is a risk of death.

    Naltrexone has a hepatotoxic effect. Therefore, with prolonged use, it is necessary to monitor liver function.

    Naltrexone should be discontinued at least 48 hours before surgery, which requires the use of opioid analgesics. In case of emergency analgesia, caution is prescribed for opioids in a higher dose (for overcoming antagonism), since respiratory depression will be deeper and more prolonged. To prevent the development of acute withdrawal symptoms, patients should at least 7-10 days later stop taking opioids and medications containing them,mandatory determination of opioids in the urine and conducting a provocative test with naloxone; Abstinence syndrome may occur if these requirements are not met.

    A persistent decrease in appetite and progressive weight loss require discontinuation of therapy.

    Ineffective in the treatment of cocaine, as well as non-opioid drug dependence.

    Perhaps the development of eosinophilic pneumonia resistant to antibiotic therapy; with the development of progressive dyspnoea and hypoxia, you should immediately consult a doctor.

    Patients should be warned that:

    - when seeking medical care, patients are required to inform health professionals about treatment with naltrexone;

    - in the case of abdominal pain, darkening of the urine, yellowing of the sclera, it is necessary to stop taking the medicine and consult a doctor;

    - at independent heroin and other opioids in small doses, their effect will not be a further increase in dose opio- idnyh means lead to death (cessation of breathing).

    Effect on the ability to drive transp. cf. and fur:

    During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    Capsules 50 mg.

    Packaging:10 capsules per contour cell packaging made of polyvinylchloride film and aluminum foil. 1, 2 or 5 contour squares with instructions for use in a pack of cardboard. 100, 200, 300 contour cell packs with an equal number of instructions for use, respectively, in a box or box (for inpatient).
    Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.
    Shelf life:

    3 years.

    Do not use after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-002591
    Date of registration:20.08.2014
    Expiration Date:20.08.2019
    The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia
    Manufacturer: & nbsp
    Information update date: & nbsp28.05.2018
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