Buprenorphine - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Opioid narcotic analgesics

Included in the formulation

Bupralal®

solution for injections

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Transtec

patch through.

Grünenthal GmbH Germany

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

N.07.B.C.01 Buprenorphine

Pharmacodynamics:

Highly lipophilic semisynthetic derivative of thebaine (alkaloid poppy dormant), is a partial (partial) agonist of mu-opioid receptors that binds firmly to them, and a kappa receptor antagonist.

Buprenorphine disrupts pain impulses in the afferent pathways of the central nervous system (impaired transmission of impulses from the end of the primary afferents to intercalary neurons of the spinal cord). By stimulating opioid receptors in the presynaptic endings of the axons of the primary afferents, it reduces the release of substance P and glutamate, thus impairing the transmission of pain impulses to the intercalary neurons of the posterior horns of the spinal cord.

Due to the stimulation of postsynaptic opioid receptors, the process of depolarization of the postsynaptic membrane is disrupted and the activation of the inserted neurons is inhibited by the mediator.

Strengthens the inhibitory effects of the descending antinociceptive system on pain impulses in the afferent pathways of the central nervous system.

Buprenorphine changes the emotional coloration of pain and reaction to it. All this leads to a violation of transmission of pain impulses at the level of the spinal cord.

Has low narcogenic potential.

Pharmacokinetics:

The onset of action sublingually after 30 minutes, intramuscularly - after 15 minutes, intravenously more rapidly, when used as an antagonist after 15 minutes; respiratory depression 1-3 hours after intramuscular injection. The maximum effect is intramuscular after 1 hour, intravenously less than 1 hour, when used as an antagonist after 1.5-2 hours. Duration of action intramuscularly and intravenously - 6 hours (up to 10 hours), epidurally 6-12 hours (dose-dependent effect), in children 2-12 years - 4-5 hours; when used as an antagonist - 4 hours; respiratory depression is significantly longer than in morphine.

Evenly distributed through the tissues, it penetrates the blood-brain barrier. Metabolized in the liver, metabolic products are secreted with bile, a small amount is excreted by the kidneys.

Indications:Pain syndrome (strong and medium intensity): in cancer patients, postoperativeI have pain, stenocardia, myocardial infarction, renal colic, burns.

ICD-10

IX.I20-I25.I20 Angina pectoris [angina pectoris]

IX.I20-I25.I21 Acute myocardial infarction

IX.I20-I25.I22 Repeated myocardial infarction

XVIII.R50-R69.R52.0 Acute pain

XVIII.R50-R69.R52.1 Constant unrestrained pain

XVIII.R50-R69.R52.2 Another constant pain

XIX.T20-T32.T30 Thermal and chemical burns, unspecified

Contraindications:Hypersensitivitytion. Drug dependence. Conditions accompanied by respiratory depression or severe oppression central nervous system. Convulsive conditions. Increased intracranial pressure

. Craniocerebral injury. Acute alcoholic conditions and alcoholic psychosis. Bronchial asthma. Paralytic ileus. CardiopulmonaryI insufficiency. Heart rhythm disturbances. Acute surgical diseases of the abdominal cavity before diagnosis. Pregnancy and lactation.

Carefully:

They are used with caution in case of impaired breathing, liver and / or renal failure, myxedema, hypothyroidism, adrenal insufficiency, central nervous system depression, craniocerebral trauma, toxic psychosis, hypertrophy of the prostate, urethral stricture, alcoholism, against the action of monoamine oxidase inhibitors, as well as drugs that depress the central nervous system, in the elderly.

Impact on the ability to drive vehicles and manage mechanisms

During the application of buprenorphine, it is not recommended to engage in activities requiring high concentration of attention and rapid psychomotor reactions.

Pregnancy and lactation:

Recommendations Food and Drug Administration (US Food and Drug Administration) category C. The risk of dependence in the fetus and the development of the phenomenon of withdrawal in a newborn (irritability, convulsions, excessive tearfulness, tremor, lively reflexes, fever, nausea, diarrhea, sneezing and yawning). Adequate and well-controlled studies on humans have not been conducted. In animals in large doses (1,000 times higher than the average therapeutic) caused the formation of an additional rib, a decrease in the survival rate of the fruit.

In small amounts penetrates into breast milk, violations are not registered. Oppresses lactation.

Dosing and Administration:

A single dose for adults with intravenous and intramuscular injection is 0.3-0.45 mg. If necessary, repeat the injection every 6-8 hours.

At sublingual admission - 0,2-0,4 mg with an interval between reception of 6-8 hours. the maximum daily dose is 1.8 mg.

Side effects:

On the part of the digestive system: nausea, vomiting, constipation, dry mouth, anorexia, biliary tract spasm, cholestasis (in the main bile duct), gastralgia, stomach cramps, hepatotoxicity (dark urine, pale stool, icteric sclera and skin) with severe inflammatory bowel diseases: intestinal atony, paralytic intestinal obstruction, toxic megacolon (constipation, flatulence, nausea, spasms in the stomach, vomiting).

From the cardiovascular system: lowering blood pressure, tachycardia, AV-blockade, bradycardia, increased blood pressure.

On the part of the respiratory system: depression of the respiratory center; bronchospasm, atelectasis.

On the part of the nervous system: fainting, drowsiness, dizziness, unusual fatigue, general weakness, sweating, headache, blurred vision, euphoria, tremor, involuntary muscle twitching,discordination of muscular movements, paresthesia, nervousness, depression, confusion (hallucinations, depersonalization), increased intracranial pressure with the probability of subsequent cerebral circulatory disorders, insomnia, restless sleep, central nervous system depression, against a background of large doses: muscle stiffness (especially respiratory) in children: paradoxical agitation, anxiety; convulsions, nightmares, sedative or stimulating effects (especially in elderly patients), delirium, decreased ability to concentrate.

On the part of the genitourinary system: decreased diuresis, spasm of ureters (difficulty and pain with urination, frequent urge to urinate), decreased libido, decreased potency; spasm of the sphincter of the urinary bladder, a violation of the outflow of urine or the aggravation of this condition when hyperplasia of the prostate and stenosis of the urethra.

Allergic reactions: wheezing, facial hyperemia, rash on the skin of the face; conjunctivitis, skin rash, urticaria, skin itch, face swelling, edema of the trachea, laryngospasm, chills.

Local reactions: hyperemia, edema, burning at the injection site.

Other: increased sweating, dysphonia; violation of the clarity of visual perception (including diplopia), miosis, nystagmus, imaginary feeling of well-being, a feeling of discomfort; tinnitus, drug dependence, tolerance, withdrawal symptoms (muscle pain, diarrhea, tachycardia, mydriasis, pyrexia, rhinitis, sneezing, sweating, yawning, anorexia, nausea, vomiting, nervousness, fatigue, irritability, tremor, cramps in the stomach, expanding pupils, general weakness, hypoxia, muscle contractions, headache, increased blood pressure and other vegetative symptoms).

Overdose:

Symptoms of acute and chronic overdose: cold sticky sweat, confusion, dizziness, drowsiness, lowering of blood pressure, nervousness, fatigue, miosis, bradycardia, severe weakness, slow labored breathing, hypothermia, anxiety, dry mouth, delirious psychosis, intracranial hypertension up to the violation of cerebral circulation), hallucinations, muscle rigidity, convulsions, in severe cases - loss of consciousness, respiratory arrest, coma.

Treatment: gastric lavage, restoring breathing and maintaining cardiac activity and blood pressure; intravenous administration of a specific antagonist opioid analgesics - naloxone in a single dose of 0.2-0.4 mg with repeated administration 2-3 minutes before the total dose of 10 mg; the initial dose of naloxone for children is 0.01 mg / kg.

Interaction:

Alcohol: intensifying the oppressive effect on central nervous system, including the respiratory center (reduce the dose of buprenorphine 2 times).

Means, depressing central nervous system: strengthening of oppressive influence on central nervous system, including the respiratory center (reduce the dose of buprenorphine 2 times).

Naloxone, naltrexone: prevent respiratory depression, but if it has already developed, even high doses of antagonists eliminate it not immediately due to the high affinity of buprenorphine to the opioid receptor.

Narcotic analgesics: a decrease in the therapeutic activity of pure agonists, a reduction in respiratory depression, the development of an abstinence syndrome.

Means that inhibit CYP3A4: increase the therapeutic concentration of buprenorphine (reduce the dose by 2 times).

Means that induce CYP3A4: a decrease in the therapeutic concentration of buprenorphine.

Special instructions:

In equivalent doses, the analgesic effect is 2-2.5 times weaker than morphine, less than other narcotic analgesics cause euphoria, so there is less likelihood of developing addiction.

Buprenorphine intrathecal in addition to spinal anesthesia in cesarean section contributed to the reduction of postoperative pain, inferior to morphine in effectiveness.

Buprenorphine is more effective than clonidine, in reducing the symptoms of opioid withdrawal. Buprenorphine can be associated with fewer side effects than clonidine, and a smaller dropout from studies due to side effects. Buprenorphine and methadone in decreasing doses are comparable in effectiveness in stopping the symptoms of opioid withdrawal, but with buprenorphine withdrawal symptoms can be resolved more quickly (completion of opioid withdrawal: RR 1.30, 95% CI 0.97 to 1.73; 3 studies, 156 participants). However, more research is needed, especially on the effectiveness after the withdrawal of buprenorphine and methadone in decreasing doses.The gradual reduction in the dose of buprenorphine in maintenance therapy is more effective than rapid dose reduction. However, knowledge remains limited and further research is needed to determine the optimal approach to abolishing buprenorphine after prolonged substitution treatment.

Buprenorphine is an effective treatment (maintenance therapy) of heroin dependence in comparison with placebo.

It is not recommended to apply during and after short (less than 3 hours) surgical interventions.

It should not be used against the background of monoamine oxidase inhibitors and for another 14 days after their cancellation.

It is not recommended to use at the age of 16 years.

Instructions

Buprenorphine (Buprenorphinum)