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

Benzodiazepine derivative of medium duration of action; causes CNS depression from mild sedation to coma, depending on the dose. The exact mechanism is not known; amplification of the effects of γ-aminobutyric acid (GABA, the main inhibitory neurotransmitter of the CNS) by stronger binding to type A receptors (GABA); agonist of benzodiazepine receptors, known as benzodiazepine-HAMBA-receptor-chloride-ionophore complex; located on the neuronal membrane, ion channel for Cl-; when the GABA-receptor is activated, the ion channel is opened and the Cl- enters the neuron, its excitability decreases and the effects of depolarizing excitatory transmitters are reduced.

Pharmacological effects

Anxiolytic. Sedative-hypnotic (moderate, shortens the period of falling asleep, increases the duration of sleep, reduces the number of nocturnal awakenings). Anti-panic. Decreased tremor.

Pharmacokinetics:

Absorption after oral administration is rapid (2 h) and complete.Can pass through the placenta, GEB, penetrate into breast milk. The connection with plasma proteins is 80%. Css in plasma is usually achieved within 2-3 days. Metabolised in the liver by hydroxylation to low-activity (≤1 / 2 activity of alprazolam) or inactive metabolites. In the metabolism of the drug, isozymes CYP3A4, CYP3A5 and CYP3A7 are involved. T1 / 2 - 11 (6,3-26,9) h (average duration of action); TCmax after ingestion 1-2 hours. Elimination by the kidneys (in the form of compounds with glucuronic acid). Accumulation with a reappointment is minimal (refers to benzodiazepines with an average T1 / 2), excretion after cessation of treatment is rapid. After withdrawal, the concentration in the plasma is reduced to subclinical within 24 hours. It is not removed during hemodialysis.

Indications:

Disturbing conditions, neuroses accompanied by a sense of anxiety, danger, anxiety, tension, deterioration of sleep, irritability, and somatic disorders; mixed anxiety-depressive conditions; neurotic reactive-depressive conditions, accompanied by a decrease in mood, loss of interest in the environment, anxiety, loss of sleep, loss of appetite,somatic disorders; anxious states and neurotic depression, developed against a background of somatic diseases; panic disorder in combination and without symptoms of phobia.

ICD-10

V.F30-F39.F32 Depressive episode

V.F30-F39.F33 Recurrent depressive disorder

V.F40-F48.F40 Phobic anxiety disorders

V.F40-F48.F41.0 Panic disorder [episodic paroxysmal anxiety]

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

V.F40-F48.F43 Reaction to severe stress and adaptation disorders

V.F40-F48.F48.0 Neurasthenia

V.F50-F59.F51.2 Sleep and wakefulness disorder inorganic etiology

Contraindications:

Hypersensitivity to alprazolam, any other benzodiazepine or any component of the dosage form. Acute poisoning with narcotic analgesics, hypnotics and psychoactive drugs, acute respiratory failure, pregnancy (especially I trimester), breast-feeding. Age younger than 18 years (safety and efficacy not studied). Carefully! Coma, shock, myasthenia gravis, acute alcohol poisoning (with impaired vital functions), severe COPD (progression of respiratory failure), severe depression (suicidal tendencies may manifest).

Carefully:

Severe COPD (progression of respiratory failure), severe depression (suicidal tendencies may manifest).

Pregnancy and lactation:

Recommendations FDA category D1. Perhaps it penetrates the placenta. Chlordiazepoxide and diazepam, used in the I trimester, more often cause congenital anomalies; because of the structural similarity, this probably applies to alprazolam. Regular use of alprazolam in pregnancy can lead to a withdrawal syndrome in a newborn, use in recent weeks of pregnancy and during childbirth causes CNS depression, lethargy, hypothermia, breathing and feeding disorders in a newborn. It is recommended to avoid use during pregnancy, carefully correlate potential risks and benefits and exclude pregnancy before starting treatment.

Lactation

Probably penetrates into breast milk; since newborns metabolize benzodiazepines more slowly, sedation, feeding disorders and / or a decrease in the weight of the newborn are possible.

Dosing and Administration:

Alarming conditions (in the form of short-term therapy for the purpose of rapid relief of symptoms).Inside, the initial dose of 250-500 mcg (0.25-0.5 mg) 3 times a day; if necessary, the dose is gradually increased to ≤4 mg / day. Weakened patients: inside, the initial dose of 250 mcg (0.25 mg) 2-3 times a day; if necessary and good tolerability dose is increased. In elderly patients: inside, the initial dose of 250 mcg (0.25 mg) 2-3 times a day; if necessary and good tolerability dose is increased.

It is possible to reduce the initial dose with the development of side effects.

Benzodiazepines are not indicated in the treatment of anxiety due to chronic stress, since their effectiveness with prolonged therapy is not known. It is necessary to periodically monitor the response to treatment, the patient's condition and correction of the treatment regimen.

Anxiety associated with depression (as part of complex therapy). Inside, the initial dose of 250-500 mcg (0.25-0.5 mg) 3 times a day; if necessary and tolerability, the dose is gradually increased to ≤4 mg / day. Weakened patients: inside, the initial dose of 250 mcg (0.25 mg) 2-3 times a day; if necessary and good tolerability dose is increased. In elderly patients: inside, the initial dose of 250 mcg (0.25 mg) 2-3 times a day; if necessary and good tolerability dose is increased. It is possible to reduce the initial dose with the development of side effects.The effectiveness of benzodiazepines in long-term therapy is not known. It is necessary to periodically monitor the response to treatment, the patient's condition and correction of the treatment regimen.

Transient insomnia, caused by a sharp change in time zones during long flights or a change in the wakefulness regime.

Panic disorders. Inside, the initial dose of 500 mcg (0.5 mg) 3 times a day; if necessary and the tolerability dose is gradually increased to ≤10 mg / day.

The presence of anxiety early in the morning or between meals in the treatment of panic disorders may indicate the development of tolerance or that the inter-dose interval is longer than the period of the dose. The manufacturer recommends in such cases that the prescribed dose is not sufficient to maintain the necessary concentration in the blood plasma, and recommends the intake of the same dose at shorter intervals.

Agoraphobia. Headache of tension. Tremor (senile, essential, family).

Insomnia (difficulty falling asleep, frequent night awakening, early awakening). If insomnia does not stop and intensifies after 7-10 days of treatment, or new changes in behavior or thinking appear, this may indicate a mental or physical illness.

Use in children

Efficiency and safety have not been studied.

Side effects:

From the side of the central nervous system: at the beginning of treatment (especially in elderly patients) drowsiness, fatigue, dizziness, decreased ability to concentrate, ataxia, disorientation, unsteadiness of gait, slowing of mental and motor reactions; rarely - headache, euphoria, depression, tremor, memory loss, movement coordination disorders, mood depression, confusion, dystonic extrapyramidal reactions (uncontrolled movements, including the eye), weakness, myasthenia gravis, dysarthria; in some cases, paradoxical reactions (aggressive flashes, confusion, psychomotor agitation, fear, suicidal tendencies, muscle spasm, hallucinations, agitation, irritability, anxiety, insomnia).

From the hemopoietic system: leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, excessive fatigue or weakness), anemia, thrombocytopenia.

On the part of the digestive system: dry mouth or salivation, heartburn, nausea, vomiting, decreased appetite, constipation or diarrhea, impaired liver function, increased activity of hepatic transaminases and alkaline phosphatase, jaundice.

From the cardiovascular system: it is possible to reduce blood pressure, tachycardia.

From the urinary system: incontinence, urinary retention, renal dysfunction, decreased or increased libido, dysmenorrhea are possible.

On the part of the endocrine system: there may be a change in body weight, libido disorders, menstrual cycle disorders.

Allergic reactions: skin rash, itching are possible.

Overdose:

If there is no combination with other drugs or alcohol, the serious consequences of an overdose are rare, but the lethal outcome of mono-underdosed benzodiazepines has been described. When combined with alcohol, death occurs when the concentration of alcohol and benzodiazepines is less lethal for each of them separately.

Clinical manifestations: prolonged confusion, decreased reflexes, pronounced drowsiness or coma, convulsions, swaying, slow pulse, slurred speech, difficulty breathing, pronounced weakness.

Treatment:

Reduction of absorption: if the patient is conscious and if there is no risk of his loss or seizures - induction of vomiting, intake of activated carbon; unconscious patients may wash the stomach through an endotracheal tube with a cuff (to prevent aspiration of vomit).

Acceleration of elimination: infusion therapy.

Specific therapy: after providing respiration and catheterization of the peripheral vein, flumazenil (a specific antagonist of benzodiazepine receptors, which is a sedative effect of benzodiazepines) is possible. After the administration, it is necessary to monitor for sedation relapse. Flumazenil can provoke cramps, especially with prolonged therapy with benzodiazepines or when combined with cyclic antidepressants, so the use of flumazenil is not recommended in patients with epilepsy.

With respiratory depression: oxygen.

Hypotension: intravenous vasopressors (dopamine, norepinephrine, metaminol).

Monitoring: BHD, heart rate, blood pressure.

Supportive therapy: ventilation (maintenance of adequate ventilation), infusion therapy (maintenance of blood pressure at an adequate level).

During excitation, barbiturates can not be used (possibly increased excitation and / or prolonged CNS depression).

The role of dialysis in the treatment of benzodiazepine overdose is unknown.

Interaction:

With the simultaneous use of psychotropic, anticonvulsant,means and ethanol, an increase in the inhibitory effect of alprazolam on the CNS is observed.

With simultaneous use of blockers of histamine H₂-receptors reduce the clearance of alprazolam and increase the inhibitory effect of alprazolam on the CNS; antibiotics from the group of macrolides - reduce the clearance of alprazolam.

With simultaneous application of hormonal contraceptives for oral administration increase T_1/2 alprazolam.

With the simultaneous use of alprazolam with dextropropoxyphene, CNS depression is more pronounced than in combination with other benzodiazepines, because it is possible to increase the concentration of alprazolam in the blood plasma.

Simultaneous reception of digoxin increases the risk of developing intoxication with cardiac glycosides.

Alprazolam increases the concentration of imipramine in the blood plasma.

With simultaneous application itraconazole, ketoconazole increase the effects of alprazolam.

With the simultaneous use of paroxetine, the effects of alprazolam may be increased, due to the inhibition of its metabolism.

Fluvoxamine increases the concentration of alprazolam in the blood plasma and the risk of developing its side effects.

With the simultaneous use of fluoxetine, an increase in the concentration of alprazolam in the blood plasma is possible due to a decrease in its metabolism and clearance under the influence of fluoxetine, which is accompanied by psychomotor disorders.

It is impossible to exclude the possibility of enhancing the effect of alprazolam with simultaneous use with erythromycin.

Special instructions:

Benzodiazepine derivative of medium duration of action. The duration of taking alprazolam - from several days (in acute condition of fear) to 3 months. Because of the possibility of developing drug dependence, a longer continuous use of the drug is not recommended. When using a concentrated solution for oral administration (1 mg / ml): the dose is measured with a measuring pipette, available in the package. Each dose is carefully dissolved in a liquid or mushy food product (water, carbonated water, apple juice, pudding) immediately after the fence. The resulting mixture should be used immediately after preparation: it is not subject to storage.

When using dividable tablets.

The tablet from the vial is extracted with dry hands, after which it is closed.Then the tablet placed on the tongue, where it dissolves and is swallowed with the saliva. To drink it is not required.

The unused portion of the tablet is to be disposed of (unstable when stored).

First time opening the bottle, you need to remove it from the cotton and then tightly closed (moisture has gotten inside, can cause dissolution tablets).

Instructions

Alprazolam (Alprazolamum)