Helex^® SR (Tablets) Instructions for Use

ATC Code

N05BA12 (Alprazolam)

Active Substance

Alprazolam (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Anxiolytic (tranquilizer)

Pharmacotherapeutic Group

Anxiolytic agent (tranquilizer)

Pharmacological Action

Anxiolytic agent (tranquilizer), a triazolo-benzodiazepine derivative. It has anxiolytic, sedative, hypnotic, anticonvulsant, and central muscle relaxant effects.

The mechanism of action involves enhancing the inhibitory effect of endogenous GABA in the CNS by increasing the sensitivity of GABA receptors to the mediator as a result of stimulation of benzodiazepine receptors located in the allosteric center of postsynaptic GABA receptors of the ascending activating reticular formation of the brainstem and interneurons of the lateral horns of the spinal cord; it reduces the excitability of subcortical brain structures (limbic system, thalamus, hypothalamus), and inhibits polysynaptic spinal reflexes.

Pronounced anxiolytic activity (reduction of emotional tension, alleviation of anxiety, fear, restlessness) is combined with a moderately pronounced hypnotic effect; it shortens sleep onset latency, increases sleep duration, and reduces the number of nighttime awakenings.

The mechanism of the hypnotic effect involves inhibition of cells of the reticular formation of the brainstem. It reduces the impact of emotional, vegetative, and motor stimuli that disrupt the mechanism of falling asleep.

Pharmacokinetics

After oral administration, Alprazolam is rapidly and completely absorbed from the gastrointestinal tract. C_max in plasma is reached within 1-2 hours.

Plasma protein binding is 80%.

It is metabolized in the liver.

T_1/2 averages 12-15 hours. Alprazolam and its metabolites are excreted mainly by the kidneys.

Indications

Anxiety disorders, neuroses accompanied by feelings of anxiety, danger, restlessness, tension, sleep disturbances, irritability, as well as somatic disorders; mixed anxiety-depressive states; neurotic reactive-depressive states accompanied by depressed mood, loss of interest in surroundings, anxiety, insomnia, loss of appetite, somatic disorders; anxiety states and neurotic depressions developed against the background of somatic diseases; panic disorders with and without phobic symptoms.

ICD codes

Dosage Regimen

Tablets

Individual. It is recommended to use the minimum effective doses. The dose is adjusted during treatment depending on the achieved effect and tolerance. If a dose increase is necessary, it should be increased gradually, first in the evening dose, and then in the daytime dose.

The initial dose is 250-500 mcg 3 times/day, if necessary, a gradual increase to 4.5 mg/day is possible.

For elderly or debilitated patients, the initial dose is 250 mcg 2-3 times/day, maintenance doses are 500-750 mcg/day, if necessary, taking into account tolerance, the dose can be increased.

Discontinuation or dose reduction of alprazolam should be carried out gradually, reducing the daily dose by no more than 500 mcg every 3 days; sometimes an even slower withdrawal may be required.

Adverse Reactions

From the CNS at the beginning of treatment (especially in elderly patients): drowsiness, feeling of fatigue, dizziness, decreased ability to concentrate, ataxia, disorientation, unsteady gait, slowing of mental and motor reactions; rarely – headache, euphoria, depression, tremor, memory impairment, impaired coordination of movements, depressed mood, confusion, dystonic extrapyramidal reactions (uncontrolled movements, including eye movements), weakness, myasthenia, dysarthria; in some cases – paradoxical reactions (aggressive outbursts, confusion, psychomotor agitation, fear, suicidal tendency, muscle spasm, hallucinations, agitation, irritability, anxiety, insomnia).

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

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

From the urinary system: urinary incontinence, urinary retention, impaired renal function, decreased or increased libido, dysmenorrhea.

From the endocrine system: changes in body weight, libido disorders, menstrual cycle disorders.

From the cardiovascular system: decreased BP, tachycardia.

Allergic reactions: skin rash, itching.

Contraindications

Coma, shock, myasthenia gravis, closed-angle glaucoma (acute attack or predisposition), acute alcohol poisoning (with weakening of vital functions), opioid analgesics, hypnotics and psychotropic drugs, chronic obstructive airway diseases with initial manifestations of respiratory failure, acute respiratory failure, severe depression (suicidal tendencies may manifest), pregnancy (especially the first trimester), lactation period, children and adolescents under 18 years of age, hypersensitivity to benzodiazepines.

Use in Pregnancy and Lactation

Alprazolam has a toxic effect on the fetus and increases the risk of congenital malformations when used in the first trimester of pregnancy. Continuous use during pregnancy can lead to physical dependence with the development of a withdrawal syndrome in the newborn. Use in therapeutic doses later in pregnancy can cause CNS depression in the newborn. Use immediately before or during childbirth can cause respiratory depression, decreased muscle tone, hypotension, hypothermia, and weak sucking in the newborn (neonatal floppy infant syndrome).

Benzodiazepines may be excreted in breast milk, which can cause drowsiness and feeding difficulties in the newborn.

In experimental studies, it has been shown that Alprazolam and its metabolites are excreted in breast milk.

Use in Hepatic Impairment

Alprazolam should be used with caution in patients with impaired liver function.

Use in Renal Impairment

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

Pediatric Use

Contraindication: children and adolescents under 18 years of age.

Geriatric Use

For elderly or debilitated patients, the initial dose is 250 mcg 2-3 times/day, maintenance doses are 500-750 mcg/day, if necessary, taking into account tolerance, the dose can be increased.

Special Precautions

In endogenous depressions, Alprazolam can be used in combination with antidepressants. When using alprazolam in patients with depression, cases of hypomanic and manic state development have been noted.

Alprazolam should be used with caution in patients with impaired liver and/or kidney function.

In patients who have not previously taken drugs affecting the CNS, Alprazolam is effective at lower doses compared to patients who have received antidepressants, anxiolytics, or those suffering from chronic alcoholism.

With long-term use in high doses, the development of tolerance and formation of drug dependence is possible, especially in patients prone to drug abuse.

With rapid dose reduction or abrupt withdrawal of alprazolam, a withdrawal syndrome is observed, the symptoms of which can range from mild dysphoria and insomnia to a severe syndrome with abdominal and skeletal muscle cramps, vomiting, increased sweating, tremor, and convulsions. Withdrawal syndrome is more common in individuals who have received Alprazolam for a long time (more than 8-12 weeks).

Other tranquilizers should not be used simultaneously with alprazolam.

The safety of alprazolam use in children and adolescents under 18 years of age has not been established. Children, especially young children, are very sensitive to the CNS depressant effect of benzodiazepines.

During treatment, alcohol consumption should be avoided.

Effect on the ability to drive vehicles and operate machinery

During treatment, one should refrain from engaging in potentially hazardous activities requiring increased attention and speed of psychomotor reactions (driving vehicles or working with machinery).

Drug Interactions

With simultaneous use of psychotropic, anticonvulsant drugs, and ethanol, an enhancement of the inhibitory effect of alprazolam on the CNS is observed.

With simultaneous use, histamine H₂-receptor blockers reduce the clearance of alprazolam and enhance the inhibitory effect of alprazolam on the CNS; antibiotics from the macrolide group – reduce the clearance of alprazolam.

With simultaneous use, oral hormonal contraceptives increase the T_1/2 of alprazolam.

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

Concomitant use of digoxin increases the risk of cardiac glycoside intoxication.

Alprazolam increases the plasma concentration of imipramine.

With simultaneous use, itraconazole, ketoconazole enhance the effects of alprazolam.

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

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

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

The possibility of enhancing the action of alprazolam with simultaneous use with erythromycin cannot be excluded.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.