Amixide (Tablets) Instructions for Use

ATC Code

N06CA01 (Amitriptyline and psycholeptics)

Active Substances

Chlordiazepoxide (Rec.INN registered by WHO)

Amitriptyline (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug with antidepressant and anxiolytic action

Pharmacotherapeutic Group

Antidepressant

Pharmacological Action

Amitriptyline is a tricyclic antidepressant from the group of non-selective inhibitors of neuronal monoamine reuptake. It has a pronounced thymoanaleptic and sedative effect.

Chlordiazepoxide is a tranquilizer from the benzodiazepine group. It has a pronounced tranquilizing, anxiolytic, and moderate central muscle relaxant effect.

The probable mechanism of action of the drug is based on the simultaneous influence of the tranquilizer chlordiazepoxide on the limbic system, responsible for emotional state, and the antidepressant amitriptyline on the synthesis of norepinephrine and serotonin in the synapses of CNS neurons.

Pharmacokinetics

After oral administration of Amixide, C_max in plasma is reached within 4-8 hours. Since amitriptyline slows gastrointestinal transit time, absorption may be delayed, especially in overdose. Amitriptyline is 94% bound to plasma proteins; T_1/2 is about 20 hours. Chlordiazepoxide is 96% bound to plasma proteins; T_1/2 is about 10 hours. Both components are metabolized in the liver. T_1/2 of the active metabolite of amitriptyline (nortriptyline) is 30 hours. T_1/2 of the active metabolite of chlordiazepoxide (desmethylchlordiazepoxide) is 1-4 days.

The drug crosses the placental barrier and is excreted in breast milk.

Indications

• Depressions of various origins, in the structure of which there is an anxiety syndrome of varying severity.

ICD codes

Dosage Regimen

Tablets

It is prescribed orally (after meals), the doses of the drug are set individually.

The initial daily dose is 1 tablet 2-3 times/day. If necessary, the dose of the drug can be increased to 6 tablets (with the maximum content of active substances)/day (in 2-3 doses).

After achieving a stable antidepressant effect in 2-4 weeks, the doses are gradually and slowly reduced. If signs of depression appear when reducing the doses, it is necessary to return to the previous dose.

If the patient’s condition does not improve within 3-4 weeks of treatment, further therapy is not advisable.

In elderly patients with mild disorders, in outpatient practice, doses are 12.5/5 mg; 25/5 mg or 25/10 mg usually once/day at night.

Adverse Reactions

Mainly associated with the anticholinergic action of the drug accommodation disturbance, mydriasis, increased intraocular pressure, dry mouth, stool retention, intestinal obstruction, urinary retention, increased body temperature, drowsiness. All these phenomena usually disappear after adaptation to the drug or dose reduction.

From the cardiovascular system: tachycardia, orthostatic arterial hypotension or increased blood pressure, impaired cardiac muscle conduction; isolated cases of stroke and myocardial infarction have been described.

From the digestive system: nausea, vomiting, anorexia, stomatitis, taste disturbances, black discoloration of the tongue, epigastric discomfort, diarrhea, rarely liver function disorders.

From the endocrine system: gynecomastia, galactorrhea, change in antidiuretic hormone secretion, decreased libido, potency.

Other: bone marrow function depression, skin rash, hair loss, lymph node enlargement, weight gain with prolonged use.

Contraindications

• Decompensated heart defects;
• Acute and recovery period of myocardial infarction;
• Impaired cardiac muscle conduction;
• Stage III hypertension;
• Acute liver and kidney diseases with severe impairment of functions;
• Blood diseases;
• Hyperthyroidism and simultaneous treatment with thyrotropic drugs;
• Gastric and duodenal ulcer in the acute stage;
• Glaucoma;
• Prostatic hypertrophy;
• Bladder atony;
• Pyloric stenosis, paralytic ileus;
• Simultaneous treatment with MAO inhibitors;
• Severe myasthenia;
• Pregnancy;
• Lactation period;
• Childhood;
• Hypersensitivity to any of the components of the drug.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in acute liver diseases with severe impairment of functions.

Use in Renal Impairment

Contraindicated in acute kidney diseases with severe impairment of functions.

Pediatric Use

Contraindicated.

Geriatric Use

In elderly patients with mild disorders, in outpatient practice, doses are 12.5/5 mg; 25/5 mg or 25/10 mg usually once/day at night.

Special Precautions

Treatment with Amixide in old age should be under careful supervision and with the use of minimal doses of the drug, increasing them gradually, to avoid the development of delirious disorders, hypomania and other complications.

Patients with the depressive phase of manic-depressive psychosis may transition to the manic stage.

Effect on the ability to drive vehicles and operate machinery

While taking amitriptyline, driving vehicles, operating machinery, and other types of work requiring increased concentration are prohibited.

Overdose

Symptoms drowsiness, disorientation, confusion, dysarthria, agitation, hallucinations, numbness of the extremities, convulsive seizures, muscle rigidity, stupor, coma, vomiting, arrhythmia, hypotension, heart failure, respiratory depression.

Treatment discontinuation of amitriptyline therapy, gastric lavage, fluid infusion, detoxification, administration of physostigmine 1-3 mg every 1/2-2 hours intramuscularly or intravenously, symptomatic therapy, maintenance of blood pressure and water-electrolyte balance. Prolonged observation is indicated because a recurrence of intoxication symptoms may occur after 48 hours.

Drug Interactions

The active components in Amixide potentiate CNS depression by the following drugs: neuroleptics, sedatives and hypnotics, anticonvulsants, central and opioid analgesics, anesthetics, alcohol. When Amixide is used concomitantly with neuroleptics and/or anticholinergic drugs, a febrile temperature reaction and paralytic ileus may occur.

The active components in Amixide potentiate the hypertensive effects of catecholamines but inhibit the effects of drugs affecting the release of norepinephrine (tyramine).

The active components in Amixide may block the antihypertensive effect of guanethidine and drugs with a similar mechanism of action.

Concomitant use of Amixide and cimetidine may lead to an increase in plasma concentration of amitriptyline.

Concomitant use of Amixide with MAO inhibitors can be fatal. The treatment interval between taking MAO inhibitors and tricyclic antidepressants should be at least 14 days.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.