Trittico^® (Tablets) Instructions for Use

ATC Code

N06AX05 (Trazodone)

Active Substance

Trazodone (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Psychoanaleptics, antidepressants

Pharmacological Action

Antidepressant, a thiazolopyridine derivative. It also has thymoleptic, anxiolytic, sedative, and muscle relaxant effects. It has a high affinity for some subtypes of serotonin receptors and inhibits serotonin reuptake; it has little effect on the neuronal reuptake of norepinephrine and dopamine.

It does not have anticholinergic effects, does not inhibit MAO, and does not change body weight. It eliminates both mental (affective tension, irritability, fear, insomnia) and somatic manifestations of anxiety (palpitations, headache, myalgia, frequent urination, increased sweating). It increases the depth and duration of sleep in patients with depression and restores its physiological structure.

It reduces pathological craving for ethanol. It is effective in withdrawal syndrome in patients with drug dependence on benzodiazepine-derived anxiolytics, eliminating anxiety-depressive states and sleep disorders (during remission, benzodiazepines can be completely replaced by trazodone). It does not cause addiction. It helps restore libido and potency.

The therapeutic effect is observed in 50% of patients after 3-7 days, and in 25% after 2-4 weeks.

Pharmacokinetics

After oral administration, absorption from the gastrointestinal tract is high. The time to reach C_max in blood plasma is 1-2 hours. Taking trazodone during or immediately after a meal increases absorption, reduces C_max, and increases the time to reach it.

It penetrates through histohematic barriers, including the BBB. It penetrates into tissues and fluids (bile, saliva, breast milk). Plasma protein binding is 89-95%.

It is metabolized in the liver by hydroxylation. The metabolism of the drug involves the isoenzymes CYP3A4, CYP3A5, and CYP3A7.

T_1/2 in the α-phase is 3-6 hours, in the β-phase – 5-9 hours. It is excreted by the kidneys – 75% as inactive metabolites within 98 hours after administration; 20% – with bile.

Indications

Various forms of depression (endogenous, psychotic, neurotic, somatogenic), including those with pronounced anxiety, comprising at least 4 of the following signs: sleep disturbances, appetite disturbances, psychomotor agitation or retardation, decreased interest in surroundings, decreased sexual activity, feelings of guilt, increased fatigue, slowed thinking, decreased ability to concentrate, suicidal attempts/thoughts; bulimia, kleptomania, anxiety, phobias. Benzodiazepine drug dependence; acute alcohol withdrawal syndrome. Decreased libido, impotence. Prevention of migraine attacks.

ICD codes

Dosage Regimen

Administer the tablets orally.

Initiate therapy with an initial daily dose of 150-200 mg, divided into three separate doses.

For mild forms of depression, titrate to an average maintenance dose of 150 mg per day.

For moderate to severe depression, the typical maintenance dose is 300 mg per day.

If clinically indicated, increase the dose gradually. The maximum recommended daily dose is 600 mg.

Take the medication during or immediately after a meal to improve tolerability and moderate peak plasma concentrations.

Administer the larger portion of the total daily dose at bedtime to utilize the drug’s sedative properties and manage insomnia.

Adhere strictly to the prescribed dosing schedule. Do not abruptly discontinue treatment.

In patients with renal impairment or hepatic impairment, use a cautious dosing approach; consider lower initial doses and slower titration.

Exercise caution when determining the dosage for elderly patients, initiating therapy at the lower end of the dosing range.

Adverse Reactions

From the central and peripheral nervous system: drowsiness, increased fatigue, dizziness, insomnia, headache, agitation, myalgia, impaired coordination of movements, paresthesia, disorientation, clouding of consciousness, tremor.

From the cardiovascular system: arrhythmia, conduction disturbance, bradycardia, ventricular fibrillation, decreased blood pressure, orthostatic hypotension, fainting.

From the digestive system: nausea, vomiting, diarrhea, dry mouth and bitter taste in the mouth.

From the organ of vision: visual impairment, eye irritation.

From the hematopoietic system: leukopenia, neutropenia (usually mild).

Other: nasal congestion, priapism with subsequent impotence, allergic reactions.

Contraindications

Ventricular arrhythmia, tachycardia, myocardial infarction (early recovery period), history of priapism, pregnancy, lactation period, hypersensitivity to trazodone.

Use in Pregnancy and Lactation

Use during pregnancy and lactation is contraindicated.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

Use with caution in children and adolescents under 18 years of age.

Special Precautions

Use with caution in heart disease, arterial hypotension, arterial hypertension, renal and/or hepatic insufficiency, in children and adolescents under 18 years of age.

Should not be used concurrently with MAO inhibitors.

Drug Interactions

A case of torsades de pointes arrhythmia has been described with the simultaneous use of trazodone and amiodarone.

A case of moderately pronounced decrease in the anticoagulant effect of warfarin has been described with simultaneous use with trazodone.

With simultaneous use, an increase in the plasma concentration of digoxin and the development of symptoms of intoxication are possible.

A case of increased plasma concentration of carbamazepine has been described with simultaneous use with carbamazepine.

With simultaneous use with lithium salts, tremor and reversible symptoms of neurotoxic action are possible.

A case of anxiety, panic, clouding of consciousness, and depersonalization has been described when taking pseudoephedrine during trazodone therapy.

With simultaneous use with thioridazine, an increase in the plasma concentration of trazodone is possible; with tryptophan – a case of anorexia, psychosis, hypomania has been described; with phenytoin – a case of increased side effects of phenytoin has been described; with fluoxetine – an increase in side effects is possible; with chlorpromazine, trifluoperazine – the development of arterial hypotension is possible.

With simultaneous use with ethanol, the depressant effect on the central nervous system is enhanced.

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.