Trittico

Use during pregnancy and breastfeeding

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

Use for liver dysfunction

The drug should be prescribed with caution to patients with liver failure.

Use for renal impairment

The drug should be prescribed with caution to patients with renal failure.

Use in children

The use of the drug in children and adolescents under 18 years of age is contraindicated (the safety of trazodone for children has not been established).

Use in elderly patients

For elderly and debilitated patients, the initial dose is up to 100 mg/day in fractional doses or 1 time/day before bedtime. The dose may be increased under medical supervision, depending on the effectiveness and tolerability of the drug. Usually no dose exceeding 300 mg/day is required.

special instructions

People with depression have an increased risk of suicidal thoughts, self-harm, or suicide. The risk may last until significant remission occurs. Since improvement may not occur for the first few weeks of treatment or more, patients should be closely monitored until such improvement occurs. It is common clinical experience that the risk of suicide may increase in the early stages of recovery. It is known that patients with a history of suicidal events, or patients who exhibit a significant degree of suicidal ideation even before treatment, have a higher risk of suicidal ideation or suicide attempts, and should be closely monitored during treatment. The results of a meta-analysis of placebo-controlled clinical trials of antidepressants used in adults with mental disorders showed an increased risk of suicidal behavior in patients under the age of 24 years while taking antidepressants compared with placebo. Careful monitoring of patients, especially those at high risk, should accompany drug therapy, especially in its early stages and after dose changes. Patients (and their caregivers) should be warned to monitor for any clinical deterioration, suicidal behavior or thoughts, or unusual changes in behavior, and to immediately seek professional advice if such symptoms occur.

Since the drug has some adrenergic blocking activity, bradycardia and a decrease in blood pressure may develop. Therefore, caution should be exercised when prescribing the drug to patients with a tendency to prolong the QT interval, AV block of varying severity, and patients with a recent myocardial infarction.

When treated with trazodone in patients with bipolar disorder, depressive episodes can range from manic-depressive to manic psychosis. In these cases, it is necessary to interrupt treatment.

If you have epilepsy, use trazodone with caution, in particular avoiding sudden increases or decreases in dose.

With simultaneous use of trazodone with drugs that have serotonergic activity (tricyclic antidepressants, selective serotonin reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors and MAO inhibitors) and antipsychotics, serotonin syndrome may occur.

When trazodone is used simultaneously with drugs containing St. John's wort, side effects may be more frequent.

When using trazodone, agranulocytosis may develop, so it is recommended to conduct peripheral blood tests, especially if there is a sore throat when swallowing and fever.

Trazodone is effective for sleep disorders in patients with depression, increases the depth and duration of sleep, and restores its physiological structure and quality.

The use of the drug does not affect body weight.

The drug is not addictive.

Impact on the ability to drive vehicles and operate machinery

During the period of use of the drug, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Pharmacokinetics

Absorption of the drug from the gastrointestinal tract after oral administration is high. Taking trazodone during or immediately after a meal slows the rate of absorption, reduces Cmax of the drug in blood plasma and increases Tmax. Tmax of the drug is achieved 1/2–2 hours after oral administration.

The drug penetrates histohematic barriers, as well as into tissues and fluids (bile, saliva, breast milk).

Plasma protein binding is 89–95%.

Trazodone is metabolized in the liver, the active metabolite is 1-m-chlorophenylpiperazine. T1/2 in the first phase is 3-6 hours, in the second phase - 5-9 hours. The majority of the metabolized drug is excreted through the kidneys, in the urine (about 75%) and is completely completed 98 hours after taking the drug, excreted in the bile about 20%.

In vitro studies on human microsomes have shown that trazodone is primarily metabolized by cytochrome P450 CYP3A4.

Interaction

Trazodone may enhance the effect of some antihypertensive drugs and usually requires a dose reduction.

Simultaneous administration with drugs that depress the central nervous system (including clonidine, methyldopa) enhances the effect of the latter.

Antihistamines and drugs with anticholinergic activity enhance the anticholinergic effect of trazodone.

Trazodone enhances and prolongs the sedative and anticholinergic effects of tricyclic antidepressants, haloperidol, loxapine, maprotiline, phenothiazine, pimozidane and thioxanthine.

When tricyclic antidepressants and trazodone are prescribed simultaneously, cardiovascular side effects may occur.

MAO inhibitors increase the risk of side effects.

When used together, it increases the concentration of digoxin and phenytoin in the blood plasma.

In vitro drug metabolism studies indicate the potential for pharmacological interaction of trazodone with cytochrome P450 CYP3A4 inhibitors such as ketoconazole, ritonavir, indinavir and fluoxetine. Inhibitors of CYP3A4 may lead to significant increases in plasma concentrations of trazodone, thereby increasing the likelihood of adverse events. Therefore, when used in combination with potent CYP3A4 inhibitors, the dose of trazodone should be reduced.

When trazodone is taken in combination with carbamazepine, the plasma concentration of trazodone is reduced. Therefore, patients taking trazodone and carbamazepine concomitantly should be closely monitored.

Directions for use and doses

Orally, 30 minutes before or 2–4 hours after meals. The tablets should be taken whole, without chewing and with plenty of water.

The initial dose is 50–100 mg, once before bedtime. On the 4th day it is possible to increase the dose to 150 mg. Further increases in dosage should be made by 50 mg/day every 3–4 days until the optimal dose is reached. A daily dose of more than 150 mg should be divided into 2 doses, with the smaller dose taken after lunch and the main dose before bed.

The maximum daily dose for outpatients is 450 mg, for inpatients - 600 mg.

Children 6–18 years old: initial daily dose of 1.5–2 mg/kg/day, divided into several doses. If necessary, the dose is gradually (with an interval of 3-4 days) increased to 6 mg/kg/day.

What will happen now?

According to the manufacturer, the drug was imported to Russia and is in the process of being put into circulation. This means that it may appear in pharmacies in the near future. AIDS.CENTER sources in pharmaceutical circles say that we will have to wait until the end of the year for the medicine.

According to Roszdravnadzor, more than 49,000 packages of the medicine were released into civilian circulation this year. There have been no reports of suspension or discontinuation of production of the drug.

“We can’t do anything; logistics is a very complicated process. Literally the day before our conversation, I called the representative office of the supplier company, where the representative of the company responsible for trazodone assured me that everything in their power had been done and the medicine was now in the distributors’ warehouses; the next stage was shipment directly to pharmacies. It follows from this that within the next few days the shortage of medicine must be replenished,” the doctor said.

Contraindications

hypersensitivity to the drug;

pregnancy period;

lactation period;

children under 6 years of age.

The drug should be prescribed with caution to patients with AV block, myocardial infarction (early recovery period), arterial hypertension (dose adjustment of antihypertensive drugs may be required), ventricular arrhythmia, a history of priapism, renal and/or liver failure. Patients under the age of 18 years, due to the possibility of developing the risk of suicidal behavior (suicidal plans, aggressiveness, tendency to contradict, anger).

Where and why did the antidepressant disappear?

"Dear Customer! The requested product, unfortunately, is not currently available in pharmacies,” says many pharmacy websites when trying to buy trazodone (sold under the sole trade name Trittico).

As AIDS.CENTER wrote, the Italian pharmaceutical company Angelini, which produces the drug, associated the interruptions with a change in the structure of the supply chain and the launch of a labeling system in July. This has become the reason that the process of introducing drugs into civilian circulation takes much longer than before.

At the same time, representatives of the single operator of the labeling system (CPRT) stated that not a single labeled package of the drug has yet been put into circulation in Russia, but the pharmaceutical company received permission from the Roszdravnadzor commission to continue supplying unlabeled packages of the antidepressant. “At the same time, Angelini has already ordered 226,000 marking codes, but has not yet applied them to the packaging. To date, there has not been a single request from the company to the CRPT technical support service, which would indicate any difficulties,” said representatives of the operator.

According to the analytical company DSM Group, sales of trazodone began to fall in the first ten days of August; in September, sales growth doubled, but from the middle of the month sales began to decline again. If in October 2021 more than 18,000 packages were sold in Russia, then during the same period in 2021 - only 13,500.

“I don’t remember any interruptions in the availability of trazodone specifically, but interruptions in medications in general and psychotropic medications in particular sometimes happen. We mostly learn about such situations from our patients who cannot purchase medicine in pharmacies. I am not aware of any interruptions at present with any other medications,” says the psychiatrist.

Side effects

From the side of the central nervous system: increased fatigue, drowsiness, agitation, headache, dizziness, weakness, myalgia, incoordination, paresthesia, disorientation, tremor.

From the cardiovascular system and hematopoietic system: decreased blood pressure, orthostatic hypotension caused by adrenolytic action (especially in persons with vasomotor lability), arrhythmia, conduction disturbances, bradycardia; leukopenia and neutropenia (usually minor)..

From the gastrointestinal tract: dryness and bitterness in the mouth, nausea, vomiting, diarrhea, loss of appetite.

Other: allergic reactions, eye irritation, priapism (you should immediately stop taking the drug and consult a doctor).

Why is it important?

Trazodone has no analogues, and it is one of the most popular drugs in its class. “It is difficult to reliably assess the popularity of trazodone among other psychopharmacological drugs, but I think I will not be mistaken if I say that it is among the top ten antidepressants and the top twenty of all psychotropic drugs. I prescribe it with approximately the same frequency: one out of ten to fifteen prescriptions for antidepressants,” says Maxim Marachev.

Based on the data from the State Register of Medicines (GRLS), no more drugs have been registered under the generic name trazodone, that is, there are no analogues with this active substance on the domestic market. However, the doctor urged not to panic. “There is no direct analogue of trazodone on the Russian market, but this does not mean that its absence in pharmacies will lead to fatal consequences, the range of psychopharmacological agents is quite wide, and you can always find a replacement without losing anything significant in effectiveness/tolerability,” said doctor.