Trittico 150 mg 20 pcs. tablets aziende chimiche riunite angelini france

Pharmacodynamics

Trazodone, being a triazolopyridine derivative, has a predominantly antidepressant effect, with some sedative and anxiolytic effects. Trazodone has no effect on MAO, which distinguishes it from MAO inhibitors and tricyclic antidepressants.

Quickly affects mental (affective tension, irritability, fear, insomnia) and somatic symptoms of anxiety (palpitations, headache, muscle pain, frequent urination, sweating, hyperventilation).

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

Trazodone stabilizes the emotional state, improves mood, reduces pathological craving for alcohol in patients suffering from chronic alcoholism during the period of alcohol withdrawal syndrome, also in remission. For withdrawal symptoms in patients suffering from dependence on benzodiazepine derivatives, trazodone is effective in the treatment of anxiety, depression and sleep disorders. During remission, benzodiazepines can be completely replaced by trazodone.

The drug is not addictive.

Helps restore libido and potency, both in patients with depression and in people who do not suffer from depression.

The mechanism of action of trazodone is associated with the high affinity of the drug for certain subtypes of serotonin receptors, with which trazodone enters into an antagonistic or agonistic interaction depending on the subtype, as well as with the specific ability to cause inhibition of serotonin reuptake.

The neutral uptake of norepinephrine and dopamine has little effect.

The drug does not affect body weight.

Trittico

Trazodone (Trittiko), sold under many brand names around the world, is an antidepressant. Trittico is used to treat major depressive disorders, anxiety disorders and, in addition to other treatments, alcohol dependence. Common side effects include: dry mouth, vomiting, feeling weak and headache. More serious side effects may include suicidal thoughts, bipolar disorder, heart rhythm disturbances, and priapism. It remains unclear whether Trittico is safe for women to use during pregnancy or breastfeeding.

Trittico is a phenylpiperazine serotonin antagonist and reuptake inhibitor (SSRI) compound. Trazodone also has a calming (sedative) effect.

Trittico is a relatively old drug and the most commonly prescribed antidepressant in the state psychiatric system, which is likely due to its effective lobbying by pharmaceutical companies. Trazodone was approved for medical use in the United States back in 1981.

Data from open-label and double-blind studies indicate that the antidepressant trazodone has comparable efficacy to amitriptyline, doxepin, and mianserin. Because trazodone has minimal anticholinergic activity, it was especially prescribed as a treatment for geriatric patients with depression when the drug first came to market. However, a side effect of trazodone, orthostatic hypotension, which can cause dizziness and increase the risk of falling, has dangerous consequences in older patients; thus, this side effect, along with sedation, often makes trazodone less acceptable for the treatment of elderly patients compared with newer compounds that share the lack of anticholinergic activity but not the rest of the side effect profile. Two recent reviews have found trazodone to be the second-best prescribed treatment for insomnia, but since most studies are limited to patients with depression, few studies truly support the use of trittico in the treatment of primary insomnia.

Note that if the patient is under 18 years of age and Trittico (trazodone) is combined with other antidepressants, it may increase the likelihood of suicidal thoughts or actions. The possibility of suicide in patients with depression persists throughout treatment and until stable remission occurs. Trittico has been reported in the literature to cause seizures in a small number of patients who took this drug concomitantly with anti-seizure medications.

Although not a true member of the SSRI antidepressant group, Tritico does have many SSRI properties, especially the potential for withdrawal symptoms if this medication is stopped too quickly, so it should be taken with caution when weaning off the medication, usually through a gradual tapering process doses over a period of time. Because trazodone may impair the cognitive and/or physical abilities needed to perform potentially hazardous tasks such as driving, the patient should be warned not to engage in such activities while taking tritico.

Because of its lack of anticholinergic side effects, trazodone is particularly useful in situations where antimuscarinic effects are particularly harmful (eg, patients with benign prostatic hyperplasia, closed-point glaucoma, or frequent constipation). Trazodone's tendency to cause sedation is a double-edged sword. For many patients, relief from agitation, restlessness, and insomnia can be rapid; For other patients, including those with significant psychomotor retardation and decreased energy, trazodone may not be suitable for use due to sedation. Trazodone causes orthostatic hypotension in some patients, probably as a consequence of α1-adrenergic blockade. Mania has been observed in association with trazodone treatment, including in patients with bipolar disorder, as well as in patients with previous diagnoses of major depression.

In patients taking Trittico, cardiac arrhythmias were observed that occurred in connection with treatment with this drug, both in patients with a previously established diagnosis of mitral valve prolapse and in patients with a family history of cardiovascular disease. QT segment prolongation has been reported with trazodone therapy. During treatment with Trittico, closely monitor patients with previously diagnosed cardiac disease, especially cardiac arrhythmias. Trazodone is not recommended for use during the initial recovery phase of myocardial infarction. Concomitant administration of drugs that prolong the QT interval or CYP3A4 inhibitors may increase the risk of cardiac arrhythmias.

A relatively rare but dramatic side effect associated with trazodone is priapism, likely due to its antagonism at α-adrenergic receptors. The risk of this side effect appears to be greatest during the first month of treatment at low doses (ie, <150 mg/day). Early recognition of any abnormal erectile function (including prolonged or abnormal erections) is important and should prompt the patient to discontinue treatment with trazodone. Clinical reports have also described trittico-associated psychosexual side effects in women, including increased libido, clitoral priapism, and spontaneous orgasms. Rare cases of idiosyncratic hepatotoxicity have been observed, possibly due to the formation of reactive metabolites. Increased prolactin concentrations have been observed in patients taking trazodone.

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.

Choosing an antidepressant based on effectiveness and tolerability

Summary

A classification of side effects of antidepressants is presented. Side effects may be toxic or neuronal. Neuronal side effects are divided into “non-therapeutic” (persistent or reversible) and “para-therapeutic” side effects. Seven categories of antidepressant tolerability have been defined. The lowest category VII included clomipramine, imipramine, maprotiline, agomelatine. Category VI includes amitriptyline, V - pipofezin, trazodone, mianserin and mirtazapine, IV - vortioxetine, III - venlafaxine and duloxetine, II - sertraline, paroxetine, citalopram, escitalopram, fluoxetine, fluvoxamine and milnacipran, I - pirlindole and moclobemide. Among the most effective antidepressants (amitriptyline, imipramine, venlafaxine in high daily doses), venlafaxine had the best tolerability category. This drug is the most effective and tolerable antidepressant. Other options for the practical use of classifications are discussed.

Summary

A classification of the side effects of antidepressants is presented. Side effects can be toxic or neuronal. Neuronal side effects are divided into “extratherapeutic” (persistent or reversible), as well as “paratherapeutic”. Seven antidepressant tolerance categories have been identified. The lowest category VII included clomipramine, imipramine, maprotiline, agomelatine. Amitriptyline belongs to the VI category, pipofezin, trazodone, mianserin and mirtazapine to the V category, vortioxetine belongs to the IV category, venlafaxine and duloxetine to the III category, sertraline, paroxetine, citalopram, escitalopram, fluoxetine, fluvoxamine and milnacipran to the II category, and pirlindole and moclobemide to the I category. Among the most effective antidepressants (amitriptyline, imipramine, venlafaxine in high daily doses), venlafaxine was in the best category of tolerance. This drug is the most effective and tolerable antidepressant. Other options for the practical use of classifications are discussed.

The previous article presented a description of the mechanism of action of various antidepressants (tricyclic - TcA, sertonin-modulating - SMA, tetracyclic - CtsA, reversible inhibitors of monoamine oxidase type "A" - OIMAO-A, selective serotonin reuptake inhibitors - SSRIs, selective serotonin and norepinephrine reuptake inhibitors – SNRIs, norepinephrine and selective serotonin – NaSSA, melatonergic – MeA, multimodal – MmA) (Table 1).

Table 1. Antidepressants known in Russia, their effect on neurons and the “formula” of the mechanism of action (1-4).

* - white color - the drug does not affect neurons, dark gray - a pronounced increase in activity, light gray - a moderate increase in activity, ** - in high doses, IOR - neurotransmitter reuptake inhibitors, SVRR - agents affecting regulatory receptors, OIMAO-A are reversible inhibitors of monoamine oxidase type “A”.

All these drugs, to varying degrees, contribute to the activation of serotonin (↑C or ↑c), norepinephrine (↑H or ↑n), dopamine (↑D or ↑d) or melatonin (↑M or ↑m) neurons, the “tone” of which decreases for depression. But the most pronounced effect on the vital activity of neurons is ↑SNd antidepressants: amitriptyline and imipramine (TcA), as well as venlafaxine (SNRI) in high daily doses. It is no coincidence that many experts consider them to be the most effective drugs for treating depression (5).

Of course, the choice of any antidepressant should be related not only to its therapeutic properties (efficacy), but also to side effects (tolerability). The vast majority of authors agree that tolerability is best with SSRIs and worse with TCAs (6–9), with other drugs falling in between (1). This assessment of the tolerability of antidepressants is correct, but is of a generalized nature. To clarify it, you should refer to data on the mechanisms of side effects.

A minority of them are due to the toxic effect of antidepressants on the organs and tissues of patients. These “toxic” side effects are very dangerous (10). For example, while taking some TCAs (clomipramine, imipramine), as well as MeA (agomelaptine), drug-induced hepatitis is observed, which leads to the death of patients (10, 11). Maprotiline also has serious toxic side effects, causing agranulocytosis and leukopenia (12). Fortunately, toxic side effects are very rare and can be detected promptly by test results.

For example, when it was discovered that agomelatine causes severe and drug-induced hepatitis, detailed precautions were added to its instructions (11). They include a biochemical blood test, which is prescribed to all patients (without exception) before prescribing the drug, as well as while taking it. Similar analysis is required in patients receiving clomipramine and imipramine (13,14). However, when prescribing these antidepressants, biochemical analysis is required only for patients with existing liver diseases. Finally, regular general blood tests to detect agranulocytosis and leukopenia are also necessary during maprotiline treatment (12).

Obviously, the need for additional tests can significantly complicate the use of antidepressants. Fortunately, this is only required when using the medications listed. When prescribing other antidepressants, there is no need to resort to additional examinations. However, their tolerability may be impaired due to the drugs' adverse effects on neurons. As a result, “neural” side effects are formed, which, however, do not directly threaten the lives of patients and are easily diagnosed based on their complaints.

Some of the neuronal side effects are due to the effect of the antidepressant on histamine and acetylcholine neurons, which do not reduce their activity in the formation of mental disorders that are indications for the prescription of antidepressants (2,15). Accordingly, such pharmacological properties can be designated as “non-therapeutic” (extra, unrelated to the treatment process) side effects. They only increase the number of neuronal systems that the patient suffers. Most often, “non-medicinal” side effects are persistent. They may occur throughout the course of treatment, particularly when the antidepressant blocks excitatory receptors on histamine and acetylcholine neurons (15).

This mechanism of action, characteristic of neuroleptics rather than antidepressants, leads to a sharp drop in the activity (inhibition) of these nerve cells (↓G and ↓A) (1,2). Moreover, normal histamine and acetylcholine neurons cannot restore their functions, since there are no effective compensatory mechanisms for this. Accordingly, patients develop persistent mental and somatic symptoms, which seriously complicate treatment (Table 2).

Table 2. The main “non-therapeutic” side effects of antidepressants associated with the blockade of excitatory receptors on histamine and acetylcholine neurons (1,2)

Characterized by drowsiness, fatigue, deterioration of memory and attention. There are complaints of dry mouth, disturbances of accommodation and urination, constipation, pain in the eyes due to increased intraocular pressure, heart rhythm disturbances, increased appetite and weight gain.

There is, however, an antidepressant whose “non-medicinal” side effects are not persistent. This drug is vortioxetine. It does not inhibit histamine and acetylcholine neurons (due to blockade of excitatory receptors), but increases their “tone” due to its influence on regulatory receptors (16). On the one hand, this provides vortioxetine with a unique nature of “non-therapeutic” side effects. In particular, when taking this antidepressant, agitation, anger, “unusual” dreams, and insomnia may occur (Table 3).

Table 3. “Non-medicinal” side effects of vortioxetine (16,17).

Characterized by ketoacidosis, somatic complaints of dizziness, itching (including generalized), sweating, hot flashes, nausea, diarrhea, vomiting. On the other hand, these side effects are fundamentally reversible, since neurons have special mechanisms that are aimed at combating excessive activation. To do this, they can, for example, reduce the sensitivity of their regulatory receptors (a mechanism known as autoregulation). Therefore, “non-therapeutic” side effects of vortioxetine often reduce spontaneously in the first two weeks of treatment (16).

Moving now to the rest of the antidepressants, we point out that the vast majority of them do not have any “non-therapeutic” side effects that increase the number of affected neuronal systems (2). Many drugs do not affect histamine and acetylcholine neurons. Moreover, they increase the activity of only those neurons (serotonin, norepinephrine and dopamine) whose “tone” decreases in mental disorders that are indications for the prescription of antidepressants. However, even this feature cannot relieve antidepressants from “neural” side effects. The latter will arise due to the fact that within any affected neuronal system, the activity of only part of the nerve cells decreases, while the functions of the other part are not impaired. Antidepressants both activate “damaged” neurons and create therapeutic effects, and increase the “tone” of normally functioning nerve cells and cause side effects.

At the same time, the tolerability of antidepressants paradoxically turns out to be “hostage” to their therapeutic properties. The more effectively the drug activates the affected neurons, the more it affects similar nerve cells that are still functioning at the proper level. Therefore, it is advisable to designate the side effects under consideration as “paratherapeutic”. They are manifested by restlessness, restlessness, insomnia and anxiety (Table 4).

Table 4. Main “paramedical” side effects of antidepressants (15)

Somatic complaints are represented by sexual dysfunction, disruption of the digestive system and heart rhythm, and fluctuations in blood pressure. As a rule, “paratherapeutic” side effects are reversible. They may resolve on their own in the second or third week of treatment (18). This is due to the already noted above ability of “normal” neurons to quickly adapt to excessive activation, reducing their sensitivity to neurotransmitters (2)2.

The presented data on toxic and neuronal side effects can be used to classify antidepressants into seven tolerability categories, with the seventh being the worst and the first being the best (Table 5).

Table 5. Categories of tolerability of antidepressants, taking into account toxic and neuronal side effects.

Thus, antidepressants from the lowest category VII (clomipramine, imipramine, maprotiline, agomelatine) have toxic side effects that directly threaten the lives of patients. Moreover, when prescribing them, additional examination of patients is required. Problems with tolerability of other antidepressants are due to neuronal side effects. All of them are not fatal, and their identification usually does not require additional examination.

Neuronal side effects are divided into “non-therapeutic” and “para-therapeutic” side effects. The first, as already mentioned above, are associated with “additional” dysfunction of histamine and acetylcholine neurons, which do not reduce their activity in mental disorders that are indications for the prescription of antidepressants. Accordingly, “non-therapeutic” side effects that expand the range of affected neuronal systems determine whether drugs belong to lower tolerability categories (VI, V and IV). In particular, amitriptyline promotes a persistent decrease in the activity of histamine and acetylcholine neurons and is therefore classified as tolerability category VI. “Non-therapeutic” side effects of antidepressants classified as category V are more limited. After all, pipofezin, trazodone, mianserin and mirtazapine contribute to a persistent decrease in the activity of only histamine neurons. Vortioxetine is classified into the next higher tolerability category IV. This antidepressant has the ability to increase the activity of histamine and acetylcholine neurons. However, the associated side effects are often reversible.

The highest tolerability categories I – III include antidepressants that act only on serotonin, norepinephrine and dopamine neurons, which suffer in mental disorders that are indications for prescribing drugs. These drugs are characterized by “paratherapeutic” side effects that do not increase the number of affected neuronal systems (Table 5). They arise due to the activation of part of the serotonin, norepinephrine and dopamine neurons, which still maintain normal “tone” (2). At the same time, the severity of “paratherapeutic” side effects depends, first of all, on the ability of the antidepressant to affect serotonin and norepinephrine nerve cells, since they all have a weak effect on dopamine nerve cells (Table 1).

Accordingly, tolerability category III includes antidepressants that simultaneously effectively activate serotonin and norepinephrine neurons. These drugs are venlafaxine and duloxetine (Tables 1 and 5). The first of them, depending on the dose, is a ↑SN- or ↑SNd-antidepressant. As for duloxetine, it has the properties of a ↑CH drug. Category II includes antidepressants that promote pronounced activation of only serotonin or only norepinephrine neurons (Tables 1 and 5). These include all ↑C-antidepressants (sertraline, paroxetine, citalopram, escitalopram, fluoxetine, fluvoxamine), as well as the ↑sND antidepressant – milnacipran. Finally, the highest category I of tolerability is possessed by drugs that are not capable of strongly activating serotonin and norepinephrine neurons (Tables 1 and 5). These are two ↑SND antidepressants - pirlindole and moclobemide.

In conclusion, it should be noted that the presented classification of antidepressants by tolerability does not pretend to be comprehensive. However, it provides clear criteria for assessing the main side effects, which allow different drugs to be compared with each other. This seems to be especially significant in a situation where there are no clear recommendations for taking into account side effects when prescribing antidepressants. For example, a generalized formula is currently used in various publications and instructions. It is recommended that an antidepressant be used “only after a careful assessment of the expected benefits versus risks in patients” (11). But the results of such a “careful assessment” are usually in favor of prescribing the drug.

In particular, about agomelatine they write that if all the requirements of the instructions for prescribing an antidepressant are met, then the risk of developing drug-induced hepatitis becomes minimal (19). At the same time, the unique mechanism of action attributed to agomelatine allows us to state that the benefits of prescribing an antidepressant are much greater than the certain inconveniences that are associated with its hepatotoxicity (19). Meanwhile, the uniqueness of the mechanism of action of agomelatine comes down to the possibility of influencing the neurons of the suprachiasmatic nucleus, the neurotransmitter of which is melatonin. And this effect is not at all required for the treatment of depression, since any antidepressant that activates serotonin and norepinephrine neurons can compensate for the deficiency of melatonin activity (20).

The “careful assessment” recommendations presented here are not the only example of facile judgments regarding the tolerability of antidepressants. Some authors believe that side effects are poorly related to the mechanism of action of the drugs. It is argued that side effects are nonspecific, probabilistic and therefore almost unpredictable (18). Other authors are at least looking for the reasons for the formation of side effects in order to take them into account when prescribing antidepressants. Unfortunately, they find these reasons not in the mechanisms of action of the drugs, but in the characteristics of depression, public opinion or the psychology of the patient.

Thus, it is reported that even with the use of any “most easily tolerated drugs in 80% of patients with mild to moderate depression” (21), heterogeneous adverse events are observed. They most often occur in dysthymia, early depressive states, with anxiety and somatic symptoms (21, 22), in people over 45 years of age, with high body weight deficiency (22), and a history of negative placebo reactions (23). It is reported that poor tolerability of antidepressants is associated with patients’ high demands on quality of life (24) and their concerns about social maladjustment (25). An initially negative attitude towards psychiatry on the part of public opinion, the patient’s low awareness of his own illness and the therapy recommended by the doctor, unsatisfactory experience of previous treatment, etc. also contribute to the problem. (22, 26).

The speculative nature of such constructions is obvious. To refute them, it is enough to say that the side effects of drugs, according to the WHO definition, are caused by their pharmacological properties (37). It is difficult to imagine that inhibition of histamine and acetylcholine neurons arises due to the patient’s high demands on quality of life, excessive activation of serotonin, norepinephrine and dopamine neurons due to negative attitudes towards psychiatry from public opinion, and drug-induced hepatitis due to concerns about social maladjustment.

Thus, the presented classification of antidepressants according to tolerability categories allows us to return the study of side effects to the mainstream of biological psychiatry. In addition, this classification is easy to use in practical medicine. In particular, the lower the category of tolerability of an antidepressant, the greater the need for a special justification for its prescription (efficacy, positive experience of treatment in the past, the patient’s desire, etc.). In turn, the appearance of such a detailed justification in the medical history will allow one to avoid many problems (psychological, social and other) that arise during the treatment process between the doctor and his patient.

Using the presented classification, it is easy to resolve the issue of choosing the most effective and tolerable antidepressant. This requires only comparing the tolerability categories of the most effective drugs: amitriptyline (TcA), imipramine (TcA) and venlafaxine (SNRI) (5). The first of them (amitriptyline) belongs to category VI of tolerability (Table 5). The side effects of the second antidepressant (imipramine) are even more serious. This drug belongs to category VII of tolerability. As for venlafaxine, the side effects of this antidepressant are much weaker, and this drug belongs to category III of tolerability. Thus, venlafaxine, when used in high doses, is the most effective and tolerable drug in the treatment of depression.

Venlafaxine is well known in our country under the trade name Velaxin (Egis). This drug has been studied in leading scientific organizations conducting advanced research in the field of psychiatry. Among them are the Federal State Budgetary Institutions “State Scientific Center for Social and Forensic Psychiatry named after V.P. Serbsky" and "Moscow Research Institute of Psychiatry" of the Russian Ministry of Health, St. Petersburg Research Institute named after. V.M. Bekhterev (28,29). Long-acting capsules (Velaxin retard) are also well known (30), with the use of which there is a significant reduction in the frequency of such side effects of the drug as nausea (31). In addition, the study of Velaxin was successfully carried out not only in psychiatry, but also in neurology (32).

A video by M.Yu. Drobizhev on the same topic can be viewed at the link: https://www.youtube.com/watch?v=SwtO_bC_838&t=11s

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M.Yu. Drobizhev , Doctor of Medical Sciences, Head of the educational department of the Training Center of the Association of Medical and Pharmaceutical Universities of Russia. Contact Information -

E.Yu. Antokhin , Candidate of Medical Sciences, Associate Professor, Head of the Department of Clinical Psychology and Psychotherapy of the Orenburg State Medical University of the Russian Ministry of Health.

R.I. Palaeva is an assistant at the Department of Clinical Psychology and Psychotherapy at the Orenburg State Medical University of the Russian Ministry of Health.

S. V. Kikta , Candidate of Medical Sciences, Head. Department of the Federal State Budgetary Institution "Polyclinic No. 3" of the Administration of the President of the Russian Federation, Moscow

1 There are probably side effects due to excessive activation of melatonin nerve cells. However, they are not yet described even in the instructions for agomelatine, a melatonergic drug that has a direct effect on them (11).

2 Theoretically, “para-therapeutic” side effects can be observed even against the background of “non-therapeutic” side effects. After all, any antidepressant activates serotonin, norepinephrine or dopamine neurons to varying degrees. However, the drugs are dominated by “non-therapeutic” side effects, if only because they are most often persistent. At the same time, “paratherapeutic” side effects are always reversible. In addition, not all antidepressants that have “non-therapeutic” side effects are capable of seriously activating serotonin, norepinephrine and dopamine neurons.

Indications for the drug Trittico

anxiety-depressive states of endogenous nature (including involutional depression);

psychogenic depression (including reactive and neurotic depression);

anxiety-depressive states against the background of organic diseases of the central nervous system (dementia, Alzheimer's disease, cerebral atherosclerosis);

depressive states with prolonged pain syndrome;

alcoholic depression;

benzodiazepine dependence;

libido and potency disorders (including erectile dysfunction in depressive conditions).

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).

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).

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.

Trittico 150 mg 20 pcs. tablets aziende chimiche riunite angelini france

pharmachologic effect

Antidepressant.

Composition and release form Trittiko 150 mg 20 pcs. tablets aziende chimiche riunite angelini france

Tablets - 1 tablet:

• Active ingredient: trazodone hydrochloride 150.0 mg;
• Excipients: sucrose 84.0 mg; carnauba wax 24.0 mg; povidone 24.0 mg; magnesium stearate 6.0 mg.

10 tablets in a PVC/aluminum foil blister.

2 or 6 blisters along with instructions for use in a cardboard box.

Description of the dosage form

Biconvex tablets, white or white with a yellowish tint, oval in color with two parallel lines on both sides.

Characteristic

Triazolopyridine derivative.

Directions for use and doses

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

Initial dose of the drug: 100 mg, taken once before bed after meals. On the 4th day you can increase the dose to 150 mg. Further increases in the dose in order to achieve the optimal therapeutic effect 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.

Maximum daily dose for inpatients. 600 mg.

For elderly and debilitated patients, the initial dose is up to 100 mg/day in divided doses or once before bedtime. It can be increased under medical supervision, depending on the effectiveness and tolerability of the drug. A dose exceeding 300 mg/day is usually not required.

Pharmacodynamics

Pharmacodynamics: trazodone inhibits neuronal reuptake of serotonin, is an antagonist of 5-HT2A/2c-serotonin receptors and an α1-adrenergic receptor blocker and has an antidepressant effect.

Pharmacokinetics

Absorption of trazodone from the gastrointestinal tract after oral administration is high. Taking trazodone during or immediately after a meal slows the rate of absorption, reduces the maximum plasma concentration of trazodone, and increases the time to reach maximum concentration (TCmax).

TCmax is achieved 1/2-2 hours after oral administration.

Trazodone penetrates through histohematic barriers into tissues and fluids (bile, saliva, breast milk).

Communication with plasma proteins is 89 - 95%.

Trazodone is metabolized in the liver, the active metabolite is 1-m-chlorophenylpiperazine. The half-life is 3-6 hours, in the second phase 5-9 hours. Elimination of most of the metabolized trazodone is carried out by the kidneys with urine - about 75%, and is completely completed 98 hours after administration; About 20% is administered with bile. In vitro studies on human microsomes have shown that trazodone is primarily metabolized by the cytochrome P450 isoenzyme (CYP3A4 isoenzyme).

Indications for use Trittico 150 mg 20 pcs. tablets aziende chimiche riunite angelini france

Depression with or without anxiety.

Contraindications

• Hypersensitivity to the active substance or any excipient;
• pregnancy period;
• lactation period;
• alcohol intoxication and intoxication with sleeping pills;
• The safety of trazodone for children under 18 years of age has not been established, therefore the use of the drug in children and adolescents is not recommended;
• sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption, since the drug contains sucrose.

With caution: 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, and renal and/or liver failure.

Application of Trittico 150 mg 20 pcs. tablets aziende chimiche riunite angelini france during pregnancy and breastfeeding

The drug is not recommended for use by pregnant women. The drug is not recommended for use during breastfeeding.

special instructions

Suicide/suicidal ideation or worsening clinical symptoms: Depressive conditions have an increased risk of suicidal ideation, 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. 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 24 years of age when 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, atrioventricular 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 depression 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 with serotonergic activity (tricyclic antidepressants, selective serotonin reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors and monoamine oxidase 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 Tritgiko, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: drowsiness, dizziness, nausea, vomiting. In more severe cases, coma, tachycardia, hypotension, hyponatremia, seizures and respiratory failure. Impaired function of the cardiovascular system (prolongation of the QT interval, bradycardia). After an overdose, symptoms may take 24 hours or more to appear.

Treatment: There is no specific antidote for trazodone. In cases of overdose, gastric lavage and administration of activated charcoal are necessary within 1 hour after taking the overdose. Symptomatic and supportive treatment is carried out.

Side effects Trittico 150 mg 20 pcs. tablets aziende chimiche riunite angelini france

Trittico may cause side effects, although not all patients experience them.

From the blood and lymphatic system: agranulocytosis, thrombocytopenia, eosinophilia, leukopenia and anemia.

From the immune system: allergic reactions.

From the endocrine system: syndrome of inappropriate secretion of antidiuretic hormone (SNA ADH).

Mental disorders: suicidal thoughts or behavior, confusion, mania, phobias, emotional instability, delirium, hallucinations.

From the nervous system: epileptic seizures, dizziness, headache, insomnia or drowsiness, amnesia, tremor, convulsions, paresthesia, impaired taste.

From the cardiovascular system: palpitations, tachycardia, bradycardia, ventricular extrasystoles, ventricular paroxysmal tachycardia, prolongation of the QT interval, increased blood pressure (BP), decreased blood pressure, fainting.

From the gastrointestinal tract: nausea, vomiting, dry mouth, dyspepsia; abdominal pain, diarrhea, increased salivation, paralytic ileus.

From the skin and subcutaneous tissues: itching, erythematous rash, sweating.

Musculoskeletal and connective tissue disorders: myalgia, arthralgia.

From the kidneys and urinary tract: urinary disorders.

On the part of the genital organs and breast: priapism (patients who experience this side effect should immediately stop taking the drug and consult a doctor).

Other: increased fatigue, weakness, increased body temperature, flu-like syndrome.

Drug interactions

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

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

H1-histamine receptor blockers and drugs with m-anticholinergic activity enhance the m-anticholinergic effect of trazodone.

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

With the simultaneous use of tricyclic antidepressants and trazodone, 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 possibility of pharmacological interaction of trazodone with inhibitors of the cytochrome P450 isoenzyme (CYP3A4 isoenzyme), such as ketoconazole, ritonavir, indinavir and fluoxetine. Inhibitors of the CYP3A4 isoenzyme may lead to a significant increase in plasma concentrations of trazodone, thereby increasing the likelihood of adverse events. Therefore, when taken in combination with potent inhibitors of the CYP3A4 isoenzyme, 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.

Elderly and debilitated patients: initial dose up to 100 mg/day in several doses or once before bedtime. If necessary, the dose can be increased (usually no more than 300 mg/day).

Treatment of libido disorders: recommended daily dose of 50 mg.

Treatment of erectile dysfunction: monotherapy - recommended daily dose - 150-200 mg, combination therapy - 50 mg.

Treatment of benzodiazepine dependence: The recommended treatment regimen is based on a gradual, sometimes over several months, reduction of the benzodiazepine dose. Each time, reducing the benzodiazepine dose by 1/4 or 1/2 tablet, 50 mg of trazodone is added at the same time. This ratio is left unchanged for 3 weeks, then a further gradual reduction in the dose of benzodiazepines is started until their complete withdrawal. After this, reduce the daily dose of trazodone by 50 mg every 3 weeks.

Trittico tab 150mg N20 (Aziende Quimique Riunite Angelini Francesco)

Use in children and adolescents (up to 18 years of age). Trazodone should not be used in children and adolescents under 18 years of age. Suicide/suicidal ideation or worsening clinical symptoms Depressive conditions have an increased risk of suicidal ideation, self-harm, or suicide. This risk persists until significant remission occurs. Since improvement may not occur for the first few weeks of treatment or more, patients should be closely monitored until 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. 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 25 years of age with 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. To minimize the potential risk of suicide attempts, especially at the beginning of treatment, the minimum required dose should be prescribed in each specific case. If jaundice develops, trazodone therapy should be discontinued. The use of antidepressants in patients with schizophrenia or other mental disorders may result in possible worsening of psychiatric symptoms. Paranoid thoughts may get worse. When treated with trazodone, depressive episodes can range from manic depression to manic psychosis. In this case, trazodone should be discontinued. Interactions with the development of serotonin syndrome or neuroleptic malignant syndrome. Fatal neuroleptic malignant syndrome has been reported in cases of concomitant use with antipsychotics for which this syndrome was a known possible adverse drug reaction. Since agranulocytosis can manifest itself as a flu-like syndrome, sore throat and fever, it is recommended to monitor the blood count when these symptoms appear. Cases of hypotension, including orthostatic hypotension and syncope, have been reported in patients receiving trazodone. Concomitant use with antihypertensive drugs may require a reduction in the dose of the antihypertensive drug. Elderly patients. Elderly patients are often more responsive to antidepressants, and orthostatic hypotension, somnolence, and other anticholinergic effects of trazodone are more commonly reported. Particular attention should be paid to potential additive effects due to concomitant use of other psychotropic or antihypertensive drugs or in the presence of risk factors, such as concomitant diseases, that may exacerbate these reactions. It is recommended that the patient or caregiver be informed of the possible occurrence of such effects. It is necessary to carefully monitor their manifestation in the patient after initiation of therapy, before and after titration in an increasing dose. During long-term therapy with trazodone, a gradual dose reduction is recommended before discontinuation of the drug to minimize withdrawal symptoms such as nausea, headache, and malaise. There is no evidence that trazodone hydrochloride has any addictive properties. As with other antidepressants, QT prolongation has been reported very rarely with trazodone. Caution should be exercised when administering trazodone with drugs that prolong the QT interval. Trazodone should be used with caution in patients with known cardiovascular disease, including QT prolongation. Strong CYP3A4 inhibitors may result in increased serum levels of trazodone. As with other drugs with alpha-adrenolytic activity, trazodone is very rarely associated with priapism. This can be corrected by intracavernosal injection of an alpha-adrenergic agent such as epinephrine or metaraminol. However, there are reports of trazodone-induced priapism that required surgery or resulted in permanent sexual dysfunction. Patients who develop this suspected adverse reaction should stop taking trazodone immediately. Effect on urine test results. When immunoassays are used to monitor drugs in urine, the reactivity of the trazodone metabolite meta-chlorophenylpiperazine (m-CPP), which is structurally similar to methylenedioxymethamphetamine (MDMA, ecstasy), may cause a false-positive reaction to amphetamine. In these cases, confirmatory analysis using mass spectrometry is recommended.

special instructions

Since the drug has some adrenolytic activity, bradycardia and a decrease in blood pressure may develop. Therefore, caution should be exercised when prescribing the drug to patients with cardiac conduction disorders, AV block of varying severity, or recent myocardial infarction. When using trazodone, a slight decrease in the number of leukocytes is possible, which does not require specific treatment, except in cases of severe leukopenia. Therefore, it is recommended to conduct peripheral blood tests, especially if there is a sore throat when swallowing and fever.

The drug does not have an anticholinergic effect, so it can be prescribed to elderly patients suffering from prostatic hypertrophy, angle-closure glaucoma, and cognitive impairment.

If you experience prolonged and inadequate erections, you should consult a doctor.

There have been no relevant studies on the effectiveness of the drug in pediatrics, so the drug should be used with caution in persons under 18 years of age. Doses for children under 6 years of age have not been established.

During treatment you should refrain from drinking alcohol.

Influence on the ability to drive vehicles and machinery. Since the drug has anxiolytic and sedative activity, a decrease in attention and reaction speed is possible. During treatment, you should refrain from engaging in potentially hazardous activities that require concentration and rapid psychomotor reactions.

Precautions for the substance Trazodone

During treatment, a general blood test should be performed regularly (for timely detection of leuko- and neutropenia); ECG monitoring is desirable in patients with cardiovascular diseases. Careful monitoring of patients with suicidal tendencies is required, especially in the first weeks of treatment. Treatment is immediately stopped with the development of priapism, severe neutro- and leukopenia; in other cases, drug withdrawal should be carried out gradually. During treatment you should avoid drinking alcohol.

Use with caution during work for vehicle drivers and people whose activities involve increased concentration.