Trittico, sustained release pills 150mg 20pcs

Composition

One extended-release tablet contains:

active ingredient: trazodone hydrochloride 150.0 mg;

excipients: sucrose (pressed sugar), Carnauba wax, povidone K 25 (polyvinylpyrrolidone), magnesium stearate.

Pharmacological action

Pharmacotherapy group: antidepressant

ATX code: N06AX05

Pharmacological properties

Pharmacodynamics

Trazodone is a triazolopyridine derivative that is effective for treating depressive disorders, including depression associated with anxiety and sleep disorders, and is characterized by a short latency period (about a week).

Trazodone is a serotonin reuptake inhibitor and antagonist of 5-HT2 receptors, the activation of which is mainly associated with insomnia, anxiety, psychomotor agitation and changes in sexual function.

Unlike other psychotropic drugs, trazodone is not contraindicated in glaucoma, urinary tract diseases, does not have extrapyramidal effects, does not potentiate adrenergic transmission; due to the lack of anticholinergic activity, trazodone does not have the typical effects of tricyclic antidepressants on cardiac activity.

Pharmacokinetics

After oral use of a single dose of 75 mg of trazodone with prolonged release, C_max about 0.7 mcg / ml is reached after a tmax of 4 hours after use, AUC (area under the concentration-time curve) it is about 8 micrograms/ml/h. After oral use of a single dose of 150 mg of trazodone with prolonged release C_max approximately 1.2 mcg / ml is achieved at a tmax of 4 hours after use, with an AUC of about 18 mcg/ml/h. The elimination half-life is about 12 hours.

A food interaction study found no significant changes in cmax and AUC when using the drug Trittico, a 150 mg long-release tablet, before or after a meal.

In vitro studies on human liver microsomes have shown that trazodone is mainly metabolized by cytochrome P4503A4 (CYP3A4).

Indications

Depressive disorder with or without anxiety.

Use during pregnancy and lactation

Pregnancy

Data on a limited number of pregnant women who took the drug during pregnancy ( There is no other available epidemiological data.

Animal studies have shown no direct or indirect adverse effects on pregnancy, fetal / fetal development, delivery, or postnatal development at therapeutic doses.

Studies of teratogenicity in rats revealed increased embryoletality when using the drug only in doses toxic to the mother’s body (300-450 mg / kg / day). Embryonic effects and rare cases of congenital anomalies were observed in rabbits when the drug was used only in doses toxic to the mother’s body (150-450 mg / kg / day). The absence of a direct effect on the embryo is confirmed by studies of trazodone penetration through the placental barrier in rats: only insignificant concentrations of trazodone were found in embryo tissues and in amniotic fluid.

The drug should be prescribed to pregnant women only if the potential benefit to the woman justifies the possible risks to the fetus. When used before delivery, newborns should be monitored for withdrawal symptoms.

Breast-feeding period

Limited data indicate that a small amount of trazodone passes into breast milk, but the level of the active metabolite is unknown. Due to insufficient data, the decision to continue/stop taking the drug or to continue / stop breastfeeding should be made taking into account the benefits of breast-feeding for the child and the benefits of therapy for the mother.

Contraindications

• : hypersensitivity to trazodone or any excipient;
• alcohol intoxication and intoxication with sleeping pills;
• acute myocardial infarction;
• sucrose/isomaltose deficiency, fructose intolerance, glucose-galactose malabsorption, since the drug contains sucrose;
• age up to 18 years (safety has not been established).

With caution

Careful dosing and regular monitoring of patients with the following conditions are recommended:

• epilepsy, especially a sharp increase or decrease in dose;
• patients with hepatic and/or renal failure, especially severe;
• patients with heart diseases such as angina pectoris, conduction disorders or atrioventricular (AV) blockade of various degrees, myocardial infarction (early recovery period);
• hyperthyroidism;
• urination disorders, such as prostate hypertrophy, despite a slight anticholinergic effect of trazodone;

acute angle-closure glaucoma, increased intraocular pressure, although minor anticholinergic effect of trazodone major changes are not expected.

Side effects

Suicidal ideation and suicidal behavior have been reported during trazodone therapy or in the early post-treatment period.

The following symptoms, some of which have also been reported in cases of untreated depression, have been reported in patients taking trazodone.

Organ System Class (MedDRA) Frequency unknown (frequency cannot be determined from available data)

Blood and lymphatic system disorders Agranulocytosis, thrombocytopenia, eosinophilia, leukopenia, anemia

Immune system disorders Allergic reactions

Endocrine disorders Syndrome of inadequate secretion of antidiuretic hormone (SNA ADH)

Metabolic and nutritional disorders Hyponatremia 1, weight loss, anorexia, increased appetite

Mental disorders Suicidal thoughts or suicidal behavior 2, confusion, insomnia, disorientation, mania, anxiety, nervousness, agitation (very rarely escalating to delirium attacks), delirium, aggressive reaction, hallucinations, nightmares, decreased libido, withdrawal syndrome

Nervous system disorders Serotonin syndrome, seizures, neuroleptic malignant syndrome, dizziness, vertigo, headache, drowsiness 3, anxiety, decreased alertness, tremor, visual impairment, memory impairment, myoclonic seizures, severe aphasia, paresthesia, dystonia, taste changes

Cardiac disorders Cardiac arrhythmia 4 (including polymorphic ventricular tachycardia), rapid heartbeat, premature ventricular contraction, two consecutive sets of premature ventricular contractions, ventricular tachycardia, bradycardia, tachycardia, prolongation of the QT interval

Vascular disorders Orthostatic hypotension, arterial hypertension, syncope

Respiratory, thoracic and mediastinal disorders Nasal congestion, shortness of breath

Gastrointestinal disorders Nausea, vomiting, dry mouth, constipation, diarrhea, dyspepsia, abdominal pain, gastroenteritis, increased salivation, paralytic intestinal obstruction

Liver and biliary tract disorders

Liver function disorders (including jaundice and liver cell damage) 5, intrahepatic cholestasis

Skin and subcutaneous tissue disorders Skin rash, pruritus, hyperhidrosis

Musculoskeletal and connective tissue disorders Limb pain, back pain, myalgia, arthralgia

Disorders of the kidneys and urinary tract Urination disorder

Genital and breast disorders Priapism 6

General disorders and disorders at the injection site Weakness, swelling, flu-like symptoms, fatigue, chest pain, fever

Laboratory and instrumental data Elevated liver enzymes

Interaction

General information

The sedative effect of antipsychotics, sleeping pills, sedatives, anxiolytics and antihistamines may increase; in such cases, a dose reduction is recommended.

The metabolism of antidepressants is accelerated due to the hepatic effects of oral contraceptives, phenytoin, carbamazepine and barbiturates. The metabolism of antidepressants is inhibited by cimetidine and some other antipsychotic drugs.

CYP3A4 inhibitors

In vitro studies of drug metabolism indicate that there is potential for drug interactions when trazodone is prescribed with cytochrome P4503A4 (CYP3A4) inhibitors such as erythromycin, ketoconazole, itraconazole, ritonavir, indinavir, and nefazodone. If trazodone is used with a potent CYP3A4 inhibitor, a lower dose of trazodone is required.

The use of CYP3A4 inhibitors should be avoided as much as possible.

Carbamazepine

The results of combined use are expressed in a decrease in the concentration of trazodone in plasma. Concomitant use of carbamazepine at a daily dose of 400 mg resulted in a decrease in the plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine to 76% and 60%, respectively.For this reason, patients taking trazodone in combination with carbamazepine should be constantly monitored for the need to increase the dosage of trazodone.

Tricyclic antidepressants

Concomitant use with trazodone should be avoided due to the risk of interaction. You should be wary of serotonin syndrome and side effects for heart activity.

Fluoxetine

Rare cases of elevated trazodone plasma concentrations and side effects have been reported when trazodone was combined with fluoxetine, a CYP1A2/2D6 inhibitor. The mechanism of their pharmacokinetic interaction has not been studied. Pharmacodynamic interaction (serotonin syndrome) cannot be excluded.

MAO inhibitors

Possible interactions with monoamine oxidase (MAO) inhibitors have been reported. Despite the fact that some doctors prescribe two drugs at the same time, the use of trazodone simultaneously with MAO inhibitors or within two weeks after the end of taking MAO inhibitors is not recommended. The use of MAO inhibitors for one week after trazodone therapy is also not recommended.

Phenothiazines

Serious orthostatic hypotension has been reported with concomitant use with phenothiazines, such as chlorpromazine, fluphenazine, and perphenazine.

Anesthetics/ muscle relaxants

Trazodone hydrochloride may increase the effects of muscle relaxants and volatile anesthetics, and should be used with caution.

Alcohol

Trazodone enhances the sedative effect of alcohol. Alcohol consumption should be avoided during trazodone therapy.

Levodopa

Antidepressants can accelerate the metabolism of levodopa.

Other

Concomitant use of trazodone with drugs that prolong the QT interval may increase the risk of ventricular arrhythmia, including polymorphic ventricular tachycardia. Caution should be exercised when they are co-administered with trazodone.

Since trazodone is a weak norepinephrine reuptake inhibitor and does not alter the blood pressure response to tyramine, an effect on the hypotensive effect of compounds such as guanethidine is unlikely. However, animal studies suggest that trazodone may inhibit much of the acute effect of clonidine. For other antihypertensive drugs, the possibility of potentiation should be considered, although clinically no interaction has been proven.

Side effects may occur more frequently with the simultaneous use of trazodone with drugs containing St. John’s wort (Hypericum Perforatum).

Changes in prothrombin time have been reported in patients taking trazodone and warfarin concomitantly.

Concomitant use of digoxin or phenytoin with trazodone may lead to increased serum levels of digoxin and phenytoin. Serum digoxin and phenytoin levels should be monitored in these patients.

How to take, course of use and dosage

Tablets should be taken whole, without chewing, and washed down with a sufficient amount of water.

Therapy should begin with an evening intake and a gradual increase in daily doses.

The drug can be taken regardless of food intake.

The drug should be taken in cycles of at least one month.

Adults

75-150 mg / day as a single dose in the evening before bedtime. The dose can be increased to 300 mg / day, divided into two doses.

In hospitalized patients, the dose may be gradually increased to 600 mg / day in repeated doses.

Elderly patients

For elderly or debilitated patients, the recommended daily dose should be reduced to 100 mg / day in fractional doses or as a single dose in the evening before bedtime. This dose can be gradually increased under the supervision of a doctor, depending on the effectiveness and tolerability of the drug. In most cases, a single dose of more than 100 mg should be avoided for these patients. Usually, a dose exceeding 300 mg/day is not required.

Overdose

Symptoms: drowsiness, dizziness, nausea, vomiting. In more severe cases, coma, tachycardia, hypotension, hyponatremia, convulsions, and respiratory arrest were reported. In terms of cardiac activity, these may include bradycardia, QT prolongation, and polymorphic ventricular tachycardia.

Symptoms may occur within 24 hours or later after an overdose. An overdose of trazodone in combination with other antidepressants can cause serotonin syndrome.

Treatment: There is no specific antidote for trazodone. Activated charcoal can be used by adults who have taken more than 1 g of trazodone or by children who have taken more than 150 mg of trazodone within 1 hour of the onset of symptoms. As an alternative therapy, adults may be given gastric lavage within 1 hour after taking a potentially life-threatening dose.

Follow-up is required for at least 12 hours after taking the drug, as well as monitoring of blood pressure, pulse and Glasgow Coma scale indicators. If the Glasgow coma scale is lowered, blood oxygen saturation is monitored. Monitoring of cardiac function is necessary in patients with appropriate symptoms.

Isolated short seizures do not require therapy. Frequent or prolonged seizures are corrected by intravenous diazepam (0.1-0.3 mg/kg body weight) or lorazepam (4 mg for adults or 0.05 mg/kg body weight for children).

If these measures do not control seizures, intravenous use of phenytoin may be recommended. To correct the acid-base balance and metabolic disorders, it is necessary to use oxygen by inhalation.

In case of hypotension and excessive sedation, symptomatic and supportive therapy should be performed. If severe hypotension persists, the use of dopamine or dobutamine should be considered.

Description

Biconvex tablets are white or white-yellowish in color, oval in shape with two parallel risks on both sides.

Special instructions

Use in children and adolescents (under 18 years of age)

Trazodone should not be used in children and adolescents under 18 years of age.

Suicide / suicidal thoughts or worsening of clinical symptoms

Depressive states have an increased risk of suicidal thoughts, self-harm, or suicide. This risk persists until a pronounced remission occurs. Since improvement may not occur within the first few weeks of treatment or longer, patients should be closely monitored until improvement occurs. According to general clinical experience, 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 starting treatment, have a higher risk of suicidal thoughts or suicide attempts, and should be closely monitored during treatment. Results of a meta-analysis of placebo-controlled clinical trials of antidepressants used in adults with psychiatric disorders showed an increased risk of suicidal behavior in patients younger than 25 years of age 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 any clinical deterioration, suicidal behavior or suicidal thoughts, or unusual behavioral changes, and 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 case.

If jaundice develops, trazodone therapy should be discontinued.

The use of antidepressants in patients with schizophrenia or other psychiatric disorders may lead to possible worsening of psychiatric symptoms. Paranoid thoughts can get worse. When treated with trazodone, depressive attacks can range from manic-depressive to manic psychosis. In this case, trazodone should be discontinued.

Interactions with the development of serotonin syndrome or neuroleptic malignant syndrome have been reported when trazodone is administered concomitantly with drugs with serotonergic activity, such as other antidepressants (e. g., tricyclic antidepressants, selective serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors and MAO inhibitors) and neuroleptics. Neuroleptic malignant syndrome with a fatal outcome has been reported in cases of concomitant use with neuroleptics, for which this syndrome was a known possible adverse drug reaction.

Since agranulocytosis can manifest as a flu-like syndrome, sore throat and fever, it is recommended to monitor the blood picture when these symptoms occur.

Cases of hypotension, including orthostatic hypotension and syncope, have been reported in patients taking trazodone. Concomitant use with antihypertensive drugs may require a reduction in the dose of the antihypertensive drug.

Elderly patients

Elderly patients are often more susceptible to antidepressants, in particular, cases of orthostatic hypotension, drowsiness and other anticholinergic effects of trazodone are more often reported.

Particular attention should be paid to potential additive effects associated with the concomitant use of other psychotropic or antihypertensive medications, or in the presence of risk factors such as comorbidities that may exacerbate these reactions.

It is recommended that the patient or caregiver be informed about the possible occurrence of such effects. It is necessary to carefully monitor their manifestation in the patient after the start of therapy, before and after titration in an increasing dose.

With long-term trazodone therapy, it is recommended to gradually reduce the dose before discontinuing the drug to minimize withdrawal symptoms, such as nausea, headache, malaise.

There is no evidence that trazodone hydrochloride has any addictive properties.

As with other antidepressants, cases of QT prolongation with trazodone have been reported very rarely. Caution should be exercised when prescribing trazodone with medications that prolong the QT interval.

Trazodone should be used with caution in patients with known cardiovascular diseases, including those with prolonged QT interval. Strong CYP3A4 inhibitors can lead to increased serum trazodone levels.

As with other drugs with alpha-adrenolytic activity, trazodone is very rarely associated with priapism. This can be corrected by an intra-cavernous 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 immediately stop taking trazodone.

Impact on urinalysis results

When using immunoassays to control narcotic substances in the urine, the reactivity of the trazodone metabolite meta-chlorophenylpiperazine (m-CPP), which is structurally similar to methylenedioxymethamphetamine (MDMA, ecstasy), can cause a false positive reaction to amphetamine. In these cases, it is recommended to perform a confirmatory analysis using mass spectrometry.

Influence on the ability to drive vehicles and mechanisms

Trazodone has little or no effect on the ability to drive vehicles or mechanisms. The patient should be warned about the risks of driving vehicles or operating machinery until they are sure that they are not experiencing drowsiness, lethargy, dizziness, confusion, or blurred vision.

Form of production

Long-release tablets,150 mg.

10 tablets in a blister of PVC / aluminum foil.

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

Storage conditions

At a temperature not exceeding 25 ° C. Keep out of reach of children!

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Trazodone

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets

Purpose

For adults

Indications

Depression, Mental Disorders, Erectile Dysfunction