Trittico xr

Patient Information Leaflet

Trittico XR
150 mg, prolonged-release coated tablets
300 mg, prolonged-release coated tablets
Trazodoni hydrochloridum
Please read the entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others.
• This medicine may harm others, even if their symptoms are similar.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist immediately. See section 4.

Table of Contents:

1. What Trittico XR is and what it is used for
2. Important information before taking Trittico XR
3. How to take Trittico XR
4. Possible side effects
5. How to store Trittico XR
6. Contents of the pack and other information

1. What Trittico XR is and what it is used for

Trittico XR contains trazodone hydrochloride, which has antidepressant and anxiolytic effects.
Therapeutic effects are usually observed after approximately one week of treatment.
Trittico XR is indicated for the treatment of depressive disorders of various origins, including depression associated with anxiety.

2. Important information before using Trittico XR

When not to use Trittico XR
If the patient is allergic (hypersensitive) to trazodone hydrochloride or any of the
other components of the medicine.
If the patient is under the influence of alcohol or sedative medicines.
If the patient has acute myocardial infarction.

Warnings and precautions
Before starting treatment with Trittico XR, discuss this with your doctor or pharmacist.

• Trittico XR should be used with caution and under close medical supervision in patients with liver, kidney, or heart disease, particularly those with conduction disorders, prolonged QT interval on ECG, atrioventricular block of any degree, or recent history of myocardial infarction.
• Trazodone may slow heart function and cause a drop in blood pressure, especially upon changing to an upright position, which may be accompanied by reflex tachycardia. Therefore, in patients taking antihypertensive drugs concomitantly with trazodone, dose reduction of antihypertensives may be necessary. The decision on dose reduction of antihypertensive drugs is made by the physician.
• Patients with depression may sometimes have thoughts of self-harm or suicide. Such symptoms or behaviors may worsen at the beginning of treatment with antidepressants, as these medicines usually take about two weeks to start working, sometimes longer.
• The occurrence of suicidal thoughts, thoughts of self-harm, or suicide attempts is more likely if:
  • the patient previously had suicidal thoughts or a desire for self-harm;
  • the patient is a young adult, as clinical trial data indicate an increased risk of suicidal behavior in individuals under 25 years of age with psychiatric disorders treated with antidepressants.
• If the patient experiences suicidal or self-harming thoughts, they should contact their doctor immediately or go to a hospital. It may be helpful to inform family members or friends about the depression or anxiety disorder and ask them to read this leaflet. The patient may request help from relatives or friends and ask them to inform the patient if they notice worsening of depression or anxiety, or other concerning behavioral changes. Close monitoring of the patient is especially required at the beginning of treatment and after dose adjustments.
• Extreme caution should be exercised when using antidepressants in patients with schizophrenia or other psychotic disorders. Paranoid thoughts may intensify. If symptoms worsen, trazodone should be discontinued.
• Particular caution is also required when using trazodone in patients with epilepsy; abrupt increases or decreases in dose should especially be avoided.
• Caution is also advised in patients with hyperthyroidism, urinary retention (e.g., due to benign prostatic hyperplasia), acute angle-closure glaucoma, or increased intraocular pressure.
• Particular caution is recommended when using anticoagulant and/or antiplatelet drugs, and in patients with a known predisposition to bleeding.
• In elderly patients, trazodone may more frequently cause hypotension (especially upon changing to an upright position) or somnolence. These symptoms should be carefully monitored, especially at the beginning of treatment and with each dose increase. Concomitant use of psychotropic or antihypertensive drugs, as well as the presence of comorbid conditions, may exacerbate these symptoms.
• Hematological disorders such as agranulocytosis (manifesting as flu-like symptoms, sore throat, and fever) may occur occasionally during treatment with trazodone. Rarely, liver function disturbances, sometimes severe, such as jaundice and hepatocellular damage, have been reported. In such cases, trazodone should be discontinued immediately and medical advice sought.
• Very rarely, prolonged painful erection (priapism) has occurred, requiring discontinuation of trazodone and prompt medical intervention.
• Concomitant use of other antidepressants with neuroleptics (medicines used in schizophrenia) may cause very serious and life-threatening adverse reactions such as serotonin syndrome and neuroleptic malignant syndrome. Therefore, if symptoms such as confusion, muscle rigidity, seizures, shivering, and fever occur, trazodone should be discontinued immediately and medical advice sought.
• Gradual increase of the daily dose up to the maximum recommended reduces the risk of adverse reactions.
• When discontinuing trazodone treatment, especially long-term treatment, gradual dose reduction until complete discontinuation is recommended to minimize the risk of withdrawal symptoms such as nausea, headache, and malaise.
• This medicine should not be used in children and adolescents under 18 years of age. Use of medicines in this class in patients under 18 years may increase the risk of adverse reactions such as suicidal ideation and attempts, and hostility (aggression, defiance, anger outbursts). Furthermore, there are no data confirming the long-term safety of Trittico XR in children and adolescents regarding its effects on growth, maturation, and cognitive and behavioral development.
• The doctor will determine the lowest effective dose. Treatment with Trittico XR requires regular visits to the doctor, who will decide at each visit whether treatment should continue.

If any of the above situations apply to the patient (or the patient is unsure), they should
consult a doctor or pharmacist before using Trittico XR.

Effect on urine test results
In screening urine tests performed by a specific method (immunological tests), patients taking Trittico XR may show false-positive results indicating the presence of amphetamine. This is due to structural similarity between trazodone's metabolite and a derivative of amphetamine (ecstasy). In such cases, consultation with a doctor is recommended to perform additional testing using another method (mass spectrometry or liquid chromatography–tandem mass spectrometry).

Trittico XR and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take.

Some medicines may interact with each other or should not be used simultaneously with Trittico XR for other reasons.

These include, among others:

• Antipsychotics, hypnotics, sedatives, anxiolytics, and antihistamines (trazodone may enhance their effects; the doctor will recommend appropriate dose adjustments).
• Oral contraceptives, phenytoin, carbamazepine, and barbiturates (may reduce the effect of trazodone).
• Cimetidine and certain antipsychotics (may enhance or prolong the effects of antidepressants).
• Erythromycin, ketoconazole, itraconazole, ritonavir, indinavir, and nefazodone (may enhance adverse effects of Trittico XR; if possible, avoid concomitant use with trazodone, or the doctor may consider reducing the trazodone dose).
• Carbamazepine (reduces trazodone plasma concentration; the doctor, after careful observation, may increase the dose).
• Tricyclic antidepressants (concomitant use with trazodone should be avoided due to the risk of serotonin syndrome and cardiovascular adverse effects).
• Fluoxetine (may increase the risk of serotonin syndrome).
• Monoamine oxidase inhibitors (MAOIs) (trazodone should not be used during MAOI treatment or within two weeks after discontinuation. MAOIs should not be administered within one week after stopping trazodone).
• Phenothiazine derivatives such as chlorpromazine, fluphenazine, levomepromazine, or perphenazine (may cause severe orthostatic hypotension).
• Skeletal muscle relaxants and inhalational anesthetics (trazodone may enhance their effects; caution is required during concomitant use).
• Alcohol (trazodone enhances its sedative effect; avoid alcohol consumption during treatment with trazodone).
• Levodopa (trazodone may reduce its effect).
• Clonidine (trazodone significantly reduces the effect of clonidine in animal studies. There are no human reports on interactions between trazodone and other antihypertensives, but a potential effect of trazodone on their efficacy should be considered).
• Medicines known to prolong the QT interval (increase the risk of serious ventricular arrhythmias; caution is required when used concomitantly with trazodone).
• St. John’s wort (Hypericum perforatum) preparations may enhance adverse effects caused by trazodone.
• Anticoagulants and/or antiplatelet agents (used to reduce blood coagulability): blood clotting may be altered, increasing the risk of bleeding.
• Digoxin, phenytoin (trazodone may increase their serum concentration, enhancing their effects).

Trittico XR with food and alcohol
Take tablets on an empty stomach, with a glass of water.
Trazodone enhances the sedative effect of alcohol. Alcohol should not be consumed during treatment with Trittico XR.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
If trazodone was used during pregnancy until delivery, the newborn should be monitored for withdrawal symptoms.
In breastfeeding women, the possibility of the drug passing into breast milk should be considered.
The use of Trittico XR during pregnancy and breastfeeding should be limited to exceptional cases, after careful evaluation by the doctor of the benefit-risk ratio.

Driving and operating machinery
Trazodone may slightly or moderately impair the ability to drive and operate machinery. Patients should not drive or operate machinery if they experience drowsiness, excessive sedation, dizziness, confusion, or blurred vision.

Trittico XR contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., the medicine is considered "sodium-free".

3. How to use Trittico XR

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
Tablets with a scored line may be divided, which allows gradual dose escalation.
Adults
The recommended initial dose is 150 mg once daily.
This dose may be increased by 75 mg daily (half a 150 mg tablet) every 3 days (meaning, for example,
that on the fourth day of treatment the dose is 225 mg daily), up to a maximum daily dose of 300 mg.
Sometimes the doctor may recommend reducing the initial daily dose to 75 mg (half a 150 mg tablet),
then gradually increasing the dose by 75 mg daily (half a 150 mg tablet) every 3 days, up to a maximum
daily dose of 300 mg.
Depending on the individual patient's response to treatment, the doctor may decide to use a trazodone
dose lower than 300 mg.
Children and adolescents
Trittico XR should not be used in children and adolescents under 18 years of age.
Frail and elderly patients
The recommended starting dose in elderly or frail patients is 75 mg once daily, taken in the evening
before bedtime. The doctor may then gradually increase the dose according to individual tolerance and
efficacy.
Patients with hepatic impairment
Trazodone is extensively metabolized in the liver and may have toxic effects on this organ. For this
reason, caution should be exercised when using Trittico XR in patients with liver impairment,
particularly in cases of severe hepatic insufficiency. The doctor may recommend periodic monitoring
of liver function.
Patients with renal impairment
Dose adjustment is usually not necessary; however, caution should be exercised when administering
the medicine to patients with severe renal impairment.
Method of administration
Tablets should always be taken once daily, in the evening or just before bedtime, on an empty stomach,
with a glass of water. To ensure prolonged release, the tablets must not be crushed or chewed.
Taking more Trittico XR than recommended
The most common symptoms of trazodone overdose are drowsiness, dizziness, nausea, and vomiting.
In more severe cases, coma, tachycardia (rapid heartbeat), hypotension, hyponatremia (low blood
sodium levels), seizures, respiratory disturbances, and ECG changes have been observed. Symptoms
may occur within 24 hours after overdose or later.
Overdose of trazodone together with other antidepressant medicines may cause serotonin syndrome.
After an overdose, the doctor will attempt to empty the patient's stomach as quickly as possible by
inducing vomiting, or, if the patient is conscious, by administering activated charcoal or gastric
lavage. Electrolyte imbalances in the blood will also be corrected. There is no known specific antidote.
If an overdose of Trittico XR has been taken, seek immediate medical advice from a doctor or
pharmacist, and bring the medicine packaging with you.
Missing a dose of Trittico XR
If a dose is missed, do not take a double dose to make up for the missed dose. Instead, take the next
dose at the time specified in the recommended dosing schedule.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although they do not occur in everyone.
Reports have been received of suicidal thoughts and behaviours during treatment with trazodone or shortly after discontinuation.
The following adverse effects of unknown frequency (frequency cannot be estimated from the available data) have been observed in patients treated with trazodone, some of which also commonly occur in patients with untreated depression:
Abnormal blood test results, including marked decrease in white blood cells – granulocytes (agranulocytosis), decrease in platelets (thrombocytopenia), increase in eosinophils (eosinophilia), decrease in leukocytes (leukopenia), and anaemia (reduced number of red blood cells).
Allergic reactions.
Syndrome of inappropriate antidiuretic hormone secretion (causing fluid retention in the body).
Decreased sodium concentration in blood, weight loss, anorexia, increased appetite.
Suicidal thoughts or behaviours, confusion (disturbance of consciousness), insomnia, disorientation, mania, anxiety, restlessness, agitation (very rarely progressing to delirium), delusions, aggressive behaviour, hallucinations, nightmares, decreased sexual drive, withdrawal syndrome.
Serotonin syndrome, seizures, neuroleptic malignant syndrome, dizziness, impaired balance, headache, somnolence, restlessness (mainly motor), reduced alertness, tremor, blurred vision, memory impairment, brief, violent muscle contractions (clonic muscle jerks), inability to express certain words (expressive aphasia), sensations of pricking, tingling and numbness in limbs (paresthesia), involuntary body movements, altered taste.
Cardiac arrhythmias (including torsade de pointes, palpitations, premature ventricular contractions, ventricular extrasystoles, ventricular tachycardia), bradycardia, tachycardia, abnormal ECG (prolonged QT interval).
Drop in blood pressure upon standing, causing dizziness or fainting (orthostatic hypotension), arterial hypertension, fainting.
Nasal congestion, dyspnoea.
Nausea, vomiting, dry mouth, constipation, diarrhoea, indigestion, abdominal pain, gastritis and enteritis, hypersalivation, marked reduction or cessation of intestinal peristalsis (paralytic ileus).
Abnormal liver function (including jaundice and hepatocellular injury), intrahepatic cholestasis.
Skin rash, pruritus, excessive sweating.
Pain in limbs, back, muscles, joints.
Urinary disorders, urinary incontinence (loss of urine), urinary retention (inability to pass urine).
Painful prolonged erection (priapism).
Weakness, oedema, influenza-like symptoms, fatigue, chest pain, fever.
Increased liver enzyme activity.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel. +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Trittico XR

Keep out of sight and reach of children.
No special precautions for storage are required.
Do not use this medicine after the expiry date stated on the carton.
The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist
what to do with medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Trittico XR contains
The active substance is trazodone hydrochloride.
Trittico XR 150 mg prolonged-release coated tablets: each prolonged-release coated tablet contains 150 mg of trazodone hydrochloride, equivalent to 136.6 mg of trazodone.
The other components are:
Tablet core: granulated Contramid (pregelatinized modified starch), hypromellose, colloidal anhydrous silica, sodium stearyl fumarate.
Coating: Yellow Opadry II (partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, yellow iron oxide, red iron oxide).
Trittico XR 300 mg prolonged-release coated tablets: each prolonged-release coated tablet contains 300 mg of trazodone hydrochloride, equivalent to 273.2 mg of trazodone.
The other components are:
Tablet core: granulated Contramid (pregelatinized modified starch), hypromellose, colloidal anhydrous silica, sodium stearyl fumarate.
Coating: Pink Opadry II (partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, yellow iron oxide, red iron oxide).

What Trittico XR looks like and contents of the pack
Trittico XR 150 mg: yellowish-beige prolonged-release coated tablets, with a score line on both sides to facilitate division into two equal doses.
Trittico XR 300 mg: beige-orange prolonged-release coated tablets, with a score line on both sides to facilitate division into two equal doses.
The immediate packaging consists of blisters made of PVC/PVDC/Aluminium foil containing 7 or 10 prolonged-release coated tablets.
The outer packaging (cardboard box) contains: 10, 14, 20, 28 or 30 prolonged-release coated tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A.
Viale Amelia 70
00181 Rome, Italy
Manufacturer:
Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A.
Via Vecchia del Pinocchio 22
60131 Ancona, Italy
Representative of the Marketing Authorisation Holder:
Angelini Pharma Polska Sp. z o.o.
Aleje Jerozolimskie 181B
02-222 Warsaw, Poland
tel.: (22) 70 28 200
e-mail: [email protected]
The patient information leaflet in an accessible format for blind or partially sighted persons is available at the premises of the representative of the Marketing Authorisation Holder.