Active ingredients: Trazodone (Trazodone hydrochloride)
TRITTICO 75 mg prolonged-release tablets
TRITTICO 150 mg prolonged-release tablets
The package inserts of Triptych are available for the packs: - TRITTICO 75 mg prolonged-release tablets, TRITTICO 150 mg prolonged-release tablets
- TRITTICO 50 mg film-coated tablets, TRITTICO 100 mg film-coated tablets, TRITTICO 25 mg / ml oral drops, solution, TRITTICO 60 mg / ml oral drops, solution
- TRITTICO 50 mg / 5 ml solution for injection
- TRITTICO 150 mg prolonged-release film-coated tablets - CONTRAMID tablets, TRITTICO 300 mg prolonged-release film-coated tablets - CONTRAMID tablets
Indications Why is Trittico used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antidepressant.
THERAPEUTIC INDICATIONS
Depressive disorders with or without an anxious component.
Contraindications When Trittico should not be used
Hypersensitivity to the active substance or to any of the excipients.
Generally contraindicated in pregnancy and lactation (see "Pregnancy and lactation")
Alcoholic intoxication and hypnotic intoxication.
Acute myocardial infarction.
Precautions for use What you need to know before taking Trittico
Use in children and adolescents under the age of 18
Triptych should not be taken by children and adolescents under 18 years of age. It should also be known that, when taking this class of medicines, patients under 18 years of age have an increased risk of side effects such as suicide attempts and suicidal thoughts and hostility (essentially aggression, oppositional behavior and anger). Furthermore, the long-term safety effects of Trittico related to growth, maturation and cognitive and behavioral development have not yet been demonstrated.
Suicide / suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide / related events). This risk persists until significant remission occurs. As improvement may not occur during the first or immediate weeks of treatment, patients should be monitored closely until improvement occurs. It is generally clinical experience that the risk of suicide may increase in the early stages of improvement.
Patients with a history of suicidal behavior or thoughts, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are at increased risk of suicidal thoughts or suicidal thoughts, and should be closely monitored during treatment. of clinical trials conducted with antidepressant drugs in comparison with placebo in the therapy of psychiatric disorders, showed an increased risk of suicidal behavior in the age group below 25 years of patients treated with antidepressants compared to placebo.
Pharmacological therapy with antidepressants should always be associated with close surveillance of patients, particularly those at high risk, especially in the initial stages of treatment and after dose changes. Patients (or caregivers) should take special care and immediately report any worsening of the clinical picture, the onset of suicidal behavior or thoughts, or changes in behavior to the physician.
Talk to your doctor before taking Triptych if you suffer from:
- epilepsy, especially avoid abrupt increases or decreases in dosage
- liver or kidney failure, especially if severe
- heart disease, such as angina pectoris, conduction or A-V block disorders of varying degrees, recent myocardial infarction
- hyperthyroidism
- urination disorders, such as prostatic hypertrophy
- acute angle glaucoma (increased pressure inside the eye)
Discontinue treatment if jaundice occurs.
Administration of antidepressants to patients with schizophrenia or other psychotic disorders may lead to worsening of psychotic symptoms. Paranoid thoughts can intensify. During therapy with trazodone the depressive episode may vary from manic-depressive to manic psychosis, in which case the treatment should be discontinued.
Cases of interactions in terms of serotonin syndrome / neuroleptic malignant syndrome have been reported with the concomitant use of substances with serotonergic action (such as tricyclic antidepressants, SSRIs, SNRIs, MAOIs) and neuroleptics. malignant neuroleptic syndrome is a known adverse reaction, cases of malignant neuroleptic syndromes, including fatal ones, have been reported (see "Interactions" and "Undesirable Effects" for more information).
If sore throat and fever occur, blood tests are recommended, since agranulocytosis can manifest itself with flu-like symptoms.
Hypotension, including orthostatic hypotension and syncope, has been reported with the use of Trittico. Concomitant administration of antihypertensive therapy and Trittico may require a reduction in the dosage of the antihypertensive drug. Elderly patients are often more sensitive to antidepressants, especially as regards orthostatic hypotension and other anticholinergic effects.
Following treatment with trazodone, particularly if prolonged, a gradual reduction of the dosage is recommended before stopping treatment, in order to minimize the appearance of withdrawal symptoms, characterized by nausea, headache, malaise.
There is no evidence that trazodone can give rise to abuse / addiction phenomena.
As with other antidepressants, cases of QT interval prolongation have rarely been reported with Triptych. Special precautions are recommended when administering trazodone with other drugs known to cause QT interval prolongation. Triptych should be used with caution in patients with cardiovascular disease, including those associated with QT interval prolongation.
CYP3A4 inhibitors can cause a substantial increase in the plasma concentration of trazodone. See "Interactions" for more information. As with other drugs with alpha-adrenolytic effects, rare cases of priapism have been reported during treatment with Trittico which can be treated with an intracavernous injection of an alpha-adrenergic agent such as adrenaline or metaraminol. trazodone-induced priapism has required surgery or has resulted in permanent sexual dysfunction Immediately discontinue treatment in patients who develop this suspected adverse reaction.
Interactions Which drugs or foods can modify the effect of Trittico
Tell your doctor or pharmacist if you have recently taken any medicines, even those without a prescription.
General
The sedative effects of antipsychotic, hypnotic, sedative, anxiolytic, and antihistamine medications can be intensified; in these cases reduce the dosage. The metabolism of antidepressants is accelerated by the hepatic effects of oral contraceptives, phenytoin, carbamazepine and barbiturates. The metabolism of antidepressants is inhibited by cimetidine and other antipsychotics. Tell your doctor if you are taking any of the following medicines:
CYP3A4 inhibitors
They include erythromycin, ketoconazole, itraconazole, ritonavir, indinavir and nefazodone. These medicines increase the side effects of Triptych. Consequently, concomitant use should be avoided where possible, or a reduced dosage of Trittico should be employed.
Carbamazepine
Co-administration of carbamazepine in combination with Trittico reduces its plasma concentration. For this reason, patients taking Trittico in combination with carbamazepine should be closely monitored.
Tricyclic antidepressants
Avoid concomitant use with trazodone due to the risk of interaction. Carefully evaluate the possible occurrence of serotonin syndrome of adverse cardiovascular effects.
Fluoxetine
There have been rare reports of increased plasma levels of trazodone and the occurrence of adverse effects when trazodone is administered with fluoxetine. A possible pharmacodynamic interaction (serotonin syndrome) cannot be excluded.
Monoamine oxidase inhibitors (MAOIs)
Occasionally cases of interaction with monoamine oxidase inhibitors (MAOIs). Although some physicians are used to prescribe these drugs at the same time, concomitant administration of trazodone with MAOIs is not recommended, or within two weeks of stopping MAOI. It is also not recommended to administer MAOIs in the week following stopping MAOI. trazodone.
Phenothiazines
The concomitant use of Trittico with chlorpromazine, fluphenazine, levomepromazine, perphenazine can cause severe orthostatic hypotension.
Anesthetics and muscle relaxants
Triptych may enhance the effects of muscle relaxants and volatile anesthetics, therefore caution should be exercised in case of concomitant use.
Alcohol
Trazodone potentiates the sedative effects of alcohol. Avoid alcohol intake while taking trazodone.
Levodopa
Antidepressants can speed up the metabolism of levodopa.
Other
Concomitant use of Triptych with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmia, including "torsades de pointes". Caution should be exercised when these drugs are co-administered with trazodone.
Trazodone can inhibit the action of clonidine.
Since trazodone is a weak norepinephrine re-uptake inhibitor and does not modify the pressure response to tyramine, interference with the hypotensive action of guanethidine-like compounds is unlikely. However, studies in laboratory animals suggest that trazodone may inhibit much of the acute actions of clonidine. Although no cases of clinical interaction with other antihypertensive drugs are reported, the possibility of a potentiating effect should still be considered.
Undesirable effects may be more frequent during the simultaneous use of Hypericum perforatum-based preparations (St. John's wort or St. John's wort).
Concomitant use of trazodone and warfarin may cause changes in prothrombin time.
Concomitant use with triptych increases blood levels of digoxin and phenytoin.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine. Data on animals and on a limited number of pregnant women (<200) have shown that there are no adverse effects on pregnancy and the health of the fetus / neonate. However, no other epidemiological data are available.
When trazodone is used until delivery, neonates should be monitored for the appearance of withdrawal syndrome.
In nursing women, the possibility of trazodone being excreted with milk should be considered.
Therefore, the use of Trittico during pregnancy and breastfeeding must be limited to cases of real necessity, after carefully evaluating the risk-benefit ratio with the doctor.
Effects on ability to drive and use machines
Trazodone has a mild or moderate influence on the ability to drive and use machines. Patients should be alerted to the risks of driving or using machines, unless they are sure they are not suffering from drowsiness, sedation, dizziness, confusion or blurred vision.
Important information about some of the ingredients of Trittico
Trittico tablets contain sucrose: patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency, should not take this medicine.
Dosage and method of use How to use Triptych: Dosage
The use of the product is limited to adult patients. It is advisable to start the therapeutic cycle with an evening administration and with increasing daily dosages, according to the doctor's judgment.
Take the drug preferably for therapeutic courses of at least one month. Taking Triptych after meals reduces the onset of side effects.
The tablets are divisible into 3 portions to allow a progressive dosage with divided doses, according to the severity of the disease, weight, age and general condition of the patient.
Adults: 75-150 mg per day to be administered as a single dose in the evening before bedtime. The dose can then be increased up to 300 mg per day to be divided into two doses.
In hospitalized patients the dose can be further increased up to 600 mg per day in repeated doses.
Elderly: In very elderly or defunct patients, the recommended starting dose is 100 mg per day, administered in repeated dosing or as a single dose, to be administered in the evening. This dose can then be increased, as described in the posology for adults, according to the judgment of the doctor, according to tolerability and efficacy. In general single doses above 100 mg should be avoided in these patients. However, dosages above 300 mg per day are unlikely.
Children: Triptych is not recommended for children and adolescents under 18 years of age.
Hepatic impairment: Triptych is subject to intense hepatic metabolism and has also been associated with hepatotoxicity, see sections "Precautions for use" and "Undesirable effects".
Patients with hepatic insufficiency, especially in cases of severe hepatic insufficiency, should warn the doctor, who will evaluate the need for periodic monitoring of liver functions.
Renal impairment: in general no dosage adjustment is necessary. However, patients with renal insufficiency, particularly if severe, should inform their physician before starting therapy with Trittico (see also "Precautions for use").
INSTRUCTIONS FOR USE
A double breakline on the tablets allows for increasing daily dosages, according to the doctor's judgment.
Overdose What to do if you have taken too much Triptych
The most frequently reported reactions in the event of overdose include somnolence, dizziness, nausea and vomiting. In more serious cases, coma, tachycardia, hypotension, hyponatremia, convulsions and respiratory failure have been reported. Heart changes may include bradycardia, QT interval prolongation and “torsades de pointes.” Symptoms may appear within 24 hours or more after overdose.
Overdose of trazodone in combination with other antidepressants can cause serotonin syndrome.
In case of accidental ingestion / intake of an excessive dose of Trittico, notify your doctor immediately or go to the nearest hospital. Take this leaflet with you.
In the event of an overdose, the use of activated charcoal or gastric lavage and correction of blood electrolytes is indicated. There is no specific antidote for trazodone.
IF YOU HAVE ANY DOUBT ABOUT THE USE OF TRIPTYCH, CONTACT YOUR DOCTOR OR PHARMACIST
Side Effects What are the side effects of Triptych
Like all medicines, Trittico can cause side effects, although not everybody gets them. Cases of suicidal ideation and behavior have been reported during therapy with Triptych or in the early stages following treatment discontinuation.
The following symptoms, some of which are commonly reported in untreated depression, and the frequency of which is not known (cannot be estimated from the available data), have been recorded in patients treated with trazodone:
- Blood dyscrasia (agranulocytosis, thrombocytopenia, eosinophilia, leukopenia and anemia).
- Allergic reactions.
- Syndrome of inappropriate antidiuretic hormone secretion.
- Lowered blood sodium levels, weight loss, anorexia, increased appetite.
- Suicidal thoughts or suicidal behavior, confusion, insomnia, disorientation, mania, anxiety, nervousness, agitation (which quite occasionally exacerbate to delirium), delirium, aggressive reaction, hallucinations, nightmares, decreased libido, withdrawal syndrome.
- Serotonin syndrome, seizures, neuroleptic malignant syndrome, dizziness, vertigo, headache, somnolence, restlessness, reduced alertness, tremor, blurred vision, memory disturbance, myoclonus, expressive aphasia, paraesthesia, dystonia, altered taste.
- Cardiac arrhythmias (including torsades de pointes, palpitations, premature ventricular contractions, ventricular pairs, ventricular tachycardia), bradycardia, tachycardia, electrocardiographic abnormalities (QT prolongation).
- Orthostatic hypotension, hypertension, syncope.
- Nasal congestion, dyspnoea.
- Nausea, vomiting, dry mouth, constipation, diarrhea, digestive difficulties, stomach pain, gastroenteritis, increased salivation, paralytic ileus.
- Abnormality of liver function (including jaundice and hepatocellular damage), intrahepatic cholestasis.
- Skin rash, itching, hyperhidrosis.
- Pain in the limbs, back pain, myalgia, arthralgia.
- Disorder of urination.
- Priapism.
- Weakness, edema, flu-like symptoms, fatigue, chest pain, fever.
- Increased liver enzymes.
If any of the side effects gets serious, or if you notice a side effect not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date indicated on the package.
Warning: do not use the medicine after the expiry date indicated on the package. The expiry date indicated refers to the product in intact packaging, correctly stored.
Store at a temperature not exceeding 25 ° C.
Keep this medicine out of the reach and sight of children.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
COMPOSITION
TRITTICO 75 mg prolonged-release tablets
Each tablet contains: Active ingredient: Trazodone hydrochloride 75 mg equal to trazodone 68.3 mg. Excipients: Sucrose - Povidone - Carnauba wax - Magnesium stearate.
TRITTICO 150 mg prolonged-release tablets
Each tablet contains: Active ingredient: 150 mg trazodone hydrochloride equal to 136.6 mg trazodone. Excipients: Sucrose - Povidone - Carnauba wax - Magnesium stearate.
PHARMACEUTICAL FORM AND CONTENT
Prolonged-release tablets divisible into three portions. Box of 30 tablets of 75 mg; box of 20 tablets of 150 mg.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
TRIPTYCH PROLONGED RELEASE TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Triptych 75 mg prolonged-release tablets
Each tablet contains: 75 mg trazodone hydrochloride equal to 68.3 mg trazodone.
Triptych 150 mg prolonged release tablets
Each tablet contains: 150 mg trazodone hydrochloride equal to 136.6 mg trazodone.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Prolonged-release tablets divisible into three portions.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Depressive disorders with or without an anxious component.
04.2 Posology and method of administration
The use of the product is limited to adult patients.
It is advisable to start the therapeutic cycle with an evening administration and with increasing daily dosages. Take the drug for therapeutic courses of at least one month. Taking trazodone after meals reduces the occurrence of undesirable effects (increased resorption and reduced peak plasma concentration).
The tablets are divisible into 3 portions to allow a progressive dosage with divided doses, according to the severity of the disease, weight, age and general condition of the patient.
Adults
75-150 mg per day to be administered as a single dose in the evening before bedtime.
The dose can then be increased up to 300 mg per day to be divided into two doses.
In hospitalized patients the dose can be further increased up to 600 mg per day in repeated doses.
Senior citizens:
In very elderly or defected patients, the recommended starting dose is 100 mg per day, administered in repeated dosing or as a single dose, administered in the evening. This dose can be subsequently increased, as described in the posology for adults, according to the judgment of the physician, according to tolerability and efficacy. In general, single doses above 100 mg should be avoided in these patients. However, dosages above 300 mg per day are unlikely.
Children:
The use of trazodone is not recommended in children and adolescents below 18 years of age due to a lack of safety data.
Hepatic insufficiency:
Trazodone is subject to intense hepatic metabolism, see section 5.2, and has also been associated with hepatotoxicity, see sections 4.4 and 4.8.
Caution should be exercised when trazodone is prescribed to patients with hepatic insufficiency, especially in cases of severe hepatic insufficiency. Assess the need for periodic monitoring of liver functions.
Kidney failure:
Dosage adjustments are not usually necessary, but caution should be exercised when prescribing trazodone to patients with severe renal impairment (see also sections 4.4 and 5.2).
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Generally contraindicated in pregnancy and lactation (see section 4.6).
Alcoholic intoxication and hypnotic intoxication.
Acute myocardial infarction.
04.4 Special warnings and appropriate precautions for use
Use in children and adolescents under the age of 18
Trazodone should not be used for the treatment of children and adolescents under 18 years of age. Suicidal behaviors (suicide attempts and suicidal ideation) and hostility (essentially aggression, oppositional behavior and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo. Furthermore, long-term safety data for children and adolescents are not available with regard to growth, maturation and cognitive and behavioral development.
Suicide / suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide / related events). This risk persists until significant remission occurs. As improvement may not occur during the first or immediate weeks of treatment, patients should be monitored closely until improvement occurs. It is generally clinical experience that the risk of suicide may increase in the early stages of improvement.
Patients with a history of suicidal behavior or thoughts, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are at increased risk of suicidal thoughts or suicidal thoughts, and should be closely monitored during treatment. of clinical trials conducted with antidepressant drugs in comparison with placebo in the therapy of psychiatric disorders, showed an increased risk of suicidal behavior in the age group below 25 years of patients treated with antidepressants compared to placebo.
Pharmacological therapy with antidepressants should always be associated with close surveillance of patients, particularly those at high risk, especially in the initial stages of treatment and after dose changes. Warn patients (or their carers) of the need to monitor and report immediately to their physician any clinical worsening, the onset of suicidal behavior or thoughts, or changes in behavior.
To reduce the potential risk of suicide attempts, particularly at the start of therapy, prescribe small amounts of trazodone at each visit.
It is recommended to pay particular attention to the dosage and to regularly monitor patients with:
• Epilepsy, especially avoid abrupt increases or decreases in dosage
• Hepatic or renal insufficiency, especially if severe
• Heart disease, such as angina pectoris, conduction or A-V block disorders of varying degrees, recent myocardial infarction
• Hyperthyroidism
• Disorders of urination, such as prostatic hypertrophy, although problems in this sense are not foreseeable given the negligible anticholinergic effect of trazodone
• Acute angle glaucoma, increased intraocular pressure, although severe changes have not yet been evident due to the lower anticholinergic effect of trazodone.
Discontinue treatment if jaundice occurs.
Administration of antidepressants to patients with schizophrenia or other psychotic disorders may lead to worsening of psychotic symptoms. Paranoid thoughts can intensify. During therapy with trazodone the depressive episode may vary from manic-depressive to manic psychosis, in which case the treatment should be discontinued.
Cases of interactions in terms of serotonin syndrome / neuroleptic malignant syndrome have been reported with the concomitant use of substances with serotonergic action (such as tricyclic antidepressants, SSRIs, SNRIs and MAO inhibitors) and neuroleptics. for which neuroleptic malignant syndrome is a known adverse reaction, cases of malignant neuroleptic syndromes, including fatal ones, have been reported (see sections 4.5 and 4.8 for further information).
If sore throat and fever occur, blood tests are recommended, since agranulocytosis can manifest itself with flu-like symptoms.
Hypotension, including orthostatic hypotension and syncope, has been reported with the use of trazodone. Concomitant administration of antihypertensive therapy and trazodone may require a reduction in the dosage of the antihypertensive drug. orthostatic hypotension and other anticholinergic effects.
Following treatment with trazodone, particularly if prolonged, a gradual reduction of the dosage is recommended before stopping treatment, in order to minimize the appearance of withdrawal symptoms, characterized by nausea, headache, malaise.
There is no evidence that trazodone can give rise to abuse / addiction phenomena.
As with other antidepressants, cases of QT interval prolongation have rarely been reported with trazodone. Special precautions are recommended when administering trazodone with other drugs known to cause QT interval prolongation. Trazodone should be used with caution in patients with cardiovascular diseases, including those associated with QT interval prolongation.
CYP3A4 inhibitors can cause a substantial increase in the plasma concentration of trazodone. See section 4.5 for further information.
As with other drugs with alpha-adrenolytic effects, rare cases of priapism have been reported during treatment with trazodone which can be treated with an intracavernous injection of an alpha-adrenergic agent such as adrenaline or metaraminol. trazodone-induced priapism has required surgery or has resulted in permanent sexual dysfunction Immediately discontinue treatment in patients who develop this suspected adverse reaction.
Important information about some of the excipients:
Triptych prolonged-release tablets contain sucrose: patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency, should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
General
The sedative effects of antipsychotic, hypnotic, sedative, anxiolytic, and antihistamine medications can be intensified; in these cases reduce the dosage.
The metabolism of antidepressants is accelerated by the hepatic effects of oral contraceptives, phenytoin, carbamazepine and barbiturates. The metabolism of antidepressants is inhibited by cimetidine and other antipsychotics.
CYP3A4 inhibitors
The results of in vitro drug metabolism studies suggest a potential drug interaction when trazodone is co-administered with cytochrome P4503A4 (CYP3A4) inhibitors, such as erythromycin, ketoconazole, itraconazole, ritonavir and indinavir and nefazodone. CYP3A4 inhibitors can cause a substantial increase in the plasma concentration of trazodone. Education in vivo in healthy volunteers demonstrated that a dose of ritonavir of 200 mg BID increases the plasma levels of trazodone more than double, causing nausea, syncope and hypotension. Therefore, when trazodone is co-administered with a potent CYP3A4 inhibitor, the dosage of trazodone should be reduced.
However, concomitant administration of trazodone and potent CYP3A4 inhibitors should be avoided where possible.
Carbamazepine
Co-administration of carbamazepine in combination with trazodone reduces its plasma concentration. Concomitant use of carbamazepine 400 mg daily leads to a reduction in plasma levels of trazodone and its active metabolite m-chlorophenylpiperazine by 76% and 60%, respectively. For this reason, patients taking trazodone in combination with carbamazepine should be closely monitored to determine if an increase in trazodone dosage is required.
Tricyclic antidepressants
Avoid concomitant use with trazodone due to the risk of interaction. Carefully evaluate the possible occurrence of serotonin syndrome and adverse cardiovascular effects.
Fluoxetine
There have been rare reports of increased plasma levels of trazodone and the occurrence of adverse effects when trazodone is administered with fluoxetine, a CYP1A2 / 2D6 inhibitor. The mechanism underlying the pharmacokinetic interaction is not fully understood. A "pharmacodynamic interaction (serotonin syndrome) cannot be excluded.
Monoamine oxidase inhibitors (MAOIs)
Cases of interactions with monoamine oxidase inhibitors (MAOIs) have occasionally been reported. Although some physicians are used to prescribe these drugs at the same time, concomitant administration of trazodone with MAOIs is not recommended, or within two weeks of stopping MAOI. It is also not recommended to administer MAOIs in the week following stopping treatment. with trazodone.
Phenothiazines
Severe orthostatic hypotension has been observed in case of concomitant administration of phenothiazine, such as chlorpromazine, fluphenazine, levomepromazine, perphenazine.
Anesthetics and muscle relaxants
Trazodone hydrochloride may enhance the effects of muscle relaxants and volatile anesthetics, therefore caution should be exercised with concomitant use.
Alcohol
Trazodone potentiates the sedative effects of alcohol. Avoid alcohol intake while taking trazodone.
Levodopa
Antidepressants can speed up the metabolism of levodopa.
Other
Concomitant use of Trazodone with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmia, including "torsades de pointes". Caution should be exercised when these drugs are co-administered with trazodone.
Since trazodone is a weak norepinephrine re-uptake inhibitor and does not modify the pressure response to tyramine, interference with the hypotensive action of guanethidine-like compounds is unlikely. However, studies in laboratory animals suggest that trazodone may inhibit much of the acute actions of clonidine.
Although no cases of clinical interaction with other antihypertensive drugs are reported, the possibility of a potentiating effect should still be considered.
Side effects may be more frequent during the simultaneous use of herbal preparations containing St. John's wort (Hypericum perforatum).
There have been reports of changes in prothrombin time in patients treated with trazodone and warfarin.
The combination of trazodone with digoxin and phenytoin may lead to increased blood levels of the latter. Monitor plasma concentrations in these patients.
04.6 Pregnancy and breastfeeding
Pregnancy
Data on a limited number (fetal / newborn health. To date no other relevant epidemiological data are available. Animal studies have not indicated direct or indirect harmful effects on pregnancy or on embryonic / fetal development, parturition or postnatal development at doses therapeutic (see section 5.3).
Caution should be exercised when trazodone is administered to pregnant women.When trazodone is used until delivery, neonates should be monitored for the appearance of withdrawal syndrome.
Feeding time
A limited amount of data indicates that the excretion of trazodone in human milk is low, while the levels of its active metabolite are unknown. Given the paucity of data, the decision on the use of trazodone during lactation should be made taking into account the benefits of breastfeeding and the benefits of trazodone therapy for women.
04.7 Effects on ability to drive and use machines
Trazodone has a mild or moderate influence on the ability to drive and use machines. Patients should be alerted to the risks of driving or using machines, unless they are sure they are not suffering from drowsiness, sedation, dizziness, confusion or blurred vision.
04.8 Undesirable effects
Cases of suicidal ideation and behavior have been reported during trazodone therapy or in the early stages following treatment discontinuation.
The following symptoms, some of which are commonly reported in untreated depression, have been reported in patients treated with trazodone:
1 Fluid and electrolyte status should be monitored in symptomatic patients.
2 See also section 4.4
3 Trazodone is an antidepressant with sedative properties and somnolence, sometimes occurring in the first few days of treatment, usually disappears later in therapy
4 Animal studies have shown that trazodone is less cardiotoxic than tricyclic antidepressants, and clinical studies suggest that it is less likely to cause cardiac arrhythmias in humans. Clinical studies in patients with pre-existing heart disease indicate that trazodone may be arrhythmogenic in some patients than that population.
5 Adverse effects on liver function, sometimes severe, have been reported rarely.
6 See also section 4.4.
04.9 Overdose
Characteristics of toxicity
The most frequently reported reactions in the event of overdose include somnolence, dizziness, nausea and vomiting.
In more serious cases, coma, tachycardia, hypotension, hyponatremia, convulsions and respiratory failure have been reported.
Heart changes may include bradycardia, QT prolongation and "Torsade de Pointes".
Symptoms can appear within 24 hours or more after the overdose.
Overdose of trazodone in combination with other antidepressants can cause serotonin syndrome.
Treatment
There is no specific antidote to trazodone. Activated charcoal can be used in adults who have ingested more than 1g of trazodone or in children who have taken more than 150mg of trazodone within 1 hour of symptom onset. Alternatively, gastric lavage in adults can be performed within one hour of taking a potentially dangerous dose.
In the event of an overdose, patients should be monitored for at least 6 hours after intake (or 12 hours in the case of extended release pharmaceutical forms).
Monitor blood pressure, pulse and Glasgow Coma Scale (GCS). Monitor oxygen saturation if GCS is low.
Cardiac monitoring is appropriate in symptomatic patients.
Short, single seizures do not require treatment. Frequent and prolonged seizures should be treated with intravenous administration of diazepam (0.1-0.3 mg / kg body weight) or lorazepam (4 mg in adults and 0.05 mg / kg in children).
If these measures do not control the seizure, proceed with an intravenous infusion of phenytoin.
Administer oxygen and correct acid-base balance and metabolic disturbances as needed.
In case of hypotension and excessive sedation, treatment is symptomatic and supportive. If severe hypotension persists, consider the use of inotropes, such as dopamine or dobutamine.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Psychoanaleptics, antidepressants
ATC code: N06AX05
Trazodone is a triazolpyridine derivative effective in the treatment of all depressive disorders, including depression associated with anxiety and sleep disorders (ATC code: N06AX05), characterized by a short latency of the therapeutic effect (about one week).
Trazodone is a serotonin reuptake inhibitor and a 5-HT2 receptor antagonist, activation of which is commonly associated with insomnia, anxiety, psychomotor agitation and impaired sexual function.
Unlike other psychotropic drugs, trazodone is not contraindicated in glaucoma and urination disorders, it does not produce extrapyramidal phenomena and, furthermore, by not enhancing adrenergic transmission and being virtually devoid of anti-cholinergic effects, it does not have the characteristic effects of tricyclic antidepressants. on cardiac conduction.
05.2 Pharmacokinetic properties
After single oral administration of Trittico 75 mg a Cmax of about 0.7 mg / ml is reached, with a Tmax at 4 hours post-dosing and an AUC of about 8 mg / ml / h.
After single oral administration of Trittico AC 150 mg a Cmax of approximately 1.2 mg / ml is reached, with a Tmax at 4 hours post-dosing. The half-life is approximately 12 hours and the AUC is approximately 18 mg / ml / h.
In vitro studies in human liver microsomes indicate that trazodone is primarily metabolised by cytochrome P4503A4 (CYP3A4).
05.3 Preclinical safety data
Acute toxicity. The LD50 of oral trazodone is 610 mg / kg in mice, 486 mg / kg in rats and 560 mg / kg in rabbits. The observed effects consisted of sedation, salivation, eyelid ptosis and clonic seizures.
Repeated toxicity. Subchronic studies in rats, rabbits and dogs and chronic studies in rats, dogs and monkeys were conducted. Doses administered orally ranged from 15 to 450 mg / kg / day in rats, from 15 to 100 mg / kg / day in rabbits, from 3 to 100 mg / kg / day in dogs and from 20 to 80 mg / day. kg / day in monkeys. In the rat, the treatment induced hypertrophy of the hepatocytes and the smooth endoplasmic reticulum resulting in hepatomegaly. This last effect is the result of a detoxification mechanism, which cannot be interpreted as a pathological phenomenon. Furthermore, doses with lethal effects have also induced effects already observed in acute toxicity studies. The relative NOEL (No Observed Adverse Effect Level ) results to be equal to 30 mg / kg / day. In the rabbit only depressant effects on the central nervous system were observed and the relative NOEL results to be 50 mg / kg / day. In the dog, the symptoms already observed with intoxication acute are aggravated with repeated administration and the relative NOEL is equal to 10 mg / kg / day. The monkey appears to be more resistant than the dog and has only pharmacodynamic disturbances. The NOEL results to be equal to 20 mg / kg / day.
Reproductive toxicity. No effects on fertility were observed in rats up to a dose of 300 mg / kg / day. Teratogenic studies in rats have shown an increase in embryolethality only at doses with toxic effects on the maternal organism (300-450 mg / kg / day). In rabbits, embryolethality and rare cases of congenital anomalies have been observed only at maternal toxic doses (210-450 mg / kg / day). The absence of direct effects on the embryo is confirmed by studies of the passage of trazodone through the placental barrier in the rat: concentrations of the drug in embryonic tissues and amniotic fluid were negligible. Peri and postnatal studies in rats showed only a reduction in the weight gain of neonates at doses above 30 mg / kg / day.
Mutagenicity. In vitro mutagenicity tests (in bacterial cells, Chinese hamster V77 cells, murine lymphoma cells, chromosomal aberration in CHO, CHL / IU cells and human lymphocytes) as well as in vivo mutagenesis tests (micronucleus in the mouse and chromosomal metaphase analysis in the rat) showed no mutagenic effects.
Carcinogenic potential. Studies were conducted in mice and rats and no potential risk of cancer was highlighted.
Antigenicity. Trazodone was found to be devoid of antigenic activity.
Cardiotoxicity. The cardiovascular effects of trazodone have been studied in rats, guinea pigs, cats and dogs. The drug was found to be practically devoid of cardiotoxicity as it does not induce changes in the ECG trace at non-hypotensive doses.
Hormonal effects. Single doses above 20 mg / kg intraperitoneally in the female rat induced a slight increase in prolactin. This effect disappeared with chronic administration in the diet.
Drug addiction. Two studies conducted in rats allowed for the exclusion of potential drug addiction effects.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sucrose, povidone, carnauba wax, magnesium stearate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store at a temperature not exceeding 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
Triptych 75 mg prolonged-release tablets: PVC / aluminum blister, pack of 30 tablets.
Triptych 150 mg prolonged-release tablets: PVC / aluminum blister, pack of 20 tablets.
06.6 Instructions for use and handling
A double breakline on the tablets allows for increasing daily dosages, according to the doctor's judgment.
07.0 MARKETING AUTHORIZATION HOLDER
Joint Chemical Companies Angelini Francesco - A.C.R.A.F. S.p.A.
Viale Amelia, 70 - 00181 ROME
08.0 MARKETING AUTHORIZATION NUMBER
Triptych 75 mg prolonged-release tablets, 30 tablets: 022323063
Triptych 150 mg prolonged-release tablets, 20 tablets: 022323075
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
15.10.1971/01.06.2010
10.0 DATE OF REVISION OF THE TEXT
December 2010
