TRAZODONE HYDROCHLORIDE G.L.

Posology Adults Starting dose is 150 mg/day in divided doses after food or as a single dose before retiring. This may be increased to 300 mg/day, the major portion of which is preferably taken on retiring. In hospitalised patients dosage may be further increased to 600 mg/day.

4). This may be incrementally increased, under supervision, according to efficacy and tolerance. In general, single doses above 100 mg should be avoided in these patients. Doses above 300 mg/day are unlikely to be required. In conformity with current psychiatric opinion, it is suggested that trazodone be continued for several months after remission.

Cessation of trazodone treatment should be gradual. 8). Therefore caution should be exercised when prescribing for patients with hepatic impairment, particularly in cases of severe hepatic impairment. Periodic monitoring of liver function may be considered.

2). Paediatric population There are insufficient data on safety to recommend the use of trazodone in children and adolescents below the age of 18 years. Method of administration Oral use. A decrease in side effects (increase of the resorption and decrease of the peak plasma concentration) can be reached by taking trazodone hydrochloride with or after a meal.

4). The following symptoms, some of which are commonly reported in cases of untreated depression, have also been recorded in patients receiving trazodone therapy. MedDRA System Organ Class Frequency not known (cannot be estimated from the available data) Blood and the lymphatic system disorders Haematological alterations (including agranulocytosis, thrombocytopenia, eosinophilia, leukopenia and anaemia) Immune system disorders Allergic reaction Endocrine disorders Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Metabolism and nutrition disorders Hyponatraemia1, weight loss, anorexia, increased appetite Psychiatric disorders Suicidal ideation or suicidal behaviours2, confusional state, insomnia, disorientation, mania, anxiety, nervousness, agitation (very occasionally exacerbating to delirium), delusion, aggressive reaction, hallucinations, nightmares, libido decreased, withdrawal syndrome Nervous system disorders Serotonin syndrome, convulsion, neuroleptic malignant syndrome, dizziness, vertigo, headache, drowsiness3, restlessness, decreased alertness, tremor, blurred vision, memory disturbance, myoclonus, expressive aphasia, paraesthesia, dystonia, taste altered Cardiac disorders Cardiac arrhythmias4 (including torsade de pointes, palpitations, premature ventricular contractions, ventricular couplets, ventricular tachycardia), bradycardia, tachycardia, ECG abnormalities (QT prolongation)2 Vascular disorders Orthostatic hypotension, hypertension, syncope Respiratory, thoracic and mediastinal disorders Nasal congestion, dyspnoea Gastrointestinal disorders Nausea, vomiting, dry mouth, constipation, diarrhoea, dyspepsia, stomach pain, gastroenteritis, increased salivation, paralytic ileus Hepatobiliary disorders Hepatic function abnormalities (including jaundice and hepatocellular damage)5, cholestasis intrahepatic, severe hepatic disorders such as hepatitis/fulminant hepatitis, hepatic failure with potentially fatal outcome MedDRA System Organ Class Frequency not known (cannot be estimated from the available data) Skin and subcutaneous tissue disorders Skin rash, pruritus, hyperhidrosis Musculoskeletal and connective tissue disorders Pain in limb, back pain, myalgia, arthralgia Renal and urinary disorders Micturition disorder Reproductive system and breast disorders Priapism2 General disorders and administration site conditions Weakness, oedema, influenza-like symptoms, fatigue, chest pain, fever Investigations Elevated liver enzymes 1 Fluid and electrolyte status should be monitored in symptomatic patients.

4. 3 Trazodone is a sedative antidepressant and drowsiness, sometimes experienced during the first days of treatment, usually disappears on continued therapy. 4 Studies in animals have shown that trazodone is less cardiotoxic than the tricyclic antidepressants, and clinical studies suggest that the drug may be less likely to cause cardiac arrhythmias in man.

Clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population. 5 Adverse effects on hepatic function, sometimes severe, have been rarely reported. Should such effects occur, trazodone should be immediately discontinued.

In contrast to the tricyclic antidepressants, trazodone is devoid of anticholinergic activity. Consequently, troublesome side effects such as dry mouth, blurred vision and urinary hesitancy have occurred no more frequently than in patients receiving placebo therapy.

This may be of importance when treating depressed patients who are at risk from conditions such as glaucoma, urinary retention and prostatic hypertrophy. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store.

Paediatric population Trazodone should not be used in children and adolescents under 18 years old. Suicidal behaviour (suicidal attempt and suicidal planning) and hostility (essentially aggressiveness, opposing behaviour and anger) has been observed in a clinical study on children and adolescents treated with antidepressant more frequently than with placebo.

Moreover, long-term safety data on children and adolescents regarding growth, maturation and cognitive and behavioural development are not available. 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 few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which trazodone is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.

A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

To minimise the potential risk of suicide attempts, particularly at therapy initiation, only restricted quantities of trazodone should be prescribed at each occasion. Special precaution in the following patient groups It is recommended that careful dosing and regular monitoring is adopted in patients with the following conditions: - Epilepsy, specifically abrupt increases or decreases of dosage should be avoided - Patients with hepatic or renal impairment, particularly if severe - Patients with cardiac disease, such as angina pectoris, conduction disorders or AV blocks of different degree, recent myocardial infarction - Hyperthyroidism - Micturition disorders, such as prostate hypertrophy, although problems would not be anticipated as the anticholinergic effect of trazodone is only minor - Acute narrow angle glaucoma, raised intra-ocular pressure, although major changes would not be anticipated due to the minor anticholinergic effect of trazodone Hepatic impairment Should jaundice occur in a patient, trazodone therapy must be withdrawn.

8). Patients should be instructed to report immediately signs such as asthenia, anorexia, nausea, vomiting, abdominal pain or icterus to a physician. Investigations including clinical examination and laboratory checks of liver function should be undertaken immediately, and withdrawal of trazodone therapy should be considered.

Psychotic disorders Administration of antidepressants in patients with schizophrenia or other psychotic disorders may result in a possible worsening of psychotic symptoms. Paranoid thoughts may be intensified. During therapy with trazodone a depressive phase can change from a manic-depressive psychosis into a manic phase.

In that case trazodone must be stopped. g. tricyclic antidepressants, SSRI's, SNRI's and MAO- inhibitors) and neuroleptics. 8). Agranulocytosis Since agranulocytosis may clinically reveal itself with influenza-like symptoms, sore throat, and fever, in these cases it is recommended to check haematology.

Hypotension Hypotension, including orthostatic hypotension and syncope, has been reported to occur in patients receiving trazodone. Concomitant administration of antihypertensive therapy with trazodone may require a reduction in the dose of the antihypertensive drug.

Elderly Elderly patients may more often experience orthostatic hypotension, somnolence and other anticholinergic effects of trazodone. Careful consideration should be given to the potential for additive effects with concomitant medication use such as with other psychotropics or antihypertensives or in the presence of risk factors such as comorbid disease, which may exacerbate these reactions.

It is recommended that the patient/carer is informed of the potential for these reactions and monitored closely for such effects following initiation of therapy, prior to and following upward dose titration. Withdrawal symptoms Following therapy with trazodone, particularly for a prolonged period, an incremental dosage reduction to withdrawal is recommended, to minimise the occurrence of withdrawal symptoms, characterised by nausea, headache, and malaise.

There is no evidence that trazodone […]

1 - Alcohol intoxication or intoxication with hypnotics - Acute myocardial infarction