TRAZODONE

Posology Adults:

Initially 150mg/day in divided doses after a meal or as a single dose on retiring. g. every 3-4 days by steps of 50 mg, up to a maximum of 300mg/day in a single or divided doses. The major portion of a divided dose to be taken on retiring.

The dose may be further increased to 600mg/day in divided doses in hospitalised patients. After reaching an effective dose, clinical response is usually evident within two to four weeks. In the case of non-responders the dose may be increased to the maximimum recommended.

If, following this, there is no response after two to four weeks, therapy should be discontinued. After reaching a satisfactory clinical response, the dose should be maintained for a minimum of four weeks. Following this period, generally the dose can be incrementally decreased, depending on therapeutic response.

Patients should be maintained on the lowest effective dose and be periodically reassessed to determine the continued need for maintenance treatment. In general, it is preferable to continue therapy with an antidepressant until the patient has been symptomless for four to six months.

In order to avoid withdrawal symptoms abrupt discontinuation of treatment should be avoided. At the end of treatment, the dose should be gradually decreased. 4). This may be incrementally increased, as described under Adults, under supervision, according to tolerance and efficacy.

In general, single doses above 100 mg should be avoided in these patients. It is unlikely that a dose of 300 mg per day will be exceeded. 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). 4). Method of administration Oral use. A decrease in undesirable effects can be reached by taking Trazodone after a meal. Trazodone should be taken together with a glass of water.

4). The most frequently reported adverse reactions are: somnolence, sedation, dizziness, dry mouth, gastrointestinal disorders, sleep disorders, headache, agitation, orthostatic hypotension. The following symptoms 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 Blood dyscrasias (including agranulocytosis, thrombocytopenia, eosinophilia, leucopenia and anaemia) Immune system disorders Allergic reactions, angioedema Endocrine disorders Syndrome of Inappropriate Antidiuretic Hormone Secretion Metabolism and nutrition disorders Hyponatraemia4, weight loss, anorexia, increased appetite, weight gain Psychiatric disorders Suicidal ideation or suicidal behaviours5, 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, drowsiness6, somnolence, sedation, ataxia, restlessness, decreased alertness, tremor, blurred vision, memory disturbance, myoclonus, expressive aphasia, paraesthesia, dystonia, taste altered Cardiac disorders Cardiac arrhythmias7 (including Torsade de Pointes, palpitations, premature ventricular contractions, ventricular couplets, ventricular tachycardia), bradycardia, tachycardia, ECG, abnormalities (QT prolongation) 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 Hepato-biliary disorders Severe hepatic disorders such as hepatitis/fulminant hepatitis, hepatic failure with potential fatal outcome.

Hepatic function abnormalities (including jaundice and hepatocellular damage)8, cholestasis intrahepatic. 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 Priapism9 General disorders and administration site conditions Weakness, oedema, influenza-like symptoms, fatigue, chest pain, fever Investigations Elevated liver enzymes 4 Fluid and electrolyte status should be monitored in symptomatic patients.

4. 6 Trazodone is a sedative antidepressant and drowsiness, sometimes experienced during the first days of treatment, usually disappears on continued therapy. 7 Clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population.

8 Adverse effects on hepatic function, sometimes severe, have been rarely reported. Should such effects occur, trazodone should be immediately discontinued. 4 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.

Elderly Elderly patients may more often experience orthostatic hypotension, somnolence and other anticholinergic effects of trazodone. 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.

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 medicinal products 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 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. It is recommended that careful dosing and regular monitoring is adopted in patients with the following conditions: • Epilepsy, specifically abrupt increases or decreases of dose should be avoided • Patients with hepatic or renal impairment, particularly if severe • Patients with cardiac and vascular disease, such as cardiovascular insufficiency, angina pectoris, conduction disorders or AV blocks of different degree, arrhythmias recent myocardial infarction, congenital long QT syndrome or bradycardia.

Trazodone should be used with particular caution in these patients • Patients with hypokalaemia or hypomagneseia. These electrolyte- disturbances increase the risk for malignant arrhythmias and should be corrected before treatment with trazodone is started.

• 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.

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 biological assessment of liver function should be undertaken immediately, and withdrawal of tradozone therapy be considered.

Should jaundice occur in a patient, Trazodone therapy must be withdrawn. 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, tryptophan and MAO-inhibitors), triptans and neuroleptics.

8 for further information. Treatment with trazodone must be stopped immediately and supportive symptomatic treatment should be initiated. 5). If concomitant treatment with other serotonergic agents is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms.

Since agranulocytosis may clinically reveal itself with influenza-like symptoms, sore throat, and fever, in these cases it is recommended to check haematology. 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 medicinal product. 8). Careful consideration should be given to the potential for additive effects with concomitant medicinal product 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 […]

1. Alcohol intoxication and intoxication with hypnotics. Acute myocardial infarction.