Molipaxin

Molipaxin 100 mg Capsules/Trazodone hydrochloride 100 mg Capsules

Trazodone hydrochloride 100mg per capsule.

For excipients see 6.1

Capsules.

Anxiety, depression, mixed anxiety and depression.

Route of administration: Oral.

DEPRESSION:

Adults:

Initially 150mg/day in divided doses after food or as a single dose on retiring.

This may be increased up to 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.

Elderly:

For very elderly or frail patients, the recommended initial starting dose is reduced to 100 mg/day given in divided doses or as a single night-time dose. This may be incrementally increased, under supervision, according to efficacy and tolerance. In general, single doses above 100mg should be avoided in these patients. It is unlikely that 300 mg/day will be exceeded.

Children:

There are insufficient data on safety to recommend the use of Molipaxin/Trazodone in children below the age of 18 years.

DEPRESSION ACCOMPANIED BY ANXIETY:

As for depression.

ANXIETY:

75 mg/day increasing to 300 mg/day as necessary.

A decrease in side-effects (increase of the resorption and decrease of the peak plasma concentration) can be reached by taking Molipaxin/Trazodone after a meal.

Hepatic Impairment:

Renal Impairment:

- Known sensitivity to trazodone and any of the excipients.

- Alcohol intoxication and intoxication with hypnotics.

- Acute myocardial infarction.

Use in children and adolescents under 18

Molipaxin/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 behavior 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 behavioral 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).8 for further information.

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 Molipaxin/Trazodone.

As with other drugs with alpha-adrenolytic activity, Molipaxin/Trazodone has very rarely been associated with priapism. This may be treated with an intracavernosum injection of an alpha-adrenergic agent such as adrenaline or metaraminol. However there are reports of Molipaxin/Trazodone -induced priapism which have required surgical intervention or led to permanent sexual dysfunction. Patients developing this suspected adverse reaction should cease Molipaxin/Trazodone immediately.

Molipaxin/Trazodone hydrochloride contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Molipaxin/Trazodone has minor or moderate influence on the ability to drive and use machines.As with all other drugs acting on the central nervous system, patients should be cautioned against the risks of driving or operating machinery until they are sure they are not affected by drowsiness, sedation, dizziness, confusional states, or blurred vision.

.

Cases of suicidal ideation and suicidal behaviours have been reported during Molipaxin/Trazodone therapy or early after treatment discontinuation.

Molipaxin/Trazodone has had no effect on arterial blood pCO₂ or pO₂ levels in patients with severe respiratory insufficiency due to chronic bronchial or pulmonary disease.

The following symptoms, some of which are commonly reported in cases of untreated depression, have also been recorded in patients receiving Molipaxin/Trazodone therapy.

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.

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Features of toxicity

The most frequently reported reactions to overdose have included drowsiness, dizziness, nausea and vomiting. In more serious cases coma, tachycardia, hypotension, hyponatraemia, convulsions and respiratory failure have been reported. Cardiac features may include bradycardia, QT prolongation and torsade de pointes. Symptoms may appear 24 hours or more after overdose.

Overdoses of Molipaxin/Trazodone in combination with other antidepressants may cause serotonin syndrome.

Management

There is no specific antidote to trazodone. Activated charcoal should be considered in adults who have ingested more than 1 g trazodone, or in children who have ingested more than 150 mg trazodone within 1 hour of presentation. Alternatively, in adults, gastric lavage may be considered within 1 hour of ingestion of a potentially life-threatening overdose.

Observe for at least 6 hours after ingestion (or 12 hours if a sustained release preparation has been taken). Monitor BP, pulse and Glasgow Coma Scale (GCS). Monitor oxygen saturation if GCS is reduced. Cardiac monitoring is appropriate in symptomatic patients.

Single brief convulsions do not require treatment. Control frequent or prolonged convulsions with intravenous diazepam (0.1-0.3 mg/kg body weight) or lorazepam (4 mg in an adult and 0.05 mg/kg in a child). If these measures do not control the fits, an intravenous infusion of phenytoin may be useful. Give oxygen and correct acid base and metabolic disturbances as required.

Treatment should be symptomatic and supportive in the case of hypotension and excessive sedation. If severe hypotension persists consider use of inotropes, e.g. dopamine or dobutamine

ATC code: N06A X05. Other antidepressants.

Molipaxin/Trazodone is a potent antidepressant. It also has anxiety reducing activity. Molipaxin/Trazodone is a triazolopyridine derivative chemically unrelated to known tricyclic, tetracyclic and other antidepressant agents. It has negligible effect on noradrenaline re-uptake mechanisms. Whilst the mode of action of Molipaxin/Trazodone is not known precisely, its antidepressant activity may concern noradrenergic potentiation by mechanisms other than uptake blockade. A central antiserotonin effect may account for the drug's anxiety reducing properties.

Trazodone is rapidly absorbed from the gastro-intestinal tract and extensively metabolised. Paths of metabolism of trazodone include n-oxidation and hydroxylation. The metabolic m-chlorophenylpiperazine is active. Trazodone is excreted in the urine almost entirely in the form of its metabolites, either in free or in conjugated form. The elimination of Trazodone is biphasic, with a terminal elimination half-life of 5 to 13 hours. Trazodone is excreted in breast milk.

There was an approximate two-fold increase in terminal phase half-life and significantly higher plasma concentrations of trazodone in 10 subjects aged 65 to 74 years compared with 12 subjects aged 23 to 30 years following a 100mg dose of trazodone. It was suggested that there is an age-related reduction in the hepatic metabolism of trazodone.

In vitro studies in human liver microsomes show that trazodone is metabolised by cytochrome P4503A4 (CYP3A4) to form m-chlorophenylpiperazine. Whilst significant, the role of this pathway in the total clearance of trazodone in vivo has not been fully determined.

None stated.

Lactose

Magnesium stearate

Gelatin

Titanium dioxide E171

Erythrosine E127

Indigo Carmine E132

Red iron oxide E172

Yellow iron oxide E172

Ink ( black iron oxide E172, shellac, propylene glycol and ammonium hydroxide (pH adjustment) or black iron oxide E172, shellac, propylene glycol, strong ammonia solution (pH adjustment) and potassium hydroxide (pH adjustment))

None stated.

36 months.

Blister packs: Store below 30°C in a dry place.

Glass bottles and securitainers: Store below 30°C.

i) Amber glass bottles with jay-cap closures: contents 100 capsules.

ii) PVdC coated 250μm PVC blisters sealed with 20μm aluminium foil: contents 56 and 100 capsules.

iii) Securitainers: contents 1000 capsules.

Not applicable.

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

Trading as:-

Zentiva, One Onslow Street, Guildford, Surrey, GU1 4YS, UK

PL 17780/0618

26 August 2009

29/04/2015