Molipaxin 50mg. 100mg Capsule

MOLIPAXIN is indicated in the treatment of depression and mixed anxiety and depression.

The dosage is dependent upon the diagnosis and the severity of the condition and the individual patientu2019s response. The daily dosage is usually administered in three divided doses.

Adults:

Depression: The optimal dosage is between 300 - 400 mg/day. It is suggested that a starting dose of 150 mg/day is given for the first week, increasing to 300 mg/day u2013 400 mg/day according to the clinical response. The dose may be further increased to 600 mg/day in divided doses in hospitalised patients.

Mixed anxiety and depression: The recommended starting dose is between 100 u2013 150 mg/day. When depression is the predominant symptom, a dose of 300 u2013 400 mg daily may be required to obtain a satisfactory response.

Children and adolescents under 18 years of age: MOLIPAXIN is not recommended for use in children and adolescents under 18 years of age.

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 100 mg should be avoided in these patients. It is unlikely that 300 mg/day will be exceeded.

• Known hypersensitivity to trazodone or to any of the excipients of MOLIPAXIN.
• Combined use with other psychotropic medicines should only be undertaken with due recognition of the possibility of potentiation (see INTERACTIONS).
• Concurrent administration with monoamine oxidase inhibitors (MAOIs), or within two weeks of stopping treatment with these compounds. Administration of MAOIs within one week of stopping MOLIPAXIN.
• Alcohol intoxication and intoxication with hypnotics.
• Acute myocardial infarction (see WARNINGS AND SPECIAL PRECAUTIONS).

Use in children and adolescents under 18 years of age: MOLIPAXIN should not be used in children and adolescents under 18 years of age. Suicidal behaviour (suicidal attempt and suicidal planning) and hostility (essentially aggressiveness, opposing behaviour and anger) has been observed in clinical studies 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 MOLIPAXIN is prescribed may 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 medication 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 MOLIPAXIN 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 MOLIPAXIN should be prescribed at each occasion.

MOLIPAXIN should be administered with care and regular monitoring should be adopted in patients with the following conditions:

• epilepsy, avoiding in particular, abrupt increases or decreases in dosage (see INTERACTIONS)
• hepatic or renal impairment, particularly if severe
• cardiac disease, such as angina pectoris, conduction disorders or AV blocks of different degree and its use is not recommended in the immediate recovery phase after myocardial infarction (see CONTRAINDICATIONS)
• hyperthyroidism
• micturition disorders, such as prostate hypertrophy
• acute narrow angle glaucoma, raised intra-ocular pressure.

MOLIPAXIN should be stopped immediately if patients develop signs of hepatic dysfunction, or blood dyscrasias. Severe hepatic disorders with potential fatal outcome have been reported with MOLIPAXIN use (see SIDE EFFECTS). Patients should be instructed to report immediately signs such as asthenia, anorexia, nausea, vomiting, abdominal pain or icterus to a doctor or healthcare professional. Investigations including clinical examination and biological assessment of liver function should be undertaken immediately, and withdrawal of MOLIPAXIN initiated.

Since agranulocytosis may clinically reveal itself with influenza-like symptoms, sore throat, and fever, in these cases it is recommended to check haematology.

Administration of antidepressants in patients with schizophrenia or other psychotic disorders may result in a worsening of psychotic symptoms. Paranoid thoughts may be intensified. During therapy with MOLIPAXIN a depressive phase can change from a manic u2013 depressive psychosis into a manic phase. In that case MOLIPAXIN must be stopped.

Interactions in terms of serotonin syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of other serotonergically acting substances like other antidepressants (e.g. tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIu2019s), serotonin and norepinephrine reuptake inhibitors (SNRIu2019s), MAOIs and neuroleptics (see SIDE EFFECTS). Malignant neuroleptic syndromes with fatal outcome have been reported in cases of co-administration with neuroleptics, for which this syndrome is a known possible side effect.

Hypotension, including orthostatic hypotension and syncope, has occurred in patients receiving MOLIPAXIN. Concomitant administration of antihypertensive therapy with MOLIPAXIN may require a reduction in the dose of the antihypertensive medicine.

Elderly patients are often more sensitive to antidepressants, in particular to orthostatic hypotension and other anticholinergic effects.

Following therapy with MOLIPAXIN, 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.

Cases of QT interval prolongation have been reported with MOLIPAXIN less frequently. Caution is advised when prescribing MOLIPAXIN with medicinal products known to prolong the QT interval. MOLIPAXIN should be used with caution in patients with known cardiovascular disease including those associated with prolongation of the QT interval (see INTERACTIONS).

MOLIPAXIN should be administered with care to patients receiving barbiturates, muscle relaxants and volatile anaesthetics, since it has been shown to potentiate the action of these substances.

Potent CYP3A4 inhibitors may lead to increases in MOLIPAXIN serum levels (see INTERACTIONS).

Alcohol: MOLIPAXIN intensifies the sedative effects of alcohol. Alcohol should be avoided during MOLIPAXIN therapy (see CONTRAINDICATIONS).

Tricyclic antidepressants: Concurrent administration should be avoided due to the risk of interaction. Serotonin syndrome and cardiovascular side effects should be bewared (see WARNINGS AND SPECIAL PRECAUTIONS).

Fluoxetine: Less frequent cases have been reported of elevated trazodone plasma levels and adverse effects when MOLIPAXIN had been combined with fluoxetine, a CYP1A2/2D6 inhibitor. The mechanism underlying a pharmacokinetic interaction is not fully understood. A pharmacodynamic interaction (serotonine syndrome) could not be excluded. The concurrent use of tricyclic or related antidepressants and lithium may promote neurotoxic side effects.

CYP3A4 inhibitors: In vitro medicine metabolism studies suggest that there is a potential for medicine interactions when MOLIPAXIN is given with potent CYP3A4 inhibitors such as erythromycin, ketoconazole, itraconazole, ritonavir, indinavir, and nefazodone. It is likely that potent CYP3A4 inhibitors may lead to substantial increases in MOLIPAXIN plasma concentrations with the potential for adverse effects. Exposure to ritonavir during initiation or resumption of treatment in patients receiving MOLIPAXIN will increase the potential for excessive sedation, cardiovascular, and gastrointestinal effects. If MOLIPAXIN is used with a potent CYP3A4 inhibitor, a lower dose of MOLIPAXIN should be considered. However, the co-administration of MOLIPAXIN and potent CYP3A4 inhibitors should be avoided where possible.

General: The sedative effects of antipsychotics, hypnotics, sedatives, anxiolytics, and antihistaminic medicines may be intensified; dosage reduction is recommended in such instances (see CONTRAINDICATIONS). The metabolism of antidepressants is accelerated due to hepatic effects by oral contraceptives, phenytoin, carbamazepine and barbiturates. The metabolism of antidepressants is inhibited by cimetidine and some other antipsychotics.

Carbamazepine: Carbamazepine reduced plasma concentrations of MOLIPAXIN when co-administered. Patients should be closely monitored to see if there is a need for an increased dose of MOLIPAXIN when treated concomitantly with carbamazepine.

Anaesthetics/muscle relaxants: MOLIPAXIN may enhance the effects of muscle relaxants and volatile anaesthetics. Antidepressants may accelerate the metabolism of levodopa.

Phenothiazines: Severe orthostatic hypotension has been observed in case of concomitant use of phenothiazines such as chlorpromazine (see WARNINGS AND SPECIAL PRECAUTIONS).

Other: Since MOLIPAXIN is only a very weak inhibitor of noradrenaline re-uptake and does not modify the blood pressure response to tyramine, interference with the hypotensive action of guanethidine-like compounds is unlikely. However, studies in laboratory animals suggest that MOLIPAXIN may inhibit most of the acute actions of clonidine. In the case of other types of antihypertensive medicines, the possibility of potentiation should be considered.

Concomitant use of apraclonidine or brimonidine and MOLIPAXIN is not recommended. Concomitant use of MOLIPAXIN with the anti-dysrhythmic medicine amiodarone or other medicines known to prolong the QT interval may increase the risk of ventricular dysrhythmias, including Torsade de Pointes. Caution should be used when these medicines are co-administered with MOLIPAXIN.

Concurrent use with MOLIPAXIN may result in elevated serum levels of digoxin or phenytoin. Monitoring of serum levels should be considered in these patients. In general, antidepressants may antagonise the anti-convulsant effect of anti-epileptics by lowering the seizure threshold (see WARNINGS AND SPECIAL PRECAUTION).

Warfarin: Increases and decreases in INR/prothrombin time have been reported in patients concomitantly receiving MOLIPAXIN and warfarin. Therefore it is prudent to monitor the INR in patients taking warfarin, when treatment with MOLIPAXIN is started or stopped, and adjusting the warfarin dose if necessary.

Tryptophan: Since both MOLIPAXIN and tryptophan lead to an increase in 5-HT level at the synapse via different mechanisms of action, there is a possibility of a pharmacodynamic interaction which may lead to serotonin syndrome. Undesirable effects may be more frequent when MOLIPAXIN is administered together with preparations containing Hypericum perforatum (St Johnu2019s Wort).

The safety of MOLIPAXIN in pregnancy and breastfeeding has not been established. MOLIPAXIN is excreted in the breastmilk and may have an effect on the breastfeeding infant. Mothers on treatment with MOLIPAXIN should not breastfeed their infants.

Patients should be warned about the possibility of their judgement being impaired by drowsiness, sedation, dizziness, confusional states, or blurred vision when operating dangerous machinery and when driving.

The following side effects have been reported and the frequencies have been indicated where known.

Blood and lymphatic system disorders:

Less frequent: blood dyscrasias, including agranulocytosis, thrombocytopenia, anaemia (see WARNINGS AND SPECIAL PRECAUTIONS)

Frequency unknown: eosinophilia, leucopenia

Immune system disorders:

Frequency unknown: allergic reactions

Endocrine disorders:

Frequency unknown: Syndrome of Inappropriate Antidiuretic Hormone Secretion

Metabolism and nutrition disorders:

Frequency unknown: hyponatraemia*, weight loss, anorexia, increased appetite

* Fluid and electrolyte status should be monitored in symptomatic patients

Psychiatric disorders:

Frequent: confusional states

Frequency unknown: suicidal ideation or suicidal behaviours (see WARNINGS AND SPECIAL PRECAUTIONS), insomnia, disorientation, mania, anxiety, nervousness, agitation (less frequently exacerbating to delirium), delusion, aggressive reaction, hallucinations, nightmares, libido decreased, withdrawal syndrome

Nervous system disorders:

Frequent: headache, dizziness, drowsiness, tremor, excitement

Frequency unknown: vertigo, decreased alertness, restlessness, irritability, memory disturbance, expressive aphasia, dystonia, taste altered, paraesthesia, myoclonus

There have been reports of serotonin syndrome and convulsions associated with the use of MOLIPAXIN (see WARNINGS AND SPECIAL PRECAUTIONS and INTERACTIONS), especially when associated with other psychotropic medicines. Neuroleptic malignant syndrome has been reported

Eye disorders:

Less frequent: blurred vision

Cardiac disorders:

Less frequent: bradycardia or tachycardia

Frequencies unknown: Clinical studies in patients with pre-existing cardiac disease indicate that MOLIPAXIN may be dysrhythmogenic in some patients in that population. Dysrhythmias identified include Torsade de Pointes, palpitations, premature ventricular contractions, ventricular couplets, short episodes (3-4 beats) of ventricular tachycardia and ECG abnormalities (QT prolongation) (see WARNINGS AND SPECIAL PRECAUTIONS).

Vascular disorders:

Less frequent: orthostatic hypotension

Frequency unknown: hypertension, syncope

Respiratory, thoracic and mediastinal disorders:

Frequency unknown: nasal congestion, dyspnoea

Gastrointestinal disorders:

Frequent: nausea, vomiting, dry mouth

Less frequent: constipation, diarrhoea

Frequency unknown: dyspepsia, increased salivation, stomach pain, gastroenteritis, paralytic ileus

Hepato-biliary disorders:

Frequency unknown: severe hepatic disorders such as hepatitis/fulminant hepatitis, hepatic failure with potential fatal outcome, cholestasis intrahepatic. Should adverse effects on hepatic function, including jaundice and hepatocellular damage occur, MOLIPAXIN should be discontinued immediately (see WARNINGS AND SPECIAL PRECAUTION).

Skin and subcutaneous tissue disorders:

Less frequent: skin rashes

Frequency unknown: hyperhidrosis, pruritus

Musculoskeletal and connective tissue disorders:

Frequency unknown: pain in limb, back pain, myalgia, arthralgia

Renal and urinary disorders:

Frequency unknown: micturition disorder

Reproductive system and breast disorders:

Less frequent: priapism (see WARNINGS AND SPECIAL PRECAUTIONS)

General disorders and administration site conditions:

Less frequent: weakness

Frequency unknown: oedema, influenza-like symptoms, chest pain, fatigue, fever

Investigations:

Frequency unknown: elevated liver enzymes

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 in combination with other antidepressants may cause serotonin syndrome.

Management: There is no specific antidote to MOLIPAXIN. The stomach should be emptied as quickly as possible and symptomatic and supportive therapy given.