RANCANGAN LEAFLET LUVOX FLUVOXAMINE MALEATE COMPOSITION Luvox film-coated tablet 50 mg: Each film-coated tablet contains fluvoxamine maleate 50 mg Luvox film-coated tablet 100 mg: Each film-coated tablet contains fluvoxamine maleate 100 mg ACTIONS PHARMACOLOGICAL PROPERTIES Pharmacodynamic properties The mechanism of action of fluvoxamine maleate is thought to be related to selective serotonin re-uptake inhibition in brain neurons. There is minimum interference with noradrenergic processes. Receptor binding studies have demonstrated that fluvoxamine maleate has negligible binding capacity to alpha-adrenergic, beta-adrenergic, histaminergic, muscarine cholinergic, dopaminergic or serotonergic receptors. Pharmacokinetic properties Fluvoxamine maleate is completely absorbed following oral administration. Maximum plasma concentrations occur within 3-8 hours of dosing. The mean plasma halflife is approximately 13-15 hours after a single dose, and slightly longer (17-22 hours) during repeated dosing, when steady-state plasma levels are usually achieved within 10-14 days. Fluvoxamine maleate undergoes extensive hepatic transformation, mainly via oxidative demethylation, into at least nine metabolites, which are excreted by the kidneys. The two major metabolites showed negligible pharmacological activity. The other metabolites are not expected to be pharmacologically active. In vitro binding of fluvoxamine maleate to human plasma is about 80%, INDICATIONS Treatment of depressive illness and symptoms of depressive disorder. DOSAGE AND ADMINISTRATION The recommended starting dose is 50 or 100 mg, given as single dose in the evening, Itis recommended to increase the dose gradually until an effective dose is reached. The usual effective dose is 100 mg per day and should be adjusted on individual patient response. Doses of up to 300 mg per day have been given. Dosage above 150 mg should be given in divided doses. Jn agreement with the consensus statement of the WHO, antidepressant medication should be continued for at least 6 months after recovery from a depressive episode Luvox ata fixed single daily dose of 100 mg is the recommended dose for the prevention of recurrence of depression.CONTRAINDICATIONS Luvox tablets are contraindicated in combination with monoamine oxide inhibitors (MAOIs). ‘Treatment with Luvox can be initiated: © Two weeks after discontinuation of an irreversible MAOI, or © The following day after discontinuation of reversible MAOI (e.g. moclobemide). At least one week should elapse between discontinuation of Luvox and initiation of therapy with any MAOL Furthermore Luvox is contraindicated in patients with hypersensitivity to any component of the product (see list of excipients), PRECAUTIONS AND WARNINGS — The possibility of suicide attempt is inherent in patients suffering from depressive illness and may persist until significant remission occurs. = Patients suffering from hepatic or renal insufficiency should start on a low dose and be carefully monitored. — Rarely: treatment with Luvox has been associated with an increase in hepatic enzymes, mostly accompanied by clinical symptoms. In these cases treatment should be discontinued. = Although in animal studies fluvoxamine has no proconvulsive properties, caution is recommended when drug is administered to patients with a history of convulsive disorders. Treatment with Luvox should be discontinued if seizures occur. = On rare occasions development of a serotonin syndrome has been reported in association with treatment of fluvoxamine, particularly when given in combination with other serotonergic drugs and appeared to be reversible upon discontinuation and/or symptomatic treatment. — Data in elderly subjects give no indication of clinically significant differences in normal daily dosages compared to younger subjects. However, upward dose titration should be done slower in the elderly, and dosing should always be done with caution, — Luvox may cause an insignificant decrease in heartbeat (2-6 beats per minute) — Due to lack of clinical experience the use of Luvox in children for the treatment of depression cannot be recommended. — There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura with SSRIs. — Caution is advised patient taking SSRIs, particularly in concomitant use with drugs known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most TCAs, acetosal, NSAIDs) as well in patient with a history of bleeding disorders.SIDE EFFECTS ‘Nausea, sometimes accompanied by vomiting, is the most frequently observed symptom associated with Luvox treatment. This side effect usually diminishes within the first two weeks of treatment. Other adverse evebts, observed in clinical studies at frequencies listed below, are often associated with the illness and are not necessarily related to treatment, commen (frequency 1-5%) Body: asthenia, headache, malaise Cardiovascular: palpitation/tachycardia Digestive system: abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia © Nervous system: agitation, anxiety, dizziness, insomnia, nervousness, somnolence, tremor © Skin: sweating Uncommon (frequency <1%) ¢ Cardiovascular: (postural) hypotension. Musculoskeletal: arthralgia, myalgia ¢ Nervous system: ataxia confusion, extrapyramidal symptoms, hallucinations * Urogenital: abnormal (delayed) ejaculation © Skin: rash, pruritus Rare (frequency <0,1%) ¢ Digestive system: liver function abnormality ‘¢ Nervous system: convulsions, mania © Urogenital: galactorrhoea Skin: photosensitivity ‘As with other SSRIs, hyponatremia has been rarely reported, and appears to be reversible when Luvox was discontinued. Some cases were possibly due to the syndrome of inappropriate anti diuretic hormone secretion. The majority of reports were associated with older patients, Haemorrhage: “see Precautions and Warnings” Incidentally, weight gain or weight loss have been reported. Withdrawal reactions, including paresthesia, headache, nausea, dizziness and anxiety, have been rarely reported after abrupt discontinuation of Luvox. These are usually mild and self-limiting, and do not necessarily imply dependence. Before stopping treatment, gradual dosage reduction may be considered. Some of the events mentioned above may be symptoms of the depressive illness and are not necessarily induced by the drug.