Agotin is indicated for the major depressive disorder in adults especially in non-responders and intolerant to selective serotonin reuptake inhibitors (SSRIs) including prevention of relapse.
Agomelatine is a melatonergic agonist (MT 1 and MT2 receptors) and 5-HT 2C antagonist. Binding studies indicate that agomelatine has no effect on monoamine uptake and no affinity for a, (3 adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine receptors. Agomelatine resynchronises circadian rhythms in animal models of circadian rhythm disruption. Agomelatine increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin.
The effective dose of agomelatine is 25 mg per day given once at bed time for two weeks and can be increased to 50 mg per day in patients with inadequate response. Night time dosing is recommended because agomelatine improves the quality of sleep without day time sedation. For oral administration with or without food. Most adult patients should take a dosage of 25 mg (one tablet) daily. It is usually taking prior to bed time. If no improvement is noticed after two weeks, the dosage can be increased to 50 mg (two tablets) daily. Children under 18 years : Should be given only on medical advice. Use in children and adolescents : Agomelatine is not recommended in the treatment of depression in patients <18 years since safety and efficacy of agomelatine have not been established in this age group. In clinical trials among children and adolescents treated with other antidepressants, suicide-related behavior (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behavior and anger) were more frequently observed compared to those treated with placebo. Use in the elderly : The efficacy and safety of agomelatine (25 to 50 mg/day) have been established in elderly patients with MDD (aged <75 years). As efficacy has not been established in every elder patients aged >75 years agomelatine should not be used in this patient group.
Always consult a registered doctor before taking any medicine. This information is for general knowledge only.
The commonly reported adverse effects in the clinical trials of Agotin are headache, nausea and diarrhea. It is found to increase the level of liver enzymes and so monitoring of enzyme level is warranted before starting therapy and therefore every 6 weeks. It is also contraindicated in patients with hepatic impairment. A meta-analysis of the treatment emergent sexual dysfunction with antidepressants has revealed that it has no significant difference with placebo.
Hypersensitivity to the active substances or to any of the excipients. Hepatic impairment (i.e cirrhosis or active liver disease), or transaminases exceeding 3 times upper limit of normal. Concomitant use of potent CYPIA2 inhibitors (eg. Fluvoxamine, ciprofloxacin).
Agotin is metabolised mainly by cytochrome P450 1A2 (CYP1A2) (90%) and by CYP2C9/19 (10%). Medicinal products that interact with these isoenzymes may decrease or increase the bioavailability of Agotin. Fluvoxamine, a potent CYP1A2 and moderate CYP2C9 inhibitor markedly inhibits the metabolism of Agotin resulting in a 60-fold (range 12-412) increase of Agotin exposure. Consequently, co-administration of Agotin with potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) is contraindicated.
Caution should be exercised before starting treatment and close surveillance should be performed throughout the treatment period in all patients, especially if hepatic injury risk factors or concomitant medicinal products associated with risk of hepatic injury are present. Baseline liver function tests should be undertaken in all patients and treatment should not be initiated in patients with baseline values of ALT and/or AST >3 times upper limit of normal. Agotin should be used with caution in the elderly (≥75 years) due to lack of clinical data. Agotin should not be used for the treatment of major depressive episodes in elderly patients with dementia since the safety and efficacy of Agotin have not been established in these patients. Agotin is not recommended in the treatment of depression in patients under 18 years of age. Agotin should be used with caution in patients with a history of bipolar disorder, mania or hypomania.