Agomelatine is indicated for: Major depressive disorder especially in non-responders and intolerant to SSRIs, Generalized anxiety disorder, Bipolar depression, Sleep disturbances, Seasonal affective disorder, Migraine and cluster headaches.
Atypical anti-depressant drugs
Agomelatine is a melatonergic agonist (MT1 and MT2 receptors) and 5-HT2C 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.
Agomelatine 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 agomelatine. Fluvoxamine, a potent CYP1A2 and moderate CYP2C9 inhibitor markedly inhibits the metabolism of agomelatine resulting in a 60-fold (range 12-412) increase of agomelatine exposure. Consequently, co-administration of agomelatine with potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) is contraindicated.
It is contraindicated in patients with hepatic impairment and hypersensitivity to the active substances or any of the excipients. 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.
The commonly reported adverse effects in the clinical trials of agomelatine are headache, nausea and diarrhea.
Use in pregnancy: For agomelatine, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see Toxicology: Preclinical Safety Data under Actions). Caution should be exercised when prescribing to pregnant women. Use in lactation: It is not known whether Agomelatine is excreted into human milk. agomelatine or its metabolites are excreted in the milk of lactating rats. Potential effects of agomelatine on the breastfeeding infant have not been established. If treatment with agomelatine is considered necessary, breastfeeding should be discontinued.
There is limited experience with agomelatine overdose. During the clinical development, there were a few reports of agomelatine overdose, taken alone (up to 450 mg) or in combination (up to 525 mg) with other psychotropic medicinal products. Signs and symptoms of overdose were limited and included drowsiness and epigastralgia. No specific antidotes for agomelatine are known. Management of overdose should consist of treatment of clinical symptoms and routine monitoring. Medical follow-up in a specialised environment is recommended.
To be dispensed only on the prescription of a registered physician. Store below 30°C, in a cool and dry place. Keep away from light. Keep out of the reach of children.
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