Agotin25 mg

Agotin 25 mg 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

This compound binds to the melatoninergic receptors and the serotoninergic 5-HT2c receptor giving rise to the Melatonin Agonist and Selective Serotonin Antagonist (MASSA) concept. The melatoninergic receptors MT1 and MT2, are G protein coupled receptors and they act through decreasing cAMP and cGMP. Agotin 25 mg strongly binds to and stimulates the activity of MT1 and MT2 receptors normalizing the disturbed circadian rhythms and disrupted sleep-wake cycles. Unlike the existing antidepressants, Agotin 25 mg does not inhibit the uptake of serotonin, norepinephrine or dopamine. It inhibits 5HT-2C receptor (G protein coupled receptor which increases IP3/DAG secondary messenger system) found abundantly in the SCN, frontal cortex, hippocampus and basal ganglia involved in the mood, motor and cognitive deficits associated with depressive states. 5HT-2C receptor antagonism increases norepinephrine and dopamine levels in the frontal cortex of the brain. This action of Agotin 25 mg produces antidepressant, antianxiety and also increases slow-wave sleep which is decreased in depression. It has been observed that it can increase neurogenesis in the hippocampus and may also have neuroprotective effects (by influencing glutamate release, glucocorticoid receptor gene expression and various neurotropic factors) which might also contribute to its antidepressant effects. A study has shown that Agotin 25 mg alleviates sleep disturbances after one week of therapy and by two weeks antidepressant effects manifest. The combined actions of Agotin 25 mg at MT1, MT2, and 5HT-2C receptors can improve the disturbed circadian rhythm and abnormal sleep pattern thus produce the antidepressant effect. These unique effects suggest that it might be effective for the treatment of seasonal affective disorder like anxiety and bipolar depression.

The effective dose of Agotin 25 mg 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 Agotin 25 mg 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.

Potential interactions affecting Agotin 25 mg: Agotin 25 mg is metabolised mainly by cytochrome P450 1A2 (CYP1A2) (90%) and by CYP2C9 (10%). Medicinal products that interact with these isoenzymes may decrease or increase the bioavailability of Agotin 25 mg. Fluvoxamine, a potent CYP1A2 and moderate CYP2C9 inhibitor markedly inhibits the metabolism of Agotin 25 mg resulting in a 60-fold (range 12-412) increase of Agotin 25 mg exposure. Consequently, co-administration of Agotin 25 mg 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.

The commonly reported adverse effects in the clinical trials of Agotin 25 mg are headache, nausea and diarrhea.

For Agotin 25 mg, 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. It is not known whether Agotin 25 mg is excreted into human milk. Agotin 25 mg or its metabolites are excreted in the milk of lactating rats. Potential effects of Agotin 25 mg on the breastfeeding infant have not been established. If treatment with Agotin 25 mg is considered necessary, breastfeeding should be discontinued.

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.

There is limited experience with Agotin 25 mg overdose. During the clinical development, there were a few reports of Agotin 25 mg 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 Agotin 25 mg are known. Management of overdose should consist of treatment of clinical symptoms and routine monitoring. Medical follow-up in a specialised environment is recommended.

Store in a cool and dry place away from light. Keep out of the reach of children.

Children under 18 years: Should be given only on medical advice.Children and adolescents: Agotin 25 mg is not recommended in the treatment of depression in patients .Use in the elderly: Efficacy has not been clearly demonstrated in the elderly (65 years). Only limited clinical data is available on the use of Agotin 25 mg in elderly patients 65 years with major depressive episodes. Therefore, caution should be exercised when prescribing Agotin 25 mg to these patients.

Atypical anti-depressant drugs

This compound binds to the melatoninergic receptors and the serotoninergic 5-HT2c receptor giving rise to the Melatonin Agonist and Selective Serotonin Antagonist (MASSA) concept. The melatoninergic receptors MT1 and MT2, are G protein coupled receptors and they act through decreasing cAMP and cGMP. Agotin 25 mg strongly binds to and stimulates the activity of MT1 and MT2 receptors normalizing the disturbed circadian rhythms and disrupted sleep-wake cycles. Unlike the existing antidepressants, Agotin 25 mg does not inhibit the uptake of serotonin, norepinephrine or dopamine. It inhibits 5HT-2C receptor (G protein coupled receptor which increases IP3/DAG secondary messenger system) found abundantly in the SCN, frontal cortex, hippocampus and basal ganglia involved in the mood, motor and cognitive deficits associated with depressive states. 5HT-2C receptor antagonism increases norepinephrine and dopamine levels in the frontal cortex of the brain. This action of Agotin 25 mg produces antidepressant, antianxiety and also increases slow-wave sleep which is decreased in depression. It has been observed that it can increase neurogenesis in the hippocampus and may also have neuroprotective effects (by influencing glutamate release, glucocorticoid receptor gene expression and various neurotropic factors) which might also contribute to its antidepressant effects. A study has shown that Agotin 25 mg alleviates sleep disturbances after one week of therapy and by two weeks antidepressant effects manifest. The combined actions of Agotin 25 mg at MT1, MT2, and 5HT-2C receptors can improve the disturbed circadian rhythm and abnormal sleep pattern thus produce the antidepressant effect. These unique effects suggest that it might be effective for the treatment of seasonal affective disorder like anxiety and bipolar depression.

For Agotin 25 mg, 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. It is not known whether Agotin 25 mg is excreted into human milk. Agotin 25 mg or its metabolites are excreted in the milk of lactating rats. Potential effects of Agotin 25 mg on the breastfeeding infant have not been established. If treatment with Agotin 25 mg is considered necessary, breastfeeding should be discontinued.

Children under 18 years: Should be given only on medical advice.Children and adolescents: Agotin 25 mg is not recommended in the treatment of depression in patients .Use in the elderly: Efficacy has not been clearly demonstrated in the elderly (65 years). Only limited clinical data is available on the use of Agotin 25 mg in elderly patients 65 years with major depressive episodes. Therefore, caution should be exercised when prescribing Agotin 25 mg to these patients.