Hepatic impairment (cirrhosis or active liver disease), transaminases >3 times ULN. Concomitant use with strong CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin).
Special Precautions
Patient with history of suicidal activity or ideation; mild transaminase elevation ≤3 times ULN, risk factors for hepatic injury (e.g. obesity, diabetes mellitus, excessive alcohol consumption, alcoholism); history of bipolar disorder, mania or hypomania. Smokers (particularly those who smoke ≥15 cigarettes/day). Moderate to severe renal impairment. Avoid use in elderly ≥75 years (due to lack of efficacy) or elderly with dementia (due to lack of data on safety and efficacy). Pregnancy and lactation.
Adverse Reactions
Significant: Increased hepatic enzymes >10 times ULN, hepatitis, jaundice; increased risk of suicidal thoughts and behaviour. Eye disorders: Blurred vision. Gastrointestinal disorders: Nausea, diarrhoea, constipation, abdominal pain, vomiting. General disorders and administration site conditions: Fatigue. Investigations: Increased weight. Musculoskeletal and connective tissue disorders: Back pain. Nervous system disorders: Headache, dizziness, somnolence, migraine, paraesthesia, restless legs syndrome. Psychiatric disorders: Insomnia, anxiety, abnormal dreams, nightmares, aggression, agitation. Skin and subcutaneous tissue disorders: Pruritus, eczema, hyperhidrosis, urticaria. Potentially Fatal: Hepatic failure.
Patient Counseling Information
This drug may cause dizziness and drowsiness, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor LFT at baseline, then after 3, 6, 12, and 24 weeks of therapy, and thereafter when clinically indicated; repeat monitoring at the same frequency as when initiating treatment if the dose is increased. Closely monitor for unusual changes in behaviour, clinical worsening, and suicidal thoughts or behaviour (particularly during early treatment and after dose adjustments).
May increase exposure with moderate CYP1A2 inhibitors (e.g. estrogens, propranolol, enoxacin). May decrease bioavailability with rifampicin. Potentially Fatal: Strong CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) significantly increase agomelatine exposure.
Action
Description: Mechanism of Action: Agomelatine is an agonist at melatonin (MT1 and MT2) receptors and an antagonist at serotonin (5-HT2C) receptor. It elevates norepinephrine and dopamine release, specifically in the frontal cortex, without affecting extracellular serotonin levels or monoamine reuptake. Pharmacokinetics: Absorption: Rapidly and well absorbed. Bioavailability: <5%. Time to peak plasma concentration: 1-2 hours. Distribution: Plasma protein binding: Approx 95%. Metabolism: Rapidly metabolised in the liver by CYP1A2 and to a lesser extent by CYP2C9 and CYP2C19 isoenzymes into inactive metabolites. Excretion: Mainly via urine (80%, as metabolites). Elimination half-life: 1-2 hours.
Chemical Structure
Agomelatine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 82148, Agomelatine. https://pubchem.ncbi.nlm.nih.gov/compound/Agomelatine. Accessed Sept. 24, 2024.
Sign Out
