Agomelatine

Oral
Depression

Contraindicated.

May be taken with or without food.

Dementia. Elderly >75 yr. Hepatic impairment (i.e. active liver disease, cirrhosis) or serum transaminases >3 times upper limit of normal (ULN). Concomitant use w/ potent CYP1A2 inhibitors.

Patient w/ bipolar disorder, mania, hypomania, DM, non-alcoholic fatty liver disease, pre-treatment elevated transaminases, history of suicide-related events or those who exhibit significant degree of suicidal ideation. Obese and alcoholic patients, smokers. Moderate to severe renal impairment.

Significant: Suicidal thoughts and behaviour, increased liver enzymes, hepatitis, jaundice.
Nervous: Headache, migraine, insomnia, anxiety, delirium, tremor, aggression, agitation, nightmares, hallucinations, paraesthesia, restless leg syndrome, fatigue.
GI: Nausea, abdominal pain, dry mouth, dyspepsia, diarrhoea, constipation, vomiting.
Resp: Nasopharyngitis.
Musculoskeletal: Back pain.
Ophthalmologic: Blurred vision.
Dermatologic: Rash, pruritus, urticaria, eczema, hyperhidrosis.
Immunologic: Influenza.
Potentially Fatal: Hepatic failure.

This drug may cause dizziness or somnolence, if affected, do not drive or operate machinery.

Perform LFT at baseline, before dose increase, at 3, 6, 12, 24 wk of treatment, then as clinically indicated. Monitor for signs/symptoms of hepatic injury (e.g. dark urine, light coloured stools, yellow skin/eyes, unexplained fatigue, pain in the upper right abdomen).

Symptoms: Epigastralgia, fatigue, agitation, somnolence, dizziness, anxiety, tension, malaise. Management: Symptomatic treatment.

Increased exposure w/ moderate CYP1A2 inhibitors (estrogen, enoxacin, propranolol). Decreased bioavailability w/ rifampicin.
Potentially Fatal: Potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) may markedly increase agomelatine exposure.

Avoid alcohol.

Description:
Mechanism of Action: Agomelatine, a melatonin receptor (MT₁ and MT₂) agonist and serotonin (5-HT_2C) antagonist, increases norepinephrine and dopamine release in the prefrontal cortex and has no influence on the extracellular levels of serotonin. It induces a phase advance of sleep, body temp decline, and melatonin onset. It has no effect on monoamine uptake and no affinity for α or β adrenergic, cholinergic, dopaminergic, histaminergic, and benzodiazepine receptors.
Pharmacokinetics:
Absorption: Rapidly and well absorbed. Absolute bioavailability: <5%. Time to peak plasma concentration: W/in 1-2 hr.
Distribution: Plasma protein binding: Approx 95%.
Metabolism: Rapidly metabolised in the liver, mainly by CYP1A2 enzyme, and to a lesser extent by CYP2C9 and CYP2C19 enzymes.
Excretion: Mainly via urine (80%, as inactive metabolites). Plasma half-life: 1-2 hr.

Source: National Center for Biotechnology Information. PubChem Database. Agomelatine, CID=82148, https://pubchem.ncbi.nlm.nih.gov/compound/Agomelatine (accessed on Jan. 20, 2020)

Store below 30°C.

Antidepressants

N06AX22 - agomelatine ; Belongs to the class of other antidepressants.

Buckingham R (ed). Agomelatine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/04/2017.

Joint Formulary Committee. Agomelatine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/04/2017.