Products
Agomelatine is commercially available in the form of film-coated tablets (Valdoxan, generic). It was approved in the EU in 2009 and in many countries in 2010.
Structure and properties
Agomelatine (C15H17NO2, Mr = 243.30 g/mol) exists as a white powder that is practically insoluble in water. It is a naphthalene analog of the epiphyseal and sleep hormone melatonin, which is itself derived from serotonin.
Effects
Agomelatine (ATC N06AX22) has antidepressant and sleep-inducing properties. It normalizes circadian rhythms, which may be disrupted in depression. The effects are due, on the one hand, to high-affinity agonism at MT1– and MT2–melatonin receptors. On the other hand, it is an antagonist at serotonin-5-HT2C receptors. Agomelatine has a short half-life of 1-2 hours.
Indications
For the treatment of depressive episodes in adults and for subsequent maintenance therapy.
Dosage
According to the drug label. The drug is taken once daily in the evening, independent of meals.
Contraindications
- Hypersensitivity
- Impaired liver function or transaminase elevation more than 3 times the upper normal limit
- Concurrent use of strong CYP1A2 inhibitors, such as fluvoxamine and ciprofloxacin.
Liver function tests must be performed before and during treatment. Full precautions can be found in the drug label.
Interactions
Agomelatine is metabolized primarily by CYP1A2 (90%) and by CYP2C9 / CYP2C19 (10%). Strong inhibitors of CYP1A2 such as fluvoxamine and ciprofloxacin can significantly increase concentrations of agomelatine and are contraindicated. Moderate-strength inhibitors may result in a moderate increase in agomelatin concentrations and should be used with caution. Combination of agomelatine with alcohol is not recommended.
Adverse effects
The most common adverse effects include fatigue, drowsiness, insomnia, headache, migraine, dizziness, anxiety, nausea, diarrhea, constipation, upper abdominal pain, increased sweating, back pain, and elevated liver enzymes. Rarely, cases of liver injury have been reported.
