Therapeutic Indications

Agomelatine is indicated for:

Major depressive episodes

Irrespective of gender only Adults (18 - 65 years old)

Agomelatine is indicated for the treatment of major depressive episodes in adults.

For this indication, the medical literature mentions below treatments (click for details):

Treatment 1: Oral - 25 - 50 mg once daily

Contraindications

Active ingredient Agomelatine is contraindicated in the following cases:

Hepatic impairment

No gender/age discrimination

Agomelatine is contraindicated in patients with hepatic impairment.

Monitoring of liver function

Cases of liver injury, including hepatic failure (few cases were exceptionally reported with fatal outcome or liver transplantation in patients with hepatic risk factors), elevations of liver enzymes exceeding 10 times upper limit of normal, hepatitis and jaundice have been reported in patients treated with agomelatine in the post-marketing setting. Most of them occurred during the first months of treatment. The pattern of liver damage is predominantly hepatocellular with serum transaminases which usually return to normal levels on cessation of agomelatine.

Caution should be exercised before starting treatment and close surveillance should be performed throughout the treatment period in all patients, especially if hepatic injury risk factors or concomitant medicinal products associated with risk of hepatic injury are present.

Before starting treatment

Treatment with agomelatine should only be prescribed after careful consideration of benefit and risk in patients with hepatic injury risk factors e.g.:

  • obesity/overweight/non-alcoholic fatty liver disease, diabetes
  • alcohol use disorder and/or substantial alcohol intake

and in patients receiving concomitant medicinal products associated with risk of hepatic injury.
Baseline liver function tests should be undertaken in all patients and treatment should not be initiated in patients with baseline values of ALT and/or AST >3 X upper limit of normal.

Caution should be exercised when agomelatine is administered to patients with pretreatment elevated transaminases (> the upper limit of the normal ranges and ≤3 times the upper limit of the normal range).

Frequency of liver function tests

  • Before starting treatment
  • And then:
    • after around 3 weeks,
    • after around 6 weeks (end of acute phase),
    • after around 12 and 24 weeks (end of maintenance phase),
    • and thereafter when clinically indicated.
  • When increasing the dosage, liver function tests should again be performed at the same frequency as when initiating treatment.

Any patient who develops increased serum transaminases should have his/her liver function tests repeated within 48 hours.

During treatment period

Agomelatine treatment should be discontinued immediately if:

  • patient develops symptoms or signs of potential liver injury (such as dark urine, light coloured stools, yellow skin/eyes, pain in the upper right belly, sustained new-onset and unexplained fatigue).
  • the increase in serum transaminases exceeds 3 X upper limit of normal.

Following discontinuation of agomelatine therapy liver function tests should be repeated until serum transaminases return to normal.

Alcohol

No gender/age discrimination

The combination of agomelatine and alcohol is not advisable.

Pregnancy

No gender/age discrimination

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of agomelatine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of agomelatine during pregnancy.