Risk update: Extra caution with Agomelatine


Servier lab  who markets Agomelatine in UK) recently wrote to all prescribers asking them to be more vigilant of hepatic failure. There are new reports of hepatotoxicity with Agomelatine. Several serious cases of liver damage has been reported since its marketing in 2009. Post marketing studies show cases of liver injury, including hepatic failure,elevations of liver enzymes 10 times the upper limit of normal, hepatitis and jaundice. Majority of these occurred in the first month of treatment. Pattern of damage is mainly hepatocellular . When Agomelatine was discontinued, the serum transaminases (usually) returned to normal levels. The problem may be more with higher dose ie 50 mg/day. ( 2.5% vs 1.4% when receiving 25 mg /day)

Agomelatine is  contraindicated in patients with hepatic impairment.

Practice points

1. LFT to be done before starting treatment with Agomelatine.

2.Repeat LFT at 3 , 6, 12, 24 weeks.

3. Do  as in 2 when you increase the dose. ( ie LFT at 3, 6, 12, 24 weeks after increase in dose also)

4.Clinical symptoms suggesting any liver problem- repeat LFT.

5.Any patient with increased trasaminase levels, repeat LFT with in 48 hours

6.Stop Agomelatine  immediately, if serum transaminase is 3 times normal OR if patients present with symptoms or signs 0f potential liver injury. ( Dark urine, light stools, yellow skins, pain upper right belly, new  onset/sustained fatigue)

7.Inform patients/carers of symptoms of liver injury, advise them to stop medication immediately and seek help

8. Prescribe carefully in patients with hepatic risk factors: obesity/non alcoholic liver disease, heavy alcohol intake, other medications that can damage liver, diabetes.

Summary of the letter sent to UK prescribers by Servier labs as agreed by MHRA and European Medicines Agency.

7 thoughts on “Risk update: Extra caution with Agomelatine

  1. Nice to see this warning before the launch .Many companies are lobbying it too much as very novel anti depressant.I happend to see a NRI patient who was already on this drug ,I feel it is not really so potent as it is potrayed.

  2. thanks v much Manoj.They are just launching it in Thrissur Psy Guild….and i am chairing…i shall defenitely pass on Ur important information….regs, madhavan

  3. 2 days back Sun Pharma launched it in Chennai, the speaker did not highlight this issue and just was describing that the increase in taransaminases in agomelatine was lesser than that of duloxetine (for obvious reasons). The audience had to point the severity of this problem

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