Servier Laboratories Limited

2012-03 Changes to Valdoxan SPC (in red)

Section 4.2 (Posology…)

-         Added:

Liver function tests should be performed in all patients : at initiation of treatment, and then periodically after around three weeks, six weeks…

Section 4.4 (Special warnings…)

-         Added:

Liver function tests should be performed in all patients: at initiation of treatment and then periodically after around three weeks, six weeks…

-         Deleted:

Caution should be exercised when Valdoxan 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), preferably by laboratory tests within the first 3 weeks of treatment.

Section 4.8 (Undesirable effects)

-         Added:

Rare: hallucinations*

-         Frequency update for the following Undesirable Effects:

Uncommon :

agitation and related symptoms* (such as irritability and restlessness), aggression*, nightmares*, abnormal dreams*

Rare :

mania/hypomania*. These symptoms may also be due to the underlying disease (see section 4.4).

Uncommon :

pruritus*

-         Updated

Common: increased ALAT and/or ASAT (in clinical studies, increases >3 times the upper limit of the normal range for ALAT and/or ASAT were seen in 1.1% 1.3% of patients on agomelatine 25/50mg vs 0.7% on placebo).

Rare: hepatitis, increased  gamma-glutamyltransferase* (GGT) (>3 times the upper limit of the normal range), increased alkaline phosphatase* (>3 times the upper limit of the normal range)

* Frequency estimated from clinical trials for adverse events detected from spontaneous report

Changes to Valdoxan SPC:

- Section 7 (Marketing Authorisation Holder)

Change of address of Les Laboratoires Servier:

50, rue Carnot

92284 Suresnes cedex

France

- Section 10 (Date of revision of the text)
09/2011

Section 4.4 (Special warnings…)

– Added:

-         Caution in patients with a history of bipolar disorder

-         Caution should be exercised when Valdoxan 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), preferably by laboratory tests within the first 3 weeks of treatment.

– Reworded:

-         Caution should be exercised when prescribing Valdoxan for patients with hepatic injury risk factors e.g. obesity/overweight/non-alcoholic fatty liver disease, substantial alcohol intake or concomitant medicinal products associated with risk of hepatic injury.

Section 4.8 (Undesirable effects)

-         Added: aggression, nightmares, abnormal dreams

Frequency not known

-         Added: abdominal pain

Frequency not known

Changes to Valdoxan SPC

Section 4.4 (Special warnings…) – Added:

-         See section 4.8 (Mania/Hypomania)

-         Caution should be exercised when Valdoxan is administered to patients with obesity/overweight/non-alcoholic fatty liver disease

Section 4.6 (Fertility…) – Reformatting of the section Fertility

Section 4.8 (Undesirable effects)

-         Added: Mania/hypomania. These symptoms may also be due to the underlying disease (see section 4.4), Frequency not known

-         Reformatting + Added: Agitation and related symptoms (as irritability and restlessness)
Frequency not known

-         Added:
Frequency not known: pruritus

Section 4.9 (Overdose) - Rewording + Added: Experience with agomelatine in overdose (dose up to 2500 mg) has indicated that epigastralgia, somnolence, fatigue, agitation, anxiety, tension, dizziness, cyanosis or malaise have been reported.

One person having ingested 2450 mg agomelatine, recovered spontaneously without cardiovascular and biological abnormalities.

Section 4.1 (Therapeutic Indications) - Added: Valdoxan is indicated in adults.

Section 4.2 (Posology…) - Rewording: Paediatric population The safety and efficacy of Valdoxan in children aged below 18 years have not been established.  No data are available.

Section 4.4 (Special warnings…) - Rewording: Use in paediatric population

Section 4.5 (Interaction…) - Added: Paediatric population Interaction studies have only been performed in adults.

Section 4.6 (Fertility…) - Added: Fertility Reproduction studies in the rat and the rabbit showed no effect of agomelatine on fertility, embryofoetal development and pre- and post natal development. (see section 5.3).

Section 4.8 (Undesirable effects) - Reformatting + Added: agitation (post-marketing experience) Frequency not known.

Section 4.9 (Overdose) - Rewording + Added: Experience with agomelatine in overdose (dose up to 2500mg) has indicated limited signs and symptoms including drowsiness and epigastralgia. Patients have recovered spontaneously without cardiovascular and biological abnormalities.

Section 10 (Date of revision of the text): August 2010