The CHMP has issued a question and answer document dated 18 December 2008, about the review of sertraline (Zoloft and associated names)
Questions and answers on the referral for Zoloft – Sertraline
Hard capsules and Film coated tablets – 25 mg, 50 mg, and 100 mg
Concentrate for oral solution – 20 mg/ml
The European Medicines Agency (EMEA) has completed a review of Zoloft. The Agency’s Committee for Medicinal Products for Human Use (CHMP) has concluded that there is a need to harmonise the prescribing information for Zoloft in the European Union and the European Economic Area (EEA). The review was carried out under an ‘Article 30’ referral
1.What is Zoloft?
Zoloft contains the active ingredient sertraline. Sertraline is one of a group of medicines called Selective Serotonin Re-uptake Inhibitors (SSRIs); these medicines are used to treat depression and or anxiety disorders. Zoloft can be used to treat in adults: Depression and prevention of recurrence of
depression, social anxiety disorder, post traumatic stress disorder (PTSD), panic disorder; and to treat obsessive compulsive disorder (OCD) in adults and children and adolescents, aged 6-17 years old, Zoloft can also be available in the EU and the EEA under other trade names: Tresleen, Serlain,
Lustral, Tatig, Sertraline and Besitran.
Why was Zoloft reviewed?
Zoloft is authorised in the European Union (EU) via national procedures. This has led to divergences across member states on the way the medicine can be used, as seen in the differences observed in the Summaries of Product Characteristics (SPCs), labelling and package leaflets in the countries where the product is marketed. Zoloft has been identified as needing harmonisation by the Co-ordination Group on the Mutual and Decentralised Procedures – Human (CMD(h)).
On 18 October 2007, the European Commission referred the matter to the Committee for Medicinal Products for Human Use (CHMP) in order to harmonise the marketing authorisations for Zoloft in the EU and the EEA.
What are the conclusions of the CHMP?
The CHMP, in the light of the data submitted and the scientific discussion within the Committee, was of the opinion that the SPCs, labelling and package leaflets should be harmonised across the EU. The areas harmonised include:
Panic disorder with or without agoraphobia disorder. The CHMP discussed the results of the clinical programme that indicated significant improvement in reducing the average of panic attacks.
The CHMP concluded that short-term efficacy has been demonstrated, but that concerns remain over the lack of evidence with respect to relapse. Although the safety profile of sertraline is acceptable, the CHMP implemented the section ‘Posology and Method of Administration’ of the SPC, to indicate that the need for continued treatment should be regularly evaluated.
The CHMP endorsed the harmonised indication: “Panic disorder with or without agoraphobia”.
Article 30 of Directive 2001/83/EC as amended, referral on the grounds of divergent decisions adopted by member States
Post-traumatic Stress Disorder (PTSD). The CHMP also discussed this indication.
Data from the clinical programme for the indication PTSD were submitted and the results showed that only two of the four studies demonstrated efficacy. Considering the incidence of AEs in the PTSD, CHMP agreed that the safety of sertraline in the treatment of PTSD is similar to that of major
depressive disorder (MDD) and does not present any new issues.
The CHMP endorsed the harmonised indication:
“Sertraline is indicated for the treatment of post traumatic stress disorder (PTSD)”,
The CHMP, considered the benefit/risk balance, approved the following indication:
“Sertraline is indicated for the treatment of social anxiety disorder”.
Obsessive Compulsive Disorder (OCD, in adults). The clinical programme for the indication OCD was submitted and sertraline demonstrated a modest short-term effect and no safety concerns.
Therefore the CHMP endorsed the following indication:
“Sertraline is indicated for the treatment of obsessive compulsive disorder (OCD) in adults”,
Obsessive Compulsive Disorder (OCD, in paediatric patients).In order to support the paediatric indication, one single study was submitted including children and adolescents aged 6-17. Paediatric-onset OCD shares important similarities with the adult disorder but also shows important differences.
The CHMP concluded that the safety in children and adolescents has not sufficiently been established and that a commitment to further investigate safety in paediatric patients is required in order to adopt the following indication:
“Sertraline is indicated for the treatment of obsessive compulsive disorder (OCD) in adults and paediatric patients aged 6-17 years.”
With the condition that the following text is inserted in the section 5.1 “Pharmacodynamic Properties”
of the SPC:
“Long term safety and efficacy data are lacking for this paediatric population. No data is available for children under 6 years of age.”
Depression (MDD). The CHMP considered acceptable the evidence in support of the MDD indication. Prevention of relapse and recurrence was proposed during the assessment by the CHMP. Noting that MDD is considered to be a chronic or chronic intermittent condition, the CHMP considered it unnecessary to accept this separate indication.
The CHMP adopted the following:
“Sertraline is indicated for the treatment of major depressive episodes. Prevention of recurrence of major depressive episodes”
Posology and Method of Administration
The CHMP considered the wordings proposed for this section to be acceptable.
Regarding the dosing of paediatric patients with OCD, the CHMP requested the insertion of the following wording in this section:
“Subsequent doses may be increased in case of less than desired response in 50 mg increments over a period of some weeks, as needed. The maximum dosage is 200 mg daily. However, the generally lower body weights of children compared to those of adults should be taken into consideration when increasing the dose from 50 mg. Dose changes should not occur at intervals of less than one week.”
Regarding the use of sertraline in Hepatic Insufficiency and in Renal Insufficiency, the CHMP agreed with the wording proposed by the MAH for harmonisation.
Pimozide. The CHMP endorsed the following: “Concomitant intake of pimozide is contraindicated (see section 4.5)”
Hepatic Impairment. The CHMP considered that patients with significant hepatic impairment are not strictly contraindicated with sertraline and that appropriate warnings are provided in the concerning section of the product information.
A European Commission decision on this opinion will be issued in due course.