I report down here PRAC minutes, that is a sinthesis of September’s 2018 meeting.
You can find it using the link below:
https://www.ema.europa.eu/documents/min … 018_en.pdf
4 October 2018
EMA/PRAC/675727/2018
Inspections, Human Medicines Pharmacovigilance and Committees Division
Pharmacovigilance Risk Assessment Committee (PRAC)
Minutes of the meeting on 03-06 September 2018
Chair: Sabine Straus – Vice-Chair: vacant
New signals detected from other sources
See also Annex I 14.2.
4.2.1. Clomipramine (NAP);
Serotonin and noradrenaline reuptake inhibitors (SNRI)5: desvenlafaxine (NAP);
duloxetine - ARICLAIM (CAP), CYMBALTA (CAP), DULOXETINE LILLY (CAP),
DULOXETINE MYLAN (CAP), DULOXETINE ZENTIVA (CAP), XERISTAR (CAP),
YENTREVE (CAP); milnacipran (NAP); venlafaxine (NAP);
Selective serotonin reuptake inhibitors (SSRI)6: citalopram (NAP); escitalopram
(NAP); fluoxetine (NAP); fluvoxamine (NAP); paroxetine (NAP); sertraline (NAP);
Vortioxetine – BRINTELLIX (CAP)
Applicant(s): Eli Lilly Nederland B.V. (Cymbalta, Duloxetine Lilly, Xeristar, Yentreve),
Generics UK Limited (Duloxetine Mylan), H. Lundbeck A/S (Brintellix), Zentiva k.s.
(Duloxetine Zentiva), various
PRAC Rapporteur: Menno van der Elst
Scope: Signal of persistent sexual dysfunction after drug withdrawal
EPITT 19277 – New signal
Background
Clomipramine is a non-selective monoamine reuptake inhibitor indicated, among others, for the treatment of major depressive disorder. Desvenlafaxine, duloxetine, milnacipran and venlafaxine are serotonin and noradrenaline reuptake inhibitors (SNRIs) indicated, among others, for the treatment of major depressive disorder. Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline are selective serotonin reuptake inhibitors (SSRIs) indicated, among others, for the treatment of major depressive disorder. Brintellix is a centrally authorised product containing vortioxetine, a psychoanaleptic antidepressant. It is indicated for the treatment of major depressive disorders in adults.
Cymbalta and Yentreve, centrally authorised medicines containing duloxetine, are estimated to have been used by approximately 91,636,000 patients worldwide (all indications) in the period from first authorisations in 2004 to 2017. Milnacipran capsule for major depressive episodes7 is estimated to have been used by more than 8,611,639 patients (corresponding to 15,296,991 patients-months) worldwide in the period from first authorisation in 1966 to 2018. Escitalopram (all indication) is estimated8 to have been used by approximately 402,748,747 patients worldwide in the period from first authorisation in 2001 to 2016. The exposure for fluvoxamine (all indications) is estimated9 to have been approximately 1,560,498 patient treatment years worldwide in the period from first authorisation in 1983 to 2017. Paroxetine (all indications) is estimated10 to have been used by more than 400 million patients worldwide in the period from first authorisation in 1990 to 2017. The exposure to sertraline (all indications) is estimated11 to have been approximately 146,798,100 patient-years worldwide in the period from first authorisation in 1990 to 2017. The exposure for Brintellix (vortioxetine) is estimated to have been approximately 2,429,103 patient-years worldwide in the period from first authorisation in 2013 to 2017. The exposure for fluoxetine (all indications) is estimated to have been approximately 121,620,000 patient-years worldwide in the period from first authorisation in 1986 to 2017.
Following some ongoing procedures, where some EU Member States have reviewed information on persistent sexual dysfunction for SSRIs and SNRIs, including spontaneous data in EudraVigilance (EV), recent literature and a petition from a group of professors, psychiatrists and related healthcare professionals (HCPs) concerning persistent sexual disorders with SSRIs and SNRIs, where authors refer to literature cases of genital anaesthesia, persistent genital arousal disorder (PGAD) and post-SSRI sexual dysfunctions (PSSD) and postulate changes in product information, risk minimisation measures taken by MAHs and communication to both HCPs and patients, a signal of persistent sexual dysfunction after drug withdrawal was identified by EMA. The Netherlands confirmed that the signal needed initial analysis and prioritisation by the PRAC.
Discussion
Having considered the available data, including a publication in the International Journal of Risk & Safety in Medicine by Healy D. et al.12 and 574 case reports retrieved for duloxetine in EV with relevant MedDRA HLT13, the PRAC concluded that the signal merits further investigation.
The PRAC appointed Menno van der Elst as Rapporteur for the signal.
Summary of recommendation(s)
• The Lead Member States (LMS)/Rapporteurs for the concerned active substances will review the literature referenced in the above-mentioned petition received by the Agency. In addition, EMA will perform literature reviews, EV data analysis and will explore the feasibility for a pharmacoepidemiological study. Finally, EMA in collaboration with the LMS/Rapporteurs will elaborate on appropriate case definitions for the sexual dysfunction disorders adverse drug reactions (ADRs), using read codes and MedDRA terms, to facilitate further assessments.
• A 30-day timetable was recommended for the assessment of this review leading to a further PRAC recommendation.
5 Indicated in the treatment of major depressive disorder (MDD)
6 Indicated in the treatment of major depressive disorder (MDD)
7 Ixel. Joncia, Dalcipran, Tivanyl, Savella, Toledomin, Milnacipran Pierre Fabre
8 By H. Lundbeck A/S
9 By Mylan
10 By GlaxoSmithKline Research & development
11 By Pfizer
12 Healy D, Le Noury J, Mangin D. Enduring Sexual Dysfunction after Treatment with Antidepressants, 5α-Reductase Inhibitors and Isotretinoin: 300 Cases. Int. J. Risk. Saf. Med. 2018. doi:10.3233/JRS-180744
13 Medical dictionary for regulatory activities – High level term
