Committee for medicinal products for human use (CHMP)

systemic concentrations.
-Update of section 5.2 of the SmPC in order to
update the elimination section of the SmPC as a
result of the submission of study E1508I0242 to
fulfil the following post authorisation measures:
PAM 13: The applicant committed to evaluate and
the conversion of the Z-enantiomer of
ospemifene to its E-enantiomer post marketing.
PAM 14: The applicant committed to evaluate the
metabolism and excretion of ospemifene and its
metabolites using the commercial ospemifene 60
mg under fed conditions in a postauthorization
study.
-Update of section 5.2 of the SmPC in order to
update the distribution section as a result of the
submission of study OSP-PF-046-N and
OSP-PF-047-N to fulfil the following post
authorisation measures:
PAM 6: The in vitro plasma protein binding data of
M-1 in the non-clinical species will be provided
post-authorisation for interspecies comparison
between non-clinical species and humans.
However the protocol should be adapted; the
Applicant is requested to investigate a
concentration range, e.g. 50 to 200 ng/mL for
M1.
PAM 7: The blood-to-plasma ratio data for
ospemifene in monkey and rat and the blood-to
plasma ratio for M-1 in rat, monkey and human
will be provided post-authorisation.
However the protocol should be adapted; the
Applicant is requested to investigate a
concentration range, e.g. 500 to 1200 ng/mL for
ospemifene and 50 to 200 ng/mL for M 1.
-Update of section 5.2 of the SmPC in order to
update the biotransformation section as a result
of the submission of study OSP-PF-041-N to fulfil
the following post authorisation measure:
PAM 9: The Applicant will provide BSEP
transporter studies post-marketing.
As a consequence, an updated RMP version 1.2 is
provided accordingly.”
Sivextro - tedizolid phosphate -
EMEA/H/C/002846/II/0009
MAH: Merck Sharp & Dohme Limited,
Rapporteur: Bruno Sepodes, PRAC Rapporteur:
Dolores Montero Corominas, “Update of sections
4.4, 4.5 and 5.2 of the SmPC based on the
completed Drug-Drug Interaction study
MK-1986-004. The Package Leaflet has been
Annex to November 2016 CHMP Agenda
EMA/CHMP/682759/2016 Page 27/43