15 September 2016
EMA/604919/2016
Compliance and Inspection
List of centrally authorised products requiring a
notification of a change for update of annexes
Parallel distributors are only required to inform the EMA of changes to the labelling or leaflet related to
any update of the annexes of marketing authorisation once a year in their annual update application,
except in cases related to safety or quality issues. The following table lists the centrally authorised
products for which the EMA requires a notification of change before implementation.
Name
EU number
Date of
Rationale
communication
Aprovel
All presentations
15/07/2016
Update of section 4.8 of the summary of product
characteristics (SmPC) to add thrombocytopenia with
the frequency not known. The package leaflet has
been updated accordingly.
Parallel distributors must use the annexes dated
24/06/2016 (PSUSA/1782/201508), which are
available on the European Commission website.
Cancidas
All presentations
15/09/2016
Update of sections 4.4, 4.8 of the SmPC in order to
add a warning on serious cutaneous reactions and to
include the new ADRs toxic epidermal necrolysis and
Stevens-Johnson Syndrome with the frequency not
known based on the post-marketing experience. The
package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
23/06/2016 (II/0061), which are available on
the Agency’s website.
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Cialis
All presentations
15/09/2016
Update of section 4.8 of the SmPC of medicinal
products containing tadalafil with erectile dysfunction
indication to update the numbers of patients taking
tadalafil and placebo, to update the numbers of
patients taking tadalafil and placebo; to add as
adverse events: nausea, fatigue, vomiting, and
oedema peripheral, with an uncommon frequency; to
update the frequency of the following adverse events:
gastro-oesophageal reflux (from common to
uncommon), hyperhidrosis, penile haemorrhage and
haematospermia (from uncommon to rare); to add a
footnote on seizures and to delete a footnote on
priapism; to add data regarding diarrhoea in elderly
patients, in subsection other special population. The
package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
22/07/2016 (PSUSA/2841/201510), which are
available on the Agency’s website.
Conbriza
All presentations
15/08/2016
Update of section 4.8 of the SmPC to move the
adverse reactions visual acuity reduced, blurred
vision, photopsia, visual field defect, visual
impairment, dry eye, eyelid oedema, blepharospasm,
eye pain and eye swelling to the tabulated list of
adverse reactions under vision disorders/ocular events
with a frequency unknown. The package leaflet is
updated accordingly.
Parallel distributors must use the annexes dated
22/07/2016 (PSUSA/0302/201510), which are
available on the European Commission website.
Cubicin
All presentations
15/07/2016
Update of section 4.8 of the SmPC to add the adverse
reaction acute generalized exanthematous pustulosis
with a frequency not known. The package leaflet was
updated accordingly.
Parallel distributors must use the annexes dated
24/06/2016 (PSUSA/ 931/201509), which are
available on the European Commission website.
List of centrally authorised products requiring a notification of a change for update of
annexes
EMA/604919/2016
Page 2/9
Exjade
All presentations
15/08/2016
Update of section 4.4 to revise the wording related to
the warning on Toxic Epidermal Necrolysis (TEN); and
update of section 4.8 of the SmPC to add the adverse
reactions acute pancreatitis under gastrointestinal
disorders SOC, and TEN under skin and subcutaneous
tissue disorders SOC, both with a frequency not
known. Section paediatric population on section 4.8 of
the SmPC should be also updated given the warning
of acute pancreatitis reported in children and
adolescents. The package leaflet is updated
accordingly.
Parallel distributors must use the annexes dated
15/07/2016 (PSUSA/939/201510), which are
available on the European Commission website.
Granupas
All presentations
15/08/2016
Update of sections 4.4 and 4.8 of the SmPC to include
a warning and a description, respectively, of an
increased risk of hypothyroidism in HIV co-infected
patients treated with a regimen including paraaminosalicylic acid and ethionamide/propionamide.
The package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
22/07/2016 (PSUSA/10171/201510), which are
available on the European Commission website.
Halaven
All presentations
15/09/2016
Update of section 4.8 of the SmPC to add the adverse
reactions Stevens-Johnson syndrome and toxic
epidermal necrolysis with a frequency not known. The
package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
16/08/2016 (PSUSA/1254/201511), which are
available on the Agency’s website.
Harvoni
All presentations
15/08/2016
Update of section 4.8 of the SmPC to add the adverse
reaction rash with a frequency common. The package
leaflet is updated accordingly.
Parallel distributors must use the annexes dated
22/07/2016 (PSUSA/10306/201510), which are
available on the Agency’s website.
Irbesartan
Zentiva
All presentations
15/07/2016
Update of section 4.8 of the SmPC to add
thrombocytopenia with the frequency not known. The
package leaflet has been updated accordingly.
Parallel distributors must use the annexes dated
21/06/2016 (PSUSA/1782/201508), which are
available on the European Commission website.
List of centrally authorised products requiring a notification of a change for update of
annexes
EMA/604919/2016
Page 3/9
Jakavi
All presentations
15/09/2016
Update of sections 4.2 and 4.5 of the SmPC in order
to include information that the concomitant use of
Jakavi with fluconazole doses greater than 200 mg
daily should be avoided.
Parallel distributors must use the annexes dated
29/07/2016 (II/0025), which are available on
the Agency’s website.
Jardiance
All presentations
15/08/2016
Update of section 4.8 of the SmPC to add the adverse
reactions blood creatinine increased and glomerular
filtration rate decreased with a frequency uncommon.
The package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
15/07/2016 (PSUSA/10388/201510), which are
available on the European Commission website.
Kaletra
All presentations
15/09/2016
Update of sections 4.3 and 4.5 to add information
regarding the interaction of Lopinavir/ritonavir and
dronedarone. In addition, sections 4.3, 4.4 and 4.5
have been updated to include information regarding
the contraindication with colchicine in patients with
renal or hepatic impairment and in patients with
normal renal or hepatic function if strong CYP3A4inhibitor (such as ritonavir-boosted PI) is
coadministered. The package leaflet is updated
accordingly..
Parallel distributors must use the annexes dated
18/08/2016 (II/158), which are available on
the European Commission website.
Karvea
All presentations
15/07/2016
Update of section 4.8 of the SmPC to add
thrombocytopenia with the frequency not known. The
package leaflet has been updated accordingly.
Parallel distributors must use the annexes dated
21/06/2016 (PSUSA/1782/201508), which are
available on the Agency’s website.
List of centrally authorised products requiring a notification of a change for update of
annexes
EMA/604919/2016
Page 4/9
Ketoconazole
HRA
All presentations
15/09/2016
Update of section 4.5 of the SmPC to update the table
1. Interactions and recommendations for coadministration. In addition, section 4.3 is updated to
include the contraindication with the direct-acting
antiviral (DAAV) combination of ombitasvirparitaprevir-ritonavir. The pckage leaflet is updated
accordingly.
Parallel distributors must use the annexes dated
31/08/2016 (PSUSA/10316/201511), which are
available on the European Commission website.
Lemtrada
All presentations
15/07/2016
To update the product information to include
listeriosis/listeria meningitis and bradycardia as an
infusion related adverse reaction” in sections 4.4. The
package leaflet was updated accordingly.
Parallel distributors must use the annexes dated
21/06/2016 (PSUSA/10055/201509), which are
available on the European Commission website.
Mekinist
All presentations
15/09/2016
Update to the existing SmPC 4.4 warnings on left
ventricular ejection fraction (LVEF) reduction / left
ventricular dysfunction, and update of section 4.8 of
the SmPC to add the adverse reaction myocarditis
with a frequency unknown for trametinib and
dabrafenib combination therapy. The package leaflet
is updated accordingly.
Parallel distributors must use the annexes dated
16/08/2016 (PSUSA/10262/201511), which are
available on the European Commission website.
Noxafil
All presentations
15/09/2016
Update of section 4.2 of the SmPC in order to
strengthen the information about noninterchangeability of the oral formulations based on
new reports of medication errors related to confusion
between posaconazole tablets and oral suspension in
prescribing. Changes in the blister labelling packaging
for the tablets have been introduced to further
address the reduction of potential medication errors
with the product. The package leaflet and the labelling
have been updated accordingly.
Parallel distributors must use the annexes dated
22/07/2016 (II/0044), which are available on
the Agency’s website.
List of centrally authorised products requiring a notification of a change for update of
annexes
EMA/604919/2016
Page 5/9
Ofev
All presentations
15/09/2016
Update of section 4.8 of the SmPC to add bleeding
and to delete epistaxis under the vascular disorders
SOC with a frequency common; and to add
pancreatitis under the gastrointestinal disorders SOC
with a frequency uncommon. The package leaflet is
updated accordingly.
Parallel distributors must use the annexes dated
22/07/2016 (PSUSA/00010319/201510), which
are available on the European Commission
website.
Olysio
All presentations
15/09/2016
Update of section 4.8 of the SmPC to add information
about hepatic failure symptoms in patients at risk of
hepatic decompensation and failure with the use
of simeprevir.
Parallel distributors must use the annexes dated
18/08/2016 (PSUSA/10255/201511), which are
available on the European Commission website.
Otezla
All presentations
15/07/2016
Update of section 4.8 of the SmPC to add
gastrointestinal haemorrhage. The package leaflet is
updated accordingly.
Parallel distributors must use the annexes dated
08/07/2016 (PSUSA/10338/201509), which are
available on the European Commission website.
Plenadren
All presentations
15/07/2016
Update of sections 4.4 and 4.8 of the SmPC in order
to add acute adrenocortical insufficiency as a new
ADR. The package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
25/05/2016 (II/0021), which are available on
the Agency’s website.
Privigen
All presentations
15/09/2016
Update of sections 4.4, 4.8 and 5.1 of the SmPC in
order to include the results of an immune
thrombocytopenia study with a consequential update
of the safety information particularly to amend the
existing information on haemolysis and to include
transfusion-related acute lung injury (TRALI). The
package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
28/04/2016 (II/0010), which are available on
the Agency’s website.
List of centrally authorised products requiring a notification of a change for update of
annexes
EMA/604919/2016
Page 6/9
Renagel
All presentations
15/09/2016
Update of section 4.4 of the SmPC to add a warning
regarding gastrointestinal disorders associated with
sevelamer crystals.
Parallel distributors must use the annexes dated
31/08/2016 (PSUSA/2697/201510), which are
available on the Agency’s website.
Renvela
All presentations
15/09/2016
Update of section 4.4 of the SmPC to add a warning
regarding gastrointestinal disorders associated with
sevelamer crystals.
Parallel distributors must use the annexes dated
25/08/2016 (PSUSA/2697/201510), which are
available on the Agency’s website.
Sevelamer
carbonate
Zentiva
All presentations
15/09/2016
Update of section 4.4 of the SmPC to add a warning
regarding gastrointestinal disorders associated with
sevelamer crystals.
Parallel distributors must use the annexes dated
18/08/2016 (PSUSA/2697/201510), which are
available on the Agency’s website.
Synjardy
All presentations
15/08/2016
Update of section 4.8 of the SmPC to add the adverse
reactions blood creatinine increased and glomerular
filtration rate decreased with a frequency uncommon.
The package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
15/07/2016 (PSUSA/10388/201510), which are
available on the Agency’s website.
Tasermity
All presentations
15/09/2016
Update of section 4.4 of the SmPC to add a warning
regarding gastrointestinal disorders associated with
sevelamer crystals.
Parallel distributors must use the annexes dated
25/08/2016 (PSUSA/2697/201510), which are
available on the European Commission website.
Thalidomide
Celgene
All presentations
15/08/2016
Update of sections 4.4 and 4.8 of the SmPC to include
warnings on viral reactivation and pulmonary
hypertension and to reflect the case reports
associated with treatment with thalidomide. The
package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
15/07/2016 (PSUSA/2919/201510), which are
available on the European Commission website.
List of centrally authorised products requiring a notification of a change for update of
annexes
EMA/604919/2016
Page 7/9
Vargatef
All presentations
15/09/2016
Update of section 4.4 and 4.8 of the SmPC to add a
warning on gamma-glutamyltransferase increased,
and to add the adverse reaction gammaglutamyltransferase increased with a frequency
common. The package leaflet is updated accordingly.
Parallel distributors must use the annexes dated
18/08/2016 (PSUSA/10318/201511), which are
available on the European Commission website.
Zoledronic acid
medac
All presentations
15/08/2016
Update of section 4.8 of the SmPC to add acquired
Fanconi syndrome as adverse reaction with the
frequency rare. The package leaflet has been updated
accordingly.
Parallel distributors must use the annexes dated
29/06/2016 (PSUSA/3149/201508), which are
available on the European Commission website.
List of centrally authorised products requiring a notification of a change for update of
annexes
EMA/604919/2016
Page 8/9
Index:
Aprovel, .................................................... 1
Cancidas, .................................................. 1
Cialis, ....................................................... 2
Conbriza, .................................................. 2
Cubicin, .................................................... 2
Exjade, ..................................................... 3
Granupas, ................................................. 3
Halaven, ................................................... 3
Harvoni, ................................................... 3
Irbesartan Zentiva, .................................... 3
Jakavi, ...................................................... 4
Jardiance, ................................................. 4
Kaletra, .................................................... 4
Karvea, ..................................................... 4
Ketoconazole HRA, ..................................... 5
Lemtrada, ................................................. 5
Mekinist, ................................................... 5
Noxafil, ..................................................... 5
Ofev, ........................................................ 6
Olysio, ...................................................... 6
Otezla, ..................................................... 6
Plenadren, ................................................ 6
Privigen, ................................................... 6
Renagel, ................................................... 7
Renvela, ................................................... 7
Synjardy, .................................................. 7
Tasermity, ................................................ 7
Thalidomide Celgene, ................................. 7
Vargatef, .................................................. 8
Zoledronic acid medac, ............................... 8
List of centrally authorised products requiring a notification of a change for update of
annexes
EMA/604919/2016
Page 9/9