ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Panretin 0.1 % gel
2.
1 g of gel contains 1 mg alitretinoin (0.1%).
For a full list of excipients, see section 6.1.
3.
Gel.
Clear yellow gel.
4.
Panretin gel is indicated for the topical treatment of cutaneous lesions in patients with AIDS-related
Kaposi’s sarcoma (KS) when:
-
lesions are not ulcerated or lymphoedematous, and
-
treatment of visceral KS is not required, and
-
lesions are not responding to systemic antiretroviral therapy, and
-
radiotherapy or chemotherapy are not appropriate
Posology
Panretin therapy should only be initiated and maintained by specialist physicians experienced in the
treatment of patients with KS.
Men
Patients should apply Panretin to cutaneous KS lesions using sufficient gel so as to cover each lesion
with a generous coating.
Frequency of application
Patients should initially apply Panretin twice a day to cutaneous KS lesions. The application frequency
can be increased stepwise to three or four times a day according to individual lesion tolerance,
allowing no less than two weeks between dose increases. The frequency of application should be
adjusted for each lesion independently. If application site toxicity occurs, the application frequency
can be reduced as described below. There are no data on the efficacy of Panretin applied less
frequently than twice daily.
Local dermal irritation may be graded according to the five-point scale shown in
Table 1
. Guidelines
for treatment adjustments necessitated by local dermal treatment-related toxicity are specified in
Table 2
.
Table 1: Grading of local dermal irritation
2
GRADE
DEFINING CLINICAL SIGNS
0 = No reaction
None
1 = Mild
Definite pink to red coloration
2 = Moderate
Increased redness, possible oedema
3 = Severe
Very red, with oedema, with or without vesiculation
4 = Very severe
Deep red, swelling and oedema with or without signs of bullae formation
and necrosis
Table 2: Adjustment guidelines for treatment-limiting toxicity
LOCAL DERMAL IRRITATION
(Graded per Table 1)
TREATMENT ADJUSTMENTS
Grade 0, 1 or 2
No action required except continued monitoring.
Grade 3
Treatment frequency for that lesion should be reduced or
suspended. When dermal irritation improves to Grade 0 or 1,
treatment may be restarted at twice daily, increasing every two
weeks as tolerated.
Grade 4
As for Grade 3 irritation. However, treatment should not be
restarted if Grade 4 toxicity occurred at an application
frequency of less than twice a day.
Duration of application
It is recommended that Panretin should be applied to lesions for an initial period of up to 12 weeks.
Treatment of lesions that have not shown a decrease in area and/or height by week 12 should be
discontinued.
For those lesions that have shown a decrease in height and/or area by week 12, applications may be
continued providing that there is continued improvement or at least maintenance of the response and
that the product continues to be tolerated.
Treatment of any lesion that has fully resolved on clinical assessment should be discontinued.
Precautions to be taken before handling or administering the medicinal product
Patients should wash their hands before and after applications; it is not necessary to wear gloves.
The gel must be allowed to dry for three to five minutes before covering with clothing. Occlusive
dressings should be avoided.
Care must be taken to avoid application of the gel to normal skin surrounding the lesions.
Gel should not be applied on or near eyes or mucosal surfaces of the body. Showering, bathing, or
swimming for at least three hours after any application should be avoided.
Women
Safety and effectiveness in women have not been established because of the paucity of clinical data.
AIDS-related Kaposi’s sarcoma is infrequent in women.
Paediatric population
The safety and efficacy of Panretin gel in children under 18 years has not been established.
No data are available.
Panretin is not approved for use in children and adolescents under 18 years of age.
Elderly men
There are no specific recommendations for use in elderly men (above 65 years of age). AIDS-related
Kaposi’s sarcoma is infrequent in this population.
Renal or hepatic impairment
3
There are no data regarding the use of Panretin gel in patients with renal insufficiency or liver disease.
Pharmacokinetic studies indicate that the range and frequency of detection of quantifiable 9-
cis
-
retinoic acid plasma concentrations in patients with KS after application of the medicinal product were
comparable to the range and frequency of detection of quantifiable plasma concentrations of
circulating, naturally-occurring 9-
cis
-retinoic acid in untreated individuals (see section 5.2). On a
theoretical basis, no dose adjustment is necessary in patients with renal insufficiency or liver disease,
but these patients should be closely monitored and treatment frequency reduced, or withdrawn, if they
experience adverse effects.
•
Hypersensitivity to retinoids in general, to alitretinoin or to any of the excipients.
•
Pregnancy and breast-feeding (see section 4.6).
•
Treatment of KS lesions in close proximity to other skin disorders.
Retinoids as a class have been associated with photosensitivity. There were no reports of
photosensitivity associated with the use of Panretin gel in the clinical studies. However, patients must
be cautioned to minimise exposure of treated areas to sunlight or other ultraviolet (UV) light. (see
section 5.3).
It is recommended that daily dietary intake of vitamin A should not exceed the Recommended Dietary
Intake value.
Alitretinoin may cause harm to the foetus. Women of child-bearing potential must use a reliable form
of contraception during treatment with Panretin gel (see section 4.6) and until one month after
cessation of treatment.
The use of other topical products on Panretin treated KS lesions should be avoided. Mineral oil may be
used between Panretin applications in order to help prevent excessive dryness or itching. However,
mineral oil should not be applied for at least two hours before or after the application of Panretin.
It is not recommended for patients to apply Panretin gel concurrently with products that contain
N,N
-
diethyl-
m
-toluamide (DEET ), a common component of insect repellent products. Animal toxicology
studies showed increased DEET toxicity when DEET was included as part of the formulation.
The range and frequency of detection of quantifiable plasma 9-
cis
-retinoic acid concentrations in
patients with KS applying the medicinal product to up to 64 lesions were comparable to respective
values in untreated patients. Therefore, there is a low potential for interactions with systemic
medicinal products.
There was no clinical evidence in the vehicle-controlled studies of interactions with systemic
antiretroviral agents, including protease inhibitors; macrolide antibiotics and azole antifungals. While
no data are available, it is possible that co-administration of medicinal products which induce CYP
isozymes may reduce circulating levels of alitretinoin, with a possible negative effect on the efficacy
of Panretin gel.
4.6
Women of child-bearing potential
4
Women of child-bearing potential must use effective contraception during, and up to one month after
cessation of treatment.
Men using Panretin should take precautions to ensure that their female partners do not become pregnant.
Pregnancy
Panretin is contraindicated (see section 4.3) in pregnancy, as alitretinoin may cause foetal harm when
administered systemically to a pregnant woman. In rabbits, alitretinoin was shown to be teratogenic at a
dose which resulted in plasma concentrations about 60 times the highest observed plasma concentration in
male patients with KS following topical application of the gel. However, it is not currently certain to what
extent topical treatment with Panretin gel would increase 9-
cis
-retinoic acid plasma concentrations, in
women with KS above naturally occurring levels; therefore, alitretinoin should not be used in pregnant
women.
Breast-feeding
It is not known whether this medicinal product is excreted in human milk. Based on the plasma
concentrations observed in patients, milk concentrations of 9-
cis
-retinoic acid probably pose a low risk
for the infant. However, because of the potential for undesirable effects from Panretin gel in infants
being breast-fed, mothers must discontinue breast-feeding prior to using the medicinal product and not
initiate breast-feeding while using the medicinal product.
Care should be taken not to bring the neonate into skin contact with areas to which Panretin has been
recently applied. It is recommended that HIV-infected mothers do not breast-feed their children to exclude
the risk of transmission of the virus.
Fertility
No specific studies on fertility have been conducted in men or women. However, alitretinoin is teratogenic
so both men and women should take adequate precautions to avoid female partners becoming pregnant.
4.7
Panretin gel is for cutaneous use and is unlikely to have an effect on one’s ability to drive or operate
machines.
4.8
Adverse events associated with the use of Panretin gel in AIDS-related KS occurred almost
exclusively at the site of application. The dermal toxicity typically begins as erythema; with continued
application of Panretin gel erythema may increase and oedema may develop. Dermal toxicity may
become treatment-limiting, with intense erythema, oedema, and vesiculation. When applying Panretin
gel, 69.1% of patients experienced adverse drug reactions at the application site.
The following application-site drug-related adverse reactions were reported during clinical studies in
patients with KS. The frequency of adverse events are classified as very common (≥1/10), common
(≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), and very rare
(<1/10,000). Adverse events include verbatim terms in parentheses.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Blood and lymphatic system disorders
Uncommon:
Lymphadenopathy
5
Nervous system disorders
Common:
Paraesthesia (stinging, tingling)
Vascular disorders
Common:
Haemorrhage (bleeding at or around lesions), Oedema (oedema, swelling,
inflammation), Peripheral oedema
Uncommon:
Phlebitis, Vascular disorder
Skin and subcutaneous tissue disorders
Very common: Skin disorder (cracking, scab, crusting, excoriation, drainage, oozing), Rash
(erythema, redness, scaling, irritation, dermatitis), Pruritus (itching, pruritus)
Common:
Skin ulcer, Serous drainage, Exfoliative dermatitis (flaking, peeling, desquamation,
exfoliation), Skin discoloration (brown discoloration, surrounding
hyperpigmentation, paler), Dry skin
Uncommon:
Cellulitis, Vesiculobullous rash, Maculopapular rash, Allergic reaction
General disorders and administration site conditions
Very common: Pain (burning, pain, soreness)
Uncommon:
Infection, including bacterial infection
The safety of Panretin gel has been assessed in clinical studies of more than 469 patients with AIDS-
related KS, 439 of whom were treated with an alitretinoin concentration of 0.1%.
The incidence of drug-related skin disorder, skin ulcer, pain and rash appeared to be greater in patients
applying Panretin gel four times daily than in those applying it less frequently. However, the incidence
of other equally common drug-related adverse events such as pruritus, oedema, exfoliative dermatitis
and dry skin did not appear to increase as a function of the frequency of application.
The incidence of mild/moderate rash (all events regardless of causality) was less in patients treated for
less than 16 weeks than in those treated for 16 weeks or more (mild, 33% v 63%; moderate, 29% v
43%). The incidence of severe skin rash was independent of the duration of treatment (10% in both
cases).
Local dermal toxicity associated with Panretin gel therapy generally resolved with treatment
adjustment or discontinuation (see section 4.2).
Only two serious adverse reactions were reported (sepsis and cellulitis in the same patient).
The adverse events seen with Panretin gel are similar to those seen with other topical retinoids. It is
unlikely that the undesirable systemic side effects associated with oral retinoids will be observed with
the use of Panretin gel because the range and frequency of quantifiable 9-
cis
-retinoic acid plasma
levels concentrations after application of the medicinal product were comparable to the range and
frequency of quantifiable plasma concentrations of circulating, naturally occurring 9-
cis
-retinoic acid
in untreated individuals.
No case of overdose has been reported.
Systemic toxicity following acute overdose with topical application of Panretin gel is unlikely.
5.
5.1 Pharmacodynamic properties
6
Pharmacotherapeutic group: other antineoplastic agents, ATC code: LO1XX22
Although the molecular action of alitretinoin is thought to be mediated through interaction with the
retinoid receptors, the exact mechanism of action of this medicinal product in the topical treatment of
cutaneous lesions of AIDS-related KS is unknown. Alitretinoin (9-
cis
-retinoic acid), a naturally-
occurring endogenous hormone related to vitamin A, binds to and activates all known intracellular
retinoid receptor subtypes (RARα, RARβ, RARγ, RXRα, RXRβ, RXRγ). Once activated, these
receptors function as ligand dependent transcription factors that regulate the expression of specific
genes. The regulation of gene expression by alitretinoin controls the process of cellular differentiation
and proliferation in both normal and neoplastic cells. The efficacy of Panretin gel in treating KS
lesions may be related to the demonstrated ability of alitretinoin to inhibit the
in vitro
growth of KS
cells.
Panretin gel can be expected to have local therapeutic effects only and it has no role in the prevention
or treatment of visceral KS.
Two controlled, multicentre, randomised, double blind parallel group, Phase III studies provided the
data for Panretin gel in the treatment of index cutaneous lesions of KS (Table 3). The patient response
rate was evaluated using the AIDS Clinical Trials Group (ACTG) criteria for lesion response in KS.
Study 1 included an open-label phase, in which patients themselves elected to enrol. Study 2 was
followed by an open label study (Study 2a), which included only patients electing to continue from
Study 2.
Table 3: Best response according to ACTG criteria for vehicle controlled phase
Study 1 (
TID, QID)
1
Study 2
(BD)
2
Panretin
N= 134
Vehicle
N=134
Panretin
N=62
Vehicle
N=72
Clinical Complete
Response (CCR) %
0.7
0.0
1.6
0.0
Partial Response (PR) %
34.3
17.9
35.5
6.9
Stable Disease %
50.0
59.0
43.5
58.3
Progressive Disease %
14.9
23.1
19.4
34.7
37.1 6.9
p= 0.00003
1.
Protocol-specified dose regimen was application three times a day (TID) escalating to four times a day
(QID) after two weeks, with downward adjustments for toxicity
2.
Protocol-specified dose regimen was application twice a day (BD) only, with downward adjustments for
toxicity
35.1
17.9
p=0.002
In the open label phase of Study 1 (N = 184), the overall response rate increased to 66.7%. In Study 2a
(N = 99), the overall response rate increased to 56.1%.
In study 1, of 110 responding patients, 36 (33%) relapsed, while all but four still being on active
treatment.
Response rates were analysed both by the patient as the unit of analysis and by the lesion.
Table 4
provides the individual lesion response rates for patients being treated with Panretin gel in the Phase
III studies.
7
Overall Response %
Table 4: Index/indicator lesion
1
responses within patients during the first 12 weeks on study in
initial blinded phase
Patients with given number of index/indicator lesion responses (CCR or PR)
Study 1
Study 2
Number of
Responding
Panretin
(N=134)
Vehicle (N=134)
Panretin
(N=62)
Vehicle (N=72)
Lesions
2,3
N %
4
N %
4
N %
4
N %
4
At Least One
73 (54.5%)
42 (31.3%)
33 (53.2%)
21 (29.2%)
At Least Four
27 (20.1%)
8 (6.0%)
8 (12.9%)
2 (2.8%)
1.
Study 1, 6 index lesions; Study 2, up to 8 index lesions
2.
Each index lesion assessed individually for response.
3.
Lesions responding during the first 12 weeks on study, initial blinded phase, confirmed over at least four
study weeks (confirmation of response may have occurred after 12 weeks for some lesions in Study 1).
4.
Percentages calculated as number of patients with responding lesions divided by total number of patients
in the initial blinded phase.
In one trial, 29% of the lesions that had reached a partial response (PR) but had not attained clinical
complete response (CCR) within the first 12 weeks of treatment developed a CCR during continuing
treatment beyond 12 weeks. The projected time for lesions that were in partial response (PR) to later
attain clinical complete response (CCR) was 168 days. It is recommended that Panretin gel should be
applied for an initial treatment period of up to 12 weeks. In lesions that have responded to treatment
during this time, application may be continued provided that the response improves or is maintained
and the product continues to be tolerated. If a complete response of a lesion occurs, no further
application of Panretin gel should be made to the responding lesion.
There are no data regarding the efficacy of Panretin gel when applied to complicated lesions (e.g.,
when lymphoedema is present).
5.2
Pharmacokinetic properties
Plasma concentrations of 9-
cis
-retinoic acid were evaluated during clinical studies in patients with
cutaneous lesions of AIDS-related KS after repeated multiple-daily dose application of Panretin gel
for up to 60 weeks. A subset of these patients were followed during treatment of up to 64 lesions
(range 4-64, median 11.5 lesions) for up to 44 weeks (range 2-44, median 15 weeks). In this latter
group, the range and frequency of detection of quantifiable 9-
cis
-retinoic acid plasma concentrations
in patients with KS after application of the medicinal product were comparable to the range and
frequency of detection of quantifiable plasma concentrations of circulating, naturally-occurring 9-
cis
-
retinoic acid in untreated individuals.
5.3
Preclinical safety data
Toxicology
Three doses of alitretinoin (0.01%, 0.05%, or 0.5%) in a topical gel formulation were given to rats in a
28-day dermal toxicology study. Observed effects at the application site included erythema, epidermal
thickening, scaling and loosening of the stratum corneum. Clinical pathology evaluations revealed
significant increases in absolute polymorphonuclear leukocyte counts, monocyte counts, percentage of
monocytes and decreases in percentage of lymphocyte differential white blood cell counts on day 29
of rats treated with alitretinoin 0.5% gel. Clinical chemistry evaluations revealed biologically relevant
significant increases in the mean BUN and alkaline phosphatase values in females after the 28-day
treatment. Serum LDL was increased in both male and female groups at Day 29. There were no
biologically relevant haematology differences or serum chemistry differences after the 14-day period.
Observed increases in mean heart-to-final body weight differences were attributed principally to the
difference in the terminal body weights. Following treatment with alitretinoin 0.5% gel, mean plasma
concentrations in the female rats were generally below the lower limit of quantitation (5 nMol) and
8
mean plasma concentrations in the male rats were about 200 nMol. In contrast to these findings in rats,
plasma concentrations of 9-
cis
-retinoic acid in patients with KS applying Panretin gel never exceeded
0.638 ng/ml (2.13 nMol). This level is about 1/100 the mean concentration measured in male rats.
Genotoxicity
Alitretinoin was studied for genotoxic potential using the Ames test, the
in vivo
mouse micronucleus
assay, the chromosomal aberration test in human lymphocytes, and the CHO cell mutation test. The
medicinal product was not genotoxic.
Carcinogenesis, mutagenesis, impairment of fertility
Studies have not been performed to determine the carcinogenic potential of alitretinoin. However, the
mutagenic potential has been evaluated, and alitretinoin has tested negative in the Ames test, the
in vivo
mouse micronucleus assay, the chromosomal aberration test in human lymphocytes, and the
CHO cell mutation test.
Teratogenicity
In an oral dose-ranging study in rabbits, alitretinoin induced gross malformations at a dose 35 times
the topical human dose. This dose in rabbits resulted in plasma concentrations more than 60 times the
highest observed plasma concentration in patients with KS following topical application of Panretin
gel. No gross malformations were observed following oral administration to rabbits of doses 12 times
the human topical dose (which resulted in plasma concentrations 60 times the highest observed plasma
concentration in patients with KS following topical application of the gel). However, an increased rate
of fused sternebrae was observed.
Phototoxicity
The phototoxicity potential of alitretinoin was assessed based on its chemical properties and data from
a battery of
in vitro
tests. The results suggest that alitretinoin absorbs light in the UV range and is
subject to photodegradation to other isomers (predominantly all-
trans
-retinoic acid). Alitretinoin was
shown to have a weak potential to be a photo-irritant based on histidine and photoprotein binding. In
cell-based
in vitro
assays, alitretinoin showed weak phototoxic potential.
6.
6.1
List of excipients
Ethanol
Macrogol 400
Hydroxypropylcellulose
Butylhydroxytoluene
6.2
Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products. The use of other topical products on treated KS lesions should be avoided. Panretin gel
should not be used concurrently with products containing DEET.
6.3 Shelf life
Unopened:
2 years.
In-use: .
Any remaining tube should be discarded 90 days after first opening.
6.4 Special precautions for storage
9
Do not store above 25°C.
Store in the original container in order to protect from light.
Keep the container tightly closed.
After opening the tube for application, the tube cap must be replaced and closed tightly to provide an
airtight seal. Opened tubes of Panretin gel must not be stored above 25°C, and should be protected
from exposure to strong light and heat (e.g., direct sunlight).
6.5
Nature and contents of container
Panretin gel is supplied in a multi-use 60 g epoxy-lined aluminium tube.
Each carton contains one tube of gel.
6.6 Special precautions for disposal and other handling
Any unused product or waste material should be disposed of in accordance with local requirements.
Panretin gel contains alcohol, keep away from naked flame.
7.
Eisai Ltd.
European Knowledge Centre
Mosquito Way
Hatfield
Hertfordshire
AL10 9SN
United Kingdom
8.
NUMBER(S) IN THE COMMUNITY REGISTER OF MEDICINAL PRODUCTS
EU/1/00/149/001
Date of first authorization: 11 October 2000
Date of latest renewal:
Detailed information on this product is available on the website of the European Medicines Agency
10
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
C.
SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE MARKETING
AUTHORISATION HOLDER
11
A
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer responsible for batch release
Eisai Manufacturing Limited
European Knowledge Centre
Mosquito Way
Hatfield
Hertfordshire
AL10 9SN
United Kingdom
B
CONDITIONS OF THE MARKETING AUTHORISATION
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product
Characteristics, section 4.2)
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE
USE OF THE MEDICINAL PRODUCT
Not applicable.
•
OTHER CONDITIONS
Not applicable
C
SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE MARKETING
AUTHORISATION HOLDER
Not applicable.
12
ANNEX III
LABELLING AND PACKAGE LEAFLET
13
A. LABELLING
14
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE
PACKAGING
OUTER CARTON TEXT AND TUBE LABEL TEXT
1.
Panretin 0.1 % gel
alitretinoin
2.
STATEMENT OF ACTIVE SUBSTANCE
1 g of gel contains 1 mg alitretinoin (0.1%).
3.
LIST OF EXCIPIENTS
Also contains ethanol, macrogol 400, hydroxypropylcellulose, butylhydroxytoluene.
4.
Gel, 60 g
5.
METHOD AND ROUTE OF ADMINISTRATION
For cutaneous use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
Not for application to the eyes or mucous membranes.
Contains alcohol, keep away from naked flame.
8.
EXPIRY DATE
EXP
15
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Store in the original container in order to protect from light.
Keep the container tightly closed.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
11.
Eisai Ltd.
Mosquito Way
Hatfield
Hertfordshire
AL10 9SN
United Kingdom
12. MARKETING AUTHORISATION NUMBER
EU/1/00/149/001
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Panretin gel 0.1%
16
B. PACKAGE LEAFLET
17
PACKAGE LEAFLET: INFORMATION FOR THE USER
Panretin 0.1% gel
Alitretinoin
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet
:
1. What Panretin is and what it is used for
2. Before you use Panretin
3. How to use Panretin
4. Possible side effects
5.
How to store Panretin
6.
Further information
1.
WHAT PANRETIN IS AND WHAT IT IS USED FOR
Panretin belongs to a group of medicines that are related to vitamin A and known as retinoids
Panretin is used in patients with AIDS-related Kaposi’s sarcoma (KS) and is for the treatment of the
KS lesions:
- that are on the skin only;
- which have not responded to your HIV treatment;
- where the skin or lesion is not broken;
- where the surrounding skin is not swollen;
- or if your doctor thinks that other treatments are not suitable for you.
Panretin does not treat KS that is inside the body.
2.
BEFORE YOU USE PANRETIN
Do not use Panretin
-
if you are allergic to alitretinoin or to similar medicines containing retinoids.
-
if you are allergic to any of the other ingredients of Panretin
-
if you are breast-feeding
-
on KS lesions close to any other skin complaint
Take special care with Panretin
-
Panretin is not approved for use in children and adolescents under 18 years of age.
-
Do not apply the gel on or near sensitive parts of your body such as eyes, nostrils, mouth, lips,
vagina, tip of the penis, rectum, or anus.
-
Do not apply the gel to healthy skin around a KS lesion. Panretin may cause unwanted irritation
or redness on healthy skin.
-
Do not use insect repellents containing DEET (
N,N
-diethyl-
m
-toluamide) or other products
containing DEET while using Panretin.
-
Avoid prolonged exposure of the treated area to sunlight or other ultraviolet (UV) light (such as
tanning lamps).
18
-
if you are pregnant
-
Mineral oil may be used between Panretin applications in order to help prevent excessive
dryness or itching. However, mineral oil must not be applied for at least two hours before or
after the application of Panretin.
-
Women of child-bearing age must use an effective method of birth control while using Panretin,
and for one month after finishing treatment.
Using other medicines
Avoid the use of other products on your treated KS lesions such as insect repellents that you use on
your skin.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Use of Panretin with food and drink
It is recommended that you should not eat more vitamin A in your diet than the amount suggested by
your doctor.
Pregnancy
DO NOT use Panretin if you are pregnant or thinking of becoming pregnant. Your doctor can give you
more information. You must use an effective method of birth control while using Panretin, and for one
month after finishing treatment.
Breast-feeding
Do not breast-feed your baby while you are using Panretin. Care should be taken not to bring your baby
into contact with areas of your skin treated recently with Panretin.
Driving and using machines
Panretin is unlikely to affect your ability to drive or use machines.
3.
HOW TO USE PANRETIN
Always use Panretin gel exactly as your doctor has told you. If you are not sure, you should check
with your doctor or pharmacist.
To open for the first time, use the pointed portion of the cap to puncture the metal safety seal.
How to apply Panretin: For cutaneous use (on the skin) only
Apply Panretin twice a day to start with, once in the morning and once in the evening. After that, your
doctor will decide how often you should apply the gel depending on the response of your KS and any
side effects.
Apply Panretin to your KS lesions using a clean finger. Place a generous coating of gel over the whole
surface of each lesion that you want to treat. You do not need to rub the gel into the lesion. You need
to avoid applying the gel to the healthy skin around the lesion. Carefully applying the gel only to the
area of the KS lesion will help to lessen any irritation or redness that may occur. Proper application
will leave some gel visible on the surface of the lesion when you are finished.
-
Immediately after application, wipe the finger(s) you have used to apply the gel and any healthy
skin touched by the gel with a disposable tissue. Wash your hands using soap and water and
wipe the healthy skin touched by the gel.
-
Allow the gel to dry for three to five minutes before covering a treated area with loose clothing.
Do not cover the treated lesions with any bandage or other material.
-
A mild soap is recommended when bathing or showering.
-
If you think that the effect of Panretin is too strong or too weak, talk to your doctor or
pharmacist.
19
- Avoid showering, bathing, or swimming for at least three hours after any application.
-
Avoid scratching the treated areas.
-
Panretin contains alcohol. Keep away from naked flame.
Your doctor will tell you how long your treatment will last.
•
Do not be discouraged if you do not see immediate improvement.
•
It may take up to 12 weeks for any improvement to show.
•
Do not stop treatment at the first sign of improvement.
•
You may need to reduce the number of daily applications, or stop using Panretin for a short while,
if you develop unwanted skin effects. It is important that you consult your doctor, who will tell
you what to do.
If you use more Panretin than you should
There has been no experience with overdose of Panretin.
If you forget to take Panretin
Do not use a double dose to make up for forgotten individual doses. Apply the next dose at the usual
time.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Panretin can have side effects, although not everybody gets them. The side effects
are most likely to appear at the site where Panretin was applied and typically begins as redness. With
continued application of Panretin redness and irritation may increase and swelling at the site of the
application may develop. If your side effects become too uncomfortable, with intense redness and
irritation, rash, swelling, or pain, you should ask your doctor for advice on adjusting the dosage of your
treatment. Most patients can continue to use Panretin by altering the number of times a day it is
applied. Sometimes it is necessary to interrupt treatment, your doctor will inform you about this.
The following side effects have been noted on the skin where Panretin has been applied:
Very common (can occur in more than 1 in 10 patients treated):
Rash, scaling, irritation, redness
Cracking, scabbing, crusting, draining, oozing
Pain, burning, soreness
Itching
Common (can occur in less than 1 in 10 but in more than 1 in 100 patients treated):
Flaking, peeling, dry skin
Swelling, inflammation
Stinging, tingling
Bleeding
Skin discoloration
Skin ulcer
Uncommon (can occur in less than 1 in 100 but in more than 1 in 1000 patients treated):
Infection
Allergic reaction
Swollen lymph glands
Pale skin
20
If any of the side effects gets serious or if you notice any side effects not mentioned in this leaflet,
please tell your doctor or pharmacist.
5.
HOW TO STORE PANRETIN
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the end of the tube.
Do not store above 25°C.
Store in the original container in order to protect from light.
Keep the container tightly closed. Always use the cap to close the tube tightly after each use.
After opening, use within 90 days.
The opening of the Panretin tube is covered by a metal safety seal. If this seal has been punctured or is
not visible when you first open the package, DO NOT USE and return the product to your pharmacy.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Panretin contains
-
The active substance is alitretinoin. 1 g of gel contains 1 mg of alitretinoin
-
The other ingredients are ethanol, macrogol 400, hydroxypropylcellulose, and
butylhydroxytoluene.
What Panretin looks like and contents of the pack
Panretin is a clear yellow gel. It is supplied in a multi-use 60 g epoxy-lined aluminium tube.
Each carton contains one tube of gel.
Marketing Authorisation Holder
Eisai Ltd.
Mosquito Way
Hatfield
Hertfordshire
AL10 9SN
United Kingdom
Manufacturer
Eisai Manufacturing Limited
Mosquito Way
Hatfield
Hertfordshire
AL10 9SN
United Kingdom
Eisai B.V.
Strawinskylaan 909
1077 XX Amsterdam
The Netherlands
21
For any information about this medicine please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien
Cephalon BV
Tél/Tel : +31 (0)497 551 050
Luxembourg/Luxemburg
Cephalon BV
Tél/Tel : +31 (0)497 551 050
България
Cephalon Sp. zo.o.
Teл.: +48(0)22 50 40 890
Magyarország
Cephalon Sp. zo.o.
Tel: +48(0) 22 50 40 890
Česká republika
Cephalon Sp. zo.o.
Tel: +48(0) 22 50 40 890
Malta
Eisai Ltd.
Tel: +44 (0)20 8600 1400
Danmark
Cephalon Pharma ApS
Tlf: +45 3694 4868
Nederland
Cephalon BV
Tel : +31 (0)497 551 050
Deutschland
Cephalon GmbH
Tel: +49 (0)89 89 55 70 0
Norge
Cephalon Pharma ApS
Tlf: +45 3694 4868
Eesti
Cephalon Sp. zo.o.
Tel: +48(0) 22 50 40 890
Österreich
Cephalon GmbH
Tel: +49 (0)89 89 55 70 0
Ελλάδα
Ferrer-Galenica A.E.
Τηλ: +30 210 52 81 700
Polska
Cephalon Sp. zo.o.
Tel: +48(0) 22 50 40 890
España
FERRER FARMA S.A.
Tel: +34 93 600 37 00
Portugal
Ferrer Azevedos, S.A.
Tel: +351 21 4725900
France
Cephalon France
Tél: +33 (0)1 49 81 81 00
România
Cephalon Sp. zo.o.
Tel: +48(0)22 50 40 890
Ireland
Cephalon Pharma (Ireland) Ltd
Tel: +44 (0) 800 783 4869
Slovenija
Cephalon Sp. zo.o.
Tel: +48(0) 22 50 40 890
Ísland
Cephalon Pharma ApS
Sími: +45 3694 4868
Slovenská republika
Cephalon Sp. zo.o.
Tel: +48(0)22 50 40 890
Italia
SIGMA-TAU
Tel: +39 06 91391
Suomi/Finland
Cephalon Pharma ApS
Puh/Tel: +45 3694 4868
Κύπρος
Eisai Ltd.
Τηλ: +44 (0)20 8600 1400
Sverige
Cephalon Pharma ApS
Tel: +45 3694 4868
22
Latvija
Cephalon Sp. zo.o.
Tel: +48(0)22 50 40 890
United Kingdom
Cephalon Ltd
Tel: +44 (0) 800 783 4869
Lietuva
Cephalon Sp. zo.o.
Tel: +48(0)22 50 40 890
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.
23
Source: European Medicines Agency
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