Panretin

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Panretin 0.1 % gel

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 g of gel contains 1 mg alitretinoin (0.1%).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Gel.
Clear yellow gel.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

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
- treatment of visceral KS is not required
- lesions are not responding to systemic antiretroviral therapy
- radiotherapy or chemotherapy are not appropriate

4.2 Posology and method of administration

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. 



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Table 1 Grading of local dermal irritation
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.

Patients with renal or hepatic impairment
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 



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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.

4.3 Contraindications

 Hypersensitivity to retinoids in general, to the active substance alitretinoin or to any of the 
excipients listed in section 6.1.

 Pregnancy and breast-feeding (see section 4.6).
 Women planning a pregnancy.
 Treatment of KS lesions in close proximity to other skin disorders.

4.4 Special warnings and precautions for use

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.

4.5 Interaction with other medicinal products and other forms of interaction

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 Fertility, pregnancy and lactation

Women of child-bearing potential

Women of child-bearing potential must use effective contraception during, and up to one month after 
cessation of treatment.



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Men using Panretin should take precautions to ensure that their female partners do not become 
pregnant.

Pregnancy

Orally administered retinoids have been associated with congenital abnormalities. When used in 
accordance with the prescribing information topically administered retinoids are generally 
assumed to result in low systemic exposure due to minimal dermal absorption. However there 
could be individual factors (e.g. damaged skin barrier, excessive use) that contribute to an 
increased systemic exposure.
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, Panretin is contraindicated ( see section 4.3) in pregnancy, or in 
women planning a pregnancy. If the product is used during pregnancy, or if the patient becomes 
pregnant while taking this drug, treatment should be discontinued. 

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 Effects on ability to drive and use machines

Panretin gel is for cutaneous use and is unlikely to have an effect on the ability to drive and use
machines.

4.8 Undesirable effects

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.

Table 3 shows 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), and uncommon (≥1/1,000 to <1/100). Adverse 
events include verbatim terms in parentheses.



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Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness.

Table 3 Adverse reactions reported in patients in clinical trials
System Organ Class
(MedDRA terminology)

Very common Common Uncommon

Blood and lymphatic 
system disorders

Lymphadenopathy

Nervous system 
disorders

Paraesthesia (stinging, 
tingling)

Vascular disorders Haemorrhage (bleeding 
at or around lesions), 

Oedema (oedema, 
swelling, inflammation), 

Peripheral oedema

Phlebitis, Vascular 
disorder

Skin and subcutaneous 
tissue disorder

Skin disorder (cracking, 
scab, crusting, 

excoriation, drainage, 
oozing), Rash 

(erythema, redness, 
scaling, irritation, 

dermatitis), Pruritus 
(itching, pruritus)

Skin ulcer, Serous 
drainage, Exfoliative 
dermatitis (flaking, 

peeling, desquamation, 
exfoliation), Skin 

discoloration (brown 
discoloration, 
surrounding 

hyperpigmentation, 
paler), Dry skin

Cellulitis, 
Vesiculobullous rash, 
Maculopapular rash, 

Allergic reaction

General disorders and 
administration site 
conditions

Pain (burning, pain, 
soreness)

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.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. 
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 



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professionals are asked to report any suspected adverse reactions via the national reporting 
system listed in Appendix V.

4.9 Overdose

No case of overdose has been reported.

Systemic toxicity following acute overdose with topical application of Panretin gel is unlikely.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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 (RAR, RAR, RAR, RXR, RXR, RXR). 
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 4). 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 
enroll. Study 2 was followed by an open label study (Study 2a), which included only patients 
electing to continue from Study 2.

Table 4 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

Overall Response % 35.1 17.9
p=0.002

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.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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2. Protocol-specified dose regimen was application twice a day (BD) only, with downward
adjustments for toxicity.

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 5 provides the individual lesion response rates for patients being treated with Panretin gel 
in the Phase III studies.

Table 5 Index/indicator lesion1 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)

Lesions2,3 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



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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 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. PHARMACEUTICAL PARTICULARS

6.1 List of excipients



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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: 3 years.

In-use: Any remaining tube should be discarded 90 days after first opening.

6.4 Special precautions for storage

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. MARKETING AUTHORISATION HOLDER

Eisai GmbH
Lyoner Straße 36
60528 Frankfurt am Main
Germany
E-mail: medinfo_de@eisai.net 

8. NUMBER(S) IN THE COMMUNITY REGISTER OF MEDICINAL PRODUCTS

EU/1/00/149/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorization: 11 October 2000
Date of latest renewal: 27 September 2010



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10. DATE OF REVISION OF THE TEXT

Detailed information on this product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



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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



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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

Or

Eisai GmbH
Lyoner Straße 36
60528 Frankfurt am Main
Germany

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

B CONDITIONS OF THE MARKETING AUTHORISATION

- CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED 
ON THE MARKETING AUTHORISATION HOLDER

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.



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ANNEX III

LABELLING AND PACKAGE LEAFLET



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A. LABELLING



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING

OUTER CARTON TEXT AND TUBE LABEL TEXT

1. NAME OF THE MEDICINAL PRODUCT

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. PHARMACEUTICAL FORM AND CONTENTS

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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach 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

9. SPECIAL STORAGE CONDITIONS

Do not store above 25C. 
Store in the original container in order to protect from light.



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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. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Eisai GmbH
Lyoner Straße 36
60528 Frankfurt am Main
Germany

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%

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: 
SN: 
NN: 



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B. PACKAGE LEAFLET



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Package leaflet: Iinformation for the user

Panretin 0.1% gel
Alitretinoin

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- 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 signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet: 

1. What Panretin is and what it is used for
2. What you need to know before you use Panretin 
3. How to use Panretin 
4. Possible side effects
5. How to store Panretin 
6. Contents of the pack and other 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
- if your doctor thinks that other treatments are not suitable for you. 

Panretin does not treat KS that is inside the body.

2. What you need to know 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 this medicine (listed in section 6)
- if you are pregnant
- if you are planning a pregnancy
- 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.



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- 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).

- 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.

Other medicines and Panretin
Avoid the use of other products on your treated KS lesions such as insect repellents that you use 
on your skin.

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription.

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. 

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 this medicine exactly as your doctor has told you. Check with your doctor or 
pharmacist if you are not sure.

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.



21

- 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.
- 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



22

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

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.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information 
on the safety of this medicine.

5. How to store Panretin

Keep this medicine out of the sight and reach 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. Contents of the pack and other 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 GmbH
Lyoner Straße 36
60528 Frankfurt am Main
Germany
E-mail: medinfo_de@eisai.net 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


23

Manufacturer 
Eisai Manufacturing Limited
Mosquito Way
Hatfield 
Hertfordshire
AL10 9SN
United Kingdom

Or

Eisai GmbH
Lyoner Straße 36
60528 Frankfurt am Main
Germany

For any information about this medicine please contact the local representative of the Marketing 
Authorisation Holder.

België/Belgique/Belgien
Eisai SA/NV
Tél/Tel: +32 (0)800 158 58

Lietuva
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Vokietija)

България
Eisai GmbH
Teл.: + 49 (0) 69 66 58 50
(Германия)

Luxembourg/Luxemburg
Eisai SA/NV
Tél/Tel: +32 (0)800 158 58
(Belgique/Belgien)

Česká republika
Eisai GesmbH organizačni složka
Tel.: + 420 242 485 839

Magyarország
Eisai GmbH
Tel.: + 49 (0) 69 66 58 50
(Németország)

Danmark
Eisai AB
Tlf: + 46 (0) 8 501 01 600
(Sverige)

Malta
Eisai GmbH
Tel.: + 49 (0) 69 66 58 50
(Il-Ġermanja)

Deutschland
Eisai GmbH
Tel: + 49 (0) 69 66 58 50

Nederland
Eisai B.V.
Tél/Tel: + 31 (0) 900 575 3340

Eesti
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Saksamaa)

Norge
Eisai AB
Tlf: +46 (0) 8 501 01 600
(Sverige)

Ελλάδα
Arriani Pharmaceuticals S.A.
Τηλ: +30 210 668 3000

Österreich
Eisai GesmbH
Tel: + 43 (0) 1 535 1980-0

España
Eisai Farmacéutica, S.A.
Tel: + (34) 91 455 94 55

Polska
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Niemcy)



24

France
Eisai SAS
Tél: + (33) 1 47 67 00 05

Portugal
Eisai Farmacêutica, Unipessoal Lda
Tel: + 351 214 875 540

Hrvatska
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Njemačka)

România
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Germania)

Ireland
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Germany)

Slovenija
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Nemčija)

Ísland
Eisai AB
Sími: + 46 (0)8 501 01 600
(Svíþjóð)

Slovenská republika
Eisai GesmbH organizačni složka
Tel.: + 420 242 485 839
(Česká republika)

Italia
Eisai S.r.l.
Tel: + 39 02 5181401

Suomi/Finland
Eisai AB
Puh/Tel: + 46 (0) 8 501 01 600
(Ruotsi)

Κύπρος
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Γερμανία)

Sverige
Eisai AB
Tel: + 46 (0) 8 501 01 600

Latvija
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Vācija)

United Kingdom
Eisai Europe Ltd.
Tel: + 44 (0)208 600 1400

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.


	SUMMARY OF PRODUCT CHARACTERISTICS
	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
	A. LABELLING
	B. PACKAGE LEAFLET