Ledaga

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Ledaga 160 micrograms/g gel 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each gram of gel contains chlormethine hydrochloride equivalent to 160 micrograms of chlormethine. 
 
Excipients with known effect 
 
Each tube contains 10.5 grams of propylene glycol and 6 micrograms of butylhydroxytoluene. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Gel. 
 
Clear, colourless gel. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ledaga is indicated for the topical treatment of mycosis fungoides-type cutaneous T-cell lymphoma 
(MF-type CTCL) in adult patients (see section 5.1). 
 
4.2 Posology and method of administration 
 
Treatment with Ledaga should be initiated by an appropriately experienced physician. 
 
Posology 
 
A thin film of Ledaga should be applied once daily to affected areas of the skin. 
 
Treatment with Ledaga should be stopped for any grade of skin ulceration or blistering, or moderately 
severe or severe dermatitis (e.g., marked skin redness with oedema). Upon improvement, treatment 
with Ledaga can be restarted at a reduced frequency of once every 3 days. If reintroduction of 
treatment is tolerated for at least 1 week, the frequency of application can be increased to every other 
day for at least 1 week and then to once-daily application if tolerated. 
 
Elderly 
 
The dosing recommendation for elderly patients ( ≥ 65 years old) is the same as for younger adult 
patients (see section 4.8). 
 
Paediatric population 
 
The safety and efficacy of Ledaga in children aged 0 to 18 years have not been established. No data 
are available. 
 
 



3 

Method of administration 
 
Ledaga is for topical application to the skin. 
 
The following instructions should be followed by patients or caregivers when applying Ledaga: 
 
• Patients must wash hands thoroughly with soap and water immediately after handling or 

applying Ledaga. Patients should apply Ledaga to affected areas of the skin. In case of Ledaga 
exposure to non-affected areas of the skin, patients should wash the exposed area with soap and 
water.  

• Caregivers must wear disposable nitrile gloves when applying Ledaga to patients. Caregivers 
should remove gloves carefully (turning them inside out during the removal to avoid contact 
with Ledaga) and wash hands thoroughly with soap and water after removal of gloves. If there 
is accidental skin exposure to Ledaga, caregivers must immediately wash exposed areas 
thoroughly with soap and water for at least 15 minutes. Remove and wash contaminated 
clothing. 

• The opening of the tube is covered with a foil safety seal. The cap should be used to puncture 
the seal. The tube should not be used and the pharmacist should be contacted if the seal is 
missing, punctured, or lifted. 

• Ledaga should be applied immediately or within 30 minutes after removal from the refrigerator. 
The tube should be returned to the refrigerator immediately after each use. With clean hands, 
the tube should be placed back into the original box and the box should be placed in the 
supplied transparent, sealable, plastic bag for storage in the refrigerator. 

• Ledaga should be applied to completely dry skin at least 4 hours before or 30 minutes after 
showering or washing. The patient should allow treated areas to dry for 5 to 10 minutes after 
application before covering with clothing. Occlusive (air- or water-tight) dressings should not 
be used on areas of the skin where Ledaga was applied.  

• Emollients (moisturisers) or other topical products may be applied to the treated areas 2 hours 
before or 2 hours after application of Ledaga. 

• Fire, flame, and smoking must be avoided until Ledaga has dried. 
 
4.3 Contraindications 
 
Hypersensitivity to chlormethine or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Mucosal or eye exposure  
 
Contact with mucous membranes, especially those of the eyes, must be avoided. Exposure of mucous 
membranes such as the oral mucosa or nasal mucosa causes pain, redness, and ulceration, and these 
may be severe. Exposure of the eyes to chlormethine causes pain, burns, inflammation, photophobia, 
and blurred vision. Blindness and severe irreversible anterior eye injury may occur. 
 
Patients should be advised that if any mucous membrane exposure occurs: 
 
• irrigation should be performed immediately for at least 15 minutes with copious amounts of water 

(or sodium chloride 9 mg/ml (0.9%) solution for injection, or a balanced salt ophthalmic irrigating 
solution may be used if there is eye exposure), and 

• medical care should be obtained immediately (including ophthalmological consultation if there is 
eye exposure). 

 
Local skin reactions 
 
Patients should be assessed during treatment for skin reactions such as dermatitis (e.g., redness, 
swelling, inflammation), pruritus, blisters, ulceration, and skin infections. The face, genitalia, anus, and 
intertriginous skin are at increased risk of skin reactions to topical chlormethine. 



4 

For dose modification information in case of skin reactions, see section 4.2. 
 
Hypersensitivity 
 
Hypersensitivity reactions, including isolated cases of anaphylaxis, have been reported in the literature 
after the use of topical formulations of chlormethine (see sections 4.3 and 4.8). 
 
Skin cancer 
 
Skin-directed therapies for MF-type CTCL have been associated with secondary skin cancers, 
although the specific contribution of chlormethine has not been established. Patients should be 
monitored for development of skin cancers during and after discontinuation of treatment with 
chlormethine. 
 
Secondary exposure to Ledaga 
 
Direct skin contact with Ledaga should be avoided in individuals other than the patient. Risks of 
secondary exposure may include skin reactions, mucosal injury, and skin cancers. Recommended 
application instructions should be followed to prevent secondary exposure (see section 4.2). 
 
Excipients 
 
The medicinal product contains propylene glycol and butylhydroxytoluene, which may cause skin 
irritation (e.g., contact dermatitis). In addition, butylhydroxytoluene has been reported to cause 
irritation to the eyes and mucous membranes. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Ledaga is not recommended in women of childbearing potential not using contraception. 
 
Pregnancy 
 
There are limited data from the use of chlormethine in pregnant women. 
 
Studies in animals have shown reproductive toxicity after systemic administration (see section 5.3). 
 
Ledaga is not recommended during pregnancy.  
 
Breast-feeding 
 
It is unknown whether chlormethine is excreted in human milk. 
 
A risk to newborns/infants cannot be excluded due to the potential for topical or systemic exposure of 
the breast-feeding child to chlormethine through contact with the mother’s skin. 
 
A decision must be made whether to discontinue breast-feeding or to discontinue Ledaga therapy, 
taking into account the benefit of breast-feeding for the child and the benefit of therapy for the breast-
feeding mother. 



5 

 
Fertility 
 
In animals, adverse effects of chlormethine on male fertility after systemic administration have been 
documented (see section 5.3). The relevance to humans receiving topical chlormethine is unknown. 
 
4.7 Effects on ability to drive and use machines 
 
Ledaga has no or negligible influence on the ability to drive or use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In a randomised-controlled trial (n=128 exposed to Ledaga for a median duration of 52 weeks), the 
most frequent adverse reactions to Ledaga were skin related: dermatitis (54.7%; e.g., skin irritation, 
erythema, rash, urticaria, skin-burning sensation, pain of the skin), pruritus (20.3%), skin infections 
(11.7%), skin ulceration and blistering (6.3%), and skin hyperpigmentation (5.5%). Cutaneous 
hypersensitivity reactions were reported in 2.3% of the treated patients. 
 
Tabulated list of adverse reactions 
 
Adverse reactions reported with Ledaga in an active-controlled trial in patients with MF-type CTCL 
are shown below. Frequencies were defined using the following convention: 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); very 
rare (< 1/10,000); not known (cannot be estimated from the available data). Within each frequency 
grouping, adverse reactions are presented in order of decreasing severity. 
 
Skin and subcutaneous tissue disorders 
Very common Dermatitis, skin infections, pruritus 
Common Skin ulceration and blistering, skin hyperpigmentation 
Immune system disorders 
Common Hypersensitivity 

 
Elderly population 
 
In the controlled clinical trial, 31% (79/255) of the study population were aged 65 years or older. The 
safety profile observed in elderly patients was consistent with that in the overall patient population. 
 
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 professionals are 
asked to report any suspected adverse reactions via the national reporting system listed in Appendix V. 
 
4.9 Overdose 
 
No cases of overdose after cutaneous use of Ledaga were reported during the clinical development 
programme or post-marketing period. Management of overdose should consist of washing the exposed 
area with water. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, nitrogen mustard analogues, ATC code: L01AA05. 

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


6 

 
Mechanism of action 
 
Chlormethine is a bifunctional alkylating agent that inhibits rapidly proliferating cells. 
 
Clinical efficacy and safety 
 
The efficacy and safety of Ledaga were assessed in a randomised, multicentre, observer-blinded, 
active-controlled, non-inferiority clinical trial (Study 201) of 260 adult patients with Stage IA (141), 
IB (115), and IIA (4) MF-type CTCL who had received at least one prior skin-directed therapy. 
Qualifying prior therapies included topical corticosteroids, phototherapy, topical bexarotene, and 
topical nitrogen mustard. Patients were not required to be refractory to or intolerant of prior therapies. 
Patients were stratified based on stage (IA vs IB and IIA) and then randomised to receive either 
Ledaga (equivalent to 0.02% chlormethine HCl) or the comparator (a petroleum-based 0.02% 
chlormethine HCl ointment). 
 
Study medicinal product was to be applied topically once daily for 12 months. Dosing could be 
suspended or continued at reduced frequency in the case of skin reactions. The median daily usage of 
Ledaga was 1.8 g. The maximum individual daily usage in the trial was 10.5 g of gel (i.e., 2.1 mg of 
chlormethine HCl). 
 
The primary efficacy endpoint in Study 201 was the Composite Assessment of Index Lesion Severity 
(CAILS) response rate. Assessment was undertaken by a blinded observer. A response was defined as 
an at least 50% improvement in the baseline CAILS score, confirmed at a subsequent visit at least 4 
weeks later. A complete response was defined as a confirmed CAILS score of 0. A partial response 
was defined as an at least 50% reduction in the baseline CAILS score. Non-inferiority was considered 
to have been demonstrated if the lower bound of the 95% confidence interval around the ratio of 
response rates (Ledaga/comparator) was greater than or equal to 0.75. The CAILS score was adjusted 
by removal of the pigmentation score and simplification of the plaque elevation scale. 
 
As the main secondary endpoint, patients were also evaluated using the Severity Weighted Assessment 
Tool (SWAT), which was based on an assessment of all lesions. The response criteria were the same 
as for CAILS. 
 
Efficacy was evaluated in the Efficacy Evaluable (EE) population, which included all 185 patients 
who were treated for at least 6 months with no major protocol deviations [Table 1], and in the Intent-
To-Treat (ITT) population, which included all 260 randomised patients. 
 
Table 1 CAILS and SWAT-confirmed response rates by 12 months in Study 201 (efficacy 

evaluable population) 

 
Response rates (%) 

Ratio 95% CI 
Ledaga 
N=90 

Comparator 
N=95 

CAILS Overall Response (CR+PR) 
    Complete Response (CR) 
    Partial Response (PR) 

76.7% 
18.9% 
57.8%  

58.9% 
14.7% 
44.2%  

1.301 1.065–1.609 

SWAT Overall Response (CR+PR) 
    Complete Response (CR) 
    Partial Response (PR) 

63.3% 
8.9% 

54.4% 

55.8% 
4.2% 

51.6% 

1.135 0.893–1.448 

CAILS = Composite Assessment of Index Lesion Severity; CI = confidence interval; CR = Complete Response; PR = Partial 
Response; SWAT = Severity Weighted Assessment Tool. 
 
The ratio of response and the 95% confidence interval in the ITT population were 1.226 (0.974–1.552) 
for CAILS and 1.017 (0.783–1.321) for SWAT and therefore consistent with those in the EE 
population for both the overall CAILS and SWAT responses. 
 



7 

Reductions in mean CAILS scores were observed as early as at 4 weeks, with further reductions 
observed with continuing therapy. 
 
In the EE population, the percentage of patients who achieved a confirmed response by CAILS was 
similar between disease stages IA (79.6 %) and IB–IIA (73.2%). 
 
Results in other secondary endpoints (response in percentage of body surface area affected, time to 
first confirmed CAILS response, duration of first confirmed CAILS response and time to disease 
progression) were consistent with those for CAILS and SWAT. 
 
A small number of subjects (6.3%, 8/128) treated with Ledaga utilised topical corticosteroids. Thus, 
the safety of the concomitant use of Ledaga with topical corticosteroids has not yet been established.  
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Ledaga in all subsets of the paediatric population in cutaneous T-cell lymphoma (see section 4.2 for 
information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Patients who received Ledaga in Study 201 had no measurable concentrations of chlormethine in 
blood collected 1, 3 and 6 hours post-application on Day 1, and at the first month visit.  
 
Similarly, patients who received chlormethine gel 0.04% in a follow-up study (Study 202) had no 
measurable concentrations of chlormethine or its degradation product (half-mustard) in blood collected 
1 hour post-application on Day 1 or after 2, 4, or 6 months of treatment. 
 
5.3 Preclinical safety data 
 
Chlormethine was shown to be genotoxic in bacterial, plant, and mammalian cells. Chlormethine was 
carcinogenic in rat and mouse carcinogenicity studies after subcutaneous and intravenous 
administration. 
 
Dermal application of chlormethine to mice at a dose of 15 mg/kg for up to 33 weeks resulted in skin 
tumours (squamous cell carcinomas and skin papilloma). There were no reports of systemic tumours 
after topical administration of chlormethine. 
 
Intravenously administered chlormethine impaired male fertility in rats at a daily dose of ≥ 0.25 mg/kg 
for 2 weeks. No dedicated animal studies on the effects of chlormethine on female fertility have been 
reported in the literature. 
 
Chlormethine caused foetal malformations in mice and rats when given as single injections of 1–2.5 
mg/kg. Other findings in animals included embryo-lethality and growth retardation when administered 
as a single injection. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Diethylene glycol monoethyl ether 
Propylene glycol 
Isopropyl alcohol 
Glycerol 
Lactic acid 
Hydroxypropylcellulose 



8 

Sodium chloride 
Menthol racemic 
Disodium edetate 
Butylhydroxytoluene 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
Unopened tube 
3 years in the freezer (–15 °C to –25 °C). 
 
After defrosting 
60 days in the refrigerator (+2 °C to +8 °C). 
 
Ledaga should be removed from the refrigerator just prior to application and returned to the 
refrigerator immediately after each use in its box inside the child-resistant, transparent, sealable, 
plastic bag. 
 
6.4 Special precautions for storage 
 
Store and transport frozen (−15 °C to −25 °C). 
 
For storage conditions after defrosting Ledaga, see section 6.3. 
 
6.5 Nature and contents of container 
 
Ledaga is provided in a white aluminium tube with an inner lacquer and an aluminium seal and a 
white polypropylene screw cap. Each tube contains 60 g of gel. 
 
6.6 Special precautions for disposal and other handling 
 
Ledaga is a cytotoxic medicinal product.  
 
Caregivers must wear nitrile gloves when handling Ledaga. Patients and caregivers must wash hands 
after handling Ledaga. 
 
Ledaga is an alcohol-based product and is flammable. The recommended application instructions 
should be followed (see section 4.2). 
 
Unused refrigerated Ledaga should be discarded after 60 days, together with the plastic bag. 
 
Any unused medicinal product or waste material, including the plastic bag and the nitrile gloves used 
for application, must be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown 
Mulhuddart 
Dublin 15 
Ireland 
 
 



9 

8. MARKETING AUTHORISATION NUMBER 
 
EU/1/16/1171/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 3 March 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


10 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

 
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



11 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown 
Mulhuddart 
Dublin 15 
Ireland 
 
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 OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of European Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

 
• Additional risk minimisation measures 
 
In order to minimise and prevent the Important Identified Risk of “Toxicity to mucous membranes / 
eye” and the Important Potential Risk of “Secondary exposure to someone other than the patient”, the 
MAH shall ensure that, the following additional risk minimisation measures are fulfilled in each 
Member State (MS) where Ledaga is marketed: 

• Ledaga should be supplied with a transparent, sealable, child-resistant plastic bag to prevent 
secondary exposure and contamination when Ledaga is stored in the refrigerator: 



12 

o Instruction on how to accurately use, open and dispose a plastic bag should be printed 
on the plastic bag. The MAH must agree about the content and format of the text prior 
to the launch of Ledaga in each MS with the National Competent Authority (NCA). 

o The plastic bag should not be used for any other purposes and must be disposed after 
60 days, together with unused refrigerated Ledaga and any waste material, including 
nitrile gloves in accordance with local requirements. 

 
• A patient alert card, sized to be included in Ledaga outer packaging, together with the Patient 

Information Leaflet (PIL) is provided to all patients and caregivers who are expected to 
administer and use Ledaga. 

 



13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



15 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ledaga 160 micrograms/g gel 
chlormethine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each gram of gel contains 160 micrograms of chlormethine. 
 
 
3. LIST OF EXCIPIENTS 
 
Diethylene glycol monoethyl ether, propylene glycol, isopropyl alcohol, glycerol, lactic acid, 
hydroxypropylcellulose, sodium chloride, menthol racemic, disodium edetate, butylhydroxytoluene. 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Gel 
60 g 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Topical 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 
 
Cytotoxic: Handle with caution 
Flammable: Avoid fire, flame, and smoking 
 
 
8. EXPIRY DATE 
 
EXP 
Discard 60 days after defrosting: ../../.... 
 
 
 



16 

9. SPECIAL STORAGE CONDITIONS 
 
Store and transport frozen (−15 °C to −25 °C)  
After defrosting, store in a refrigerator (+2 °C to +8 °C) 
Keep Ledaga in its box and inside the child-resistant plastic bag 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Dispose of the tube, plastic bag and nitrile gloves in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown 
Mulhuddart 
Dublin 15 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1171/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ledaga 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



17 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
60 g TUBE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ledaga 160 micrograms/g gel 
chlormethine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each gram of gel contains 160 microgams of chlormethine. 
 
 
3. LIST OF EXCIPIENTS 
 
Diethylene glycol monoethyl ether, propylene glycol, isopropyl alcohol, glycerol, lactic acid, 
hydroxypropylcellulose, sodium chloride, menthol racemic, disodium edetate, butylhydroxytoluene. 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Gel 
60 g 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Topical 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 
 
Cytotoxic 
Flammable 
 
 
8. EXPIRY DATE 
 
EXP 
Discard 60 days after defrosting 
 
 



18 

9. SPECIAL STORAGE CONDITIONS 
 
Store and transport frozen. 
After defrosting, store in a refrigerator. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Dispose of the tube, plastic bag and nitrile gloves in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown 
Mulhuddart 
Dublin 15 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1171/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 



19 

Patient alert card  
 
Panel 1 

 
 
Panel 2 

 
 
Panel 3 

 
 
Panel 4 

 
 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



21 

 
Package leaflet: Information for the patient 

 
Ledaga 160 micrograms/g gel 

chlormethine 
 
Read all of this leaflet carefully before you start using 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 only. 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 Ledaga is and what it is used for 
2. What you need to know before you use Ledaga 
3. How to use Ledaga 
4. Possible side effects 
5. How to store Ledaga 
6. Contents of the pack and other information 
 
 
1. What Ledaga is and what it is used for 
 
Ledaga contains the active substance chlormethine. This is an anti-cancer medicine used on the skin to 
treat mycosis fungoides-type cutaneous T-cell lymphoma (MF-type CTCL). 
 
MF-type CTCL is a condition in which certain cells of the body’s immune system called T-
lymphocytes become cancerous and affect the skin. Chlormethine is a type of anti-cancer medicine 
called an ‘alkylating agent’. It attaches to the DNA of dividing cells, like cancer cells, which stops 
them from multiplying and growing. 
 
Ledaga is for use in adults only. 
 
 
2. What you need to know before you use Ledaga 
 
Do not use Ledaga 
- if you are allergic (hypersensitive) to chlormethine or any of the other ingredients of this 

medicine (listed in section 6). 
 
Warnings and precautions 
Talk to your doctor or pharmacist before using Ledaga. 
 
- Contact with your eyes must be avoided. Do not apply the medicine near the eyes, to the inside 

of the nostrils, the inside of the ear or on the lips. 
- If Ledaga gets in your eyes, it can cause pain, burning, swelling, redness, sensitivity to light, and 

blurred vision. It may also cause blindness and severe permanent injury to your eyes. If Ledaga 
gets in your eyes, rinse your eyes right away for at least 15 minutes with large amounts of water, 
a solution known as “0.9% sodium chloride solution” or an eye-wash solution, and seek medical 
assistance (including an eye doctor) as soon as possible. 

- If this medicine gets in your mouth or nose, it can cause pain, redness, and ulcers that may be 
severe. Rinse the affected area right away for at least 15 minutes with large amounts of water, 
and seek medical assistance as soon as possible. 



22 

- This medicine can cause skin reactions, such as inflammation of your skin (redness and 
swelling), itching, blisters, ulcers and skin infections (see section 4). The risk for inflammation 
of the skin is increased if you apply Ledaga to your face, genital area, anus or skin folds. 

- Tell your doctor if you have ever had an allergic reaction to chlormethine. Contact your doctor 
or seek immediate medical attention if you experience allergic reactions to Ledaga (see section 
4). 

- Skin cancers (abnormal growth of the cells in the skin) have been reported after application of 
chlormethine to the skin, although it is not known whether chlormethine causes this. Your 
doctor will check your skin for skin cancers during and after your treatment with Ledaga. Tell 
your doctor if you get any new damaged areas or ulcers on your skin. 

- Direct skin contact with Ledaga should be avoided in individuals other than the patient, such as 
caregivers. Risks of direct skin contact include inflammation of the skin (dermatitis), injury to 
their eyes, mouth, or nose, and skin cancers. Caregivers who accidentally come into contact 
with Ledaga must wash the affected area right away for at least 15 minutes. Remove and wash 
any contaminated clothing. Get medical help right away if Ledaga gets into your eyes, mouth, or 
nose. 

 
Children and adolescents 
Do not give this medicine to children and adolescents under the age of 18 years because the safety and 
effectiveness have not been established for this age group. 
 
Other medicines and Ledaga 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding  
If you are pregnant or breast-feeding, think you may be pregnant or are planning to become pregnant, 
ask your doctor for advice before taking this medicine. 
 
There is limited experience of chlormethine in pregnant women. Therefore, the use of this medicine is 
not recommended during pregnancy and in women of childbearing age not using contraception. 
 
It is not known whether Ledaga passes into breast milk, and there may be a risk that the breast-feeding 
baby is exposed to Ledaga via contact with the mother’s skin. Therefore, it is not recommended to 
breast-feed while taking this medicine.You should talk to your doctor before breast-feeding to 
determine whether or not it is best to breast-feed or to use Ledaga. 
 
Driving and using machines 
This medicine is not expected to have any effect on your ability to drive or to use machines. 
 
Ledaga contains propylene glycol and butylhydroxytoluene 
Propylene glycol and butylhydroxytoluene may also cause skin irritation. In addition, 
butylhydroxytoluene may also cause irritation to the eyes and mucous membranes (i.e., mouth and 
nose). 
 
 
3. How to use Ledaga 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Ledaga is intended only for use on the skin. 
 
The recommended dose is application as a thin film once a day to the affected areas. The dose is the 
same for elderly patients (aged 65 years and older) as for younger adult patients (aged 18 years and 
older). 
 



23 

Your doctor may stop your treatment if you develop severe inflammation of the skin (i.e., redness and 
swelling), blisters and ulcers. Your doctor may restart the treatment upon improvement of your 
symptoms. 
 
Instructions for use: 
 
- Use Ledaga exactly as your doctor or pharmacist tells you. 
- Caregivers must wear disposable nitrile gloves when applying this medicine to patients (this is a 

special type of glove; ask your doctor or pharmacist if you have questions). 
- Remove the cap from the tube just before use. Use the cap to pierce the seal. 
- Apply Ledaga immediately or within 30 minutes of removing it from the refrigerator. 
- Apply a thin layer of this medicine to completely dry skin at least 4 hours before or 30 minutes 

after showering or washing. 
- Apply Ledaga to affected areas of the skin. In case of Ledaga exposure to non-affected areas of 

the skin, wash the exposed area with soap and water. 
- Allow the area to dry for 5 to 10 minutes after applying your medicine and before covering with 

clothing. 
- For patients applying the gel, wash your hands with soap and water immediately after applying. 
- For caregivers applying the gel, carefully remove gloves (turning them inside out during the 

removal to avoid contact with Ledaga) and then wash hands thoroughly with soap and water. 
- Ledaga is supplied within a child-resistant transparent, sealable, plastic bag. If it is not, ask your 

pharmacist. 
- With clean hands, place Ledaga back in the box it came in and the box in the plastic bag. Return 

it to the refrigerator after each use. 
- Do not cover the treated area with air- or water-tight bandages after you have applied this 

medicine. 
- Until Ledaga has dried on the skin, avoid contact with an open flame or a lit cigarette. Ledaga 

contains alcohol and is therefore considered flammable. 
- Do not apply moisturisers or any other skin products (including medicines applied to the skin) 

for 2 hours before or 2 hours after the daily application of Ledaga. 
- Keep away from children and contact with food by storing Ledaga in its box and inside the 

plastic bag. 
 
If you use Ledaga more than you should 
Do not apply Ledaga more than once per day. If you apply more than recommended, talk to your 
doctor. 
 
If you forget to use Ledaga 
Do not use a double dose to make up for a forgotten dose. Apply your next dose when it is due. 
 
If you stop using Ledaga 
Your doctor will determine how long you should use Ledaga for and when treatment may be stopped. 
Do not stop using your medicine until your doctor advises you to do so. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
STOP taking Ledaga and tell your doctor immediately if you experience allergic reactions 
(hypersensitivity). 
 
These reactions may include some or all of the following symptoms: 
 
- Swelling of the lips, face, throat or tongue 



24 

- Rash 
- Difficulty breathing 
 
Other side effects may include 
Tell your doctor or pharmacist as soon as possible if you notice any of the following side effects listed 
below. 
 
Very common side effects on the treatment area (may affect more than 1 in 10 people): 
- Skin inflammation 
- Infections of the skin 
- Itching (pruritus) 
 
Common side effects on the treatment area (may affect up to 1 in 10 people): 
- Skin ulcers 
- Blisters 
- Darkening of the skin 
 
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 Ledaga 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date, which is stated on the tube label and box after EXP. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (+2 °C to +8 °C) at all times, ensuring the tube is in the box inside the child-
resistant, transparent, sealable, plastic bag. 
 
Do not use an opened or unopened tube of Ledaga after 60 days of storage in the refrigerator. 
 
Ask your pharmacist how to throw away used nitrile gloves, the plastic bag and the medicine you no 
longer use. Do not throw away any medicines via wastewater or household waste. These measures will 
help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Ledaga contains 
 
• The active substance is chlormethine. Each gram of gel contains 160 micrograms of chlormethine. 
 
• The other ingredients are: diethylene glycol monoethyl ether, propylene glycol, isopropyl alcohol, 

glycerol, lactic acid, hydroxypropylcellulose, sodium chloride, menthol racemic, disodium edetate, 
and butylhydroxytoluene. 
See end of section 2 for further information on propylene glycol and butylhydroxytoluene. 

 
What Ledaga looks like and contents of the pack 
 
Ledaga is a clear, colourless gel. 
Each aluminium tube contains 60 grams of gel and has a white screw cap. 
 

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


25 

Marketing Authorisation Holder and Manufacturer: 
Helsinn Birex Pharmaceuticals Ltd. 
Damastown 
Mulhuddart 
Dublin 15 
Ireland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Recordati 
Tél/Tel: +32 2 46101 36 
 

Lietuva 
Recordati AB. 
Tel: + 46 8 545 80 230 
Švedija 
 

България 
Recordati Rare Diseases 
Teл.: +33 (0)1 47 73 64 58 
Франция 
 

Luxembourg/Luxemburg 
Recordati 
Tél/Tel: +32 2 46101 36 
Belgique/Belgien 

Česká republika 
Recordati Rare Diseases 
Tel: +33 (0)1 47 73 64 58 
Francie 
 

Magyarország 
Recordati Rare Diseases 
Tel: +33 (0)1 47 73 64 58 
Franciaország 

Danmark 
Recordati AB. 
Tlf: + 46 8 545 80 230 
Sverige 
 

Malta 
Recordati Rare Diseases 
Tel: +33 1 47 73 64 58 
Franza 

Deutschland 
Recordati Rare Diseases Germany GmbH 
Tel: +49 731 140 554 0 
 

Nederland 
Recordati 
Tel: +32 2 46101 36 
België 
 

Eesti 
Recordati AB. 
Tel: + 46 8 545 80 230 
Rootsi 
 

Norge 
Recordati AB. 
Tlf: + 46 8 545 80 230 
Sverige 

Ελλάδα 
Recordati Hellas 
Τηλ: +30 210 6773822 
 

Österreich 
Recordati Rare Diseases Germany GmbH 
Tel: +49 731 140 554 0 
Deutschland 
 

España 
Recordati Rare Diseases Spain S.L.U. 
Tel: + 34 91 659 28 90 
 

Polska 
Recordati Rare Diseases 
Tel: +33 (0)1 47 73 64 58 
Francja 
 

France 
Recordati Rare Diseases 
Tél: +33 (0)1 47 73 64 58 
 

Portugal 
Jaba Recordati S.A. 
Tel: +351 21 432 95 00 



26 

Hrvatska 
Recordati Rare Diseases 
Tél: +33 (0)1 47 73 64 58 
Francuska 
 

România 
Recordati Rare Diseases 
Tel: +33 (0)1 47 73 64 58 
Franţa 

Ireland 
Recordati Rare Diseases 
Tél: +33 (0)1 47 73 64 58 
France 
 

Slovenija 
Recordati Rare Diseases 
Tel: +33 (0)1 47 73 64 58 
Francija 

Ísland 
Recordati AB. 
Simi: + 46 8 545 80 230 
Svíþjóð 
 

Slovenská republika 
Recordati Rare Diseases 
Tel: +33 (0)1 47 73 64 58 
Francúzsko 

Italia 
Recordati Rare Diseases Italy Srl 
Tel: +39 02 487 87 173 
 

Suomi/Finland 
Recordati AB. 
Puh/Tel : +46 8 545 80 230 
Sverige 
 

Κύπρος 
Recordati Rare Diseases 
Τηλ : +33 1 47 73 64 58 
Γαλλία 
 

Sverige 
Recordati AB. 
Tel : +46 8 545 80 230 

Latvija 
Recordati AB. 
Tel: + 46 8 545 80 230 
Zviedrija 

United Kingdom 
Recordati Rare Diseases UK Ltd. 
Tel: +44 (0)1491 414333 

 
 
 
This leaflet was last revised in 
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET