Protopy

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1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Protopy 0.03% ointment 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 g of Protopy 0.03% ointment contains 0.3 mg of tacrolimus as tacrolimus monohydrate (0.03%). 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Ointment 
 
A white to slightly yellowish ointment. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or 
are intolerant of conventional therapies such as topical corticosteroids. Treatment of moderate to 
severe atopic dermatitis in children (2 years of age and above) who failed to respond adequately to 
conventional therapies such as topical corticosteroids. 
 
4.2 Posology and method of administration 
 
Protopy should be initiated by physicians with experience in the diagnosis and treatment of atopic 
dermatitis. 
 
Treatment should be intermittent and not continuous.  
 
Protopy ointment should be applied as a thin layer to affected areas of the skin. Protopy ointment may 
be used on any part of the body, including face, neck and flexure areas, except on mucous membranes. 
Protopy ointment should not be applied under occlusion (see section 4.4).  
 
Each affected region of the skin should be treated with Protopy until clearance occurs and then 
treatment should be discontinued. Generally, improvement is seen within one week of starting 
treatment. If no signs of improvement are seen after two weeks of treatment, further treatment options 
should be considered. Protopy can be used for short term and intermittent long term treatment. At the 
first signs of recurrence (flares) of the disease symptoms, treatment should be re-initiated. 
 
Protopy is not recommended for use in children below age of 2 years until further data are available. 
 
Use in children (2 years of age and above) 
Treatment should be started twice a day for up to three weeks. Afterwards the frequency of application 
should be reduced to once a day until clearance of the lesion (see section 4.4). 
 
Use in adults (16 years of age and above) 
Protopy is available in two strengths, Protopy 0.03% and Protopy 0.1% ointment. Treatment should be 
started with Protopy 0.1% twice a day and treatment should be continued until clearance of the lesion. 
If symptoms recur, twice daily treatment with Protopy 0.1% should be restarted. An attempt should be 
made to reduce the frequency of application or to use the lower strength Protopy 0.03% ointment if the 
clinical condition allows. 



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Use in elderly (65 years of age and above) 
Specific studies have not been conducted in elderly patients. However, the clinical experience 
available in this patient population has not shown the necessity for any dosage adjustment. 
 
As clinical efficacy studies were performed with abrupt cessation of treatment, no information is 
available on whether tapering of the dosage would reduce recurrence rate. 
 
4.3 Contraindications 
 
Hypersensitivity to macrolides in general, to tacrolimus or to any of the excipients. 
 
4.4 Special warnings and precautions for use 
 
Protopy should not be used in patients with congenital or acquired immunodeficiencies or in patients 
on therapy that cause immunosuppression. 
 
The effect of treatment with Protopy ointment on the developing immune system of children, 
especially the young, has not yet been established and this should be taken into account when 
prescribing to this age group (see section 4.1). 
 
Exposure of the skin to sunlight should be minimised and the use of ultraviolet (UV) light from a 
solarium, therapy with UVB or UVA in combination with psoralens (PUVA) should be avoided 
during use of Protopy ointment (see section 5.3). Physicians should advise patients on appropriate sun 
protection methods, such as minimisation of the time in the sun, use of a sunscreen product and 
covering of the skin with appropriate clothing. Protopy ointment should not be applied to lesions that 
are considered to be potentially malignant or pre-malignant. 
 
Emollients should not be applied to the same area within 2 hours of applying Protopy ointment. 
Concomitant use of other topical preparations has not been assessed. There is no experience with 
concomitant use of systemic steroids or immunosuppressive agents.  
 
Protopy ointment has not been evaluated for its efficacy and safety in the treatment of clinically 
infected atopic dermatitis. Before commencing treatment with Protopy ointment, clinical infections at 
treatment sites should be cleared. Patients with atopic dermatitis are predisposed to superficial skin 
infections. Treatment with Protopy may be associated with an increased risk of herpes viral infections 
(herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’s varicelliform 
eruption). In the presence of these infections, the balance of risks and benefits associated with Protopy 
use should be evaluated. 
The potential for local immunosuppression (possibly resulting in infections or cutaneous 
malignancies) in the long term (i.e. over a period of years) is unknown (see section 5.1). 
 
Protopy contains the active substance tacrolimus, a calcineurin inhibitor. In transplant patients, 
prolonged systemic exposure to intense immunosuppression following systemic administration of 
calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin 
malignancies. In patients using tacrolimus ointment, cases of malignancies, including cutaneous and 
other types of lymphoma, and skin cancers have been reported (see section 4.8). Patients with atopic 
dermatitis treated with Protopy have not been found to have significant systemic tacrolimus levels.  
 
Lymphadenopathy was uncommonly (0.8%) reported in clinical trials. The majority of these cases 
related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy. 
Transplant patients receiving immunosuppressive regimens (e.g. systemic tacrolimus) are at increased 
risk for developing lymphoma; therefore patients who receive Protopy and who develop 
lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves. 
Lymphadenopathy present at initiation of therapy should be investigated and kept under review. In 
case of persistent lymphadenopathy, the aetiology of the lymphadenopathy should be investigated. In 



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the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious 
mononucleosis, discontinuation of Protopy should be considered. 
 
Care should be taken to avoid contact with eyes and mucous membranes. If accidentally applied to 
these areas, the ointment should be thoroughly wiped off and/or rinsed off with water.  
The use of Protopy ointment under occlusion has not been studied in patients. Occlusive dressings are 
not recommended.  
As with any topical medicinal product, patients should wash their hands after application if the hands 
are not intended for treatment.  
 
Tacrolimus is extensively metabolised in the liver and although blood concentrations are low 
following topical therapy, the ointment should be used with caution in patients with hepatic failure 
(see section 5.2).  
 
The use of Protopy ointment in patients with genetic epidermal barrier defects such as Netherton’s 
syndrome is not recommended due to the potential for permanently increased systemic absorption of 
tacrolimus. The safety of Protopy ointment has not been established in patients with generalised 
erythroderma. 
 
Care should be exercised if applying Protopy to patients with extensive skin involvement over an 
extended period of time, especially in children (see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Formal topical drug interaction studies with tacrolimus ointment have not been conducted. 
 
Tacrolimus is not metabolised in human skin, indicating that there is no potential for percutaneous 
interactions that could affect the metabolism of tacrolimus. 
 
Systemically available tacrolimus is metabolised via the hepatic Cytochrome P450 3A4 (CYP3A4). 
Systemic exposure from topical application of tacrolimus ointment is low (< 1.0 ng/ml) and is unlikely 
to be affected by concomitant use of substances known to be inhibitors of CYP3A4. However, the 
possibility of interactions cannot be ruled out and the concomitant systemic administration of known 
CYP3A4 inhibitors (e.g. erythromycin, itraconazole, ketoconazole and diltiazem) in patients with 
widespread and/or erythrodermic disease should be done with caution. 
 
A potential interaction between vaccination and application of Protopy ointment has not been 
investigated. Because of the potential risk of vaccination failure, vaccination should be administered 
prior to commencement of treatment, or during a treatment-free interval with a period of 14 days 
between the last application of Protopy and the vaccination. In case of live attenuated vaccination, this 
period should be extended to 28 days or the use of alternative vaccines should be considered. 
 
4.6 Pregnancy and lactation 
 
There are no adequate data from the use of tacrolimus ointment in pregnant women. Studies in animals 
have shown reproductive toxicity following systemic administration (see section 5.3). The potential 
risk for humans is unknown. 
 
Protopy ointment should not be used during pregnancy unless clearly necessary. 
 
Human data demonstrate that, after systemic administration, tacrolimus is excreted into breast milk. 
Although clinical data have shown that systemic exposure from application of tacrolimus ointment is 
low, breast-feeding during treatment with Protopy ointment is not recommended. 
 
4.7 Effects on ability to drive and use machines 
 



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No studies on the effects on the ability to drive and use machines have been performed. Protopy 
ointment is administered topically and is unlikely to have an effect on the ability to drive or use 
machines. 
 
4.8 Undesirable effects 
 
In clinical studies approximately 50% of patients experienced some type of skin irritation adverse 
reaction at the site of application. Burning sensation and pruritus were very common, usually mild to 
moderate in severity and tended to resolve within one week of starting treatment. Erythema was a 
common skin irritation adverse reaction. Sensation of warmth, pain, paraesthesia and rash at the site of 
application were also commonly observed. Alcohol intolerance (facial flushing or skin irritation after 
consumption of an alcoholic beverage) was common. 
Patients may be at an increased risk of folliculitis, acne and herpes viral infections. 
 
Adverse reactions with suspected relationship to treatment are listed below by system organ class. 
Frequencies are defined as very common (> 1/10), common (> 1/100, < 1/10) and uncommon  
(> 1/1,000, < 1/100). Within each frequency grouping, undesirable effects are presented in order of 
decreasing seriousness. 
 
General disorders and administration site conditions 
Very common: Application site burning, application site pruritus 
Common: Application site warmth, application site erythema, application site pain, 

application site irritation, application site paraesthesia, application site rash 
 
Infections and infestations 
Common: Herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes 

simplex [cold sores], Kaposi’s varicelliform eruption) 
 
Skin and subcutaneous tissue disorders 
Common: Folliculitis, pruritus 
Uncommon: Acne 
 
Nervous system disorders 
Common: Paraesthesias and dysaesthesias (hyperaesthesia, burning sensation) 
 
Metabolism and nutrition disorders 
Common: Alcohol intolerance (facial flushing or skin irritation after consumption of an 

alcoholic beverage) 
 
The following adverse reactions have been reported during post-marketing experience: 
Skin and subcutaneous tissue disorders: Rosacea 
 
Post-marketing: cases of malignancies, including cutaneous and other types of lymphoma, and skin 
cancers, have been reported in patients using tacrolimus ointment (see section 4.4).  
 
4.9 Overdose 
 
Overdosage following topical administration is unlikely.  
If ingested, general supportive measures may be appropriate. These may include monitoring of vital 
signs and observation of clinical status. Due to the nature of the ointment vehicle, induction of 
vomiting or gastric lavage is not recommended. 
 
 



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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other dermatologicals, ATC code: D11AX14 
 
Mechanism of action and pharmacodynamic effects 
The mechanism of action of tacrolimus in atopic dermatitis is not fully understood. While the 
following have been observed, the clinical significance of these observations in atopic dermatitis is not 
known. 
Via its binding to a specific cytoplasmic immunophilin (FKBP12), tacrolimus inhibits calcium-
dependent signal transduction pathways in T cells, thereby preventing the transcription and synthesis 
of IL-2, IL-3, IL-4, IL-5 and other cytokines such as GM-CSF, TNF-α and IFN-γ. 
In vitro, in Langerhans cells isolated from normal human skin, tacrolimus reduced the stimulatory 
activity towards T cells. Tacrolimus has also been shown to inhibit the release of inflammatory 
mediators from skin mast cells, basophils and eosinophils. 
In animals, tacrolimus ointment suppressed inflammatory reactions in experimental and spontaneous 
dermatitis models that resemble human atopic dermatitis. Tacrolimus ointment did not reduce skin 
thickness and did not cause skin atrophy in animals. 
In patients with atopic dermatitis, improvement of skin lesions during treatment with tacrolimus 
ointment was associated with reduced Fc receptor expression on Langerhans cells and a reduction of 
their hyperstimulatory activity towards T cells. Tacrolimus ointment does not affect collagen synthesis 
in humans.  
 
Results from clinical studies in patients 
The efficacy and safety of Protopy was assessed in more than 13,500 patients treated with tacrolimus 
ointment in Phase I to Phase III clinical trials. Data from four major trials are presented here. 
In a six-month multicentre double-blind randomised trial, 0.1% tacrolimus ointment was administered 
twice-a-day to adults with moderate to severe atopic dermatitis and compared to a topical 
corticosteroid based regimen (0.1% hydrocortisone butyrate on trunk and extremities, 1% 
hydrocortisone acetate on face and neck). The primary endpoint was the response rate at month 3 
defined as the proportion of patients with at least 60% improvement in the mEASI (modified Eczema 
Area and Severity Index) between baseline and month 3. The response rate in the 0.1% tacrolimus 
group (71.6%) was significantly higher than that in the topical corticosteroid based treatment group 
(50.8%; p<0.001; Table 1). The response rates at month 6 were comparable to the 3-month results.  
 
Table 1 Efficacy at month 3  
 Topical corticosteroid 

regimen§ 
(N=485) 

Tacrolimus 0.1% 
(N=487) 

Response rate of ≥ 60% 
improvement in mEASI (Primary 
Endpoint)§§ 

50.8% 71.6% 

Improvement ≥ 90% in Physician’s 
Global Evaluation 

28.5% 47.7% 

§ Topical corticosteroid regimen = 0.1% hydrocortisone butyrate on trunk and extremities, 1% 
hydrocortisone acetate on face and neck 
§§ higher values = greater improvement 
 
The incidence and nature of most adverse events were similar in the two treatment groups. Skin 
burning, herpes simplex, alcohol intolerance (facial flushing or skin sensitivity after alcohol intake), 
skin tingling, hyperaesthesia, acne and fungal dermatitis occurred more often in the tacrolimus 
treatment group. There were no clinically relevant changes in the laboratory values or vital signs in 
either treatment group throughout the study. 
 



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In the second trial, children aged from 2 to 15 years with moderate to severe atopic dermatitis received 
twice daily treatment for three weeks of 0.03% tacrolimus ointment, 0.1% tacrolimus ointment or 1% 
hydrocortisone acetate ointment. The primary endpoint was the area-under-the-curve (AUC) of the 
mEASI as a percentage of baseline averaged over the treatment period. The results of this multicentre, 
double-blind, randomised trial showed that tacrolimus ointment, 0.03% and 0.1%, is significantly 
more effective (p<0.001 for both) than 1% hydrocortisone acetate ointment (Table 2). 
 
Table 2 Efficacy at week 3  
 
 

Hydrocortisone 
acetate 1% 
(N=185) 

Tacrolimus 0.03% 
(N=189) 

Tacrolimus 0.1% 
(N=186) 

Median mEASI as Percentage of 
Baseline mean AUC (Primary 
Endpoint)§ 

64.0% 44.8% 39.8% 

Improvement ≥ 90% in Physician’s 
Global Evaluation 

15.7% 38.5% 48.4% 

§ lower values = greater improvement 
 
The incidence of local skin burning was higher in the tacrolimus treatment groups than in the 
hydrocortisone group. Pruritus decreased over time in the tacrolimus groups but not in the 
hydrocortisone group. There were no clinically relevant changes in the laboratory values or vital signs 
in either treatment group throughout the clinical trial. 
  
The purpose of the third multicentre, double-blind, randomised study was the assessment of efficacy 
and safety of 0.03% tacrolimus ointment applied once or twice a day relative to twice daily 
administration of 1% hydrocortisone acetate ointment in children with moderate to severe atopic 
dermatitis. Treatment duration was for up to three weeks. 
 
Table 3 Efficacy at week 3  
 
 

Hydrocortisone 
acetate 1% 
Twice daily 
(N=207) 

Tacrolimus 0.03% 
Once daily (N=207) 

Tacrolimus 0.03% 
Twice daily (N=210) 

Median mEASI Percentage 
Decrease (Primary Endpoint)§ 

47.2% 70.0% 78.7% 

Improvement ≥ 90% in 
Physician’s Global Evaluation  

13.6% 27.8% 36.7% 

§ higher values = greater improvement 
 
The primary endpoint was defined as the percentage decrease in mEASI from the baseline to end of 
treatment. A statistically significant better improvement was shown for once daily and twice daily 
0.03% tacrolimus ointment compared to twice daily hydrocortisone acetate ointment (p<0.001 for 
both). Twice daily treatment with 0.03% tacrolimus ointment was more effective than once daily 
administration (Table 3). The incidence of local skin burning was higher in the tacrolimus treatment 
groups than in the hydrocortisone group. There were no clinically relevant changes in the laboratory 
values or vital signs in either treatment group throughout the study. 
 
In the fourth trial, approximately 800 patients (aged ≥ 2 years) received 0.1% tacrolimus ointment 
intermittently or continuously in an open-label, long-term safety study for up to four years, with 300 
patients receiving treatment for at least three years and 79 patients receiving treatment for a minimum 
of 42 months. Based on changes from baseline in EASI score and body surface area affected, patients 
regardless of age had improvement in their atopic dermatitis at all subsequent time points. In addition, 
there was no evidence of loss of efficacy throughout the duration of the clinical trial. The overall 
incidence of adverse events tended to decrease as the study progressed for all patients independent of 
age. The three most common adverse events reported were flu-like symptoms (cold, common cold, 



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influenza, upper respiratory infection, etc.), pruritus and skin burning. No adverse events previously 
unreported in shorter duration and/or previous studies were observed in this long-term study. 
 
5.2 Pharmacokinetic properties 
 
Clinical data have shown that tacrolimus concentrations in systemic circulation after topical 
administration are low and, when measurable, transient. 
 
Absorption 
Data from healthy human subjects indicate that there is little or no systemic exposure to tacrolimus 
following single or repeated topical application of tacrolimus ointment. 
Most atopic dermatitis patients (adults and children) treated with single or repeated application of 
tacrolimus ointment (0.03 - 0.1%), and infants from age of 5 months treated with tacrolimus ointment 
(0.03%) had blood concentrations < 1.0 ng/ml. When observed, blood concentrations exceeding 
1.0 ng/ml were transient. Systemic exposure increases with increasing treatment areas. However, both 
the extent and the rate of topical absorption of tacrolimus decrease as the skin heals. In both adults and 
children with an average of 50% body surface area treated, systemic exposure (i.e. AUC) of tacrolimus 
from Protopy is approximately 30-fold less than that seen with oral immunosuppressive doses in 
kidney and liver transplant patients. The lowest tacrolimus blood concentration at which systemic 
effects can be observed is not known.  
There was no evidence of systemic accumulation of tacrolimus in patients (adults and children) treated 
for prolonged periods (up to one year) with tacrolimus ointment.  
 
Distribution 
As systemic exposure is low with tacrolimus ointment, the high binding of tacrolimus (> 98.8%) to 
plasma proteins is considered not to be clinically relevant. 
Following topical application of tacrolimus ointment, tacrolimus is selectively delivered to the skin 
with minimal diffusion into the systemic circulation. 
 
Metabolism 
Metabolism of tacrolimus by human skin was not detectable. Systemically available tacrolimus is 
extensively metabolised in the liver via CYP3A4. 
 
Elimination 
When administered intravenously, tacrolimus has been shown to have a low clearance rate. The 
average total body clearance is approximately 2.25 l/h. The hepatic clearance of systemically available 
tacrolimus could be reduced in subjects with severe hepatic impairment, or in subjects who are co-
treated with drugs that are potent inhibitors of CYP3A4. 
Following repeated topical application of the ointment the average half-life of tacrolimus was 
estimated to be 75 hours for adults and 65 hours for children. 
 
5.3 Preclinical safety data 
 
Repeated dose toxicity and local tolerance 
Repeated topical administration of tacrolimus ointment or the ointment vehicle to rats, rabbits and 
micropigs was associated with slight dermal changes such as erythema, oedema and papules.  
Long-term topical treatment of rats with tacrolimus led to systemic toxicity including alterations of 
kidneys, pancreas, eyes and nervous system. The changes were caused by high systemic exposure of 
rodents resulting from high transdermal absorption of tacrolimus. Slightly lower body weight gain in 
females was the only systemic change observed in micropigs at high ointment concentrations (3%). 
Rabbits were shown to be especially sensitive to intravenous administration of tacrolimus, reversible 
cardiotoxic effects being observed. 
 
Mutagenicity 
In vitro and in vivo tests did not indicate a genotoxic potential of tacrolimus. 
 
Carcinogenicity 



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Systemic carcinogenicity studies in mice (18 months) and rats (24 months) revealed no carcinogenic 
potential of tacrolimus.  
In a 24-month dermal carcinogenicity study performed in mice with 0.1% ointment, no skin tumours 
were observed. In the same study an increased incidence of lymphoma was detected in association 
with high systemic exposure. 
In a photocarcinogenicity study, albino hairless mice were chronically treated with tacrolimus 
ointment and UV radiation. Animals treated with tacrolimus ointment showed a statistically significant 
reduction in time to skin tumour (squamous cell carcinoma) development and an increase in the 
number of tumours. It is unclear whether the effect of tacrolimus is due to systemic 
immunosuppression or a local effect. The risk for humans cannot be completely ruled out as the 
potential for local immunosuppression with the long-term use of tacrolimus ointment is unknown.  
 
Reproduction toxicity 
Embryo/foetal toxicity was observed in rats and rabbits, but only at doses that caused significant 
toxicity in maternal animals. Reduced sperm function was noted in male rats at high subcutaneous 
doses of tacrolimus. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
White soft paraffin 
Liquid paraffin 
Propylene carbonate 
White beeswax 
Hard paraffin 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Do not store above 25°C. 
 
6.5 Nature and contents of container 
 
Laminate tube with an inner lining of low-density-polyethylene fitted with a white polypropylene 
screw cap. 
 
Package sizes: 10 g, 30 g and 60 g. Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 



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7. MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/02/202/001 
EU/1/02/202/002 
EU/1/02/202/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28/02/2002 
Date of renewal: 20/11/2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{DD/MM/YYYY} 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Protopy 0.1% ointment 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 g of Protopy 0.1% ointment contains 1.0 mg of tacrolimus as tacrolimus monohydrate (0.1%). 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Ointment 
 
A white to slightly yellowish ointment. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or 
are intolerant of conventional therapies such as topical corticosteroids. 
 
4.2 Posology and method of administration 
 
Protopy should be initiated by physicians with experience in the diagnosis and treatment of atopic 
dermatitis. 
 
Treatment should be intermittent and not continuous.  
 
Protopy ointment should be applied as a thin layer to affected areas of the skin. Protopy ointment may 
be used on any part of the body, including face, neck and flexure areas, except on mucous membranes. 
Protopy ointment should not be applied under occlusion (see section 4.4).  
 
Each affected region of the skin should be treated with Protopy until clearance occurs and then 
treatment should be discontinued. Generally, improvement is seen within one week of starting 
treatment. If no signs of improvement are seen after two weeks of treatment, further treatment options 
should be considered. Protopy can be used for short term and intermittent long term treatment. At the 
first signs of recurrence (flares) of the disease symptoms, treatment should be reinitiated. 
 
Protopy is not recommended for use in children below age of 2 years until further data are available. 
 
Use in adults (16 years of age and above) 
Protopy is available in two strengths, Protopy 0.03% and Protopy 0.1% ointment. Treatment should be 
started with Protopy 0.1% twice a day and treatment should be continued until clearance of the lesion. 
If symptoms recur, twice daily treatment with Protopy 0.1% should be restarted. An attempt should be 
made to reduce the frequency of application or to use the lower strength Protopy 0.03% ointment if the 
clinical condition allows. 
 
Use in elderly (65 years of age and above) 
Specific studies have not been conducted in elderly patients. However, the clinical experience 
available in this patient population has not shown the necessity for any dosage adjustment. 
 



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As clinical efficacy studies were performed with abrupt cessation of treatment, no information is 
available on whether tapering of the dosage would reduce recurrence rate. 
 
4.3 Contraindications 
 
Hypersensitivity to macrolides in general, to tacrolimus or to any of the excipients. 
 
4.4 Special warnings and precautions for use 
 
Protopy should not be used in patients with congenital or acquired immunodeficiencies or in patients 
on therapy that cause immunosuppression. 
 
Exposure of the skin to sunlight should be minimised and the use of ultraviolet (UV) light from a 
solarium, therapy with UVB or UVA in combination with psoralens (PUVA) should be avoided 
during use of Protopy ointment (see section 5.3). Physicians should advise patients on appropriate sun 
protection methods, such as minimisation of the time in the sun, use of a sunscreen product and 
covering of the skin with appropriate clothing. Protopy ointment should not be applied to lesions that 
are considered to be potentially malignant or pre-malignant. 
 
Emollients should not be applied to the same area within 2 hours of applying Protopy ointment. 
Concomitant use of other topical preparations has not been assessed. There is no experience with 
concomitant use of systemic steroids or immunosuppressive agents.  
 
Protopy ointment has not been evaluated for its efficacy and safety in the treatment of clinically 
infected atopic dermatitis. Before commencing treatment with Protopy ointment, clinical infections at 
treatment sites should be cleared. Patients with atopic dermatitis are predisposed to superficial skin 
infections. Treatment with Protopy may be associated with an increased risk of herpes viral infections 
(herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’s varicelliform 
eruption). In the presence of these infections, the balance of risks and benefits associated with Protopy 
use should be evaluated. 
The potential for local immunosuppression (possibly resulting in infections or cutaneous 
malignancies) in the long term (i.e. over a period of years) is unknown (see section 5.1). 
 
Protopy contains the active substance tacrolimus, a calcineurin inhibitor. In transplant patients, 
prolonged systemic exposure to intense immunosuppression following systemic administration of 
calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin 
malignancies. In patients using tacrolimus ointment, cases of malignancies, including cutaneous and 
other types of lymphoma, and skin cancers have been reported (see section 4.8). Patients with atopic 
dermatitis treated with Protopy have not been found to have significant systemic tacrolimus levels.  
 
Lymphadenopathy was uncommonly (0.8%) reported in clinical trials. The majority of these cases 
related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy. 
Transplant patients receiving immunosuppressive regimens (e.g. systemic tacrolimus) are at increased 
risk for developing lymphoma; therefore patients who receive Protopy and who develop 
lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves. 
Lymphadenopathy present at initiation of therapy should be investigated and kept under review. In 
case of persistent lymphadenopathy, the aetiology of the lymphadenopathy should be investigated. In 
the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious 
mononucleosis, discontinuation of Protopy should be considered. 
 
Care should be taken to avoid contact with eyes and mucous membranes. If accidentally applied to 
these areas, the ointment should be thoroughly wiped off and/or rinsed off with water.  
The use of Protopy ointment under occlusion has not been studied in patients. Occlusive dressings are 
not recommended.  
As with any topical medicinal product, patients should wash their hands after application if the hands 
are not intended for treatment.  
 



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Tacrolimus is extensively metabolised in the liver and although blood concentrations are low 
following topical therapy, the ointment should be used with caution in patients with hepatic failure 
(see section 5.2).  
 
The use of Protopy ointment in patients with genetic epidermal barrier defects such as Netherton’s 
syndrome is not recommended due to the potential for permanently increased systemic absorption of 
tacrolimus. The safety of Protopy ointment has not been established in patients with generalised 
erythroderma. 
 
Care should be exercised if applying Protopy to patients with extensive skin involvement over an 
extended period of time, especially in children (see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Formal topical drug interaction studies with tacrolimus ointment have not been conducted. 
 
Tacrolimus is not metabolised in human skin, indicating that there is no potential for percutaneous 
interactions that could affect the metabolism of tacrolimus. 
 
Systemically available tacrolimus is metabolised via the hepatic Cytochrome P450 3A4 (CYP3A4). 
Systemic exposure from topical application of tacrolimus ointment is low (< 1.0 ng/ml) and is unlikely 
to be affected by concomitant use of substances known to be inhibitors of CYP3A4. However, the 
possibility of interactions cannot be ruled out and the concomitant systemic administration of known 
CYP3A4 inhibitors (e.g. erythromycin, itraconazole, ketoconazole and diltiazem) in patients with 
widespread and/or erythrodermic disease should be done with caution. 
 
A potential interaction between vaccination and application of Protopy ointment has not been 
investigated. Because of the potential risk of vaccination failure, vaccination should be administered 
prior to commencement of treatment, or during a treatment-free interval with a period of 14 days 
between the last application of Protopy and the vaccination. In case of live attenuated vaccination, this 
period should be extended to 28 days or the use of alternative vaccines should be considered. 
 
4.6 Pregnancy and lactation 
 
There are no adequate data from the use of tacrolimus ointment in pregnant women. Studies in animals 
have shown reproductive toxicity following systemic administration (see section 5.3). The potential 
risk for humans is unknown. 
 
Protopy ointment should not be used during pregnancy unless clearly necessary. 
 
Human data demonstrate that, after systemic administration, tacrolimus is excreted into breast milk. 
Although clinical data have shown that systemic exposure from application of tacrolimus ointment is 
low, breast-feeding during treatment with Protopy ointment is not recommended. 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Protopy 
ointment is administered topically and is unlikely to have an effect on the ability to drive or use 
machines. 
 
4.8 Undesirable effects 
 
In clinical studies approximately 50% of patients experienced some type of skin irritation adverse 
reaction at the site of application. Burning sensation and pruritus were very common, usually mild to 
moderate in severity and tended to resolve within one week of starting treatment. Erythema was a 
common skin irritation adverse reaction. Sensation of warmth, pain, paraesthesia and rash at the site of 



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application were also commonly observed. Alcohol intolerance (facial flushing or skin irritation after 
consumption of an alcoholic beverage) was common. 
Patients may be at an increased risk of folliculitis, acne and herpes viral infections. 
 
Adverse reactions with suspected relationship to treatment are listed below by system organ class. 
Frequencies are defined as very common (> 1/10), common (> 1/100, < 1/10) and uncommon  
(> 1/1,000, < 1/100). Within each frequency grouping, undesirable effects are presented in order of 
decreasing seriousness. 
 
General disorders and administration site conditions 
Very common: Application site burning, application site pruritus 
Common: Application site warmth, application site erythema, application site pain, 

application site irritation, application site paraesthesia, application site rash 
 
Infections and infestations 
Common: Herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes 

simplex [cold sores], Kaposi’s varicelliform eruption) 
 
Skin and subcutaneous tissue disorders 
Common: Folliculitis, pruritus 
Uncommon: Acne 
 
Nervous system disorders 
Common: Paraesthesias and dysaesthesias (hyperaesthesia, burning sensation) 
 
Metabolism and nutrition disorders 
Common: Alcohol intolerance (facial flushing or skin irritation after consumption of an 

alcoholic beverage) 
 
The following adverse reactions have been reported during post-marketing experience: 
Skin and subcutaneous tissue disorders: Rosacea 
 
Post-marketing: cases of malignancies, including cutaneous and other types of lymphoma, and skin 
cancers, have been reported in patients using tacrolimus ointment (see section 4.4).  
 
4.9 Overdose 
 
Overdosage following topical administration is unlikely.  
If ingested, general supportive measures may be appropriate. These may include monitoring of vital 
signs and observation of clinical status. Due to the nature of the ointment vehicle, induction of 
vomiting or gastric lavage is not recommended. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other dermatologicals, ATC code: D11AX14 
 
Mechanism of action and pharmacodynamic effects 
The mechanism of action of tacrolimus in atopic dermatitis is not fully understood. While the 
following have been observed, the clinical significance of these observations in atopic dermatitis is not 
known. 
Via its binding to a specific cytoplasmic immunophilin (FKBP12), tacrolimus inhibits calcium-
dependent signal transduction pathways in T cells, thereby preventing the transcription and synthesis 
of IL-2, IL-3, IL-4, IL-5 and other cytokines such as GM-CSF, TNF-α and IFN-γ. 



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In vitro, in Langerhans cells isolated from normal human skin, tacrolimus reduced the stimulatory 
activity towards T cells. Tacrolimus has also been shown to inhibit the release of inflammatory 
mediators from skin mast cells, basophils and eosinophils. 
In animals, tacrolimus ointment suppressed inflammatory reactions in experimental and spontaneous 
dermatitis models that resemble human atopic dermatitis. Tacrolimus ointment did not reduce skin 
thickness and did not cause skin atrophy in animals. 
In patients with atopic dermatitis, improvement of skin lesions during treatment with tacrolimus 
ointment was associated with reduced Fc receptor expression on Langerhans cells and a reduction of 
their hyperstimulatory activity towards T cells. Tacrolimus ointment does not affect collagen synthesis 
in humans.  
 
Results from clinical studies in patients 
The efficacy and safety of Protopy was assessed in more than 13,500 patients treated with tacrolimus 
ointment in Phase I to Phase III clinical trials. Data from four major trials are presented here. 
In a six-month multicentre double-blind randomised trial, 0.1% tacrolimus ointment was administered 
twice-a-day to adults with moderate to severe atopic dermatitis and compared to a topical 
corticosteroid based regimen (0.1% hydrocortisone butyrate on trunk and extremities, 1% 
hydrocortisone acetate on face and neck). The primary endpoint was the response rate at month 3 
defined as the proportion of patients with at least 60% improvement in the mEASI (modified Eczema 
Area and Severity Index) between baseline and month 3. The response rate in the 0.1% tacrolimus 
group (71.6%) was significantly higher than that in the topical corticosteroid based treatment group 
(50.8%; p<0.001; Table 1). The response rates at month 6 were comparable to the 3-month results.  
 
Table 1 Efficacy at month 3  
 Topical corticosteroid 

regimen§ 
(N=485) 

Tacrolimus 0.1% 
(N=487) 

Response rate of ≥ 60% 
improvement in mEASI (Primary 
Endpoint)§§ 

50.8% 71.6% 

Improvement ≥ 90% in Physician’s 
Global Evaluation 

28.5% 47.7% 

§ Topical corticosteroid regimen = 0.1% hydrocortisone butyrate on trunk and extremities, 1% 
hydrocortisone acetate on face and neck 
§§ higher values = greater improvement 
 
The incidence and nature of most adverse events were similar in the two treatment groups. Skin 
burning, herpes simplex, alcohol intolerance (facial flushing or skin sensitivity after alcohol intake), 
skin tingling, hyperaesthesia, acne and fungal dermatitis occurred more often in the tacrolimus 
treatment group. There were no clinically relevant changes in the laboratory values or vital signs in 
either treatment group throughout the study. 
 
In the second trial, children aged from 2 to 15 years with moderate to severe atopic dermatitis received 
twice daily treatment for three weeks of 0.03% tacrolimus ointment, 0.1% tacrolimus ointment or 1% 
hydrocortisone acetate ointment. The primary endpoint was the area-under-the-curve (AUC) of the 
mEASI as a percentage of baseline averaged over the treatment period. The results of this multicentre, 
double-blind, randomised trial showed that tacrolimus ointment, 0.03% and 0.1%, is significantly 
more effective (p<0.001 for both) than 1% hydrocortisone acetate ointment (Table 2). 
 



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Table 2 Efficacy at week 3  
 
 

Hydrocortisone 
acetate 1% 
(N=185) 

Tacrolimus 0.03% 
(N=189) 

Tacrolimus 0.1% 
(N=186) 

Median mEASI as Percentage of 
Baseline mean AUC (Primary 
Endpoint)§ 

64.0% 44.8% 39.8% 

Improvement ≥ 90% in Physician’s 
Global Evaluation 

15.7% 38.5% 48.4% 

§ lower values = greater improvement 
 
The incidence of local skin burning was higher in the tacrolimus treatment groups than in the 
hydrocortisone group. Pruritus decreased over time in the tacrolimus groups but not in the 
hydrocortisone group. There were no clinically relevant changes in the laboratory values or vital signs 
in either treatment group throughout the clinical trial. 
  
The purpose of the third multicentre, double-blind, randomised study was the assessment of efficacy 
and safety of 0.03% tacrolimus ointment applied once or twice a day relative to twice daily 
administration of 1% hydrocortisone acetate ointment in children with moderate to severe atopic 
dermatitis. Treatment duration was for up to three weeks. 
 
Table 3 Efficacy at week 3  
 
 

Hydrocortisone 
acetate 1% 
Twice daily 
(N=207) 

Tacrolimus 0.03% 
Once daily (N=207) 

Tacrolimus 0.03% 
Twice daily (N=210) 

Median mEASI Percentage 
Decrease (Primary Endpoint)§ 

47.2% 70.0% 78.7% 

Improvement ≥ 90% in 
Physician’s Global Evaluation  

13.6% 27.8% 36.7% 

§ higher values = greater improvement 
 
The primary endpoint was defined as the percentage decrease in mEASI from the baseline to end of 
treatment. A statistically significant better improvement was shown for once daily and twice daily 
0.03% tacrolimus ointment compared to twice daily hydrocortisone acetate ointment (p<0.001 for 
both). Twice daily treatment with 0.03% tacrolimus ointment was more effective than once daily 
administration (Table 3). The incidence of local skin burning was higher in the tacrolimus treatment 
groups than in the hydrocortisone group. There were no clinically relevant changes in the laboratory 
values or vital signs in either treatment group throughout the study. 
 
In the fourth trial, approximately 800 patients (aged ≥ 2 years) received 0.1% tacrolimus ointment 
intermittently or continuously in an open-label, long-term safety study for up to four years, with 300 
patients receiving treatment for at least three years and 79 patients receiving treatment for a minimum 
of 42 months. Based on changes from baseline in EASI score and body surface area affected, patients 
regardless of age had improvement in their atopic dermatitis at all subsequent time points. In addition, 
there was no evidence of loss of efficacy throughout the duration of the clinical trial. The overall 
incidence of adverse events tended to decrease as the study progressed for all patients independent of 
age. The three most common adverse events reported were flu-like symptoms (cold, common cold, 
influenza, upper respiratory infection, etc.), pruritus and skin burning. No adverse events previously 
unreported in shorter duration and/or previous studies were observed in this long-term study. 
 
5.2 Pharmacokinetic properties 
 
Clinical data have shown that tacrolimus concentrations in systemic circulation after topical 
administration are low and, when measurable, transient. 
 



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Absorption 
Data from healthy human subjects indicate that there is little or no systemic exposure to tacrolimus 
following single or repeated topical application of tacrolimus ointment. 
Most atopic dermatitis patients (adults and children) treated with single or repeated application of 
tacrolimus ointment (0.03 - 0.1%), and infants from age of 5 months treated with tacrolimus ointment 
(0.03%) had blood concentrations < 1.0 ng/ml. When observed, blood concentrations exceeding 
1.0 ng/ml were transient. Systemic exposure increases with increasing treatment areas. However, both 
the extent and the rate of topical absorption of tacrolimus decrease as the skin heals. In both adults and 
children with an average of 50% body surface area treated, systemic exposure (i.e. AUC) of tacrolimus 
from Protopy is approximately 30-fold less than that seen with oral immunosuppressive doses in 
kidney and liver transplant patients. The lowest tacrolimus blood concentration at which systemic 
effects can be observed is not known.  
There was no evidence of systemic accumulation of tacrolimus in patients (adults and children) treated 
for prolonged periods (up to one year) with tacrolimus ointment.  
 
Distribution 
As systemic exposure is low with tacrolimus ointment, the high binding of tacrolimus (> 98.8%) to 
plasma proteins is considered not to be clinically relevant. 
Following topical application of tacrolimus ointment, tacrolimus is selectively delivered to the skin 
with minimal diffusion into the systemic circulation. 
 
Metabolism 
Metabolism of tacrolimus by human skin was not detectable. Systemically available tacrolimus is 
extensively metabolised in the liver via CYP3A4. 
 
Elimination 
When administered intravenously, tacrolimus has been shown to have a low clearance rate. The 
average total body clearance is approximately 2.25 l/h. The hepatic clearance of systemically available 
tacrolimus could be reduced in subjects with severe hepatic impairment, or in subjects who are co-
treated with drugs that are potent inhibitors of CYP3A4. 
Following repeated topical application of the ointment the average half-life of tacrolimus was 
estimated to be 75 hours for adults and 65 hours for children. 
 
5.3 Preclinical safety data 
 
Repeated dose toxicity and local tolerance 
Repeated topical administration of tacrolimus ointment or the ointment vehicle to rats, rabbits and 
micropigs was associated with slight dermal changes such as erythema, oedema and papules.  
Long-term topical treatment of rats with tacrolimus led to systemic toxicity including alterations of 
kidneys, pancreas, eyes and nervous system. The changes were caused by high systemic exposure of 
rodents resulting from high transdermal absorption of tacrolimus. Slightly lower body weight gain in 
females was the only systemic change observed in micropigs at high ointment concentrations (3%). 
Rabbits were shown to be especially sensitive to intravenous administration of tacrolimus, reversible 
cardiotoxic effects being observed. 
 
Mutagenicity 
In vitro and in vivo tests did not indicate a genotoxic potential of tacrolimus. 
 
Carcinogenicity 
Systemic carcinogenicity studies in mice (18 months) and rats (24 months) revealed no carcinogenic 
potential of tacrolimus.  
In a 24-month dermal carcinogenicity study performed in mice with 0.1% ointment, no skin tumours 
were observed. In the same study an increased incidence of lymphoma was detected in association 
with high systemic exposure. 
In a photocarcinogenicity study, albino hairless mice were chronically treated with tacrolimus 
ointment and UV radiation. Animals treated with tacrolimus ointment showed a statistically significant 
reduction in time to skin tumour (squamous cell carcinoma) development and an increase in the 



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number of tumours. It is unclear whether the effect of tacrolimus is due to systemic 
immunosuppression or a local effect. The risk for humans cannot be completely ruled out as the 
potential for local immunosuppression with the long-term use of tacrolimus ointment is unknown.  
 
Reproduction toxicity 
Embryo/foetal toxicity was observed in rats and rabbits, but only at doses that caused significant 
toxicity in maternal animals. Reduced sperm function was noted in male rats at high subcutaneous 
doses of tacrolimus. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
White soft paraffin 
Liquid paraffin 
Propylene carbonate 
White beeswax 
Hard paraffin 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Do not store above 25°C. 
 
6.5 Nature and contents of container 
 
Laminate tube with an inner lining of low-density-polyethylene fitted with a white polypropylene 
screw cap. 
 
Package sizes: 10 g, 30 g and 60 g. Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/02/202/003 
EU/1/02/202/004 



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EU/1/02/202/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28/02/2002 
Date of renewal: 20/11/2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{DD/MM/YYYY} 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu 



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ANNEX II 
 
A. MANUFACTURING AUTHORISATION HOLDER 

RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 



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A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer responsible for batch release 
 
Astellas Ireland Co. Ltd., 
Killorglin, 
Co. Kerry, 
Ireland 
 
 
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. 
 



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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  
 
PROTOPY 0.03% OINTMENT (10 g, 30 g, 60 g CARTON) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Protopy 0.03% Ointment 
Tacrolimus monohydrate 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
1 g ointment contains: 0.3 mg tacrolimus (as monohydrate), 
 
 
3. LIST OF EXCIPIENTS 
 
white soft paraffin, liquid paraffin, propylene carbonate, white beeswax, hard paraffin. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Ointment 
 
10 g 
30 g 
60 g 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
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 
 
 
8. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
 



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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 
 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/02/202/005 10 g 
EU/1/02/202/001 30 g 
EU/1/02/202/002 60 g 
 
 
13. BATCH NUMBER 
 
Lot: {number} 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Protopy 0.03% 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PROTOPY 0.03% OINTMENT (10 g TUBE)  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Protopy 0.03% Ointment 
Tacrolimus monohydrate 
Cutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
4. BATCH NUMBER 
 
Lot: {number} 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 g 
 
 
6. OTHER 
 
Keep out of the reach and sight of children. 
 
Do not store above 25°C. 
 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germany 
 
EU/1/02/202/005 
 
 



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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  
 
PROTOPY 0.03% OINTMENT (30 g, 60 g TUBE) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Protopy 0.03% Ointment 
Tacrolimus monohydrate 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
1 g ointment contains: 0.3 mg tacrolimus (as monohydrate), 
 
 
3. LIST OF EXCIPIENTS 
 
white soft paraffin, liquid paraffin, propylene carbonate, white beeswax, hard paraffin. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Ointment 
 
30 g 
60 g 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
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 
 
 
8. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
 



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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 
 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/02/202/001 30 g 
EU/1/02/202/002 60 g 
 
 
13. BATCH NUMBER 
 
Lot: {number} 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
PROTOPY 0.1% OINTMENT (10 g, 30 g, 60 g CARTON) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Protopy 0.1% Ointment 
Tacrolimus monohydrate 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
1 g ointment contains: 1.0 mg tacrolimus (as monohydrate), 
 
 
3. LIST OF EXCIPIENTS 
 
white soft paraffin, liquid paraffin, propylene carbonate, white beeswax, hard paraffin. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Ointment 
 
10 g 
30 g 
60 g 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
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 
 
 
8. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
 



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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 
 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/02/202/006 10 g 
EU/1/02/202/003 30 g 
EU/1/02/202/004 60 g 
 
 
13. BATCH NUMBER 
 
Lot: {number} 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Protopy 0.1% 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PROTOPY 0.1% OINTMENT (10 g TUBE)  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Protopy 0.1% Ointment 
Tacrolimus monohydrate 
Cutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
4. BATCH NUMBER 
 
Lot: {number} 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 g 
 
 
6. OTHER 
 
Keep out of the reach and sight of children. 
 
Do not store above 25°C. 
 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germany 
 
EU/1/02/202/006 
 
 



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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
PROTOPY 0.1% OINTMENT (30 g, 60 g TUBE) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Protopy 0.1% Ointment 
Tacrolimus monohydrate 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
1 g ointment contains: 1.0 mg tacrolimus (as monohydrate), 
 
 
3. LIST OF EXCIPIENTS 
 
white soft paraffin, liquid paraffin, propylene carbonate, white beeswax, hard paraffin. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Ointment 
 
30 g 
60 g 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
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 
 
 
8. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
 
 



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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 
 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/02/202/003 30 g 
EU/1/02/202/004 60 g 
 
 
13. MANUFACTURER’S BATCH NUMBER 
 
Lot: {number} 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 



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B. PACKAGE LEAFLET 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Protopy 0.03% Ointment 
Tacrolimus monohydrate 

 
Read all of this leaflet carefully before you start using 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 Protopy is and what it is used for 
2. Before you use Protopy 
3. How to use Protopy 
4. Possible side effects 
5. How to store Protopy 
6. Further information 
 
 
1. WHAT PROTOPY IS AND WHAT IT IS USED FOR 
 
The active substance of Protopy, tacrolimus monohydrate, is an immunomodulating agent.  
 
Protopy 0.03% ointment is used to treat moderate to severe atopic dermatitis (eczema) in adults who 
are not adequately responsive to or are intolerant of conventional therapies such as topical 
corticosteroids and in children (2 years of age and older) who failed to respond adequately to 
conventional therapies such as topical corticosteroids. In atopic dermatitis, an over-reaction of the 
skin’s immune system causes skin inflammation (itchiness, redness, dryness). Protopy alters the 
abnormal immune response and relieves the skin inflammation and the itch. 
 
 
2. BEFORE YOU USE PROTOPY 
 
Do not use Protopy 
- If you are allergic (hypersensitive) to tacrolimus or any of the other ingredients of Protopy or to 

macrolide antibiotics (e.g. azithromycin, clarithromycin, erythromycin). 
 
Take special care with Protopy 
- Protopy ointment is not approved for children younger than 2 years of age. Therefore it should 

not be used in this age group. Please consult your doctor. 
- The effect of treatment with Protopy on the developing immune system in children, especially 

the young, has not been established. 
- The safety of using Protopy for a long time is not known. A very small number of people who 

have used Protopy ointment have had malignancies (for example, skin or lymphoma). However, 
a link to Protopy ointment treatment has not been shown. 

- If you have infected lesions. Do not apply the ointment to infected lesions. 
- If you have liver failure. Talk to your doctor before using Protopy. 
- Also speak to your doctor before using Protopy if you have any skin malignancies (tumours) or 

if you have a weakened immune system (immuno-compromised) whatever the cause. 
- If you have an inherited skin barrier disease such as Netherton’s syndrome or if you suffer from 

generalised erythroderma (inflammatory reddening and scaling of the entire skin). Talk to your 
doctor before using Protopy. 



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- You should inform your doctor if you have swollen lymph nodes at initiation of treatment. If 
your lymph nodes become swollen during treatment with Protopy, consult your doctor. 

- Before receiving a vaccination tell your doctor that you are using Protopy. Vaccinations should 
not be given during treatment and for a certain time after treatment with Protopy. For live 
attenuated vaccinations (e.g. measles, mumps, rubella or oral polio) the waiting time is 28 days, 
for inactivated vaccines (e.g. tetanus, diphtheria, pertussis or influenza) 14 days. 

- Avoid exposing the skin to long periods of sunlight or artificial sunlight such as tanning beds. If 
you spend time outdoors after applying Protopy, use a sunscreen and wear loose fitting clothing 
that protects the skin from the sun. In addition, ask your doctor for advice on other appropriate 
sun protection methods. If you are prescribed light therapy, inform your doctor that you are 
using Protopy as it is not recommended to use Protopy and light therapy at the same time. 

- Avoid contact with the eyes or mucous membranes (inside of your nose or mouth). 
 
Taking or using other medicines and cosmetics 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
You may use moisturising creams and lotions during treatment with Protopy but these products should 
not be used within two hours of applying Protopy. 
 
The use of Protopy at the same time as other preparations to be used on the skin or while taking oral 
corticosteroids (e.g. cortisone) or medicines which affect the immune system has not been studied. 
 
Before receiving a vaccination tell your doctor that you are using Protopy (see Section “Take special 
care with Protopy”). 
 
Using Protopy with food and drink 
While using Protopy, drinking alcohol may cause the skin or face to become flushed or red and feel 
hot. 
 
Pregnancy and breast-feeding 
Don’t use Protopy if you are pregnant or breast-feeding. 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
 
3. HOW TO USE PROTOPY 
 
Always use Protopy exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure.  
 
Apply Protopy as a thin layer to affected areas of your skin. 
 
Protopy may be used on most parts of the body, including the face and neck and in the creases of your 
elbows and knees. 
 
Avoid using the ointment inside your nose or mouth or in your eyes. If the ointment gets on any of 
these areas, it should be thoroughly wiped off and/or rinsed off with water. 
 
Do not cover the skin being treated with bandages or wraps. 
 
Wash your hands after applying Protopy unless your hands are also being treated. 
 
Before applying Protopy after a bath or shower, be sure your skin is completely dry. 
 



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Children (2 years of age and older) 
Apply Protopy twice a day for up to three weeks, once in the morning and once in the evening. 
Afterwards the ointment should be used once a day on each affected region of the skin until the 
eczema has gone away. 
 
Adults (16 years of age and older) 
Two strengths of Protopy (Protopy 0.03% and Protopy 0.1% ointment) are available for adult patients. 
Your doctor will decide which strength is best for you. Usually, treatment is started with Protopy 0.1% 
ointment twice a day, once in the morning and once in the evening, until the eczema has cleared. If 
symptoms reappear, treatment with Protopy 0.1% twice a day should be restarted. Depending on the 
response of your eczema your doctor will decide if the frequency of application can be reduced or the 
lower strength, Protopy 0.03% ointment, can be used. 
 
Treat each affected region of your skin until the eczema has gone away. Improvement is usually seen 
within one week. If you do not see any improvement after two weeks, see your doctor about other 
possible treatments. Treatment with Protopy may be repeated if symptoms reappear. 
 
If you accidentally swallow some ointment 
If you accidentally swallow the ointment, consult your doctor or pharmacist as soon as possible. Do 
not try to induce vomiting. 
 
If you forget to use Protopy 
If you forget to apply the ointment at the scheduled time, do it as soon as you remember and then 
continue as before. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Protopy can cause side effects, although not everybody gets them. 
 
Approximately half of the patients who use Protopy have some type of skin irritation where they have 
applied the ointment. Burning sensation and itching are very common (> 10%). These symptoms are 
usually mild to moderate and generally go away within one week of using Protopy. Other common 
(> 1%) side effects are redness, feeling of warmth, pain, increased skin sensitivity (especially to hot 
and cold), skin tingling, rash, folliculitis (inflamed or infected hair follicles) and herpes viral infections 
(e.g. cold sores, generalised herpes simplex infections). Facial flushing or skin irritation after drinking 
alcohol is also common. Acne is an uncommon side effect. Rosacea and rosacea-like dermatitis have 
also been reported. 
Since commercial availability a very small number of people who have used Protopy ointment have 
had malignancies (for example, skin or lymphoma). However, a link to Protopy ointment treatment has 
not been confirmed or refuted on the available evidence so far. 
 
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. 
 
 
5. HOW TO STORE PROTOPY 
 
Keep out of the reach and sight of children. 
 
Do not use Protopy after the expiry date which is stated on the tube and carton after EXP. The expiry 
date refers to the last day of that month. 
Do not store above 25ºC. 
 



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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. 
 
 



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6. FURTHER INFORMATION 
 
What Protopy contains 
- The active substance is tacrolimus monohydrate. 

One gram of Protopy 0.03% ointment contains 0.3 mg tacrolimus (as tacrolimus monohydrate). 
- The other ingredients are white soft paraffin, liquid paraffin, propylene carbonate, white 

beeswax and hard paraffin. 
 
What Protopy looks like and contents of the pack  
Protopy is a white to slightly yellowish ointment. It is supplied in tubes containing 10, 30 or 60 grams 
of ointment. Not all pack sizes may be marketed. Protopy is available in two strengths (Protopy 0.03% 
and Protopy 0.1% ointment). 
 
Marketing Authorisation Holder: Astellas Pharma GmbH, Neumarkter Str. 61, D-81673 München, 
Germany. 
 
Manufacturer: Astellas Ireland Co. Ltd., Killorglin, County Kerry, Ireland. 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Astellas Pharma B.V. Branch 
Erasmus Park/Parc Erasme 
Square Marie Curie 50 
B-1070 Brüssel/Bruxelles 
Tél/Tel: +32 (0)2 5580737 
 

Luxembourg/Luxemburg 
Astellas Pharma B.V. Branch 
Erasmus Park/Parc Erasme 
Square Marie Curie 50 
B-1070 Brüssel/Bruxelles 
Belgique/Belgien  
Tél/Tel: +32 (0)2 5580737 
 

България 
Астелас Фарма Юръп Б.В./ЕВАГ 
ул. „Бигла” 6 
София 1407 
Teл.: + 359 2 862 53 72 
 

Magyarország 
Astellas Pharma Kft. 
Kelenhegyi út 43 
H-1118 Budapest  
Tel.: +36 (06)1 3614673 
 

Česká republika 
Astellas Pharma s.r.o. 
Meteor Centre Office Park 
Sokolovskà 100/94 
CZ-18600 Praha 8 
Tel: +420 236 080300 
 

Malta 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germanja 
Tel: +49 (0)89 454406 
 

Danmark 
Astellas Pharma a/s 
Naverland 4 
DK-2600 Glostrup 
Tlf: +45 43 430355 
 

Nederland 
Astellas Pharma B.V. 
Elisabethhof 19 
NL-2353 EW Leiderdorp 
Tel: +31 (0)71 5455745 
 

Deutschland 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Tel: +49 (0)89 454401 
 

Norge 
Astellas Pharma  
Solbråveien 47 
N-1383 Asker 
Tlf: +47 6676 4600 
 



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Eesti 
AS Sirowa Tallinn  
Salve 2c 
EE-11612 Tallinn 
Tel: +372 6 830700 
 

Österreich 
Astellas Pharma Ges.m.b.H. 
Linzer Straße 221/E02 
A-1140 Wien 
Tel: +43 (0)1 8772668 
 

Ελλάδα 
Astellas Pharmaceuticals AEBE 
10° χλμ. Εθνικής Οδού Αθηνών-Λαμίας 
GR-144 51, Μεταμόρφωση Αττικής 
Τηλ: + 30 210 2812640 

Polska 
Astellas Pharma Sp.z o.o. 
ul. Poleczki 21 
PL-02-822 Warszawa 
Tel.: +48 (0) 225451 111 
 

España 
Astellas Pharma S.A. 
Paseo del Club Deportivo n° 1  
Bloque 14-2a 
E-28223 Pozuelo de Alarcón, Madrid 
Tel: +34 91 4952700 
 

Portugal 
Astellas Farma, Lda. 
Edifício Cinema 
Rua José Fontana, n.°1, 1°Andar  
P-2770-101 Paço de Arcos 
Tel: +351 21 4401320  
 

France 
Astellas Pharma S.A.S. 
114 rue Victor Hugo 
F-92300 Levallois Perret 
Tél: +33 (0)1 55917500 
 

România 
Astellas Pharma International 
Detalii de contact pentru Romania 
Calea Bucurestilor 283  
Otopeni 075100 - RO 
Tel: +40 350 37 42 
 

Ireland 
Astellas Pharma Co. Ltd.  
25, The Courtyard  
Kilcarbery Business Park, Clondalkin 
IRL-Dublin 22 
Tel: +353 (0)1 4671555 
 

Slovenija 
Pharmaswiss d.o.o. 
Wolfova 1 
SI-1000 Ljubljana 
Tel: +386 1 2364700 
 

Ísland 
Vistor hf. 
Hörgatúni 2 
IS-210 Garðabæ 
Sími: +354 535 7000 

Slovenská republika 
Astellas Pharma s.r.o., organizačná zložka 
Záborského 29 
SK-831 03 Bratislava 
Tel: +421 2 4444 2157 
 

Italia 
Astellas Pharma S.p.A. 
Via delle Industrie 1 
I-20061 Carugate (Milano) 
Tel: +39 (0)2 921381  
 

Suomi/Finland 
Algol Pharma Oy 
PL 13 
FIN-02611 Espoo/Esbo 
Puh/Tel: +358 9 50991 
 

Κύπρος 
Astellas Pharmaceuticals AEBE 
10° χλμ. Εθνικής Οδού Αθηνών-Λαμίας 
GR-144 51, Μεταμόρφωση Αττικής 
Τηλ: + 30 210 2812640 

Sverige 
Astellas Pharma AB 
Haraldsgatan 5 
S-41314 Göteborg 
Tel: +46 (0)31 7416160 
 



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Latvija 
AS Sirowa Riga 
Katrinas dambis 16 
Riga, LV-1045 
Tel: +371 7 098 250 
 

United Kingdom 
Astellas Pharma Ltd. 
Lovett House 
Lovett Road, Staines 
Middlesex, TW18 3AZ-UK 
Tel: +44 (0) 1784 419615 
 

Lietuva 
UAB Sirowa Vilnius 
Švitrigailos g. 11b 
LT-03228 Vilnius 
Tel. +370 (5) 2394155 
 

 

 
This leaflet was last approved in {MM/YYYY}  
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web 
site: http://www.emea.europa.eu 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Protopy 0.1% Ointment 
Tacrolimus monohydrate 

 
Read all of this leaflet carefully before you start using 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 Protopy is and what it is used for 
2. Before you use Protopy 
3. How to use Protopy 
4. Possible side effects 
5. How to store Protopy 
6. Further information 
 
 
1. WHAT PROTOPY IS AND WHAT IT IS USED FOR 
 
The active substance of Protopy, tacrolimus monohydrate, is an immunomodulating agent.  
 
Protopy 0.1% ointment is used to treat moderate to severe atopic dermatitis (eczema) in adults who are 
not adequately responsive to or are intolerant of conventional therapies such as topical corticosteroids. 
In atopic dermatitis, an over-reaction of the skin’s immune system causes skin inflammation 
(itchiness, redness, dryness). Protopy alters the abnormal immune response and relieves the skin 
inflammation and the itch. 
 
 
2. BEFORE YOU USE PROTOPY 
 
Do not use Protopy 
- If you are allergic (hypersensitive) to tacrolimus or any of the other ingredients of Protopy or to 

macrolide antibiotics (e.g. azithromycin, clarithromycin, erythromycin). 
 
Take special care with Protopy 
- Protopy ointment is not approved for children younger than 2 years of age. Therefore it should 

not be used in this age group. Please consult your doctor. 
- The safety of using Protopy for a long time is not known. A very small number of people who 

have used Protopy ointment have had malignancies (for example, skin or lymphoma). However, 
a link to Protopy ointment treatment has not been shown. 

- If you have infected lesions. Do not apply the ointment to infected lesions. 
- Also speak to your doctor before using Protopy if you have any skin malignancies (tumours) or 

if you have a weakened immune system (immuno-compromised) whatever the cause. 
- If you have liver failure. Talk to your doctor before using Protopy. 
- If you have an inherited skin barrier disease such as Netherton’s syndrome or if you suffer from 

generalised erythroderma (inflammatory reddening and scaling of the entire skin). Talk to your 
doctor before using Protopy. 

- You should inform your doctor if you have swollen lymph nodes at initiation of treatment. If 
your lymph nodes become swollen during treatment with Protopy, consult your doctor. 

- Before receiving a vaccination tell your doctor that you are using Protopy. Vaccinations should 
not be given during treatment and for a certain time after treatment with Protopy. For live 



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attenuated vaccinations (e.g. measles, mumps, rubella or oral polio) the waiting time is 28 days, 
for inactivated vaccines (e.g. tetanus, diphtheria, pertussis or influenza) 14 days. 

- Avoid exposing the skin to long periods of sunlight or artificial sunlight such as tanning beds. If 
you spend time outdoors after applying Protopy, use a sunscreen and wear loose fitting clothing 
that protects the skin from the sun. In addition, ask your doctor for advice on other appropriate 
sun protection methods. If you are prescribed light therapy, inform your doctor that you are 
using Protopy as it is not recommended to use Protopy and light therapy at the same time. 

- Avoid contact with the eyes or mucous membranes (inside of your nose or mouth). 
 
Taking or using other medicines and cosmetics 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
You may use moisturising creams and lotions during treatment with Protopy but these products should 
not be used within two hours of applying Protopy. 
 
The use of Protopy at the same time as other preparations to be used on the skin or while taking oral 
corticosteroids (e.g. cortisone) or medicines which affect the immune system has not been studied. 
 
Before receiving a vaccination tell your doctor that you are using Protopy (see Section “Take special 
care with Protopy”). 
 
Using Protopy with food and drink 
While using Protopy, drinking alcohol may cause the skin or face to become flushed or red and feel 
hot. 
 
Pregnancy and breast-feeding 
Don’t use Protopy if you are pregnant or breast-feeding. 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
 
3. HOW TO USE PROTOPY 
 
Always use Protopy exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure.  
 
Apply Protopy as a thin layer to affected areas of your skin. 
 
Protopy may be used on most parts of the body, including the face and neck and in the creases of your 
elbows and knees. 
 
Avoid using the ointment inside your nose or mouth or in your eyes. If the ointment gets on any of 
these areas, it should be thoroughly wiped off and/or rinsed off with water. 
 
Do not cover the skin being treated with bandages or wraps. 
 
Wash your hands after applying Protopy unless your hands are also being treated. 
 
Before applying Protopy after a bath or shower, be sure your skin is completely dry. 
 
Two strengths of Protopy (Protopy 0.03% and Protopy 0.1% ointment) are available for adult patients 
(16 years of age and older). Your doctor will decide which strength is best for you. Usually, treatment 
is started with Protopy 0.1% ointment twice a day, once in the morning and once in the evening, until 
the eczema has cleared. If symptoms reappear, treatment with Protopy 0.1% twice a day should be 
restarted. Depending on the response of your eczema your doctor will decide if the frequency of 
application can be reduced or the lower strength, Protopy 0.03% ointment, can be used. 
 



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Treat each affected region of your skin until the eczema has gone away. Improvement is usually seen 
within one week. If you do not see any improvement after two weeks, see your doctor about other 
possible treatments. Treatment with Protopy may be repeated if symptoms reappear. 
 
If you accidentally swallow some ointment 
If you accidentally swallow the ointment, consult your doctor or pharmacist as soon as possible. Do 
not try to induce vomiting. 
 
If you forget to use Protopy 
If you forget to apply the ointment at the scheduled time, do it as soon as you remember and then 
continue as before. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Protopy can cause side effects, although not everybody gets them. 
 
Approximately half of the patients who use Protopy have some type of skin irritation where they have 
applied the ointment. Burning sensation and itching are very common (> 10%). These symptoms are 
usually mild to moderate and generally go away within one week of using Protopy. Other common 
(> 1%) side effects are redness, feeling of warmth, pain, increased skin sensitivity (especially to hot 
and cold), skin tingling, rash, folliculitis (inflamed or infected hair follicles) and herpes viral infections 
(e.g. cold sores, generalised herpes simplex infections). Facial flushing or skin irritation after drinking 
alcohol is also common. Acne is an uncommon side effect. Rosacea and rosacea-like dermatitis have 
also been reported. 
Since commercial availability a very small number of people who have used Protopy ointment have 
had malignancies (for example, skin or lymphoma). However, a link to Protopy ointment treatment has 
not been confirmed or refuted on the available evidence so far. 
 
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. 
 
 
5. HOW TO STORE PROTOPY 
 
Keep out of the reach and sight of children. 
 
Do not use Protopy after the expiry date which is stated on the tube and carton after EXP. The expiry 
date refers to the last day of that month. 
Do not store above 25ºC. 
 
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. 
 
 



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6. FURTHER INFORMATION 
 
What Protopy contains 
- The active substance is tacrolimus monohydrate. 

One gram of Protopy 0.1% ointment contains 1.0 mg tacrolimus (as tacrolimus monohydrate). 
- The other ingredients are white soft paraffin, liquid paraffin, propylene carbonate, white 

beeswax and hard paraffin. 
 
What Protopy looks like and contents of the pack  
Protopy is a white to slightly yellowish ointment. It is supplied in tubes containing 10, 30 or 60 grams 
of ointment. Not all pack sizes may be marketed. Protopy is available in two strengths (Protopy 0.03% 
and Protopy 0.1% ointment). 
 
Marketing Authorisation Holder: Astellas Pharma GmbH, Neumarkter Str. 61, D-81673 München, 
Germany. 
 
Manufacturer: Astellas Ireland Co. Ltd., Killorglin, County Kerry, Ireland. 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Astellas Pharma B.V. Branch 
Erasmus Park/Parc Erasme 
Square Marie Curie 50 
B-1070 Brüssel/Bruxelles 
Tél/Tel: +32 (0)2 5580737 
 

Luxembourg/Luxemburg 
Astellas Pharma B.V. Branch 
Erasmus Park/Parc Erasme 
Square Marie Curie 50 
B-1070 Brüssel/Bruxelles 
Belgique/Belgien  
Tél/Tel: +32 (0)2 5580737 
 

България 
Астелас Фарма Юръп Б.В./ЕВАГ  
ул. „Бигла” 6 
София 1407 
Teл.: + 359 2 862 53 72 
 

Magyarország 
Astellas Pharma Kft. 
Kelenhegyi út 43 
H-1118 Budapest  
Tel.: +36 (06)1 3614673 
 

Česká republika 
Astellas Pharma s.r.o. 
Meteor Centre Office Park 
Sokolovskà 100/94 
CZ-18600 Praha 8 
Tel: +420 236 080300 
 

Malta 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Germanja 
Tel: +49 (0)89 454406 
 

Danmark 
Astellas Pharma a/s 
Naverland 4 
DK-2600 Glostrup 
Tlf: +45 43 430355 
 

Nederland 
Astellas Pharma B.V. 
Elisabethhof 19 
NL-2353 EW Leiderdorp 
Tel: +31 (0)71 5455745 
 

Deutschland 
Astellas Pharma GmbH 
Neumarkter Str. 61 
D-81673 München 
Tel: +49 (0)89 454401 
 

Norge 
Astellas Pharma  
Solbråveien 47 
N-1383 Asker 
Tlf: +47 6676 4600 
 



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Eesti 
AS Sirowa Tallinn  
Salve 2c 
EE-11612 Tallinn 
Tel: +372 6 830700 
 

Österreich 
Astellas Pharma Ges.m.b.H. 
Linzer Straße 221/E02 
A-1140 Wien 
Tel: +43 (0)1 8772668 
 

Ελλάδα 
Astellas Pharmaceuticals AEBE 
10° χλμ. Εθνικής Οδού Αθηνών-Λαμίας 
GR-144 51, Μεταμόρφωση Αττικής 
Τηλ: + 30 210 2812640 

Polska 
Astellas Pharma Sp.z o.o. 
ul. Poleczki 21 
PL-02-822 Warszawa 
Tel.: +48 (0) 225451 111 
 

España 
Astellas Pharma S.A. 
Paseo del Club Deportivo n° 1  
Bloque 14-2a 
E-28223 Pozuelo de Alarcón, Madrid 
Tel: +34 91 4952700 
 

Portugal 
Astellas Farma, Lda. 
Edifício Cinema 
Rua José Fontana, n.°1, 1°Andar  
P-2770-101 Paço de Arcos 
Tel: +351 21 4401320  
 

France 
Astellas Pharma S.A.S. 
114 rue Victor Hugo 
F-92300 Levallois Perret 
Tél: +33 (0)1 55917500 
 

România 
Astellas Pharma International 
Detalii de contact pentru Romania 
Calea Bucurestilor 283  
Otopeni 075100 - RO 
Tel: +40 350 37 42 
 

Ireland 
Astellas Pharma Co. Ltd.  
25, The Courtyard  
Kilcarbery Business Park, Clondalkin 
IRL-Dublin 22 
Tel: +353 (0)1 4671555 
 

Slovenija 
Pharmaswiss d.o.o. 
Wolfova 1 
SI-1000 Ljubljana 
Tel: +386 1 2364700 
 

Ísland 
Vistor hf. 
Hörgatúni 2 
IS-210 Garðabæ 
Sími: +354 535 7000 
 

Slovenská republika 
Astellas Pharma s.r.o., organizačná zložka 
Záborského 29 
SK-831 03 Bratislava 
Tel: +421 2 4444 2157 
 

Italia 
Astellas Pharma S.p.A. 
Via delle Industrie 1 
I-20061 Carugate (Milano) 
Tel: +39 (0)2 921381  
 

Suomi/Finland 
Algol Pharma Oy 
PL 13 
FIN-02611 Espoo/Esbo 
Puh/Tel: +358 9 50991 
 

Κύπρος 
Astellas Pharmaceuticals AEBE 
10° χλμ. Εθνικής Οδού Αθηνών-Λαμίας 
GR-144 51, Μεταμόρφωση Αττικής 
Τηλ: + 30 210 2812640 

Sverige 
Astellas Pharma AB 
Haraldsgatan 5 
S-41314 Göteborg 
Tel: +46 (0)31 7416160 
 



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Latvija 
AS Sirowa Riga 
Katrinas dambis 16 
Riga, LV-1045 
Tel: +371 7 098 250 
 

United Kingdom 
Astellas Pharma Ltd. 
Lovett House 
Lovett Road, Staines 
Middlesex, TW18 3AZ-UK 
Tel: +44 (0) 1784 419615 
 

Lietuva 
UAB Sirowa Vilnius 
Švitrigailos g. 11b 
LT-03228 Vilnius 
Tel. +370 (5) 2394155 
 

 

 
This leaflet was last approved in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web 
site: http://www.emea.europa.eu 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCHRELEASE
	CONDITIONS OF THE MARKETING AUTHORISATION
	LABELLING
	PACKAGE LEAFLET