Zenapax

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1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Zenapax 5 mg/ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Daclizumab*…………5 mg per 1 ml infusion 
 
One vial of 5 ml contains 25 mg of daclizumab* (5 mg/ml). 
 
* Recombinant humanized IgG1 anti-Tac antibody produced in a murine NSO myeloma cell line using 
a glutamine synthetase (GS) expression system (NS_GSO) by recombinant DNA technology 
 
Excipients: 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion. 
 
Clear to slightly opalescent, colourless to slightly yellowish liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Zenapax is indicated for the prophylaxis of acute organ rejection in de novo allogenic renal 
transplantation and is to be used concomitantly with an immunosuppressive regimen, including 
cyclosporine and corticosteroids in patients who are not highly immunised. 
 
4.2 Posology and method of administration 
 
Zenapax should be prescribed only by physicians who are experienced in the use of 
immunosuppressive therapy following organ transplantation. 
 
The recommended dose for Zenapax in adult and paediatric patients is 1 mg/kg. The volume of 
Zenapax containing the appropriate dose is added to 50 ml of sterile 0.9% saline solution and is 
administered intravenously over a 15 minute period. It may be given via a peripheral or central vein.  
 
Zenapax should initially be given within 24 hours before transplantation. The next and each 
subsequent dose should be given at intervals of fourteen days, for a total of five doses.  
 
Elderly 
 
Experience with Zenapax in elderly patients (older than 65 years) is limited because of the small 
number of older patients who undergo renal transplantation, but there is no evidence that elderly 
patients require a different dosage from younger patients.  
 
Patients with severe renal impairment 
 
No dosage adjustment is necessary for patients with severe renal impairment.  
 
Patients with severe hepatic impairment 
 



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No data are available for patients with severe hepatic impairment. 
 
Instructions for the preparation of Zenapax infusions are described in section 6.6. 
 
4.3 Contraindications 
 
Zenapax is contraindicated in patients with known hypersensitivity to daclizumab or to any excipients 
of this product (see section 6.1).  
 
Zenapax is contraindicated during lactation (see section 4.6). 
 
4.4 Special warnings and precautions for use 
 
There is no experience of the use of Zenapax in patients who are highly immunised.  
 
Anaphylactic reactions following the administration of proteins can occur. Severe, acute (onset within 
24 hours) hypersensitivity reactions on both initial and subsequent exposure to Zenapax have been 
reported rarely. The clinical manifestations of these reactions include hypotension, tachycardia, 
hypoxia, dyspnoea, wheezing, laryngeal oedema, pulmonary oedema, flushing, diaphoresis, 
temperature increase, rash and pruritus. Medications for the treatment of severe hypersensitivity 
reactions should therefore be available for immediate use. 
 
Patients on immunosuppressive therapy following transplantation are at increased risk for developing 
lymphoproliferative disorders (LPDs) and opportunistic infections. While Zenapax is an 
immunosuppressive drug, to date no increase in LPDs or opportunistic infections have been observed 
in patients treated with Zenapax. 
 
In transplant recipients there is no experience of exposure to second or subsequent treatment courses 
using Zenapax. 
 
In a single randomized controlled clinical trial in cardiac transplant recipients which compared 
Zenapax to placebo, each used in combination with mycophenolate mofetil (CellCept 1.5 g bid), 
cyclosporine, and corticosteroids, there were more infection related deaths among patients who 
received Zenapax. At 1 year post-transplant 14 of 216 patients (6.5%) who received Zenapax and 4 of 
207 (1.9%) patients who received placebo died of an infection, a difference of 4.6% (95% CI: 0.3%, 
8.8%). Of these 14 Zenapax patients, 4 died more than 90 days after receiving their last dose of 
Zenapax, making it unlikely that Zenapax had a role in the infection related death. Overall, use of 
polyclonal antilymphocyte antibody therapy (OKT3, ATG, ATGAM) was similar in patients who 
received Zenapax and in patients who received placebo, 18.5% and 17.9%, respectively. However, of 
the 40 patients who received both Zenapax and antilymphocyte therapy, 8 (20.0%) died whereas of the 
37 patients who received both placebo and antilymphocyte therapy, 2 (5.4%) died. Concomitant use of 
Zenapax with another antilymphocyte antibody therapy in the context of intensive immunosuppression 
with cyclosporine, mycophenolate mofetil and corticosteroids may be a factor leading to fatal 
infection. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Because Zenapax is an immunoglobulin, no metabolic drug-drug interactions are to be expected.  
 
The following transplant medications have been administered in clinical trials with Zenapax without 
any interactions: cyclosporine, mycophenolate mofetil, gancyclovir, acyclovir, tacrolimus, 
azathioprine, antithymocyte immune globulin, muromonab-CD3 (OKT3), and corticosteroids. 
 
4.6 Pregnancy and lactation 
 
Pregnancy 



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There are limited data from the use of daclizumab in pregnant women. A study in cynomolgus 
monkeys has not shown teratogenic effects but did show an increase of early prenatal loss which 
remains in the historical spontaneous abortion rate (see section 5.3). The clinical relevance is 
unknown. 
 
Zenapax should not be used in pregnant women unless it is clearly necessary. 
 
Women of childbearing potential must use an effective contraceptive method during Zenapax therapy 
and continue its use for an additional 4 months following the last dose of Zenapax. 
 
Lactation 
Daclizumab is excreted in cynomolgus monkey milk (see section 5.3). It is not known if Zenapax is 
excreted in human milk. However due to potential harmful effects for the newborn, breast-feeding is 
contraindicated during the treatment and up to 4 months following the last dose of Zenapax. 
 
4.7 Effects on ability to drive and use machines 
 
Zenapax has no influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
The safety profile of Zenapax was studied in comparison to placebo in patients who concomitantly 
received immunosuppressive regimens containing cyclosporine and corticosteroids alone, with the 
addition of azathioprine or with the addition of mycophenolate mofetil. The data from the four studies 
(O14392, O14393, O14874 and O15301) showed that the incidence and types of adverse events were 
similar in both placebo-treated and Zenapax-treated patients. Adverse events were reported by 95% of 
placebo and 96% of daclizumab treated patients. Serious adverse events were reported by 44.4% of the 
patients in the placebo-treated group and 39.9% of the patients in the Zenapax-treated group.  
 
Adverse events occurring with a frequency of ≥2% in patients in either group during the first 3 months 
post-transplant are listed below. 
 
Within the system organ classes, undesirable effects are listed under headings of frequency, using the 
following categories: 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, undesirable effects are presented in order of 
decreasing seriousness. 
 

System organ class Frequency 
category 

Adverse event Zenapax 
(%)  
n=336 

Placebo 
(%)  
n=293 

Pharyngitis 2.4 3.8 Infections and 
infestations 

Common 
Rhinitis 3.0 3.1 
Diabetes mellitus 3.3 4.8 
Fluid overload 3.3 5.8 

Metabolism and 
nutrition disorders 

Common 

Dehydration 3.0 3.1 
Very common Insomnia 12.5 13.7 

Depression 3.3 2.0 
Psychiatric disorders 

Common 
 Anxiety 2.1 5.5 

Tremor 19.3 15.7 Very common 
Headache 15.5 14.7 
Dizziness 5.1 4.4 

Nervous system 
disorders 

Common 
Paraesthesia 3.6 0.9 

Eye disorders Common Vision blurred 2.7 4.4 
Cardiac disorders Common Tachycardia 6.5 6.8 

Very common Hypertension(incl. aggravated) 32.1 27.7 
Hypotension 8.6 10.2 

Vascular disorders 
Common 

Haemorrhage 7.4 10.6 



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System organ class Frequency 
category 

Adverse event Zenapax 
(%)  
n=336 

Placebo 
(%)  
n=293 

Lymphocele 7.4 6.5   
Thrombosis 5.4 4.4 

Very common Dyspnoea 11.9 15.4 
Pulmonary oedema 6.3 4.4 
Pleural effusion 2.1 1.4 
Atelectasis 3.3 3.8 
Hypoxia 2.7 3.1 
Respiratory tract congestion 3.3 3.8 
Rales 3.3 1.4 
Cough 5.1 4.8 

Respiratory, thoracic 
and mediastinal 
disorders 

Common 

Breath sounds abnormal 2.7 1.7 
Constipation 34.8 37.9 
Diarrhoea 15.2 16.4 
Vomiting 14.9 14.3 
Nausea 27.4 25.9 

Very common 

Dyspepsia (incl. pyrosis) 15.1 14.7 
Abdominal distension 5.7 4.4 
Gastritis 2.4 0.7 
Abdominal pain 9.8 13.0 
Abdominal pain upper (epigastric pain) 5.4 3.8 
Haemorrhoids 2.1 0.7 

Gastrointestinal 
disorders 

Common 

Flatulence 3.9 4.1 
Rash 3.3 4.4 
Acne 8.9 7.2 
Pruritus 3.9 5.8 
Night sweats 2.1 2.0 
Hyperhidrosis 2.1 1.7 

Skin and subcutaneous 
tissue disorders 

Common 

Hirsutism 4.8 2.0 
Very common Musculoskeletal pain 12.3 12.5 

Back pain 6.5 8.2 
Muscle spasms 2.4 1.4 
Arthralgia 2.7 2.7 

Musculoskeletal, 
connective tissue and 
bone disorders 

Common 

Myalgia 2.1 1.0 
Oedema 15.8 18.4 
Oedema peripheral 28.0 30.0 

Very common 

Impaired healing (without infection) 12.2 10.2 
Chest pain 8.6 8.9 
Pain 7.1 8.2 
Fatigue 7.4 9.6 
Application site reaction 4.8 5.1 
Pyrexia 5.4 10.2 
Asthenia 3.3 2.7 

General disorders and 
administration site 
conditions 

Common 

Chills 3.0 5.1 
Renal failure 3.6 3.3 
Renal tubular necrosis 7.4 6.8 
Hydronephrosis 2.1 4.4 
Renal disorder (damage) 4.5 7.8 
Haemorrhage urinary tract 2.1 3.4 
Urinary retention 2.1 3.1 
Urinary tract disorder 2.7 2.4 
Oliguria 9.5 10.6 

Renal and urinary 
disorders 

Common 

Dysuria 6.0 12.3 
Injury and poisoning Common Post-traumatic pain 20.8 20.1 

 
Incidence of malignancies: Three years after treatment, the incidence of malignancies was 7.8% in the 
placebo group compared with 6.4% in the Zenapax group. Addition of Zenapax did not increase the 



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number of post-transplant lymphomas, which occurred with a frequency of 1.5% in the placebo-
treated group and 0.7% in the Zenapax-treated group. 
 
Hyperglycaemia: No differences in abnormal haematologic or chemical laboratory test results were 
seen between placebo-treated and Zenapax-treated groups with the exception of fasting blood glucose. 
Fasting blood glucose was measured in a small number of placebo- and Zenapax-treated patients. A 
total of 16% (10 of 64 patients) of placebo-treated and 32% (28 of 88 patients) of Zenapax-treated 
patients had high fasting blood glucose values. Most of these high values occurred either on the first 
day post-transplant when patients received high doses of corticosteroids or in patients with diabetes. 
 
Deaths occurring during the first 6 months post-transplant were reported in 3.4% of the placebo- and 
in 0.6% of the Zenapax-treated groups. The twelve months mortality was 4.4% in the placebo- and 
1.5% in the Zenapax-treated groups. 
 
Infectious episodes, including viral infections, fungal infections, bacteraemia and septicaemia, and 
pneumonia, were reported in 72% of the placebo-treated patients and in 68% of Zenapax-treated 
patients. The type of infections reported was similar in both the Zenapax- and the placebo-treated 
groups. Cytomegalovirus infection was reported in 16% of the patients in the placebo group and in 
13% of the patients in the Zenapax group. 
 
In rare cases severe hypersensitivity reactions following administration of Zenapax have been reported 
(see section 4.4). 
 
Paediatric patients: The safety profile for the use of Zenapax in paediatric patients was shown to be 
comparable to that in adult patients. However, the following adverse events occurred more frequently 
in paediatric patients: diarrhoea (41%), postoperative pain (38%), fever (33%), vomiting (33%), 
hypertension (28%), pruritus (21%) and infections of the upper respiratory tract (20%) and urinary 
tract (18%).  
 
4.9 Overdose 
 
A maximum tolerated dose has not been determined in patients and could not be achieved in animals 
that received Zenapax. A dose of 1.5 mg/kg has been administered to bone marrow transplant 
recipients without any associated adverse events. In a single dose toxicity study a dose of 125 mg/kg 
was administered intravenously to mice and showed no evidence of toxicity. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: selective immunosuppressive agents 
ATC code: L04A A08 
 
Clinical Pharmacology 
Zenapax contains daclizumab, a recombinant, humanized IgG1 anti-Tac antibody, and functions as an 
interleukin 2 (IL-2) receptor antagonist. Daclizumab binds with high specificity to the alpha or Tac 
subunit of the high affinity IL-2 receptor complex (expressed on activated T cells), and inhibits IL-2 
binding and biological activity. Administration of Zenapax inhibits IL-2-mediated activation of 
lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection. 
Daclizumab saturates the Tac receptor for approximately 90 days at the recommended dosage regimen 
for the majority of patients. Antibodies to daclizumab developed in approximately 9% of Zenapax-
treated patients in clinical studies but did not appear to affect efficacy, safety, serum daclizumab 
levels, or any other clinically relevant parameter examined. 
 



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No gross changes to circulating lymphocyte numbers or cell phenotypes were observed by 
fluorescence-activated cell sorter (FACS) analysis other than the expected transient decrease in Tac+ 
cells.  
 
Combination Therapy in Renal Allograft Recipients 
 
In Phase III trials Zenapax was added to a standard immunosuppressive regimen of cyclosporine 
(5 mg/kg) and steroids (prednisone or methylprednisolone), with or without addition of azathioprine 
(4 mg/kg). 
 
Both trials showed a statistically significant superiority to placebo in reducing the rate of acute renal 
allograft rejection at six months post-transplant as confirmed by biopsy. From pooled data the 
difference in biopsy-proven acute rejection remained statistically different at one-year posttransplant 
(43% as compared with 28%). Three year graft survival rates were significantly higher among those 
patients who did not experience acute rejection within the first year posttransplant (n=345) compared 
with those who experienced acute rejection during the first year (n=190) regardless of treatment. The 
three year graft survival was not significantly different between placebo and daclizumab in the triple 
immunosuppressant trial (83% Vs. 84%) or the double immunosuppressant trial (78% Vs. 82%). The 
three year patient survival rate was significantly different between placebo and daclizumab in the 
double immunosuppressant trial (88% Vs. 96%; p = 0.017), but not in the triple immunosuppressant 
trial (94% Vs. 92%).  
 
Renal function evaluated by serum creatinine and GFR was similar in both groups at three years 
posttransplant.  
 
The beneficial effect of Zenapax prophylaxis upon the incidence of acute rejection after renal 
transplantation was not associated with adverse clinical sequelae, including the development of Post-
Transplant Lymphoproliferative Disease (PTLD), at 3 years posttransplant. 
 
5.2 Pharmacokinetic properties 
 
In clinical trials involving renal allograft patients-treated with 1 mg/kg of Zenapax every 14 days for a 
total of 5 doses, average peak serum concentrations (mean ± standard deviation) rose between the first 
dose (21 ± 14 µg/ml) and fifth doses (32 ± 22 µg/ml). The mean ± standard deviation trough serum 
concentration prior to fifth dose was 7.6 ± 4.0 µg/ml. Serum levels of 0.5 to 0.9 µg/ml are needed to 
saturate the IL-2 receptor and levels of 5-10 µg/ml are needed to inhibit IL-2 mediated biologic 
activity. The recommended regimen of daclizumab will maintain serum concentrations sufficient to 
saturate IL-2R alpha receptors on activated T lymphocytes for more than 90 days post transplantation 
in the majority of patients. This first three months, is the most critical period post-transplantation. 
 
The estimate terminal elimination half-life of daclizumab ranged from 270 to 919 hours (average 480 
hours) in renal allograft patients and is equivalent to that reported for human IgG which ranged from 
432 to 552 hours (average 480 hours). This is attributable to the humanisation of the protein.  
 
Population pharmacokinetic analysis showed that the systemic clearance of daclizumab was influenced 
by total body weight, age, gender, proteinuria, and race.  
 
The identified body weight influence on systemic clearance supports the dosing of Zenapax on a 
mg/kg basis and maintains drug exposure within 30% of the reference exposure for patient groups 
with wide range of demographic characteristics. No dosage adjustments based on other identified 
covariates (gender, proteinuria, race and age) are required for renal allograft patients.  
 
Paediatric Patients: Pharmacokinetic and pharmacodynamic properties were evaluated in 61 paediatric 
patients treated with 1 mg/kg IV dose of Zenapax every 14 days for a total of 5 doses. Peak serum 
concentrations (peak + SD) rose between the first dose (16 + 12 µg/ml) and the fifth dose (21 + 
14 µg/ml). The mean trough serum concentration before the fifth dose was 5.0 + 2.7 µg/ml. The Tac 



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subunit of the IL-2 receptor was saturated immediately after the first dose of 1.0 mg/kg of daclizumab 
and remained saturated for at least the first three months post-transplant. Saturation of the Tac subunit 
of the IL-2 receptor was similar to that observed in adult patients receiving the same dose regimen. 
 
There is no pharmacokinetic interaction between Zenapax and mycophenolic acid, the active 
metabolite of mycophenolate mofetil (CellCept). 
 
5.3 Preclinical safety data 
 
Daclizumab was well tolerated after single bolus intravenous or subcutaneous doses ranging from 
50 to 125 mg/kg in mice, rats, and rabbits and after 28 days administration of 15 mg/kg to monkeys. 
One of 18 monkeys had an anaphylactic reaction to daclizumab. Appreciable daclizumab serum levels 
were maintained except in 2 out of 18 monkeys that developed anti-daclizumab antibodies. There was 
no cross reactivity in-vitro between daclizumab and human cryosections (28 organs) at concentrations 
up to 56 mg/ml, demonstrating the absence of non-specific binding. Daclizumab was not genotoxic in 
standard tests. 
 
A non-clinical reproduction toxicity study with daclizumab has shown an increased risk of early 
prenatal loss in cynomolgus monkeys compared to placebo. However, the data show considerable 
inter-animal variation and were within the historical control range for this species. The overall prenatal 
losses for the entire gestational period ranged from 20% to 45%. The incidence of stillbirth, caesarean 
section and breech delivery were comparable between the control and treatment groups. 
 
In the same non-clinical reproduction toxicity study with daclizumab, four out of seven lactating 
cynomolgus monkeys given a 5 – 10 fold multiple (10 mg/kg) of the normal human dose were found 
to secrete very low levels of daclizumab (0.17 – 0.28% of maternal serum levels) in breast milk. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Polysorbate 80 
Sodium chloride 
Sodium dihydrogen phosphate anhydrous  
Disodium phosphate anhydrous  
Hydrochloric acid, concentrated 
Sodium hydroxide 
Water for injections 
 
6.2 Incompatibilities 
 
No incompatibility between Zenapax and polyvinyl chloride bags or infusion sets has been observed. 
 
6.3 Shelf life 
 
3 years 
 
After dilution an immediate use is recommended. Chemical and physical in-use stability has been 
demonstrated for 24 hours at 2 °C - 8 °C or for 4 hours at 25 °C. From a microbiological point of 
view, however, the diluted product should be used immediately. The product is not intended to be 
stored after dilution unless the dilution has taken place under controlled and validated aseptic 
conditions. If not used immediately, in use storage times and conditions prior to use are the 
responsibility of the user. 
 
6.4 Special precautions for storage 
 



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- Store in a refrigerator (2 °C – 8 °C). 
- Do not freeze. 
- Store in the original package in order to protect from light. 
 
6.5 Nature and contents of container 
 
5 ml in a vial (Type I glass). Pack sizes of 1 or 3. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
Instructions for use and handling 
 
Zenapax is NOT for direct injection. It should be diluted in 50 ml of sterile 0.9% sodium chloride 
solution before intravenous administration to the patients. For mixing the solution, do not shake, 
gently invert the bag in order to avoid foaming. Care must be taken to assure sterility of prepared 
solution, since the drug product does not contain any antimicrobial preservative or bacteriostatic 
agents. Zenapax is a colourless solution provided as a single use vial. Parenteral drug products should 
be inspected visually for particulate matter and discoloration before administration. Once the infusion 
is prepared it should be administered intravenously immediately. If diluted aseptically it may be stored 
for 24 hours when refrigerated between 2 °C - 8 °C or for 4 hours at 25 °C.  
 
Other drug/substances should not be added or infused simultaneously through the same intravenous 
line. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration Limited 
6 Falcon Way 
Shire Park 
Welwyn Garden City 
AL7 1TW 
United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/99/098/001 (single vial pack) 
EU/1/99/098/002 (3 vial pack) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 February 1999  
Date of renewal: 14 April 2004 
 
 
10. DATE OF REVISION OF THE TEXT 
 



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ANNEX II 
 
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURING AUTHORISATION 
HOLDER(S) RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 

 



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A MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Hoffmann-La Roche Inc.  
340 Kingsland Street 
Nutley 
New Jersey  
USA  
 
Name and address of the manufacturer responsible for batch release 
 
Roche Pharma AG 
Emil-Barell-Str. 1 
D-79639 Grenzach-Wyhlen 
GERMANY 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
● CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable. 
 
● OTHER CONDITIONS 
 
 
 



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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   
 
OUTER CARTON 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zenapax 5 mg/ml concentrate for solution for infusion 
Daclizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Daclizumab*…………5 mg per 1 ml infusion 
 
One vial of 5 ml contains 25 mg of daclizumab* (5 mg/ml). 
 
* Recombinant humanized IgG1 anti-Tac antibody produced in a murine NSO myeloma cell line using 
a glutamine synthetase (GS) expression system (NS_GSO) by recombinant DNA technology. 
 
 
3. LIST OF EXCIPIENTS 
 
Polysorbate 80, sodium chloride, sodium dihydrogen phosphate anhydrous, disodium phosphate 
anhydrous, hydrochloric acid concentrated, sodium hydroxide, water for injection. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 vial of 5 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use, for infusion after dilution  
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 
 
 
9. SPECIAL STORAGE CONDITIONS 



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Store in a refrigerator (2 °C – 8 °C) 
Do not freeze  
Store in the original package in order to protect from light 
 
 
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 
 
Roche Registration Limited 
6 Falcon Way 
Shire Park 
Welwyn Garden City 
AL7 1TW 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/098/001 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING   
 
OUTER CARTON 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zenapax 5 mg/ml concentrate for solution for infusion 
Daclizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Daclizumab*…………5 mg per 1 ml infusion 
 
One vial of 5 ml contains 25 mg of daclizumab* (5 mg/ml). 
 
* Recombinant humanized IgG1 anti-Tac antibody produced in a murine NSO myeloma cell line using 
a glutamine synthetase (GS) expression system (NS_GSO) by recombinant DNA technology. 
 
 
3. LIST OF EXCIPIENTS 
 
Polysorbate 80, sodium chloride, sodium dihydrogen phosphate anhydrous, disodium phosphate 
anhydrous, hydrochloric acid concentrated, sodium hydroxide, water for injection. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
3 vials of 5 ml each 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use, for infusion after dilution  
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 
 
 
9. SPECIAL STORAGE CONDITIONS 



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Store in a refrigerator (2 °C – 8 °C) 
Do not freeze  
Store in the original package in order to protect from light 
 
 
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 
 
Roche Registration Limited 
6 Falcon Way 
Shire Park 
Welwyn Garden City 
AL7 1TW 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/098/002 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Zenapax 5 mg/ml concentrate for solution for infusion 
Daclizumab 
 
 
2. METHOD OF ADMINISTRATION 
 
For intravenous use after dilution 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
 
 
6. OTHER 
 
 



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B. PACKAGE LEAFLET 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Zenapax 5 mg/ml concentrate for solution for infusion 
Daclizumab 

 
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 Zenapax is and what it is used for 
2. Before you use Zenapax 
3. How to use Zenapax  
4. Possible side effects 
5. How to store Zenapax 
6. Further information 
 
 
 
1. WHAT ZENAPAX IS AND WHAT IT IS USED FOR 
 
Daclizumab belongs to a group of medicines called immunosuppressants. These medicines help to 
suppress your body’s natural response to reject your transplanted organ. 
 
Daclizumab is a humanised monoclonal antibody produced in a murine NSO myeloma cell line using 
a glutamine synthetase (GS) expression system (NS_GSO) by recombinant DNA technology. 
Monoclonal antibodies are proteins which recognise and bind to other unique proteins in the body 
called antigens. Daclizumab binds to an antigen found on the surface of specific white blood cells 
called T lymphocytes. This activity suppresses the body’s natural immune response which otherwise 
might cause transplant rejection. 
 
Zenapax is used to prevent your body from rejecting transplanted kidneys. Zenapax is used together 
with other immunosuppressive drugs, including cyclosporine and corticosteroids. 
 
 
2. BEFORE YOU USE ZENAPAX 
 
Do not use Zenapax  
- if you are allergic (hypersensitive) to daclizumab or to any of the other ingredients of Zenapax.  
- if you are breast-feeding. 
 
Please read the section below on breast-feeding. 
 
Take special care with Zenapax 
- if you have ever had an allergic reaction to other immunosuppressive medicines, which help to 

suppress the body’s natural defence mechanisms. 
 
Therapy with medicines which help to suppress the body’s natural defence mechanisms can increase 
the risk for developing malignancies or infections. Zenapax does not increase this risk when it is used 
together with other immunosuppressive drugs, including cyclosporine and corticosteroids.  
 



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Serious allergic reactions may occur following the administration of proteins. Allergic reactions 
following the infusion of Zenapax have been reported rarely. In the event that you do develop an 
allergic reaction, your doctor will treat you with appropriate medication. 
 
Using other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. This is extremely important because using more 
than one medicine at the same time may strengthen or weaken the effect of the medicines you are 
taking. Therefore, Zenapax should not be used with other drugs without your doctor’s consent. 
 
Pregnancy and breast-feeding 
You must not use this medicine if you are breast-feeding. 
 
You should not use this medicine if you are pregnant unless your doctor decides that it is necessary for 
you. 
 
Zenapax may cause damage to your unborn or breast-feeding baby. Tell your doctor straightaway if 
you are pregnant, breast-feeding, become pregnant or plan to start a family in the near future. 
 
Your doctor should advise you about using contraception before treatment with Zenapax is started, 
during treatment with Zenapax, and for an additional 4 months following the last dose of Zenapax. 
 
Driving and using machines 
There is no evidence to indicate that Zenapax has an effect on your ability to drive a car or operate 
machinery. 
 
 
3. HOW TO USE ZENAPAX  
 
Zenapax  is NOT for direct injection. It should be diluted in 50 ml of sterile 0.9% sodium chloride 
solution before administration to patients. 
 
A health care professional will give you a suitable dose (normally 1 mg/kg of body weight) in the 
form of an intravenous infusion over a 15- minute period. The first dose is given within 24 hours 
before your transplant. You will receive 4 subsequent doses which are spaced 14 days apart from each 
other. In total you should receive 5 doses of Zenapax for a complete treatment course. A course of 
treatment usually lasts for 8 weeks. 
 
You may receive subsequent infusions within a day before or after the scheduled administration. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Zenapax can cause side effects, although not everybody gets them.  
 
Tell your doctor immediately if you notice any of the following side effects occur: cough and 
shortness of breath, including when laying flat, vomiting, confusion or passing less urine then normal. 
These side effects may occur when using Zenapax. These side effects can be serious and you may 
need urgent medical attention. 
 
Very common side effects (occurring in 1 or more patients out of 10) are:  
- difficulty sleeping 
- shaking (tremor) 
- headache 
- high blood pressure (hypertension) 



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- difficulty breathing 
- constipation; diarrhoea; vomiting; nausea; or heartburn 
- pain in joints and muscles 
- excess fluid in the body (oedema); swelling of the arms and legs (peripheral oedema) 
- problems with wound healing 
 
Common side effects (occurring in between 1 and 10 patients out of 100) are inflammation of the 
throat (pharyngitis); runny nose (rhinitis); diabetes mellitus; high blood sugar (hyperglycaemia); fluid 
overload; dehydration; anxiety; depression; dizziness; sensation of pins and needles; blurred vision; 
fast heart rate (tachycardia); bleeding (haemorrhage); blood clot (thrombosis); low blood pressure 
(hypotension); accumulation of lymph fluid in one part of the body (lymphocele); severe shortness of 
breath, including when laying flat at night (pulmonary oedema); fluid on the lungs (pleural effusion); 
collapsed lung (atelectasis); lack of oxygen in the body (hypoxia); congestion; cough; noisy or 
abnormal breath sounds, including crackling breath sounds (rales); bloated stomach; stomach pain or 
discomfort; flatulence; haemorrhoids; rash; itchy skin; acne; night sweats; increased sweating; 
excessive hair growth (hirsutism); back pain; muscle cramps, particularly in the legs; pain in the joints 
(arthralgia); pain in the muscles (myalgia); chest pain; pain in general; tiredness; skin irritation at the 
site of injection; fever; chills; general weakness; pain in the loins and changes or difficulty in passing 
urine (hydronephrosis); blood in the urine; pain on passing urine (dysuria); reduced urine output 
(oliguria); pain following surgery. 
 
Rarely, allergic reactions (hypersensitivity) to Zenapax may occur. 
 
Some side effects are more likely to occur in children than in adults, these include diarrhoea, pain 
following surgery, fever, vomiting, high blood pressure, itchy skin, infections of the nose and throat 
and infections in the urine. 
 
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 ZENAPAX 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2 °C – 8 °C).  
 
Keep the vial in the outer carton in order to protect from light. 
 
Do not freeze. 
 
Do not use Zenapax after the expiry date which is stated on the outer carton and on the vial label after 
the abbreviation EXP. The expiry date refers to the last day of that month.. 
 
 
6. FURTHER INFORMATION 
 
What Zenapax contains 
 
- The active substance is daclizumab. 
- The other ingredients are polysorbate 80, sodium chloride, sodium dihydrogen phosphate, 

anhydrous, disodium phosphate anhydrous, hydrochloric acid concentrated, sodium hydroxide, 
water for injections. 

 
What Zenapax looks like and contents of the pack 
 



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Zenapax 5 mg/ml concentrate for solution for infusion is a clear, colourless to slightly yellowish liquid 
is supplied in vials containing 5 ml of solution. One vial with 5 ml concentrate for solution for infusion 
contains 25 mg daclizumab.  
 
Zenapax is available in pack sizes of 1 or 3 vials. 
Not all pack sizes may be marketed. 
 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder 
Roche Registration Limited 
6 Falcon Way 
Shire Park 
Welwyn Garden City 
AL7 1TW 
United Kingdom 
 
Manufacturer 
Roche Pharma AG 
Emil-Barell-Strasse 1, 
D-79639 Grenzach-Wyhlen 
Germany 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
N.V. Roche S.A. 
Tél/Tel: +32 (0) 2 525 82 11 
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

България 
Рош България ЕООД 
Тел: +359 2 818 44 44 
 

Magyarország 
Roche (Magyarország) Kft. 
Tel: +36 - 23 446 800 
 

Česká republika 
Roche s. r. o. 
Tel: +420 - 2 20382111 

Malta 
(See United Kingdom) 

Danmark 
Roche a/s 
Tlf: +45 - 36 39 99 99 
 

Nederland 
Roche Nederland B.V. 
Tel: +31 (0) 348 438050 
 

Deutschland 
Roche Pharma AG 
Tel: +49 (0) 7624 140 
 

Norge 
Roche Norge AS 
Tlf: +47 - 22 78 90 00 
 

Eesti 
Roche Eesti OÜ 
Tel: + 372 - 6 112 401 
 

Österreich 
Roche Austria GmbH 
Tel: +43 (0) 1 27739 
 

Ελλάδα 
Roche (Hellas) A.E.  
Τηλ: +30 210 61 66 100 
 

Polska 
Roche Polska Sp.z o.o. 
Tel: +48 - 22 345 18 88 
 



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España 
Roche Farma S.A. 
Tel: +34 - 91 324 81 00 
 

Portugal 
Roche Farmacêutica Química, Lda 
Tel: +351 - 21 425 70 00 
 

France 
Roche 
Tél: +33 (0) 1 46 40 50 00 
 

România 
Roche România S.R.L. 
Tel: +40 21 206 47 01 
 

Ireland 
Roche Products (Ireland) Ltd. 
Tel: +353 (0) 1 469 0700 
 

Slovenija 
Roche farmacevtska družba d.o.o. 
Tel: +386 - 1 360 26 00 
 

Ísland  
Roche a/s 
c/o Icepharma hf 
Tel: +354 540 8000 
 

Slovenská republika  
Roche Slovensko, s.r.o. 
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A. 
Tel: +39 - 039 2471 

Suomi/Finland 
Roche Oy  
Puh/Tel: +358 (0) 9 525 331 
 

Kύπρος  
Γ.Α.Σταµάτης & Σια Λτδ. 
Τηλ: +357 - 22 76 62 76 
 

Sverige 
Roche AB 
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA 
Tel: +371 - 7 039831 
 

United Kingdom 
Roche Products Ltd. 
Tel: +44 (0) 1707 366000 
 

Lietuva 
UAB “Roche Lietuva” 
Tel: +370 5 2546799 
 

 

 
 
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.eu.int/ 


	SUMMARY OF PRODUCT CHARACTERISTICS
	MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE ANDMANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCHRELEASE
	CONDITIONS OF THE MARKETING AUTHORISATION
	LABELLING
	PACKAGE LEAFLET