LEUSTATIN 10 mg /10 Ml Раствор

Содержание инструкции

1. LEUSTATIN 10mg/10ml solution for infusion
2. LEUSTATIN must be diluted with a suitable diluent before administration. Since the

LEUSTATIN 10mg/10ml solution for infusion

Cladribine

PHARMACOTHERAPEUTIC CATEGORY
Antimetabolites, purine analogues

THERAPEUTIC INDICATIONS

• LEUSTATIN is indicated for the treatment of patients with hairy cell leukemia (HCL).
• LEUSTATIN is indicated for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during or after treatment with at least one standard therapeutic regimen containing an alkylating agent.

CONTRAINDICATIONS
Hypersensitivity to the active substance or to any of the excipients.

PRECAUTIONS FOR USE
LEUSTATIN is a potent antineoplastic agent and may cause serious toxic effects, such as
myelosuppression, persistent lymphocytopenia and opportunistic infections.

It must be administered under strict control of qualified and experienced clinicians
in the use of antineoplastic drugs.

CHRONIC LYMPHATIC LEUKEMIA
Patients who have shown disease progression during treatment with fludarabine,
are unlikely to respond to treatment with cladribine. The use of LEUSTATIN in these
patients is, therefore not recommended.
Serious adverse effects (e.g., respiratory infections, pneumonia and
viral skin infections), including fatal infections (e.g. sepsis) have been reported (see “Adverse
Effects”).
Any concomitant infections must be resolved before starting treatment with
LEUSTATIN.
In case of a positive Coombs' test, patients should be carefully monitored for
possible hemolysis.
Patients with a high white blood cell count should be treated with allopurinol and
adequately hydrated to alleviate the potential effects of tumor lysis syndrome.
Patients with concomitant Herpes infections should be treated with acyclovir.
Elderly patients should be treated after individual assessment and with careful
monitoring of blood count and renal and hepatic function. The risk requires a
case-by-case evaluation.
At any time during or after treatment, immediately inform the doctor or
nurseif:
you experience blurred vision, loss of vision or diplopia, difficulty speaking, weakness in an
arm or leg, changes in the way you walk or problems with balance,
persistent numbness, decreased sensation or loss of sensation, memory loss
or confusion. These may be symptoms of a serious brain disease that can be life-threateningknown as progressive multifocal leukoencephalopathy (PML).
If you had these symptoms before treatment with cladribine, tell your doctor about any
changes in these symptoms.

Myelodepression
The depressive effect of LEUSTATIN on bone marrow activity, including a decrease
in the number of neutrophils and platelets and anemia must always be considered. This is usually reversible and appears to be dose-dependent.
Suppression of bone marrow activity is particularly noticeable during the first month
after treatment.
During and after treatment, the hematological parameters of patients must therefore be
checked regularly (especially during the first 2 months) in order to assess the extent of
hematopoietic depression. Caution is advised in patients with severe bone marrow dysfunction of
any origin (see section ADVERSE EFFECTS).
Due to the prolonged immunosuppression associated with the use of nucleoside analogues
such as LEUSTATIN, there is a potential risk of developing secondary tumors. Primary hematological neoplasms are also a risk factor for the development of secondary
tumors.

HAIRY CELL LEUKEMIA
During and after treatment, the hematological parameters of patients must therefore be
checked regularly (especially during the first 2 months) in order to assess the extent of
hematopoietic depression.

CHRONIC LYMPHATIC LEUKEMIA
During the first two cycles of treatment with LEUSTATIN, hematological parameters
reach the lowest value usually observed in the second cycle. Toxicity does not appear to increase following subsequent cycles of therapy. Monitoring of
hematological parameters during treatment with LEUSTATIN is recommended.

Neurotoxicity
Signs of irreversible neurological toxicity (paraparesis/tetraparesis) have occurred with the use of very high doses (4 to 9 times those recommended for HCL).
Neurotoxicity appears to be dose-related; however, signs of neurotoxicity have rarely occurred in patients treated with the recommended doses (0.09 mg/kg/day for 7 days).
The doctor should consider reducing or discontinuing treatment if signs of
neurotoxicity appear.

Fever/Infections

HAIRY CELL LEUKEMIA
During clinical studies, febrile episodes associated with the use of LEUSTATIN were detected in
approximately 72% (89/124) of patients.
Most febrile episodes occurred during the 1st month of treatment and were not
associated with a confirmed infection.

CHRONIC LYMPHATIC LEUKEMIA
Episodes of hyperthermia have been reported in 22–24% of patients during the first cycle of
treatment and in less than 3% during subsequent cycles. 32.5% of patients (40/123) reported at least one infection during the first cycle.
The infections that occurred in at least 5% of cases were: respiratory infections (8.9%), pneumonia (7.3%), bacterial infections (5.7%)
and viral skin infections (5.7%).
Approximately 70% of patients reported at least one infection during the overall
clinical trial period, including treatment and the follow-up period.
Since most febrile episodes occurred in neutropenic patients, these subjects should be closely monitored during the 1st month and
should be given antibiotic therapy, if clinically indicated.
Febrile episodes should be evaluated with appropriate laboratory and
radiological investigations.
The doctor should carefully evaluate the risks and benefits of administering the drug to patients with ongoing infections. Since fever may be
accompanied by increased fluid loss, patients should be kept well hydrated
(see “Adverse Effects”).

Tumor lysis syndrome
Rare cases of tumor lysis syndrome have been reported in patients with other malignant hematological conditions
with a high tumor cell burden treated with cladribine.

Effect on hepatic and renal function
Acute renal failure has occurred in some patients treated with high doses of
LEUSTATIN.
Since there are no adequate data on the treatment of patients with renal or
hepatic insufficiency, caution should be used in administering LEUSTATIN to these patients.
As with other potent chemotherapeutics, monitoring of hepatic and renal function should be performed, especially in patients with concomitant renal and/or hepatic dysfunction. In
case of renal toxicity, discontinuation of treatment should be considered.
(see “Adverse Effects”).

Laboratory tests
During and after treatment, blood tests should be checked regularly to
assess the extent of bone marrow depression.

Important information on some excipients
LEUSTATIN contains sodium.
This medicine contains 38.2 mg of sodium (component of table salt) per
vial. This is equivalent to 1.91% of the recommended maximum daily intake with the diet
of an adult.
To be taken into consideration in people with impaired renal function or who are following a low-sodium diet.

INTERACTIONS
Tell your doctor or pharmacist if you have recently taken any other medicines, including
those available without a prescription.
Particular care is needed if LEUSTATIN is administered after or in
combination with other drugs toxic to the bone marrow.
Following the administration of LEUSTATIN, particular caution should be exercised before
starting other immunosuppressive or myelosuppressive therapies.
Due to the similar intracellular metabolism, cross-resistance may occur with other
nucleotide analogues such as fludarabine or 2'-deoxycoformycin. Therefore, the concomitant administration of nucleotide analogues with cladribine is not recommended.
Since interactions may occur with medicines that undergo intracellular phosphorylation
such as antiviral agents or adenosine uptake inhibitors (e.g. didanosine, tenofovir, adefovir), concomitant use with cladribine is not recommended.

SPECIAL WARNINGS
Pregnancy and breastfeeding
Tell your doctor or pharmacist before taking any medicine.
LEUSTATIN should not be used during pregnancy.
Women of childbearing potential must use effective contraception during treatment with
LEUSTATIN and for 6 months after the last dose of LEUSTATIN.
If LEUSTATIN is administered during pregnancy, or the patient becomes
pregnant during treatment, she should be informed of the possible
risks to the fetus. Women of childbearing potential should be advised to avoid pregnancy.
LEUSTATIN is teratogenic in mice and rabbits.
It is not known whether the drug is excreted in breast milk. Breastfeeding should not be initiated
during treatment with LEUSTATIN and for 6 months after the last dose of LEUSTATIN
Men treated with LEUSTATIN should be advised not to father a
child until 6 months after the last dose of LEUSTATIN. Family planning should
be discussed with patients on a case-by-case basis.

Carcinogenesis/Mutagenesis
Carcinogenicity studies have not been conducted with cladribine in animals. However,
based on the demonstrated genotoxicity of cladribine, the carcinogenic potential cannot
be excluded.
Cladribine has shown chromosomal effects when tested in vivo in the micronucleus test in mice and in vitro in CHO-WBL cells.

Effects on the ability to drive and operate machinery
Considering the clinical conditions of patients and the safety profile of
LEUSTATIN, caution should be exercised if a patient undertakes activities requiring
attention and vigilance.

DOSAGE, ADMINISTRATION AND DURATION OF TREATMENT

HAIRY CELL LEUKEMIA
The recommended dosage provides a single cycle of treatment, lasting 7
consecutive days, with continuous intravenous infusion of 0.09 mg/kg/day of
cladribine. Deviations from this dosage regimen are not recommended.
Patients who do not respond after the first cycle of treatment are unlikely to
benefit from subsequent treatments.

CHRONIC LYMPHATIC LEUKEMIA
The recommended dose is 0.12 mg/Kg/day (4.8 mg/m²/day) administered by continuous intravenous infusion for 2 hours for 5 consecutive days every 28 days.
It is recommended to submit responding patients to a maximum of 6 cycles of treatment with
LEUSTATIN.
In non-responders, it is recommended not to exceed two cycles of treatment.
The contents of the vial of LEUSTATIN must be diluted with appropriate diluent before
administration.
Since the preparation does not contain any bacteriostatic or bactericidal preservative, the
preparation of the solution must be carried out under aseptic conditions and adopting suitable
environmental precautions.
Children:
The safety and efficacy of LEUSTATIN in children have not been established.

INSTRUCTIONS FOR USE

LEUSTATIN must be diluted with a suitable diluent before administration. Since the

drug does not contain any antimicrobial or bacteriostatic preservative, the preparation of the
solution must be carried out using aseptic techniques and appropriate environmental
precautions.
Products intended for parenteral use must be visually inspected, if possible, before
use in order to highlight particulate matter or changes in the original color.
When LEUSTATIN is stored at low temperatures, a precipitate may form:
this can be resolubilized by leaving the vials at room temperature for a while and then
shaking them vigorously. Do not heat and do not use microwaves.
Particular attention is required to ensure the sterility of the prepared solutions.
Once diluted, LEUSTATIN solutions must be administered within a short time
or must be placed in the refrigerator (2°- 8°C) for no more than 8 hours before use.
Vials of LEUSTATIN are for single use. Any unused residue must be destroyed in
an appropriate manner.
The potential risks associated with the use of cytotoxic agents are well known and during the use and
administration of LEUSTATIN, appropriate precautions must be taken. It is
recommended to use disposable gloves and protective clothing. If LEUSTATIN comes into contact
with the skin or mucous membranes, wash the affected areas immediately with plenty of water.

HAIRY CELL LEUKEMIA

Preparation of the single daily dose
Withdraw the necessary dose of LEUSTATIN (0.09 mg/kg or 0.09 ml/kg) and transfer it into an
infusion bag containing 100 to 500 ml of physiological saline. Start the intravenous
infusion and continue it for 24 hours. Repeat the operation daily for 7 days
consecutively.

The use of 5% dextrose as a diluent is not recommended because it causes
degradation of cladribine.
The diluted solution of LEUSTATIN, in the usual PVC infusion bags, at room
temperature and with normal lighting by fluorescent lamps, is chemically and
physically stable for at least 24 hours.

CHRONIC LYMPHATIC LEUKEMIA

Preparation of the single daily dose
Withdraw the necessary dose of LEUSTATIN (0.12 mg/kg or 4.8 mg/m2) and transfer it into an
infusion bag containing 100 to 500 ml of physiological saline. Start the intravenous
infusion and continue it for 2 hours. Repeat the operation daily for 5 days
consecutively.
The use of 5% dextrose as a diluent is not recommended because it causes degradation of
cladribine.

OVERDOSAGE
Signs and symptoms of overdosage may include nausea, vomiting, diarrhea, severe
myelosuppression (including anemia, thrombocytopenia, leukopenia, and agranulocytosis),
acute renal failure, irreversible neurotoxicity (paraparesis / tetraparesis), onset
of Guillain-Barré and Brown-Séquard syndromes. Neuro- and
nephrotoxicity acute, irreversible have been described in individual patients treated with a dose that was ≥ 4 times to
that recommended for hairy cell leukemia.
There are no specific antidotes.
In case of overdosage, discontinue LEUSTATIN therapy, carefully observe the
patient and adopt appropriate supportive therapies (blood transfusions, dialysis,
hemofiltration, anti-infective therapy, etc.).
The hematological profile of patients who have received an overdose of cladribine must be
monitored regularly.
In case of accidental ingestion/intake of an excessive dose of LEUSTATIN, immediately notify
the doctor or go to the nearest hospital.
If you have any doubts about the use of LEUSTATIN, consult your doctor or pharmacist.

UNDESIRABLE EFFECTS
Like all medicines,LEUSTATIN can cause side effects, although not everyone
experiences them.

Hairy Cell Leukemia (HCL)
The safety of LEUSTATIN has been evaluated in 576 patients with hairy cell leukemia
(HCL) treated with LEUSTATIN as part of two clinical studies. These patients have
received at least one injection of LEUSTATIN and have provided safety data.
The most frequently reported adverse drug reactions (ADRs) (frequency ≥10%) were:
pyrexia (33%), fatigue (31%), nausea (22%), rash (16%), headache (14%) and
reactions at the site of administration (11%).
Table 1 reports the cumulative safety data resulting from the reporting of adverse reactions with the use of LEUSTATIN in patients treated for HCL in clinical studies,
and during post-marketing experience (non-specific indication therapy). Adverse
reactions are listed below according to classification by systems and organs and on
the frequency according to MedDRA. The frequency is classified as: very common (≥ 1/10),
common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to <
1/1,000), very rare (< 1/10,000) and not known (the frequency cannot be defined based on
available data).
Table 1: Adverse drug reactions in HCL clinical studies and post-marketing experience

Events reported as ADRs during post-marketing experience.
Hemolytic anemia includes autoimmune hemolytic anemia.
Confusion includes disorientation.
Neurological toxicity includes peripheral sensory neuropathy, motor neuropathy (paralysis), polyneuropathy and paraparesis.
Interstitial lung infiltrates include pulmonary infiltration, interstitial lung disease, pneumonia and pulmonary fibrosis.
Dyspnea includes dyspnea, exertional dyspnea and wheezing.
Abdominal pain includes abdominal distress, abdominal pain and pain
in the lower and upper abdomen.
Rash includes erythema, skin eruptions and rash (macular, maculo-papular,
papular, pruritic, pustular and erythematous).
Pain includes pain, back pain, chest pain, arthritis pain,
bone pain and limb pain.
Renal insufficiency includes acute renal failure and renal impairment.
Reactions at the site of administration include reactions at the
administration site, reactions at the catheter insertion site (cellulitis,
erythema, bleeding and pain) and infusion site reaction (erythema, edema and
pain).
Secondary tumors are a potential risk due to prolonged
immunosuppression associated with the use of nucleoside analogs such as
LEUSTATIN. Primary hematological tumors are also a risk
factor for secondary tumors.
The following safety data are based on a subgroup of 124 patients with
hairy cell leukemia (HCL) enrolled in the main clinical study. In the first month, severe
neutropenia was observed in 70% of patients and infections in 31% of patients. The
fever was observed in 72% of patients. Most non-hematological adverse events were mild to moderate in intensity. Most rashes
were mild.

Bone marrow depression
Myelosuppression has been frequently found during the 1st month after the start of therapy
with LEUSTATIN. Neutropenia (absolute neutrophil count < 500x106/L) was detected
in 69% of patients, while this finding was present in 25% of cases before the start of
treatments. Severe anemia (hemoglobin less than 8.5 g/dl) was also observed in
41% of patients (12% at baseline) and thrombocytopenia (platelets less than 20x109/L) in 15%
of patients (5% at baseline).
Lymphocyte analysis indicates that treatment with LEUSTATIN is associated with a prolonged
reduction in the number of CD4 and a transient reduction in the number of CD8
The clinical significance of the prolonged reduction in CD4 is unclear.
Prolonged bone marrow hypocellularity (<35%) has been observed.

Fever/Infections
Fever was a frequently observed side effect during the first month of
study. During this period, 12% of patients had a fever (t  40°C). Documented cases of infections were noted in less than one third of all febrile episodes.
Of the 124 patients studied, 11 had a documented infection in the month before
treatment. In the month following treatment, 31% of patients had a documented infection
: 13.7% of patients had a bacterial infection, 6.5% a viral infection and 6.5% a fungal infection. 70% of these patients were treated
empirically with antibiotics.
During the 1st month, serious infections (septicemia, pneumonia) were reported in 7% of
patients. During the 2nd month, the overall rate of documented infections was 8%;
these infections were mild or moderate and no systemic infections occurred.
After the 3rd month, the monthly incidence of infections was equal to or lower than that of the months
immediately preceding the start of LEUSTATIN therapy.
Among the 124 patients there were 6 cases of death. Of these, one was due to infection, two to
pre-existing heart disease, two to persistent leukemia with infectious complications and the last
to disease progression after treatment with another chemotherapeutic agent.

Chronic lymphocytic leukemia of the B-cell line (CLL)
The safety of LEUSTATIN has been evaluated in 266 patients with B-cell chronic lymphocytic leukemia (CLL) treated with LEUSTATIN observed in the two main clinical studies. These patients received at least one injection of LEUSTATIN and provided safety data.
Based on aggregated safety data from clinical studies on CLL, the most frequently reported adverse drug reactions (ADRs) (frequency ≥10%) were: pyrexia (28%), fatigue (22%), reactions at the injection site (21%) and headache (11%).
Table 2 reports the cumulative safety data derived from the reporting of adverse drug reactions following the use of LEUSTATIN in patients treated for CLL in clinical studies, and during post-marketing experience (non-specific therapy for indication).
Adverse reactions are listed below by systemic classification and frequency groups. The frequency is classified as: very common (≥ 1/10), common (from ≥ 1/100 to < 1/10), uncommon (from ≥ 1/1,000 to < 1/100), rare (from ≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (the frequency cannot be defined based on available data).
Table 2: Adverse drug reactions in clinical CLL studies and in the post-marketing phase

Events reported as ADRs during post-marketing experience.
Hemolytic anemia includes autoimmune hemolytic anemia.
Confusion includes disorientation.
Neurological toxicity includes peripheral sensory neuropathy, motor neuropathy (paralysis),
polyneuropathy and paraparesis.
Interstitial lung infiltrates include pulmonary infiltration, interstitial lung disease,
pneumonia and pulmonary fibrosis.
Dyspnea includes dyspnea, exertional dyspnea and wheezing
Rash includes rash (maculo-papular, pruritic and pustular) and erythema.
Pain includes pain, arthralgia, back pain, bone pain, musculoskeletal pain
and pain in the extremities.
Renal failure includes acute renal failure and renal impairment.
Reactions at the injection site include reactions at the injection site, reactions
in the catheter insertion area (erythema and infection) and infusion site reaction
(cellulitis, erythema, irritation, edema, pain, infection and phlebitis).
Secondary tumors are a potential risk due to prolonged immunosuppression
associated with the use of nucleoside analogs such as LEUSTATIN. Primary hematological
tumors are also a risk factor for secondary tumors.

Bone Marrow Depression
Patients with CLL treated with LEUSTATIN have shown greater myelosuppression at the beginning
of therapy compared to patients with CML; an increase in myelosuppression was
observed during Cycles 1 and 2 of treatment, reaching nadir values in the second cycle.
The percentage of patients with hemoglobin values < 8.5 g/dL was 16.9% before
treatment, 37.9% in the first cycle and 46.1% in the second cycle. The percentage of patients with
platelet counts < 20x10 /L was 4% before treatment, 20.2% in the first cycle and 22.5% in the second cycle. The absolute neutrophil count was < 500x10 /L in
18.5% of patients before treatment, in 56.5% of patients in cycle 1, in 61.8% in cycle
2, in 59.3% in cycle 3 and in 55.9% in cycle 4. There does not appear to be accumulation toxicity in
following multiple cycles of treatment. Some of the marked hematochemical abnormalities
highlighted during the study were pre-existing, or resolved, or were associated with death due to concomitant diseases.

Fever/Infections
During the first cycle of treatment, 23.6% of patients experienced febrile episodes and
32.5% at least one documented infection. The infections observed in more than 5% of patients
treated during cycle 1 were: respiratory/inflammatory infections (8.9%); pneumonia
(7.3%); bacterial infections (5.6%); viral skin infections (5.7%). From cycle 2 to cycle 9, 71.3% of
patients experienced at least one infection. The infections observed in more than 10%
of treated patients were: pneumonia (28.7%); bacterial infections (21.8%); viral skin infections (20.8%); upper respiratory tract infections (12.9%); other
intestinal/inflammatory infections (12.9%); oral candidiasis (11.9%); urinary tract infections (11.9%); other skin infections (11.9%). Overall, 72.4% of patients
experienced at least one infection during treatment with LEUSTATIN. Of these, 32.6%
were undergoing concomitant immunosuppressive therapy (prednisone).

Safety data following ev/sc administration in patients with Multiple Sclerosis
Although the use of cladribine cannot be recommended for indications other than
Hairy Cell Leukemia or Chronic Lymphocytic Leukemia, nor can subcutaneous administration be
recommended, data are available from research that aimed to evaluate the potential efficacy of the drug in Multiple
Sclerosis.
In two studies in which the e.v. route was used, cladribine was infused at variable doses between
0.087 and 0.1 mg/kg/day for 7 days and this regimen was repeated for 4-6 months.
Cumulative doses therefore varied between 2.8 and 3.65 mg/kg. Furthermore, in three studies that
used the s.c. route, cladribine was administered at doses between 0.07 and 0.14 mg/kg/day for 5
days and this regimen was repeated for 2-6 months.
Cumulative doses therefore varied between 0.7 and 2.1 mg/kg.
The safety profile deduced reflects the expected lymphocytotoxic and bone marrow suppressive effect
and is consistent with the safety profile attributable to the e.v. route of administration
currently recommended for the treatment of CML and CLL.
In these studies, most of the most frequently reported events, including serious adverse events, were typically associated with the underlying disease. Most occurred with overlapping frequency in patients treated with placebo and cladribine. Inflammation and pain at the drug injection site were observed. Subjects treated with
cladribine showed a higher incidence of upper respiratory tract infections,
purpura, hypertonia, muscle weakness compared to patients treated with placebo. In the two
groups, the difference in the incidence of muscle weakness was due mainly to the results
obtained from 1 single researcher, with the exception of a high incidence of thrombocytopenia after
retreatment (8%) compared to initial treatment (4%); no differences were observed in
the profile of adverse events in the first cycle of treatment versus subsequent cycles in 78
patients treated with more than 1 cycle of cladribine.
Less common, but clinically relevant adverse events included those due to
immunosuppression and impaired immune function (pneumonia, aplastic anemia,
pancytopenia, thrombocytopenia, Herpes Simplex and Zoster) and occurred both
exclusively or with an increase in the incidence of severity in patients who had received
a dose of 2.8 mg/kg or higher, particularly when the total dose was
administered over a limited period (e.g. 4 months).

Paediatric population
The safety and efficacy of LEUSTATIN in children have not been established.
undesirable.

Reporting of adverse reactions
If you experience any side effects, including those not listed in this
leaflet, please tell your doctor or pharmacist. Adverse reactions can also be
reported directly through the national reporting system at
www.agenziafarmaco.gov.it/it/responsabili”. Reporting adverse reactions
helps to provide more information on the safety of this medicine.”

EXPIRY DATE AND STORAGE
Expiry date: see the expiry date reported on the packaging.
The expiry date refers to the product in intact packaging, stored correctly.
Caution: do not use the medicine after the expiry date reported on the packaging.
LEUSTATIN vials must be stored in a refrigerated place (2°-8°C) and protected
from light.
Freezing does not negatively affect the solution. If frozen, allow
to thaw at room temperature. Do not heat or use a microwave. Once thawed, the
vial of LEUSTATIN is stable until the expiry date provided it is stored in a refrigerator. Do
not refreeze.
Once diluted, solutions containing LEUSTATIN must be used quickly
or stored in a refrigerator (2°-8°C) for a maximum of 8 hours.
Medicines should not be disposed of via drains or household waste. Ask your
pharmacist how to dispose of medicines you no longer use. This will help protect
the environment.
Keep this medicine out of the reach and sight of children.

COMPOSITION
Each 10 ml vial contains: active ingredient: cladribine 10 mg.
Excipients: sodium chloride; phosphoric acid and/or disodium phosphate heptahydrate; water for
injections.

PHARMACEUTICAL FORM AND CONTENT
Solution for infusion.
7 vials of 10 ml

MARKETING AUTHORISATION HOLDER
Atnahs Pharma Netherlands B.V.
Copenhagen Towers
Ørestads Boulevard 108, 5.tv
DK-2300 Copenhagen
Denmark

MANUFACTURER
JANSSEN PHARMACEUTICA N.V., Turnhoutseweg 30, B-2340 Beerse, Belgium

OF THE MEDICINE