ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
DepoCyte 50 mg suspension for injection
2.
Each 5 ml vial contains 50 mg cytarabine (10 mg/ml).
For a full list of excipients, see section 6.1.
3.
A white to off-white suspension for injection.
4.
Intrathecal treatment of lymphomatous meningitis. In the majority of patients such treatment will be
part of symptomatic palliation of the disease.
DepoCyte should be administered only under the supervision of a physician experienced in the use of
cancer chemotherapeutic agents.
Adults and the elderly
For the treatment of lymphomatous meningitis, the dose for adults is 50 mg (one vial) administered
intrathecally (lumbar puncture or intraventricularly via an Ommaya reservoir). The following regimen
of induction, consolidation and maintenance therapy is recommended:
Induction therapy
: 50 mg administered every 14 days for 2 doses (weeks 1 and 3).
Consolidation therapy
: 50 mg administered every 14 days for 3 doses (weeks 5, 7 and 9) followed by
an additional dose of 50 mg at week 13.
Maintenance therapy
: 50 mg administered every 28 days for 4 doses (weeks 17, 21, 25 and 29).
Method of administration:
DepoCyte
is to be administered by slow injection over a period of 1-5
minutes directly into the cerebrospinal fluid (CSF) via either an intraventricular reservoir or by direct
injection into the lumbar sac. Following administration by lumbar puncture, it is recommended that
the patient should be instructed to lie flat for one hour. All patients should be started on
dexamethasone 4 mg twice daily either orally or intravenously for 5 days beginning on the day of
injection of DepoCyte.
DepoCyte
must not be administered by any other route of administration.
DepoCyte must be used
as supplied; do not dilute (see section 6.2).
Patients should be observed by the physician for immediate toxic reactions.
2
If neurotoxicity develops, the dose should be reduced to 25 mg. If it persists, treatment with
DepoCyte should be discontinued.
Children and adolescents
Safety and efficacy in children have not been adequately demonstrated (see section 5.1). DepoCyte is
not recommended for use in children and adolescents until further data become available.
Hypersensitivity to the active substance or to any of the excipients.
Patients with active meningeal infection.
Patients receiving DepoCyte should be concurrently treated with corticosteroids (e.g. dexamethasone)
to mitigate the symptoms of arachnoiditis (see section 4.8), which is a common adverse reaction.
Arachnoiditis is a syndrome manifested primarily by nausea, vomiting, headache and fever. If left
untreated, chemical arachnoiditis may be fatal.
Patients should be informed about the expected adverse reactions of headache, nausea, vomiting and
fever, and about the early signs and symptoms of neurotoxicity. The importance of concurrent
dexamethasone administration should be emphasised at the initiation of each cycle of DepoCyte
treatment. Patients should be instructed to seek medical attention if signs or symptoms of
neurotoxicity develop, or if oral dexamethasone is not well tolerated.
Cytarabine, when administered intrathecally, has been associated with nausea, vomiting and serious
central nervous system toxicity which can lead to a permanent deficit, this includes blindness,
myelopathy and other neurological toxicity.
Administration of DepoCyte in combination with other neurotoxic chemotherapeutic agents or with
cranial/spinal irradiation may increase the risk of neurotoxicity.
Infectious meningitis may be associated with intrathecal administration. Hydrocephalus has also been
reported, possibly precipitated by arachnoiditis.
Blockage or reduction of CSF flow may result in increased free cytarabine concentrations in the CSF
with increased risk of neurotoxicity. Therefore, as with any intrathecal cytotoxic therapy,
consideration should be given to the need for assessment of CSF flow before treatment is started.
Although significant systemic exposure to free cytarabine is not expected following intrathecal
treatment, some effects on bone marrow function cannot be excluded. Systemic toxicity due to
intravenous administration of cytarabine consists primarily of bone marrow suppression with
leucopenia, thrombocytopenia and anaemia. Therefore monitoring of the haemopoietic system is
advised.
Anaphylactic reactions following intravenous administration of free cytarabine have been rarely
reported.
Since DepoCyte’s particles are similar in size and appearance to white blood cells, care must be taken
in interpreting CSF examination following DepoCyte administration.
No definite interactions between DepoCyte delivered intrathecally and other medicinal products have
been established.
3
Concomitant administration of DepoCyte with other antineoplastic agents administered by the
intrathecal route has not been studied.
Intrathecal co-administration of cytarabine with other cytotoxic agents may increase the risk of
neurotoxicity.
Teratology studies in animals have not been conducted with DepoCyte and there are no adequate and
well controlled studies in pregnant women; however cytarabine can cause foetal harm when
administered during pregnancy. Therefore, women of childbearing potential should not receive the
treatment until pregnancy is excluded and should be advised to use a reliable contraceptive method.
Given that cytarabine has a mutagenic potential which could induce chromosomal damage in the
human spermatozoa, males undergoing DepoCyte treatment and their partner should be advised to use
a reliable contraceptive method.
It is not known whether cytarabine is excreted in human milk following intrathecal administration.
The systemic exposure to free cytarabine following intrathecal treatment with DepoCyte was
negligible. Because of possible excretion in human milk and because of the potential for serious
adverse reactions in nursing infants, the use of DepoCyte is not recommended in breast-feeding
women.
There have been no reports explicitly relating to effects of DepoCyte treatment on the ability to drive
or use machines. However, on the basis of reported adverse reactions, patients should be advised
against driving or using machines during treatment.
DepoCyte has the potential of producing serious toxicity.
All patients receiving DepoCyte should be treated concurrently with dexamethasone to mitigate the
symptoms of arachnoiditis. Toxic effects may be related to a single dose or to cumulative doses.
Because toxic effects can occur at any time during therapy (although they are most likely within 5
days of administration), patients receiving DepoCyte therapy should be monitored continuously for the
development of neurotoxicity. If patients develop neurotoxicity, subsequent doses of DepoCyte
should be reduced, and DepoCyte should be discontinued if toxicity persists.
Arachnoiditis, a syndrome manifested primarily by headache, nausea, vomiting, fever, neck rigidity,
neck or back pain, meningism, convulsions, hydrocephalus, CSF pleocytosis, with or without altered
state of consciousness, is a common adverse reaction. Arachnoiditis can be fatal if left untreated.
The incidence of adverse reactions possibly reflecting meningeal irritation determined from all the
patients treated with 50 mg DepoCyte in the Phase II-IV clinical trials is given in Table 1 below:
4
Cytarabine
(n = 99 cycles)
Headache NOS 24% 16% 14%
Nausea 18% 12% 15%
Vomiting NOS 17% 11% 11%
Arachnoiditis 16% 7% 13%
Pyrexia 12% 7% 16%
Back pain 7% 7% 6%
Convulsions NOS 6% 5% 2%
Neck pain 4% 3% 3%
Neck stiffness 3% <1% 4%
Hydrocephalus acquired 2% 1% 0%
CSF Pleocytosis 1% 0% 0%
Meningism <1% 1% 1%
*Cycle length was 2 weeks during which the patient received either 1 dose of DepoCyte or
4 doses of cytarabine or methotrexate. Cytarabine and methotrexate patients not
completing all 4 doses are counted as a fraction of a cycle.
DepoCyte
(n = 929 cycles)
Methotrexate
(n = 258 cycles)
The incidence of all adverse reactions occurring in > 10% of cycles in either treatment group in Phase
1-4 studies in patients with lymphomatous meningitis receiving DepoCyte or cytarabine is given in
Table 2 below:
Table 2. Adverse reactions occurring in > 10% of cycles in either treatment group in Phase 1-
4 study patients with lymphomatous meningitis receiving DepoCyte 50 mg or cytarabine (% of
cycles* of therapy)
Number of cycles
System Organ Class
MedDRA Preferred Term
DepoCyte
(n=151 cycles)
Cytarabine
(n=99 cycles)
Nervous System Disorders
Headache NOS
23%
14%
Arachnoiditis
16%
13%
Confusion
11%
3%
Gastrointestinal Disorders
Nausea
13%
15%
Vomiting NOS
12%
11%
Diarrhoea NOS
11%
10%
General Disorders and Administrative
Site Conditions
Weakness 13% 17%
Pyrexia 14% 16%
Fatigue 6% 14%
Blood and Lymphatic System Disorders
Thrombocytopenia 10% 13%
*Induction and Maintenance cycle lengths were 2 and 4 weeks, respectively, during which the
patient received either 1 dose of DepoCyte or 4 doses of cytarabine. Cytarabine patients not
completing all 4 doses within a cycle are counted as a complete cycle.
Intrathecal administration of cytarabine may cause myelopathy and other neurologic toxicity
sometimes leading to a permanent neurological deficit. Following intrathecal administration of
DepoCyte, serious central nervous system toxicity, including persistent extreme somnolence,
confusion, hemiplegia, visual disturbances including blindness, deafness and cranial nerve palsies
have been reported. Symptoms and signs of peripheral neuropathy, such as pain, numbness,
paresthesia, hypoaesthesia, weakness, and impaired bowel and bladder control (incontinence) have
also been observed. In some cases, a combination of neurological signs and symptoms have been
5
Table 1: Adverse reactions possibly reflecting meningeal irritation in Phase II, III, and
IV patients (n [%] of cycles* of therapy)
MedDRA preferred term
reported as Cauda Equina Syndrome.
Adverse reactions more commonly associated with DepoCyte are headache, arachnoiditis and
confusion. In addition, in Phase 1-4 studies, the patient incidence of convulsions was higher in the
DepoCyte group (7/33, 21%) than in the cytarabine group (1/28, 4%).
Transient elevations in CSF protein and white blood cells have also been observed in patients
following DepoCyte administration
and also been noted after intrathecal treatment with methotrexate
or cytarabine.
No overdoses with DepoCyte have been reported. An overdose with DepoCyte may be associated
with severe arachnoiditis including encephalopathy.
In an early uncontrolled study without dexamethasone prophylaxis, single doses up to 125 mg were
administered. One patient at the 125 mg dose level died of encephalopathy 36 hours after receiving
DepoCyte intraventricularly. This patient, however, was also receiving concomitant whole brain
irradiation and had previously received intraventricular methotrexate.
There is no antidote for intrathecal DepoCyte
or unencapsulated cytarabine released from
DepoCyte.
Exchange of cerebrospinal fluid with isotonic saline has been carried out in a case of intrathecal
overdose of free cytarabine and such a procedure may be considered in the case of DepoCyte
overdose. Management of overdose should be directed at maintaining vital functions.
5.
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Antimetabolite (pyrimidine analogue), ATC code L01B C01
DepoCyte is a sustained-release formulation of cytarabine, designed for direct administration into the
cerebrospinal fluid (CSF).
Cytarabine is a cell-cycle phase specific antineoplastic agent, affecting cells only during the S-phase
of cell division. Intracellularly, cytarabine is converted into cytarabine-5’-triphosphate (ara-CTP),
which is the active metabolite. The mechanism of action is not completely understood, but it appears
that ara-CTP acts primarily through inhibition of DNA synthesis. Incorporation into DNA and RNA
may also contribute to cytarabine cytotoxicity. Cytarabine is cytotoxic to a wide variety of
proliferating mammalian cells in culture.
For cell-cycle phase specific antimetabolites the duration of exposure of neoplastic cells to cytotoxic
concentrations is an important determination of drug efficacy.
In vitro
studies, examining more than 60 cell lines, demonstrated that the median cytarabine
concentration resulting in 50% growth inhibition (IC
50
) was approximately 10 μM (2.4 μg/ml) for two
days of exposure and 0.1 μM (0.024 μg/ml) for 6 days of exposure. The studies also demonstrated
susceptibility of many solid tumour cell lines to cytarabine, particularly after longer periods of
exposure to cytarabine.
In an open-label, active-controlled, multicentre clinical study, 35 patients with lymphomatous
meningitis (with malignant cells found on CSF cytology) were randomised to intrathecal therapy with
either DepoCyte (n=18) or unencapsulated cytarabine (n=17). During the 1 month Induction phase of
treatment, DepoCyte was administered intrathecally as 50 mg every 2 weeks, and unencapsulated
cytarabine as 50 mg twice a week. Patients who did not respond discontinued protocol treatment after
4 weeks. Patients who achieved a response (defined as clearing of the CSF of malignant cells in the
6
absence of progression of neurological symptoms) went on to receive Consolidation and Maintenance
therapy for up to 29 weeks.
Responses were observed in 13/18 (72%, 95% confidence intervals: 47, 90) of DepoCyte patients
versus 3/17 (18% patients, 95% confidence intervals: 4, 43) in the unencapsulated cytarabine arm. A
statistically significant association between treatment and response was observed (Fisher’s exact test
p-value = 0.002). The majority of DepoCyte patients went on beyond Induction to receive additional
therapy. DepoCyte patients received a median of 5 cycles (doses) per patient (range 1 to 10 doses)
with a median time on therapy of 90 days (range 1 to 207 days).
No statistically significant differences were noted in secondary endpoints such as duration of response,
progression-free survival, neurological signs and symptoms, Karnofsky performance status, quality of
life and overall survival. Median progression-free survival (defined as time to neurological
progression or death) for all treated patients was 77 versus 48 days for DepoCyte versus
unencapsulated cytarabine, respectively. The proportion of patients alive at 12 months was 24% for
DepoCyte versus 19% for unencapsulated cytarabine.
In an open-label non-comparative dose escalation study in 18 paediatric patients (4 to 19 years) with
leukaemic meningitis or neoplastic meningitis due to primary brain tumour, an intrathecal dose of
35 mg was identified as the maximum tolerated dose.
5.2 Pharmacokinetic properties
Analysis of the available pharmacokinetic data shows that following intrathecal DepoCyte
administration in patients, either via the lumbar sac or by intraventricular reservoir, peaks of free
cytarabine were observed within 5 hours in both the ventricle and lumbar sac. These
peaks were
followed by a biphasic elimination
profile consisting of an initial sharp decline and subsequent slow
decline with a terminal phase half-life of 100 to 263 hours over a dose-range of 12.5 mg to 75 mg. In
contrast, intrathecal administration of 30 mg free cytarabine has shown a biphasic CSF concentration
profile with a terminal phase half-life of about 3.4 hours.
Pharmacokinetic parameters of DepoCyte (75 mg) in neoplastic meningitis patients in whom the drug
was administered either intraventricularly or by lumbar puncture suggest that exposure to the drug in
the ventricular or lumbar spaces is similar regardless of the route of administration. In addition,
compared with free cytarabine, the formulation increases the biological half-life by a factor of 27 to 71
depending upon the route of administration and the compartment sampled. Encapsulated cytarabine
concentrations and the counts of the lipid particles in which the cytarabine is encapsulated in
DepoCyte followed a similar distribution pattern. AUCs of free and encapsulated cytarabine after
ventricular injection of DepoCyte appeared to increase linearly with increasing dose, indicating that
the release of cytarabine from DepoCyte and the pharmacokinetics of cytarabine are linear in human
CSF.
The transfer rate of cytarabine from CSF to plasma is slow and the conversion to uracil arabinoside
(ara-U), the inactive metabolite, in the plasma is fast. Systemic exposure to cytarabine was
determined to be negligible following intrathecal administration of 50 mg and 75 mg of DepoCyte.
Metabolism and elimination
The primary route of elimination of cytarabine is metabolism to the inactive compound ara-U,
(
1-β-D-
arabinofuranosyluracil or uracil arabinoside)
followed by urinary excretion of ara-U. In contrast with
systemically administered cytarabine which is rapidly metabolised to ara-U, conversion to ara-U in the
CSF is negligible after intrathecal administration because of the significantly lower cytidine deaminase
activity in the CNS tissues and CSF. The CSF clearance rate of cytarabine is similar to the CSF bulk
flow rate of 0.24 ml/min.
The distribution and clearance of cytarabine and of the predominant phospholipid component of the
lipid particle (DOPC) following intrathecal administration of DepoCyte was evaluated in rodents.
Radiolabels for cytarabine and DOPC were distributed rapidly throughout the neuraxis. More than
7
90% of cytarabine was excreted by day 4 and an additional 2.7% by 21 days. The results suggest that
the lipid components undergo hydrolysis and are largely incorporated in the tissues following
breakdown in the intrathecal space.
5.3 Preclinical safety data
A review of the toxicological data available for the constituent lipids (DOPC and DPPG) or similar
phospholipids to those in DepoCyte indicates that such lipids are well tolerated in various animal
species even when administered for prolonged periods at doses in the g/kg range.
The results of acute and subacute toxicity studies performed in monkeys suggested that intrathecal
DepoCyte was tolerated up to a dose of 10 mg (comparable to a human dose of 100 mg). Slight to
moderate inflammation of the meninges in the spinal cord and brain and/or astrocytic activation were
observed in animals receiving intrathecal DepoCyte. These changes were believed to be consistent
with the toxic effects of other intrathecal agents such as unencapsulated cytarabine. Similar changes
(generally described as minimal to slight) were also observed in some animals receiving DepoFoam
alone (DepoCyte vesicles without cytarabine) but not in saline control animals. Mouse, rat and dog
studies have shown that free cytarabine is highly toxic for the haemopoietic system.
No carcinogenicity, mutagenicity or impairment of fertility studies have been conducted with
DepoCyte. The active ingredient of DepoCyte, cytarabine, was mutagenic in
in vitro
tests and was
clastogenic
in vitro
(chromosome aberrations and sister chromatid exchange in human leukocytes) and
in vivo
(chromosome aberrations and sister chromatid exchange assay in rodent bone marrow, mouse
micronucleus assay). Cytarabine caused the transformation of hamster embryo cells and rat H43 cells
in vitro
. Cytarabine was clastogenic to meiotic cells; a dose-dependent increase in sperm-head
abnormalities and chromosomal aberrations occurred in mice given i.p. cytarabine. No studies
assessing the impact of cytarabine on fertility are available in the literature. Because the systemic
exposure to free cytarabine following intrathecal treatment with DepoCyte was negligible, the risk of
impaired fertility is likely to be low.
6.
6.1 List of excipients
Cholesterol
Triolein
Dioleoylphosphatidylcholine (DOPC)
Dipalmitoylphosphatidylglycerol (DPPG)
Sodium chloride
Water for injections
6.2 Incompatibilities
No formal assessments of pharmacokinetic drug-drug interactions between DepoCyte and other agents
have been conducted. DepoCyte should not be diluted or mixed with any other medicinal products, as
any change in concentration or pH may affect the stability of the microparticles.
6.3 Shelf life
18 months
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C).
Do not freeze.
8
6.5 Nature and contents of container
DepoCyte is supplied in individual cartons each containing one single-dose Type I glass vial
containing 50 mg (in 5 ml), closed with a fluororesin faced butyl rubber stopper and sealed with an
aluminium flip-off seal.
6.6 Special precautions for disposal
Preparation of DepoCyte
Given its toxic nature, special precautions should be taken in handling DepoCyte. See ‘Precautions
for the handling and disposal of DepoCyte’ below.
Vials should be allowed to warm to room temperature (18°C -22°C) for a minimum of 30 minutes and
be gently inverted to resuspend the particles immediately prior to withdrawal from the vial. Avoid
vigorous shaking. No further reconstitution or dilution is required.
DepoCyte administration
DepoCyte must only be administered by the intrathecal route.
DepoCyte should be withdrawn from the vial immediately before administration. Since it is a single
use vial and does not contain any preservative, the drug should be used within 4 hours of withdrawal
from the vial. Unused drug must be discarded and not used subsequently. Do not mix DepoCyte with
any other medicinal products (see section 6.2). Do not dilute the suspension.
In-line filters must not be used when administering DepoCyte. DepoCyte is administered directly into
the CSF via an intraventricular reservoir or by direct injection into the lumbar sac. DepoCyte should
be injected slowly over a period of 1-5 minutes. Following drug administration by lumbar puncture,
the patient should be instructed to lie flat for one hour. Patients should be observed by the physician
for immediate toxic reactions.
All patients should be started on dexamethasone 4 mg twice daily either orally or intravenously for 5
days beginning on the day of DepoCyte injection.
Precautions for the handling and disposal of DepoCyte
The following protective recommendations are given due to the toxic nature of this substance:
•
personnel should be trained in good technique for handling anticancer agents
•
male and female staff who are trying to conceive and female staff who are pregnant should be
excluded from working with the substance
•
personnel must wear protective clothing: goggles, gowns, disposable gloves and masks
•
a designated area should be defined for preparation (preferably under a laminar flow system).
The work surface should be protected by disposable, plastic backed, absorbent paper
•
all items used during administration or cleaning should be placed in high risk, waste-disposal
bags for high temperature incineration
•
in the event of accidental contact with the skin, exposed areas should be washed immediately
with soap and water
•
in the event of accidental contact with the mucous membranes, exposed areas should be treated
immediately by copious lavage with water; medical attention should be sought.
9
7.
Pacira Limited
3 Glory Park Avenue
Wooburn Green
High Wycombe
Buckinghamshire
HP10 0DF
United Kingdom
8.
EU/1/01/187/001
9.
Date of first authorisation: 11 July 2001
Date of last renewal: 11 July 2006
10
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
11
A
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer responsible for batch release
Almac Pharma Services Limited
20 Seagoe Industrial Estate
Craigavon, Co Armagh
BT63 5QD
United Kingdom
B
CONDITIONS OF THE MARKETING AUTHORISATION
•
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
The Marketing Authorisation Holder will continue to submit yearly PSURs unless otherwise specified
by the CHMP.
12
ANNEX III
LABELLING AND PACKAGE LEAFLET
13
A. LABELLING
14
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
BOX OF 1 VIAL
1.
DepoCyte 50 mg suspension for injection.
Cytarabine.
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each vial contains 50 mg cytarabine (10 mg/ml).
3.
LIST OF EXCIPIENTS
Also contains: cholesterol, triolein, dioleoylphosphatidylcholine, dipalmitoylphosphatidylglycerol,
sodium chloride, water for injections.
4.
Suspension for injection.
One vial – 5 ml.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Intrathecal 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
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator (2ºC - 8ºC)
Do not freeze
15
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Pacira Limited
3 Glory Park Avenue
Wooburn Green
High Wycombe
Buckinghamshire
HP10 0DF
United Kingdom
EU/1/01/187/001
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
16
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL LABEL
1.
DepoCyte 50 mg suspension for injection
Cytarabine
Intrathecal use
2.
METHOD
OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
Contains 5 ml.
6.
OTHER
17
B. PACKAGE LEAFLET
18
PACKAGE LEAFLET: INFORMATION FOR THE USER
DepoCyte 50 mg suspension for injection
Cytarabine
Read all of this leaflet carefully before you receive this medicine.
-
If you have further questions, please ask your doctor.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor.
In this leaflet
:
1.
What DepoCyte is and what it is given for
3.
How DepoCyte is given
4.
Possible side effects
5.
How to store DepoCyte
6.
Further information
1.
WHAT DEPOCYTE IS AND WHAT IT IS GIVEN FOR
DepoCyte is used to treat lymphomatous meningitis.
Lymphomatous meningitis is a condition in which tumour cells have invaded the fluid or membranes
that surround the brain and spinal cord.
DepoCyte is used in adults to kill lymphoma tumour cells.
2.
BEFORE YOU ARE GIVEN DEPOCYTE
DepoCyte should not be given
-
If you are allergic (hypersensitive) to cytarabine or any of the other ingredients.
-
If you have a meningeal infection.
Taking other medicines
Please inform your doctor or physician if you are taking or using any other medicines, including
medicines obtained without a prescription.
Pregnancy and breast-feeding
DepoCyte should not be given to pregnant women as it may harm an unborn child. Women of
childbearing potential should use a reliable contraceptive to avoid pregnancy whilst being treated with
DepoCyte.
Male patients undergoing DepoCyte treatment should use a reliable contraceptive method.
Women should not breast-feed during treatment as DepoCyte may enter breast milk.
Driving and using machines
Do not drive during treatment.
Do not operate any tools or machines during treatment.
19
-
Keep this leaflet. You may need to read it again.
2.
Before you are given DepoCyte
3.
HOW DEPOCYTE IS GIVEN
Before using DepoCyte, warm the vial to room temperature (18°C – 22°C) for at least 30 minutes. Just
before withdrawing DepoCyte, gently invert the vial to mix the particles evenly. Do not shake the vial
vigorously.
A qualified and experienced doctor or physician in the treatment of cancer will inject DepoCyte in the
spinal fluid or lumber sac. DepoCyte must not be administered by any other way. Injections are given
slowly over a few minutes and you may be asked to lie flat for one hour afterwards.
You will also be given dexamethasone, usually as tablets but possibly by intravenous injection for 5
days after you receive each DepoCyte dose to help reduce any side effects which might occur.
DepoCyte must be used
as supplied without further dilution. The dose for adults is 50 mg (one vial of
DepoCyte).
For the treatment of lymphomatous meningitis, DepoCyte is given according to the following
schedules:
Start-up treatment:
one vial of DepoCyte (50 mg) administered every 14 days for 2 doses (weeks 1
and 3).
Follow-up treatment:
one vial of DepoCyte (50 mg) administered every 14 days for 3 doses (weeks
5, 7 and 9) followed by an additional dose at week 13.
Maintenance treatment:
one vial of DepoCyte (50 mg) administered every 28 days for 4 doses
(weeks 17, 21, 25 and 29).
If you are given more DepoCyte than you should
The recommended dose will be given to you by the doctor or physician as necessary. There is no
antidote for DepoCyte. Management of overdose should be directed at maintaining vital functions.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, DepoCyte can cause side effects, although not everybody gets them. Side effects
may occur after each injection, usually within the first five days.
Tell the medical staff, who will be monitoring you during this time, if you suffer from:
•
Pain, numbness or tingling (feeling of sensation of pins and needles)
•
Nausea and/or vomiting
•
Weakness
•
Confusion
•
Fever
•
Headaches
•
Fatigue
•
Convulsion
•
Dizziness
•
Neck pain
•
A stiff or rigid neck
•
Partial paralysis
•
Blindness and other visual disturbances
•
Shaking
•
Back pain
•
Persistent or extreme sleepiness
20
•
Hearing loss
•
Infection of the meninges
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
inform the medical staff looking after you.
5.
STORING DEPOCYTE
Keep out of the reach and sight of children.
Do not use DepoCyte after the expiry date which is stated on the carton and on the vial.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
6.
FURTHER INFORMATION
What DepoCyte contains
-
The other ingredients are cholesterol, triolein, dioleoylphosphatidylcholine,
dipalmitoylphosphatidylglycerol, sodium chloride and water for injections.
What DepoCyte looks like and contents of the pack
DepoCyte is a vial containing a white to off-white-suspension for injection.
Each vial contains 5 ml of suspension for a single injection.
Each pack contains a single vial.
Marketing Authorisation Holder
Pacira Limited, 3 Glory Park Avenue, Wooburn Green, High Wycombe, Buckinghamshire,
HP10 0DF, United Kingdom.
Manufacturer
Almac Pharma Services Limited, 20 Seagoe Industrial Estate, Craigavon, Co Armagh, BT63 5QD,
United Kingdom.
21
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The active substance is 50 mg cytarabine (10 mg/ml)
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien
Mundipharma Comm VA.
Schaliënhoevedreef 20H
B-2800 Mechelen
Tél/Tel: +32 (0) 15 45 11 80
Luxembourg/Luxemburg
Mundipharma Comm VA.
Schaliënhoevedreef 20H
2800 Mechelen
Belgique/Belgien
Tél: +32 (0) 15 45 11 80
България
Мундифарма България
Бул. Никола Вапцаров № 55
1407 София
Τeл: + 359 8985 99700
Magyarország
Medis, d.o.o.
Ljubljana, Szlovénia
Információsvonal: (1)- 487-5350
Česká republika
Mundipharma Ges.m.b.H. Austria
organizační složka ČR
Lerchova 9
PSČ 602 00 Brno
Tel : +420 543 215 070
Malta
3 Glory Park Avenue, Wooburn Green
High Wycombe, Buckinghamshire
HP10 0DF - Renju Unit
Τel: +44 (0) 144 228 3649
Danmark
Norpharma A/S
Slotsmarken 15
DK-2970 Hørsholm
Tlf: +45 45 17 48 00
Nederland
Mundipharma Pharmaceuticals B.V.
De Wel 20
NL-3871 MV Hoevelaken
Tel: +31 (0) 33 450 8270
Deutschland
Mundipharma GmbH
Mundipharmastrasse 2
D-65549 Limburg/Lahn
Tel: + 49 6431 701 0
Norge
Mundipharma AS
N-1366 Lysaker
Tlf: +47 67 51 89 00
Eesti
OÜ K-Büroo Marketing
Kalevi 112/2
EE - 50104 Tartu
Tel: +372 733 8080
Österreich
Mundipharma Ges.m.b.H.
Apollogasse 16-18
A-1072 Wien
Tel: + 43 (1) 523 25 05
Eλλάδα
3 Glory Park Avenue, Wooburn Green
High Wycombe, Buckinghamshire
HP10 0DF
Ηνωμένο Βασίλειο
Τηλ: +44 (0) 144 228 3649
Polska
Mundipharma Polska Sp.zoo
UL. Kochanowskiego 49A
01-864
Warszawa
Tel: +48(0) 22 866 87 12
España
Mundipharma Pharmaceuticals, S.L.
Edificio ALVENTO (Torre D)
Vía de los Poblados 1
28033 Madrid
Tel: +34 91 3821870
Portugal
Mundipharma Farmacêutica Lda
Edifício Atrium Saldanha
Praça Duque de Saldanha, 1 – 6º
Lisboa 1050-094
Tel: +351 219 258064
22
France
Mundipharma SAS
2 Rue du Docteur Lombard
F-92130 Issy Les Moulineaux
Tel: +33 (0) 155 389230
România
Mundipharma Medical GmbH
Representative Office Romania
Str. Mihail Petrini nr 4
Et. 2, apt. 6, sector 5
050582 Bucuresti
Tel: +40(21) 410 10 49
Ireland
Napp Pharmaceuticals Limited
Cambridge Science Park
Milton Road
Cambridge CB4 0GW – United Kingdom
Tel: +44 (0) 1223 424444
Slovenija
Medis, d.o.o.
Brnčičeva 1
SI - 1000 Ljubljana
Tel: +386 158969 00
Ísland
Norpharma A/S
Slotsmarken 15
2970 Hørsholm
Danmark
Tel: +45 45 17 48 00
Slovenská republika
Mundipharma Ges.m.b.H. - o.z
Jaroslavova 23
SK-851 01 Bratislava
Tel: +421 2 63811611
Italia
Mundipharma Pharmaceuticals Srl
Via G. Serbelloni no 4
I-20122 Milano
Tel: + 39.02.76001616
Suomi/Finland
Mundipharma Oy
Rajatorpantie 41B
FIN-01640 Vantaa
Puh/Tel: +358 (0)9 8520 2065
Κύπρος
Mundipharma Pharmaceuticals Ltd
13 Othellos Street
Dhali Industrial Zone
CY- 1685 Nicosia
Τηλ: +357 22 81 56 56
Sverige
Mundipharma AB
Mölndalsvägen 30B
S-412 63 Göteborg
Tel: + 46 (0)31 773 75 30
Latvija
ĀKD, SIA
A. Saharova iela 16-342
Rīga LV-1021
Tel: +371 7 800810
United Kingdom
Napp Pharmaceuticals Limited
Cambridge Science Park
Milton Road
Cambridge CB4 0GW - UK
Tel: +44 (0) 1223 424444
Lietuva
OÜ K-Büroo Marketing
Kalevi 112/2
EE - 50104 Tartu
Estija
Tel. +372 733 8080
This leaflet was last approved in
23
Source: European Medicines Agency
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