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Active substance(s): VINDESINE SULPHATE

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Eldisine *
(Vindesine Sulphate)
Read all of this leaflet carefully before you start taking this
- 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 signs of illness are the
same as yours.
- If you get any side-effects talk to your doctor or pharmacist.
This includes any possible side-effects not listed in this leaflet.
See section 4.
What is in this leaflet
1. What Eldisine is and what it is used for
2. What you need to know before you use Eldisine
3. How to use Eldisine
4. Possible side-effects
5. How to store Eldisine
6. Contents of the pack and other information
Eldisine contains vindesine sulphate. Eldisine is a cytotoxic
medicine. Cytotoxic medicines kill cells which are dividing,
including cancer cells. It is used to treat patients who have a
cancer such as leukaemia, malignant melanoma (a type of skin
cancer) or breast cancer. If your doctor gives you this medicine for
anything else, ask him or her if you have any questions.

Do not use Eldisine if you:
• are allergic to vindesine sulphate or any of the other ingredients
in Eldisine (see section 6 – Contents of the pack and other
• suffer from any disease affecting the nerves or muscles (such as
Charcot-Marie-Tooth syndrome)
• have a bacterial infection.
Warnings and precautions
Talk to your doctor or pharmacist before using Eldisine if you:
• are having radiotherapy in the liver area
• suffer from constipation
• have liver trouble
Other medicines and Eldisine
Tell your doctor or pharmacist if you are taking, have recently taken
or might take any other medicines.
• phenytoin for treating epilepsy
• mitomycin
Pregnancy, breast-feeding and fertility
Do not use Eldisine if you are pregnant or breast-feeding. If you are
planning to become pregnant, ask your doctor or pharmacist for
advice before taking this medicine. Men should not father a child
during or immediately after treatment.
Your doctor will only inject Eldisine into a vein. It must never be
injected intrathecally (into your back with the needle going into your
spine). If you have a bacterial infection, your doctor will probably
treat the infections before starting the Eldisine.
Eldisine and most other cytotoxic medicines may affect the cells in

Information for the health care professional

Eldisine Powder for Solution for Injection 5.0 mg
Eldisine Powder 5mg contains 5mg vindesine sulphate per 5ml when reconstituted.
For a full list of excipients, see section 6.1
Powder for Solution for Injection.
A clear glass vial containing a lyophilised plug of white crystalline powder.
4.1 Therapeutic Indications
Eldisine is an anti-neoplastic drug for intravenous use which can be used alone or in combination
with other oncolytic drugs. Information available at present suggests that Eldisine as a single
agent may be useful for the treatment of:
• acute lymphoblastic leukaemia of childhood resistant to other drugs;
• blastic crises of chronic myeloid leukaemia;
• malignant melanoma unresponsive to other forms of therapy;
• advanced carcinoma of the breast, unresponsive to appropriate endocrine surgery and/or
hormonal therapy.
4.2 Posology and Method of Administration
This preparation is for intravenous use only. It should be administered only by individuals
experienced in vindesine administration.
See special warnings in section 4.4 for the treatment of patients given intrathecal vindesine
Extreme care must be used in calculating and administering the dose of vindesine, since
overdosage may have a very serious or fatal outcome.
It is recommended that the drug be administered intravenously in a single rapid bolus injection at
weekly intervals. The size of the dose is determined by body surface area. In adults and the
elderly, the recommended starting dose is 3mg/m2, and children may be started at 4mg/m2.
Thereafter, granulocyte counts should be made prior to each subsequent dose to determine the
patient's sensitivity to the drug. Provided there is no granulocytopenia or other toxicity (see
section 4.8) the dosage may be increased in 0.5mg/m2 steps at weekly intervals.
In adults, the maximum total weekly dosage for which data exists is 4mg/m2. The optimum dose
of vindesine is that which produces mild to modest granulocytopenia. Sustained granulocyte
counts lower than 2,500 cells/mm3 are to be avoided.
Those with decreased marrow function from leukaemia infiltration or replacement will require full
doses to attempt to restore marrow function. This must be done under close supervision.
The dose should not be increased after that dose which: (i) reduces the granulocyte count to
below 1,500 cells/mm3 or, on rare occasions, (ii) reduces the platelet count to below
100,000/mm3; (iii) causes acute abdominal pain (see section 4.4).
On each of the above occasions there should be full recovery before administering the next dose,
which should be reduced from the one causing the adverse reaction. For most patients, however,
the weekly dosage will prove to be in the range of 3.0 to 4.0mg/m2 in adults and 4.0 to 5.0mg/m2
in children.
The use of small amounts of vindesine daily for long periods is not advised, even though the
resulting total weekly dosage may be similar to that recommended. Little or no added therapeutic
advantage has been demonstrated when such regimens have been used, and side-effects are
increased. Strict adherence to the recommended dosage schedule is very important.
As vindesine is excreted principally by the liver, it may be necessary to reduce initial doses in the
presence of significantly impaired hepatic or biliary function.
The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450
isoenzymes in the CYP3A subfamily. This metabolic pathway may be impaired in patients with
hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes. (See
section 4.5.)
To prepare a solution containing 1mg/ml add 5ml of sterile 0.9% sodium chloride intravenous
infusion to the 5mg of Eldisine in the sterile vial. The drug dissolves rapidly to give a clear
The dose of Eldisine solution (calculated to provide the desired number of milligrams per square
metre of the patient's surface area) may be injected either into the tubing of a running
intravenous infusion (compatible infusions are 5% Dextrose Intravenous Infusion BP, Sodium
Chloride Intravenous Infusion BP and dextrose/saline infusions) or directly into a vein.
The latter procedure is readily adaptable to outpatient therapy. In either case, the injection should
be completed in 1 to 3 minutes. If care is taken to ensure that the needle is securely within the
vein and that no solution containing vindesine is spilled extravascularly, cellulitis and/or phlebitis
is unlikely to occur.
Because of the enhanced possibility of thrombosis, it is considered inadvisable to inject a
solution into an extremity in which the circulation is impaired, or potentially impaired, by such
conditions as compressing or invading neoplasm, phlebitis or varicosity.
It is extremely important to choose the largest accessible vein and to be certain that the needle is
properly positioned in the vein before any vindesine is injected. If leakage into surrounding
tissues should occur during intravenous administration it may cause considerable irritation. The
injection should be discontinued as soon as leakage occurs, and any remaining portion of the
dose should then be introduced into another vein. Local injection of hyaluronidase and the
application of moderate heat to the area of leakage help disperse the drug and are thought to
minimise discomfort and the possibility of cellulitis.

your bone marrow. These cells divide quickly to make new blood
cells. Your doctor or nurse will take samples of your blood when
you are treated with Eldisine. The hospital’s laboratory will then
count the numbers of different types of blood cells (platelets, white
cells and red cells). Your doctor may decide to change the dose or
put off treating you if your blood cell counts are too low. Your blood
cell counts soon improve as the bone marrow makes new cells.
A lot of injections (more than one a week) may cause more sideeffects.
Eldisine works by sticking to certain molecules in dividing cells to
stop the cells dividing. It also sticks to the same sort of molecule in
nerves and causes side-effects to your nervous system (see
section 4 – Possible side-effects). You may not notice the start of
these side-effects until you have had several injections. Your doctor
may also decide to change the dose or put off treating you if these
side-effects are severe. The effects on your nervous system usually
get better when you stop being treated with Eldisine.
Your doctor or nurse will take great care that the Eldisine solution
does not leak out of your vein when it is being injected. Tell them
immediately if you have pain or swelling during the injection or later.
If this is not treated quickly, Eldisine can cause your tissue to be
inflamed where the solution leaked out. They will also be very
careful that Eldisine does not get into anyone’s eyes.
The usual dose is 3 milligrams for every square metre of your body
Children and adolescents
4 milligrams for every square metre of the child’s body surface.
Your nurse will measure your height and weight and work out your
body surface area from the measurements. Your doctor will use

4.3 Contra-indications
See special warnings in section 4.4 for the treatment of patients given intrathecal vindesine
Use in Patients who have drug-induced severe granulocytopenia (less than 1,500 granulocytes
per mm3) or severe thrombocytopenia.
Vindesine should not be used in the presence of bacterial infection. Such infections must be
brought under control with antiseptics or antibiotics before using vindesine. Patients with the
demyelinating form of Charcot-Marie-Tooth syndrome should not be given vindesine.
Hypersensitivity to vindesine sulphate or to any of the excipients listed in section 6.1
4.4 Special Warnings and Precautions for Use
This preparation is for intravenous use only. It should be administered by individuals experienced
in the administration of vindesine sulphate. The intrathecal administration of vindesine sulphate
usually results in death. Syringes containing this product should be labelled “FOR
provided in the pack with this warning.
Extemporaneously prepared syringes containing this product must be packaged in an overwrap
After inadvertent intrathecal administration of vinca alkaloids, immediate neurosurgical
intervention is required in order to prevent ascending paralysis leading to death. In a very small
number of patients, life-threatening paralysis and subsequent death was averted but resulted in
devastating neurological sequelae, with limited recovery afterwards.
Based on the published management of survival cases involving the related vinca alkaloid
vincristine sulphate, if vindesine is mistakenly given by the intrathecal route, the following
treatment should be initiated immediately after the injection:
1. Removal of as much CSF as is safely possible through the lumbar access.
2. Insertion of an epidural catheter into the subarachnoid space via the intervertebral space
above initial lumbar access and CSF irrigation with lactated Ringer’s solution. Fresh frozen
plasma should be requested and, when available, 25ml should be added to every 1 litre of
lactated Ringer’s solution.
3. Insertion of an intraventricular drain or catheter by a neurosurgeon and continuation of CSF
irrigation with fluid removal through the lumbar access connected to a closed drainage
system. Lactated Ringer’s solution should be given by continuous infusion at 150ml/h, or at a
rate of 75ml/h when fresh frozen plasma has been added as above.
The rate of infusion should be adjusted to maintain a spinal fluid protein level of 150mg/dl.
The following measures have also been used in addition but may not be essential:
Glutamic acid has been given IV 10gm over 24 hours, followed by 500mg tds by mouth for
1 month. Folic acid has been administered intravenously as a 100mg bolus and then infused at a
rate of 25mg/h for 24 hours, then bolus doses of 25mg 6-hourly for 1 week. Pyridoxine has been
given at a dose of 50mg 8-hourly by intravenous infusion over 30 minutes. Their roles in the
reduction of neurotoxicity are unclear.
Clinically, the dose-limiting toxicity of vindesine is granulocytopenia, although in general oncolytic
activity is obtained at doses causing little or no effect on the granulocytes. Individual patient
variation has been observed with respect to the severity of side-effects, including neurotoxicity,
granulocytopenia, alopecia and decrease in bowel motility.
When granulocytopenia occurs, the nadir in the granulocyte count may be expected to occur 3-5
days after the last day of drug administration. Recovery of the granulocyte count is rapid
thereafter and is usually complete within 7-10 days after the last dose.
The thrombocyte count is usually either unaffected or increased by weekly therapy with
vindesine. However, significant thrombocytopenia has occurred occasionally, particularly when
doses are given more frequently than once a week. It is probably more likely to occur when
patients are thrombocytopenic (less than 100,000 cells/mm3) prior to therapy with vindesine.
The effect of vindesine upon the red blood cell count and haemoglobin concentration is usually
insignificant when other treatment does not complicate the picture. It should be remembered,
however, that patients with malignant disease may exhibit anaemia even in the absence of any
If granulocytopenia with less than 1,000 granulocytes/mm3 occurs following a dose of vindesine,
the patient should be watched carefully for evidence of infection until the granulocyte count has
returned to a safe level.
While neurotoxicity is not usually dose limiting, there have been instances in which neurotoxicity
has made it necessary to reduce the dosage or temporarily discontinue use of vindesine.
Neurotoxicity induced by vindesine is believed to be generally less severe and less progressive in
nature than the effects observed with vincristine.
Particular attention should be given to dosage and neurological side-effects if vindesine is
administered to patients with pre-existing neuromuscular disease, and also when other drugs
with neurotoxic potential are being used. The neurotoxicity associated with vindesine therapy
may be additive.
Care should be exercised when vindesine has been the cause of acute abdominal pain, as
paralytic ileus may be a significant risk if further doses of vindesine are given, particularly if the
dose is increased. Prophylactic measures should be taken to prevent obstipation that may result
from a decrease in bowel motility.
Extreme care should be exercised to prevent injection outside the vein. Extravasation during
intravenous injection will cause cellulitis and phlebitis. If the amount of extravasation is great,
sloughing will occur. Healing of such wounds may require several weeks and be attended by
severe pain. The discomfort may persist after healing of the ulcer. Cytotoxic drugs should only be
administered by appropriately trained staff.





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your body surface area to work out the right dose for you.
Your doctor may decide to increase the dosage in small steps if
you have enough blood cells.
Your doctor or nurse will inject the correct amount of Eldisine –
usually once a week. Eldisine must only go into a vein. You may
have an injection every week and your doctor may treat you with
other cytotoxic medicines at the same time.
If you are being treated as an out-patient it is important that you go
to the clinic for all your appointments.
If you receive more Eldisine than you should
Since this medicine will usually be given to you by a doctor or
nurse it is unlikely that you will be given too much or that you will
miss a dose. However, if you are worried tell the doctor or nurse.
Like all medicines, this medicine can cause side-effects, although
not everybody gets them.
The following side-effects have been reported:
• hearing difficulty – sometimes with dizziness
• fits
• a low blood cell count causing a fever, a sore throat, nose bleeds
or bruising
• loss of reflexes
• nerve, or jaw pain
• a headache
• feeling or being sick
• constipation, which may be severe
• difficulty swallowing or indigestion
• abdominal pain
• diarrhoea
• pain or swelling where you have had the injection





• rashes
• fever
• chills
• infertility in men and women
• low or high blood pressure
• low mood
Reporting of side-effects
If you get any side effects, talk to your doctor, pharmacist or nurse.
This includes any possible side effects not listed in this leaflet. You
can also report side effects directly via the Yellow Card Scheme at:
By reporting side effects you can help provide more information on
the safety of this medicine.
Keep out of the sight and reach of children.
The hospital pharmacy should keep the bottles of Eldisine in a
fridge (2-8°C). When Eldisine has been dissolved, the hospital
should keep the Eldisine solution in a fridge.
Do not use this medicine after the expiry date printed on the bottle
The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household
waste. Ask your pharmacist how to throw away medicines you no
longer use. These measures will help protect the environment.

Care must be taken to avoid contamination of the eye with concentrations of vindesine used
clinically. If accidental contamination occurs, severe irritation and/or corneal ulceration may
result. The eye should be washed immediately and thoroughly with water or saline.
Interaction with Other Medicinal Products and Other Forms of Interaction
When chemotherapy is being given in conjunction with radiation therapy through portals which
include the liver, the use of vindesine should be delayed until radiation therapy has been
Acute shortness of breath and severe bronchospasm has been reported following the
administration of vindesine. These reactions have been encountered most frequently when
vindesine was used in combination with mitomycin-C and may be serious when there is preexisting pulmonary dysfunction. The onset may be within minutes, or several hours after the drug
is injected, and may occur up to 2 weeks after a dose of mitomycin-C. Progressive dyspnoea,
requiring chronic therapy, may occur. Vindesine should not be re-administered.
The simultaneous oral or intravenous administration of phenytoin and antineoplastic
chemotherapy combinations have been reported to have reduced blood levels of the
anticonvulsant and to have increased seizure activity. Although the contribution of the vinca
alkaloids has not been established, dosage adjustment of phenytoin may need to be made when
used in combination with vindesine.
Caution should be exercised in patients concurrently taking drugs shown to inhibit drug
metabolism by hepatic cytochrome P450 isoenzyme in the CYP3A subfamily, or in patients with
hepatic dysfunction. Concurrent administration of vindesine sulphate with an inhibitor of this
metabolic pathway may cause an earlier onset and/or an increased severity of side-effects.
As vindesine may impair bone marrow function and cause neurotoxicity, dosage and side-effects
should be carefully monitored when drugs with similar adverse effects are administered.
Fertility, Pregnancy and Lactation
Usage in pregnancy or lactation: The safety of this product for use during pregnancy has not
been established. Animal studies with vindesine suggest that teratogenic effects may occur. The
benefit-to-risk ratio must be carefully considered before use in pregnant patients.
Eldisine should not normally be given to mothers who are breast-feeding. Men and women
should be advised regarding contraception during treatment with vindesine due to the potential
risks involved.
Effects on Ability to Drive and Use machines
Not applicable
Undesirable Effects
Prior to the use of the drug, patients and/or their parents/guardians should be advised of the
possibility of untoward symptoms. Acute toxicity appears to be dose related and is more likely to
occur if doses above 4mg/m2 are employed. Granulocytopenia is usually the dose-limiting factor.
Neurotoxicity is common and appears to be related to the cumulative total dose given.
The following side-effects have been reported:
Gastro-intestinal: Nausea, vomiting, constipation, stomatitis, vesiculation of the mouth, ileus,
diarrhoea, anorexia, abdominal pain, dysphagia, dyspepsia, perforated duodenal ulcer (nausea
and vomiting usually may be controlled by anti-emetic agents).
Neurological: Numbness and tingling of hands/feet (paraesthesia), loss of the deep tendon
reflexes, peripheral neuritis, mental depression, headache, convulsions, difficulties with balance,
including dizziness and jaw pain.
Cortical blindness has been reported in patients treated with multiple-agent chemotherapy that
has included vindesine. The contribution of vindesine to this reaction is unknown. Treatment with
vinca alkaloids has resulted rarely in both vestibular and auditory damage to the eighth cranial
nerve. Manifestations include partial or total deafness, which may be temporary or permanent,
and difficulties with balance, including dizziness, nystagmus and vertigo. Particular caution is
warranted when vindesine sulphate is used in combination with other agents known to be
ototoxic, such as the platinum-containing oncolytics.
Haematological: Granulocytopenia, thrombocytopenia, thrombocytosis, mild anaemia.
Nausea, vomiting, constipation. Vesiculation of the mouth, ileus.
Stomatitis. Anorexia, dysphagia, dyspepsia, perforated duodenal ulcer,
Pulmonary: See section 4.5
Cutaneous: Alopecia from mild to total is the commonest side-effect. Regrowth of hair may occur
while still on therapy.
Maculopapular rashes. Cellulitis with extravasation. Injection site reaction (see section 4.2)
Miscellaneous: Generalised musculoskeletal pain, malaise, chills and fevers, asthenia.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme
Side-effects following the use of vindesine are dose related. Therefore, following administration
of more than the recommended dose, patients can be expected to experience these effects in an
exaggerated fashion.
Supportive care should include: (a) daily blood counts for guidance in transfusion requirement;
(b) prevention of the side-effects that result from the syndrome of inappropriate secretion of
antidiuretic hormone. This includes restriction of fluid intake and, perhaps, the use of a diuretic
drug acting on the loop of Henle and distal tubule function; (c) use of cathartics to prevent ileus;
(d) administration of an anticonvulsant; (e) monitoring the patient's cardiovascular system.
The use of folinic acid in addition to the other supportive measures recommended may be
considered, although, unlike vincristine, studies have not been conducted to confirm its

What Eldisine contains
• The active substance in Eldisine is vindesine sulphate. Each 10ml
bottle of Eldisine contains 5mg of vindesine sulphate.
• The other ingredient is mannitol (E421).
What Eldisine looks like and the contents of the pack
Eldisine is a white crystalline powder, supplied as a lyophilised plug
in a rubber stoppered 10ml glass vial.

PL 06831/0117
Eldisine Powder for Solution for Injection 5 mg
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Genus Pharmaceuticals,
Linthwaite, Huddersfield, HD7 5QH, UK.
Manufacturer: Cellpharm GmbH, Feodor-Lynen-Str. 35, D – 30625,
Hannover, Germany.
This leaflet was last revised in February 2016
* Eldisine (vindesine sulphate) is a registered trademark of Genus Pharmaceuticals Limited.







protective action. Clinical experience of vindesine overdosage is extremely limited, with only one
published case.
Pharmacodynamic Properties
Pharmacotherapeutic group: Cytostatic agent from the group of vinca alkaloids; mitosis inhibitor.
ATC code: L01CA03
Vindesine sulphate is an antineoplastic agent derived from vinblastine, like the other vinca
alkaloids it causes mitotic arrest in metaphase by binding to microtubular protein.
Pharmacokinetic Properties
The pharmacokinetics of vindesine are similar to those of the other vinca alkaloids. After
intravenous administration, elimination from the blood is triphasic, the drug is rapidly distributed
to body tissues. It is metabolised primarily in the liver and excreted in bile and urine.
Preclinical Safety Data
Animal studies with vindesine suggest that teratogenic effects may occur.
List of Excipients
Eldisine should never be mixed with any other drug.
3 years.
Special Precautions for Storage
Vials of Eldisine should be stored in a refrigerator between 2° and 8°C.
After reconstitution: After a portion of the solution has been removed from a vial, the remainder of
the contents of the vial may be stored in a refrigerator for future use for 24 hours without
significant loss of potency. When the reconstituted vial of Eldisine is to be stored for more than
24 hours, it is essential to reconstitute with sterile 0.9% sodium chloride intravenous infusion
preserved with 2.0% benzyl alcohol. Where preserved diluent is used, the reconstituted solution
may be stored in a refrigerator for up to 28 days without significant loss of potency.
Nature and Contents of Container
Single vials comprising Type I glass each with a rubber stopper, an aluminium sealing ring and a
polypropylene cap.
Instructions for Use/Handling
Guidelines for the safe handling of antineoplastic agents: Cytotoxic preparations should not be
handled by pregnant staff.
Trained personnel should reconstitute the drug. This should be performed in a designated area.
The work surface should be covered with disposable plastic-backed absorbent paper.
Adequate protective gloves, masks and clothing should be worn. Precautions should be taken to
avoid the drug accidentally coming into contact with the eyes. If accidental contamination
occurs, the eye should be washed with water or saline thoroughly and immediately.
Use Luer-lock fittings on all syringes and sets. Large bore needles are recommended to minimise
pressure and the possible formation of aerosols. The latter may also be reduced by the use of a
venting needle.
Adequate care and precaution should be taken in the disposal of items (syringes, needles, etc.)
used to reconstitute cytotoxic drugs.
Special dispensing information: When dispensing vindesine sulphate in other than the original
container, e.g. a syringe containing a specific dose, it is imperative that it be packaged in an
overwrap bearing the statement "DO NOT REMOVE COVER UNTIL MOMENT OF INJECTION.
specific dose must be labelled, using the auxiliary sticker provided in the pack, with this warning.
Genus Pharmaceuticals Limited, T/A Genus Pharmaceuticals,
Linthwaite, Huddersfield, HD7 5QH, UK.
PL 06831/0117
13 July 2004
November 2014

* Eldisine (vindesine sulphate) is a registered trademark of Genus Pharmaceuticals Limited.


923 5382 1409



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Eldisine 5mg per 5ml Powder
for Solution for Injection



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5mg per 5ml

IG code



300mm x 420mm

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