Vindesine Powder for Solution for Injection 5.

0 mg SMPC, Taj P harma ceutical s

VINDESI NE Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, VINDESINE D osage & Rx I nfo | VINDESINE U ses, Side E ffe cts -: Indi cations , Side Effects , Warning s, VINDES INE - Drug Infor mation - Taj Phar ma, VINDESINE dose Taj pharma ce uticals VINDESI NE interactions, Taj Phar ma ceutica l VINDESINE contraindicati ons, VIND ESINE price, VINDESINE Taj P harma Vindesine Powder for Solution for Injection 5.0 mg SMPC - Taj Phar ma . Stay connected t o all update d on VIND ESINE Taj Phar mace uticals Taj pharma ceuti cals Hyderaba d.

RX FOR INTRAVENOUS USE ONLY - FATAL IF

GIVEN BY OTHER ROUTES
VINDESINE POWDER See special warnings in section 4.4 for the
treatment of patients given intrathecal vindesine
FOR SOLUTION FOR sulphate
INJECTION Extreme care must be used in calculating and
administering the dose of vindesine, since
5 MG overdosage may have a very serious or fatal
outcome.
1.NAME OF THE MEDICINAL PRODUCT
It is recommended that the drug be administered
Vindesine Powder for Solution for Injection 5.0
intravenously in a single rapid bolus injection at
mg
weekly intervals. The size of the dose is
2. QUALITATIVE AND QUANTITATIVE determined by body surface area. In adults and
COMPOSITION the elderly, the recommended starting dose is
3mg/m2, and children may be started at 4mg/m2.
Vindesine Powder 5mg contains 5mg vindesine Thereafter, granulocyte counts should be made
sulphate per 5ml when reconstituted. prior to each subsequent dose to determine the
For a full list of excipients, see section 6.1 patient's sensitivity to the drug. Provided there is
no granulocytopenia or other toxicity (see
3. PHARMACEUTICAL FORM 'Undesirable Effects') the dosage may be
Powder for Solution for Injection increased in 0.5mg/m2 steps at weekly intervals.

A clear glass vial containing a lyophilised plug In adults, the maximum total weekly dosage for
of white crystalline powder. which data exists is 4mg/m2. The optimum dose
of vindesine is that which produces mild to
4. CLINICAL PARTICULARS modest granulocytopenia. Sustained granulocyte
counts lower than 2,500 cells/mm3 are to be
4.1 Therapeutic indications
avoided.
Vindesine is an anti-neoplastic drug for
intravenous use which can be used alone or in Those with decreased marrow function from
combination with other oncolytic drugs. leukaemia infiltration or replacement will
Information available at present suggests that require full doses to attempt to restore marrow
Vindesine as a single agent may be useful for the function. This must be done under close
treatment of: supervision.
• acute lymphoblastic leukaemia of childhood The dose should not be increased after that dose
resistant to other drugs; which: (i) reduces the granulocyte count to
below l500 cells/mm3 or, on rare occasions, (ii)
• blastic crises of chronic myeloid leukaemia;
reduces the platelet count to below
• malignant melanoma unresponsive to other 100,000/mm3; (iii) causes acute abdominal pain
forms of therapy; (see section 4.4).
• advanced carcinoma of the breast, On each of the above occasions there should be
unresponsive to appropriate endocrine surgery full recovery before administering the next dose,
and/or hormonal therapy. which should be reduced from the one causing
the adverse reaction. For most patients, however,
4.2 Posology and method of administration the weekly dosage will prove to be in the range
This preparation is for intravenous use only. It of 3.0 to 4.0mg/m2 in adults and 4.0 to
should be administered only by individuals 5.0mg/m2 in children.
experienced in vindesine administration.
Vindesine Powder for Solution for Injection 5.0 mg SMPC, Taj P harma ceutical s
VINDESI NE Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, VINDESINE D osage & Rx I nfo | VINDESINE U ses, Side E ffe cts -: Indi cations , Side Effects , Warning s, VINDES INE - Drug Infor mation - Taj Phar ma, VINDESINE dose Taj pharma ce uticals VINDESI NE interactions, Taj Phar ma ceutica l VINDESINE contraindicati ons, VIND ESINE price, VINDESINE Taj P harma Vindesine Powder for Solution for Injection 5.0 mg SMPC - Taj Phar ma . Stay connected t o all update d on VIND ESINE Taj Phar mace uticals Taj pharma ceuti cals Hyderaba d.

The use of small amounts of vindesine daily for It is extremely important to choose the largest
long periods is not advised, even though the accessible vein and to be certain that the needle
resulting total weekly dosage may be similar to is properly positioned in the vein before any
that recommended. Little or no added vindesine is injected. If leakage into surrounding
therapeutic advantage has been demonstrated tissues should occur during intravenous
when such regimens have been used, and side administration, it may cause considerable
effects are increased. Strict adherence to the irritation. The injection should be discontinued
recommended dosage schedule is very as soon as leakage occurs, and any remaining
important. portion of the dose should then be introduced
into another vein. Local injection of
As vindesine is excreted principally by the liver, hyaluronidase and the application of moderate
it may be necessary to reduce initial doses in the heat to the area of leakage help disperse the drug
presence of significantly impaired hepatic or and are thought to minimise discomfort and the
biliary function. possibility of cellulitis.
The metabolism of vinca alkaloids has been
4.3 Contraindications
shown to be mediated by hepatic cytochrome
P450 isoenzymes in the CYP 3A subfamily. FOR INTRAVENOUS USE ONLY – FATAL IF
This metabolic pathway may be impaired in GIVEN BY OTHER ROUTES
patients with hepatic dysfunction or who are See special warnings in section 4.4 for the
taking concomitant potent inhibitors of these treatment of patients given intrathecal vindesine
isoenzymes. (see section 4.5). sulphate.
To prepare a solution containing 1mg/ml add Use in patients who have drug-induced severe
5ml of sterile 0.9% sodium chloride intravenous granulocytopenia (less than 1,500 granulocytes
infusion to the 5mg of Vindesine in the sterile per mm3) or severe thrombocytopenia.
vial. The drug dissolves rapidly to give a clear
solution. Vindesine sulphate must not be used in the
presence of severe bacterial infections. Such
The dose of Vindesine solution (calculated to infections must be brought under control with
provide the desired number of milligrams per antiseptics or antibiotics before using vindesine.
square metre of the patient's surface area) may
be injected either into the tubing of a running Patients with the demyelinating form of
intravenous infusion (compatible infusions are Charcot-Marie-Tooth syndrome should not be
5% Dextrose Intravenous Infusion BP, Sodium given vindesine.
Chloride Intravenous Infusion BP and
Hypersensitivity to vindesine sulphate or to any
dextrose/saline infusions) or directly into a vein.
of the excipients
The latter procedure is readily adaptable to
4.4 Special Warnings and precautions for use
outpatient therapy. In either case, the injection
should be completed in 1 to 3 minutes. If care is This preparation is for intravenous use only. It
taken to ensure that the needle is securely within should be administered by individuals
the vein and that no solution containing experienced in the administration of vindesine
vindesine is spilled extravascularly, cellulitis sulphate. The intrathecal administration of
and/or phlebitis is unlikely to occur. vindesine sulphate usually results in death.
Syringes containing this product should be
Because of the enhanced possibility of
labelled “FOR INTRAVENOUS USE ONLY –
thrombosis, it is considered inadvisable to inject
FATAL IF GIVEN BY OTHER ROUTES.” An
a solution into an extremity in which the
auxiliary sticker is provided in the pack with this
circulation is impaired, or potentially impaired,
warning.
by such conditions as compressing or invading
neoplasm, phlebitis or varicosity. Extemporaneously prepared syringes containing
this product must be packaged in an overwrap
Caution
Vindesine Powder for Solution for Injection 5.0 mg SMPC, Taj P harma ceutical s
VINDESI NE Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, VINDESINE D osage & Rx I nfo | VINDESINE U ses, Side E ffe cts -: Indi cations , Side Effects , Warning s, VINDES INE - Drug Infor mation - Taj Phar ma, VINDESINE dose Taj pharma ce uticals VINDESI NE interactions, Taj Phar ma ceutica l VINDESINE contraindicati ons, VIND ESINE price, VINDESINE Taj P harma Vindesine Powder for Solution for Injection 5.0 mg SMPC - Taj Phar ma . Stay connected t o all update d on VIND ESINE Taj Phar mace uticals Taj pharma ceuti cals Hyderaba d.

which is labelled “DO NOT REMOVE doses of25mg 6-hourly for 1 week. Pyridoxine
COVERING UNTIL MOMENT OF has been given at a dose of 50mg 8-hourly by
INJECTION. FOR INTRAVENOUS USE intravenous infusion over 30 minutes. Their
ONLY – FATAL IF GIVEN BY OTHER roles in the reduction of neurotoxicity are
ROUTES.” unclear.
After inadvertent intrathecal administration of .Clinically, the dose-limiting toxicity of
vinca alkaloids, immediate neurosurgical vindesine is granulocytopenia, although in
intervention is required in order to prevent general oncolytic activity is obtained at doses
ascending paralysis leading to death. In a very causing little or no effect on the granulocytes.
small number of patients, life-threatening Individual patient variation has been observed
paralysis and subsequent death was averted but with respect to the severity of side-effects,
resulted in devastating neurological sequelae, including neurotoxicity, granulocytopenia,
with limited recovery afterwards. alopecia and decrease in bowel motility.
Based on the published management of survival When granulocytopenia occurs, the nadir in the
cases involving the related vinca alkaloid granulocyte count may be expected to occur 3-5
vincristine sulphate, if vindesine is mistakenly days after the last day of drug administration.
given by the intrathecal route, the following Recovery of the granulocyte count is rapid
treatment should be initiated immediately after thereafter and is usually complete within 7-10
the injection: days after the last dose.
1. Removal of as much CSF as is safely possible The thrombocyte count is usually either
through the lumbar access. unaffected or increased by weekly therapy with
vindesine. However, significant
2. Insertion of an epidural catheter into the
thrombocytopenia has occurred occasionally,
subarachnoid space via the intervertebral space
particularly when doses are given more
above initial lumbar access and CSF irrigation frequently than once a week. It is probably more
with lactated Ringer's solution. Fresh frozen likely to occur when patients are
plasma should be requested and, when available, thrombocytopenic (less than 100,000 cells/mm3)
25ml should be added to every 1 litre of lactated prior to therapy with vindesine.
Ringer's solution.
The effect of vindesine upon the red blood cell
3. Insertion of an intraventricular drain or count and haemoglobin concentration is usually
catheter by a neurosurgeon and continuation of insignificant when other treatment does not
CSF irrigation with fluid removal through the complicate the picture. It should be remembered,
lumbar access connected to a closed drainage however, that patients with malignant disease
system. Lactated Ringer's solution should be
may exhibit anaemia even in the absence of any
given by continuous infusion at 150ml/h, or at a treatment.
rate of 75ml/h when fresh frozen plasma has
been added as above. If granulocytopenia with less than 1,000
granulocytes/mm3 occurs following a dose of
The rate of infusion should be adjusted to vindesine, the patient should be watched
maintain a spinal fluid protein level of carefully for evidence of infection until the
150mg/dl. granulocyte count has returned to a safe level.
The following measures have also been used in
While neurotoxicity is not usually dose-limiting,
addition but may not be essential:
there have been instances in which neurotoxicity
Glutamic acid has been given IV 10gm over 24 has made it necessary to reduce the dosage or
hours, followed by 500mg tds by mouth for 1 temporarily discontinue use of vindesine.
months. Folic acid has been administered Neurotoxicity induced by vindesine is believed
intravenously as a 100mg bolus and then infused to be generally less severe and less progressive
at a rate of 25mg/h for 24 hours, then bolus
Vindesine Powder for Solution for Injection 5.0 mg SMPC, Taj P harma ceutical s
VINDESI NE Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, VINDESINE D osage & Rx I nfo | VINDESINE U ses, Side E ffe cts -: Indi cations , Side Effects , Warning s, VINDES INE - Drug Infor mation - Taj Phar ma, VINDESINE dose Taj pharma ce uticals VINDESI NE interactions, Taj Phar ma ceutica l VINDESINE contraindicati ons, VIND ESINE price, VINDESINE Taj P harma Vindesine Powder for Solution for Injection 5.0 mg SMPC - Taj Phar ma . Stay connected t o all update d on VIND ESINE Taj Phar mace uticals Taj pharma ceuti cals Hyderaba d.

in nature than the effects observed with after a dose of mitomycinC. Progressive
vincristine. dyspnoea, requiring chronic therapy, may occur.
Vindesine should not be re-administered.
Particular attention should be given to dosage
and neurological side-effects if vindesine is The simultaneous oral or intravenous
administered to patients with pre-existing administration of phenytoin and antineoplastic
neuromuscular disease, and also when other chemotherapy combinations have been reported
drugs with neurotoxic potential are being used. to have reduced blood levels of the
The neurotoxicity associated with vindesine anticonvulsant and to have increased seizure
therapy may be additive. activity. Although the contribution of the vinca
alkaloids has not been established, dosage
Care should be exercised when vindesine has adjustment of phenytoin may need to be made
been the cause of acute abdominal pain, as when used in combination with vindesine.
paralytic ileus may be a significant risk if further
doses of vindesine are given, particularly if the Caution should be exercised in patients
dose is increased. Prophylactic measures should concurrently taking drugs shown to inhibit drug
be taken to prevent obstipation that may result metabolism by hepatic cytochrome P450
from a decrease in bowel motility. isoenzyme in the CYP3A subfamily, or in
patients with hepatic dysfunction. Concurrent
Extreme care should be exercised to prevent administration of vindesine sulphate with an
injection outside the vein. Extravasation during inhibitor of this metabolic pathway may cause
intravenous injection will cause cellulitis and an earlier onset and/or an increased severity of
phlebitis. If the amount of extravasation is great, side effects.
sloughing will occur. Healing of such wounds
may require several weeks and be attended by 4.6 Fertility, Pregnancy and lactation
severe pain. The discomfort may persist after
Usage in pregnancy or lactation: The safety of
healing of the ulcer. Cytotoxic drugs should only
be administered by appropriately trained staff. this product for use during pregnancy has not
been established. Animal studies with vindesine
Care must be taken to avoid contamination of suggest that teratogenic effects may occur. The
the eye with concentrations of vindesine used benefit-to-risk ratio must be carefully considered
clinically. If accidental contamination occurs, before use in pregnant patients.
severe irritation and/or corneal ulceration may
result. The eye should be washed immediately Vindesine should not normally be given to
and thoroughly with water or saline. mothers who are breast-feeding.
Men and women should be advised regarding
4.5 Interaction with other medicinal
contraception during treatment with vindesine
products and other forms of interaction
due to the potential risks involved.
When chemotherapy is being given in
conjunction with radiation therapy through 4.7 Effects on ability to drive and use
portals, which include the liver, the use of machines
Not applicable
vindesine should be delayed until radiation
therapy has been completed. 4.8 Undesirable Effects
Acute shortness of breath and severe Prior to the use of the drug, patients and/or their
bronchospasm have been reported following the parents/guardians should be advised of the
administration of vindesine. These reactions possibility of untoward symptoms. Acute
have been encountered most frequently when toxicity appears to be dose related and is more
vindesine was used in combination with likely to occur if doses above 4mg/m2 are
mitomycinC and may be serious when there is employed. Granulocytopenia is usually the dose
pre-existing pulmonary dysfunction. The onset limiting factor. Neurotoxicity is common and
may be within minutes, or several hours after the appears to be related to the cumulative total dose
drug is injected and may occur up to 2 weeks given.
Vindesine Powder for Solution for Injection 5.0 mg SMPC, Taj P harma ceutical s
VINDESI NE Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, VINDESINE D osage & Rx I nfo | VINDESINE U ses, Side E ffe cts -: Indi cations , Side Effects , Warning s, VINDES INE - Drug Infor mation - Taj Phar ma, VINDESINE dose Taj pharma ce uticals VINDESI NE interactions, Taj Phar ma ceutica l VINDESINE contraindicati ons, VIND ESINE price, VINDESINE Taj P harma Vindesine Powder for Solution for Injection 5.0 mg SMPC - Taj Phar ma . Stay connected t o all update d on VIND ESINE Taj Phar mace uticals Taj pharma ceuti cals Hyderaba d.

The following side effects have been reported: dose, patients can be expected to experience
these effects in an exaggerated fashion.
Gastro-intestinal: Nausea, vomiting,
constipation, stomatitis, vesiculation of the Supportive care should include: (a) daily blood
mouth, ileus, diarrhoea, anorexia, abdominal counts for guidance in transfusion requirement;
pain, dysphagia, dyspepsia, perforated duodenal (b) prevention of the side effects that result from
ulcer (nausea and vomiting usually may be the syndrome of inappropriate secretion of
controlled by anti-emetic agents). antidiuretic hormone. This includes restriction of
fluid intake and, perhaps, the use of a diuretic
Neurological: Numbness and tingling of
drug acting on the loop of Henle and distal
hands/feet (paraesthesia), peripheral neuritis,
tubule function; (c) use of cathartics to prevent
jaw pain, mental depression, loss of deep tendon ileus; (d) administration of an anticonvulsant; (e)
reflexes, foot drop, headache, convulsions. monitoring the patient's cardiovascular system.
Cortical blindness has been reported in patients
treated with multiple agent chemotherapy that The use of folinic acid in addition to the other
has included vindesine. The contribution of supportive measures recommended may be
vindesine to this reaction is unknown. Treatment considered although, unlike vincristine, studies
with vinca alkaloids has resulted rarely in both have not been conducted to confirm its
vestibular and auditory damage to the eighth protective action. Clinical experience of
cranial nerve. Manifestations include partial or vindesine overdosage is extremely limited, with
total deafness, which may be temporary or only one published case.
permanent, and difficulties with balance,
including dizziness, nystagmus and vertigo. 5. PHARMACOLOGICAL PROPERTIES
Particular caution is warranted when vindesine 5.1 Pharmacodynamic properties
sulphate is used in combination with other Pharmacotherapeutic group: Cytostatic agent
agents known to be ototoxic, such as the from the group of vinca alkaloids; mitosis
platinum-containing oncolytics. inhibitor.
Haematological: Granulocytopenia, Vindesine sulphate is an antineoplastic agent
thrombocytopenia, thrombocytosis, mild derived from vinblastine, like the other vinca
anaemia. alkaloids it causes mitotic arrest in metaphase by
binding to microtubular protein.
Pulmonary: see section 4.5.
Cutaneous: Alopecia from mild to total is the 5.2 Pharmacokinetic properties
commonest side effect. Regrowth of hair may The pharmacokinetics of vindesine is similar to
occur while still on therapy. Maculopapular those of the other vinca alkaloids. After
rashes, cellulitis with extravasation. Injection intravenous administration, elimination from the
site reaction (see section 4.2). blood is triphasic, and the drug is rapidly
Miscellaneous: Generalised musculoskeletal distributed to body tissues. It is metabolised
pain, malaise, chills and fevers, asthenia. primarily in the liver and excreted in bile and
urine.
Reporting of suspected adverse reactions
5.3 Preclinical safety data
Reporting suspected adverse reactions after
authorisation of the medicinal product is Animal studies with vindesine suggest that
teratogenic effects may occur.
important. It allows continued monitoring of the
benefit/risk balance of the medicinal product. 6. PHARMACEUTICAL PARTICULARS
4.9 Overdose
6.1 List of excipients
Side effects following the use of vindesine are Mannitol
dose related. Therefore, following
Sulphuric acid (diluted)
administration of more than the recommended
Vindesine Powder for Solution for Injection 5.0 mg SMPC, Taj P harma ceutical s
VINDESI NE Taj Phar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, VINDESINE D osage & Rx I nfo | VINDESINE U ses, Side E ffe cts -: Indi cations , Side Effects , Warning s, VINDES INE - Drug Infor mation - Taj Phar ma, VINDESINE dose Taj pharma ce uticals VINDESI NE interactions, Taj Phar ma ceutica l VINDESINE contraindicati ons, VIND ESINE price, VINDESINE Taj P harma Vindesine Powder for Solution for Injection 5.0 mg SMPC - Taj Phar ma . Stay connected t o all update d on VIND ESINE Taj Phar mace uticals Taj pharma ceuti cals Hyderaba d.

Sodium hydroxide (diluted). aerosols. The latter may also be reduced by the
use of a venting needle.
6.2 Incompatibilities
Adequate care and precaution should be taken in
Vindesine should never be mixed with any other the disposal of items (syringes, needles, etc.)
drug. used to reconstitute cytotoxic drugs.
6.3 Shelf life
Special dispensing information: When
5 years dispensing vindesine sulphate in other than the
original container, e.g., a syringe containing a
6.4 Special precautions for storage specific dose, it is imperative that it be packaged
Vials of Vindesine should be stored in a
in an overwrap bearing the statement “DO NOT
refrigerator between 2° and 8°C.
REMOVE COVER UNTIL MOMENT OF
After reconstitution: After a portion of the INJECTION. FOR INTRAVENOUS USE
solution has been removed from a vial, the ONLY – FATAL IF GIVEN BY OTHER
remainder of the contents of the vial may be ROUTES”. A syringe containing a specific dose
stored in a refrigerator for future use for 24 must be labelled, using the auxiliary sticker
hours without significant loss of potency. When provided in the pack, with this warning.
the reconstituted vial of Vindesine is to be stored
for more than 24 hours, it is essential to
reconstitute with sterile 0.9% sodium chloride 7. MANUFACTURER:
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 Manufactured in India by:
loss of potency. TAJ PHARMACEUTICALS LTD.
6.5 Nature and contents of container Mumbai, India
At:388/34, Changodar Industrial Estate
Single vials comprising Type I glass each with a Changodar- 382 210
rubber stopper, an aluminium sealing ring and a Dist- Ahmedabad. Gujarat (India)
polypropylene cap. MFG. LIC NO: G/25A/4795-A
6.6 Special precautions for disposal and other
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