Oncovin 1mg/Ml Solution For Injection
Out of date information, search anotherPACKAGE LEAFLET: INFORMATION FOR THE USER
Oncovin *
(Vincristine Sulphate)
Read all of this leaflet carefully before you start taking this medicine.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
- If any of the side-effects get serious, or if you notice any side-effects not listed in this leaflet, please tell your doctor or pharmacist.
In this leaflet:
1. What Oncovin is and what it is used for 4. Possible side-effects
2. Before you use Oncovin 5. How to store Oncovin
3. How to use Oncovin 6. Further information
1. WHAT ONCOVIN IS AND WHAT IT IS USED FOR
Oncovin contains vincristine sulphate. It is used to treat patients who have a cancer such as leukaemia, a lymphoma (for example Hodgkin’s disease), multiple myeloma (a bone marrow disease), solid tumours in adults (for example cancers of the bone marrow, muscles, nerves, kidney, eye or brain). It is also used to treat a disease called ITP (idiopathic thrombocytopenic purpura) which is not a cancer. If your doctor gives you this medicine for anything else, and you have any questions about it, ask your doctor.
2. BEFORE YOU USE ONCOVIN Do not use Oncovin if you:
• are allergic (hypersensitive) to vincristine sulphate or any of the other ingredients of Oncovin (see section 6 - Further information for details)
• suffer from any disease affecting the nerves or muscles (such as Charcot Marie tooth syndrome).
Take special care with Oncovin if you:
• are having radiotherapy in the • have problems with your
liver area breathing
• have a bacterial infection • have liver trouble
• suffer from constipation.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Take care if you are taking any of the following medicines:
• phenytoin, for treating epilepsy • itraconazole (a drug for treating
• cytotoxic drugs called mitomycin, fungal infections) cisplatin, carboplatin or asparaginase.
Pregnancy and breast-feeding
If you are pregnant, planning to become pregnant, or are breast-feeding, ask your doctor or pharmacist for advice before taking any medicine. Important information about some of the ingredients of Oncovin Oncovin contains methyl hydroxybenzoate (E218) and propyl hydroxybenzoate (E216) as preservatives. These may cause allergic reactions (possibly delayed) and exceptionally, broncospasm.
3. HOW TO USE ONCOVIN
Your doctor will only inject Oncovin 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 Oncovin.
Oncovin and most other cytotoxic drugs may affect the cells in 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 Oncovin. 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 side-effects. Oncovin 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 (please 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 Oncovin.
Your doctor or nurse will take great care that the Oncovin solution does not leak out of your vein when it is being injected. Please tell them immediately if you have pain or swelling during the injection or later. If this is not treated quickly, Oncovin can cause your tissue to be inflamed where the solution leaked out. They will also be very careful that Oncovin does not get into anyone’s eyes.
Adults
The usual dose is 1.4 to 1.5 milligrams for every square metre of your body surface. You should not have more than 2 milligrams per week.
Children
2 milligrams for every square metre of the child’s body surface. For
Information for the health care professional
ONCOVIN*
(Vincristine Sulphate Ph. Eur.)
WARNING: FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.
1. TRADE NAME OF THE MEDICINAL PRODUCT
Oncovin (Vincristine Sulphate Ph. Eur.)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient Quantity per vial
Vincristine Sulphate Ph. Eur. 1.0 mg/1.0 ml
3. PHARMACEUTICAL FORM
Solution for intravenous injection.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications. Oncovin is an anti-neoplastic drug for intravenous use. Information available at present suggests that Oncovin may be useful either alone or in conjunction with other oncolytic drugs for the treatment of: Leukaemias, including acute lymphocytic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia and blastic crisis of chronic myelogenous leukaemia. Malignant lymphomas, including Hodgkin’s disease and non-Hodgkin’s lymphomas. Multiple myeloma. Solid tumours, including breast carcinoma, small cell bronchogenic carcinoma, head and neck carcinoma and soft tissue sarcomas. Paediatric solid tumours, including Ewing’s sarcoma, embryonal rhabdomyosarcoma, neuroblastoma, Wilms’ tumour, retinoblastoma and medulloblastoma. Idiopathic thrombocytopenic purpura. Patients with true ITP refractory to splenectomy and short-term treatment with adrenocortical steroids may respond to vincristine but the drug is not recommended as primary treatment of this disorder. Recommended weekly doses of vincristine given for 3 to 4 weeks have produced permanent remissions in some patients. If patients fail to respond after 3 to 6 doses, it is unlikely that there will be any beneficial results with additional doses.
4.2 Posology and method of administration
This preparation is for intravenous use only. It should be administered only by individuals experienced in vincristine administration.
FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.
See ‘Special warnings and special precautions for use’ section for the treatment of patients given intrathecal vincristine sulphate.
Extreme care must be used in calculating and administering the dose of vincristine, since overdosage may have a very serious or fatal outcome. The drug is administered intravenously at weekly intervals. The recommended dose is 1.4 to
1.5 mg/m2, up to a maximum weekly dose of 2 mg. The dosage must always be adjusted individually because of the narrow range between therapeutic and toxic levels, and individual variations in response.
The elderly: As for adults.
Children: The usual dose is 2 mg/m2. For children weighing 10 kg or less, the starting dose should be 0.05 mg/kg, administered once a week.
An increase in the severity of side-effects may be experienced by patients with liver disease sufficient to decrease biliary excretion. A 50 percent reduction in the dose of vincristine is recommended for patients having a direct serum bilirubin value above 3 mg/100 ml (51 micromol/l). The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily. This metabolic pathway may be impaired in patients with hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes (see ‘Interactions’). The concentration of vincristine in Oncovin solution is 1 mg/ml. Do not add extra fluid to the vial prior to removal of the dose. Withdraw the solution of Oncovin into an accurate dry syringe, measuring the dose carefully. Do not add extra fluid to the vial in an attempt to empty it completely. The calculated dose of the solution for injection is drawn up into a syringe and injected either directly into a vein or into the tubing of a running intravenous infusion of normal saline or glucose in water, whichever is more suitable for the patient. Care should be taken to avoid infiltration of subcutaneous tissues. Injection may be completed in about one minute.
Caution: If leakage into surrounding tissue should occur during intravenous administration of vincristine, it may cause considerable irritation. The injection should be discontinued immediately 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 to disperse the drug and are thought to minimise discomfort and the possibility of cellulitis.
4.3 Contra-indications
FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.
See ‘Special warnings and special precautions for use’ section for the treatment of patients given intrathecal vincristine sulphate.
Patients with the demyelinating form of Charcot-Marie-Tooth syndrome should not be given vincristine.
4.4 Special warnings and special precautions for use: This preparation is for intravenous use only. It should be administered by individuals experienced in the administration of vincristine sulphate. The intrathecal administration of vincristine sulphate usually results in death. Syringes containing this product should be labelled “FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.” An auxiliary sticker is provided in the pack with this warning. Extemporaneously prepared syringes containing this product must be packaged in an overwrap which is labelled “DO NOT REMOVE COVERING UNTIL MOMENT OF INJECTION. FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.”
After inadvertent intrathecal administration, 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, if vincristine 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, 25 ml 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 150 ml/h, or at a rate of 75 ml/h when fresh plasma has been added as above. The rate of infusion should be adjusted to maintain a spinal fluid protein level of 150 mg/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 500 mg tds by mouth for 1 month.
Folinic acid has been administered intravenously as a 100 mg bolus and then infused at a rate of 25 mg/h for 24 hours, then bolus doses of 25 mg 6-hourly for 1 week. Pyridoxine has been given at a dose of 50 mg 8-hourly by intravenous infusion over 30 minutes. Their roles in the reduction of neurotoxicity are unclear.
Effective therapy with Oncovin is less likely to be followed by leucopenia than is the case with Velbe (vinblastine sulphate) and other oncolytic agents. A study of the side-effects of Oncovin in all age groups reveals that it is usually neuromuscular rather than bone marrow toxicity that limits dosage. However, because of the possibility of leucopenia, both clinician and patient should remain alert for signs of any complicating infection. Although pre-existing leucopenia does not necessarily contra-indicate the administration of Oncovin, the appearance of leucopenia during treatment warrants careful consideration before giving the next dose.
Acute uric acid nephropathy, which may occur after the administration of oncolytic agents, has also been reported with Oncovin. If central-nervous-system leukaemia is diagnosed, additional agents may be required, since vincristine does not appear to cross the blood-brain barrier in adequate amounts.
Particular attention should be given to dosage and neurological side-effects if Oncovin is administered to patients with pre-existing neuromuscular disease and also when other drugs with neurotoxic potential are being used.
Both in vivo and in vitro laboratory tests have failed to demonstrate conclusively that this product is mutagenic. Fertility following treatment with vincristine alone for malignant disease has not been studied in humans. Clinical reports of both male and female patients who received multiple-agent chemotherapy, that included vincristine, indicate that azoospermia and amenorrhoea can occur in postpubertal patients. Recovery occurred many months after completion of chemotherapy in some but not all patients. When the same treatment is administered to prepubertal patients, it is much less likely to cause permanent azoospermia and amenorrhoea.
Patients who received vincristine chemotherapy in combination with anticancer drugs known to be carcinogenic have developed second malignancies. The contributing role of vincristine in this development has not been determined. No evidence of carcinogenicity was found following intraperitoneal administration in rats and mice, although this study was limited.
Care must be taken to avoid contamination of the eye with concentrations of Oncovin used clinically. If accidental contamination occurs, severe irritation (or, if the drug was delivered under pressure, even corneal ulceration) may result. The eye should be washed immediately and thoroughly.
4.5 Interaction with other medicaments and other forms of interaction
Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids. These reactions have been encountered most frequently when the vinca alkaloid was used in combination with mitomycin-C and may be serious when there is pre-existing pulmonary dysfunction. The onset may be within minutes or several hours after the vinca is injected and may occur up to 2 weeks following the dose of mitomycin. Progressive dyspnoea, requiring chronic therapy, may occur. Vincristine should not be re-administered.
The simultaneous oral or intravenous administration of phenytoin and anti-neoplastic chemotherapy combinations, that included vincristine sulphate, have been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. Although the contribution of the vinca alkaloids has not been established, dosage adjustment of phenytoin, based on serial blood level monitoring, may need to be made when it is used in combination with vincristine.
Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily, or in patients with hepatic dysfunction. Concurrent administration of vincristine sulphate with itraconazole (a known inhibitor of the metabolic pathway) has been reported to cause an earlier onset and/or an increased severity of neuromuscular side-effects (see ‘Undesirable effects’). This interaction is presumed to be related to inhibition of the metabolism of vincristine.
When Oncovin is used in combination with L-asparaginase, it should be given 12 to 24 hours before administration of the enzyme in order to minimise toxicity, since administering L-asparaginase first may reduce hepatic clearance of vincristine. When chemotherapy is being given in conjunction with radiation therapy through portals which include the liver, the use of vincristine should be delayed until radiation therapy has been completed.
4.6 Pregnancy and lactation
Usage in pregnancy: Caution is necessary with the use of all oncolytic drugs during pregnancy.
Vincristine can cause foetal harm when administered to a pregnant woman, although there are no adequate and well-controlled studies. In several animal species, vincristine can induce teratogenic effects, as well as embryolethality, with doses that are non-toxic to the pregnant animal.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving vincristine. If vincristine is used during pregnancy, or if the patient becomes pregnant while receiving this drug, she should be informed of the potential hazard to the foetus.
Usage in nursing mothers: It is not known whether Oncovin is excreted in human breast milk. Because of 25199001
children who weigh 10 kilograms or less, the usual starting dose is 0.05 milligrams for each kilogram of their body weight.
Your nurse will measure your height and weight and work out your body surface area from the measurements. Your doctor will use 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 Oncovin - usually once a week. Oncovin must only go into a vein. You may have an injection every week and your doctor may treat you with other cytotoxic drugs 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 Oncovin Injection than you should
As a doctor or nurse will usually give this medicine to you, 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.
4. POSSIBLE SIDE-EFFECTS
Like all medicines, Oncovin can cause side-effects, although not everybody gets them.
Tell your doctor immediately if you experience any of the following very rare or rare side-effects:
Very rare side-effects include:
• problems with your eyesight.
Rare side-effects include:
• hearing difficulty - sometimes • allergic reactions including a
with dizziness or eyeball rash, itching, swelling or
movements breathing difficulties
• fits.
Other side-effects that have been reported:
• a low blood cell count causing a • fever, a sore throat, nose bleeds
• muscle weakness and unsteady
• pain (e.g. in your jaw, throat, •
neck, nerves, muscles or bones) •
• feeling or being sick
• hair loss (the hair may regrow •
while you are still being treated)
• pain or swelling where you have
numbness or tingling in your hands or feet loss of reflexes
paralysis of your face or throat feet slapping the ground when walking
losing your sense of touch headache
constipation, which may be
severe
weight loss
diarrhoea
blockage in your small intestine feeling weak, confused or drowsy (due to lack of sodium in the blood)
being short of breath problems urinating effects on blood pressure.
If any of the side-effects get serious or if you notice any side-effects not listed in this leaflet, please tell your doctor or pharmacist.
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: www.mhra.gov.uk/yellowcard.
By reporting side effects you can help provide more information on the safety of this medicine.
5. HOW TO STORE ONCOVIN
Keep out of the sight and reach of children.
The hospital pharmacy should keep the bottles of Oncovin in a fridge (2-8°C). When Oncovin has been dissolved, the hospital should keep the Oncovin solution in a fridge.
The bottle should not be used after the expiry date printed on the bottle label. The expiry date refers to the last day of that month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment
6. FURTHER INFORMATION
The active substance in Oncovin is vincristine sulphate. The other ingredients are mannitol (E421), methyl hydroxy benzoate (E218), propyl hydroxybenzoate (E216), acetic acid, sodium acetate and water for injections
What Oncovin looks like and the contents of the pack
Oncovin is a clear, colourless solution, supplied in a rubber stoppered 10ml glass vial.
POM
PL 06831/0118 Oncovin
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 approved in September 2014
* Oncovin (vincristine sulphate) is a registered trademark of Genus Pharmaceuticals Limited.
_____________________________________________________________________________________________________________________________________
the potential for serious adverse reactions due to Oncovin in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
4.7 Effects on ability to drive and use machines Not known.
4.8 Undesirable effects
Prior to the use of this drug, patients and/or their parents/guardians should be advised of the possibility of untoward symptoms. In general, adverse reactions are reversible and are related to dosage size and cumulative dosage. The use of small amounts of vincristine daily for long periods is not advised. The most common adverse reaction is alopecia; the most troublesome adverse reactions are neuromuscular in origin.
When single weekly doses of the drug are employed, the adverse reactions of leucopenia, neuritic pain and constipation are usually of short duration (ie, less than 7 days). When the dosage is reduced, these reactions may lessen or disappear. They seem to be increased when the calculated amount of drug is given in divided doses.
Other adverse reactions, such as alopecia, sensory loss, paraesthesia, difficulty in walking, slapping gait, loss of deep-tendon reflexes and muscle wasting, may persist for at least as long as therapy is continued. Generalised sensorimotor dysfunction may become progressively more severe with continued treatment. In most instances they have disappeared by about the sixth week after discontinuance of treatment, but the neuromuscular difficulties may persist for prolonged periods in some patients. Re-growth of hair may occur while maintenance therapy continues.
The following adverse reactions have been reported:
Neuromuscular (often dose limiting): Neuritic pain, sensory loss, paraesthesiae, difficulty in walking, slapping gait, loss of deep tendon reflexes, muscle wasting, ataxia, paresis, foot drop and cranial nerve palsies, especially ocular palsies and laryngeal nerve paralysis. Jaw pain, pharyngeal pain, parotid gland pain, bone pain, back pain, limb pain and myalgias have been reported; pain in these areas may be severe. Convulsions, frequently with hypertension, have been reported in a few patients receiving vincristine. Several instances of convulsions followed by coma have been reported in children. Transient cortical blindness and optic atrophy with blindness have been reported.
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 vincristine sulphate is used in combination with other agents known to be ototoxic, such as the platinum-containing oncolytics. Frequently, there appears to be a sequence in the development of neuromuscular side-effects. Initially, one may encounter only sensory impairment and paraesthesiae. With continued treatment, neuritic pain may appear and later, motor difficulties. No reports have yet been made of any agent that can reverse the neuromuscular manifestations of Oncovin. Haematological: Leucopenia; vincristine does not appear to have any constant or significant effect upon the platelets or the red blood cells, however, anaemia and thrombocytopenia have been reported. If thrombocytopenia is present when treatment with Oncovin is begun, it may actually improve before the appearance of marrow remission. Gastro-intestinal: Constipation, abdominal cramps, paralytic ileus, diarrhoea, weight loss, nausea, vomiting, oral ulceration, intestinal necrosis and/or perforation and anorexia have occurred. The constipation which may be encountered responds well to such usual measures as enemas and laxatives. Constipation may take the form of upper colon impaction and the rectum may be found to be empty on physical examination. Colicky abdominal pain, coupled with an empty rectum, may mislead the clinician. A flat film of the abdomen is useful in demonstrating this condition.
A routine prophylactic regimen against constipation is recommended for all patients receiving Oncovin. Paralytic ileus may occur, particularly in young children. The ileus will reverse itself upon temporary discontinuance of vincristine and with symptomatic care.
Pulmonary: See under ‘Interactions'.
Endocrine: Rare occurrences of a syndrome attributable to inappropriate antidiuretic hormone secretion have been observed in patients treated with vincristine. There is a high urinary sodium excretion in the presence of hyponatraemia; renal or adrenal disease, hypotension, dehydration, azotaemia and clinical oedema are absent.
With fluid deprivation, improvement occurs in the hyponatraemia and in the renal loss of sodium.
Genitourinary: Polyuria, dysuria and urinary retention due to bladder atony have occurred. Other drugs known to cause urinary retention (particularly in the elderly) should, if possible, be discontinued for the first few days following administration of vincristine.
Cardiovascular: Hypertension and hypotension have occurred. Chemotherapy combinations which have included vincristine, when given to patients previously treated with mediastinal radiation, have been associated with coronary artery disease and myocardial infarction. Causality has not been established.
Hypersensitivity: Rare cases of allergic-type reactions, such as anaphylaxis, rash and oedema, temporally related to vincristine therapy have been reported in patients receiving vincristine as a part of multi-drug chemotherapy regimens. Cutaneous: Alopecia, rash.
Other: Fever, headache, injection site reaction (see ‘Posology and method of administration').
Reporting of suspected adverse reactions
Reporting of 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 at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Side-effects following the use of vincristine are dose related. In children under 13 years of age, death has occurred following doses of vincristine that were 10 times those recommended for therapy. Severe symptoms may occur in this patient group following dosages of 3 to 4 mg/m2. Adults can be expected to experience severe symptoms after single doses of 3 mg/m2 or more. Therefore, following administration of doses higher than those recommended, patients can be expected to experience side-effects in an exaggerated fashion. Supportive care should include the following: (a) prevention of side-effects resulting from the syndrome of inappropriate antidiuretic hormone secretion (this would include restriction of fluid intake and perhaps the administration of a diuretic affecting the function of
5.
5.1
5.2
5.3
6.
6.1
6.2
6.3
6.4
6.5
6.6
7.
8.
9.
10.
Henle's loop and the distal tubule); (b) administration of anticonvulsants; (c) use of enemas or cathartics to prevent ileus (in some instances, decompression of the gastro-intestinal tract may be necessary); (d) monitoring the cardiovascular system; (e) determining daily blood counts for guidance in transfusion requirements.
Folinic acid has been observed to have a protective effect in normal mice which were administered lethal doses of vincristine. Isolated case reports suggest that folinic acid may be helpful in treating humans who have received an overdose. A suggested schedule is to administer 100 mg of folinic acid intravenously every 3 hours for 24 hours and then every 6 hours for at least 48 hours. Theoretical tissue levels of vincristine derived from pharmacokinetic data are predicted to remain significantly elevated for at least 72 hours. Treatment with folinic acid does not eliminate the need for the above-mentioned supportive measures.
Most of an intravenous dose of vincristine is excreted into the bile after rapid tissue binding. Because only very small amounts of the drug appear in dialysate, haemodialysis is not likely to be helpful in cases of overdosage.
Enhanced faecal excretion of parenterally administered vincristine has been demonstrated in dogs pre-treated with cholestyramine. There are no published clinical data on the use of cholestyramine as an antidote in humans.
There are no published clinical data on the consequences of oral ingestion of vincristine. Should oral ingestion occur, the stomach should be evacuated, followed by oral administration of activated charcoal and a cathartic. PHARMACOLOGICAL PROPERTIES Pharmacodynamic properties
Vincristine is an anti-neoplastic drug with broad-spectrum anti-tumour activity in man. The drug may act by mitotic inhibition, causing an arrest of cell division in metaphase. The drug is relatively marrow-sparing and is thus suitable for use in combination with other cancer chemotherapeutic agents.
Pharmacokinetic properties
Vincristine is poorly absorbed orally. The clearance of the drug after rapid intravenous injection follows a triphasic decay pattern: a very rapid steep descent (alpha phase); a narrow-middle region (beta phase) and a much longer terminal region (gamma phase). The terminal phase half-life of the drug varies from 19-155 hours. Dosing with the drug more frequently than once weekly is therefore probably unnecessary.
Vincristine is primarily excreted by the biliary route. Patients with impaired hepatic or biliary function, as evidenced by a raised serum alkaline phosphatase, have been shown to have a significantly prolonged vincristine elimination half-life.
Preclinical safety data
Both in vivo and in vitro laboratory tests have failed to demonstrate conclusively that the product is mutagenic.
No evidence of carcinogenicity was found following intraperitoneal administration in rats and mice, although this study was limited. In several animal species, vincristine can induce teratogenic effects, as well as embryolethality, with doses that are non-toxic to the pregnant animal.
PHARMACEUTICAL PARTICULARS
List of excipient(s)
Mannitol, Methyl hydroxybenzoate, Propyl hydroxybenzoate, Acetic Acid, Sodium Acetate, Water for Injection Incompatibilities
Oncovin should never be mixed with any other drug and should not be diluted in solutions that raise or lower the pH outside the range of 3.5 to 5.5. It should not be mixed with anything other than normal saline or glucose in water. Shelf-life 18 months.
Special precautions for storage
Vials of Oncovin solution should be stored in a refrigerator between 2 °C and 8 °C. Protect from light.
Nature and contents of container
A type I flint glass vial with rubber stopper and aluminium seals. Pack containing a single vial of 1 ml solution. Instructions for use/handling
Special dispensing information: When dispensing vincristine sulphate in other than the original container, it is imperative that it be packaged in an overwrap bearing the statement “DO NOT REMOVE COVERING UNTIL MOMENT OF INJECTION. FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.” A syringe containing a specific dose must be labelled, using the auxiliary sticker provided in the pack, with this warning.
Guidelines for the safe handling of anti-neoplastic agents: Cytotoxic preparations should not be handled by pregnant staff. Only trained personnel should handle 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 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. Whenever solution and container permit, parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration.
MARKETING AUTHORISATION HOLDER
Genus Pharmaceuticals, Linthwaite, Huddersfield, HD7 5QH, UK. MARKETING AUTHORISATION NUMBER PL 06831/0118
DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
Date of first authorisation: 13th July 2004
DATE OF (PARTIAL) REVISION OF THE TEXT September 2014
LEGAL CATEGORY POM
* Oncovin (vincristine sulphate) is a Genus Pharmaceuticals Limited trademark
25199001
MHRA Header Box
|
Product Title |
Oncovin Img per 1ml Solution for Injection |
Colours used |
Fonts used | |
|
Component |
Leaflet |
■ |
Black |
Helvetica Neue 55 Reg 9pt |
|
Pack Size |
1mg per 1ml |
Helvetica Neue 75 Bold 9pt | ||
|
IG code |
25199001 | |||
|
Dimensions |
300 x 315 mm | |||
|
Proof No |
04 Date 02/09/2014 | |||