Cytarabine Injection BP 1000mg/10ml Taj Pharma

  1. Name of the medicinal product

Cytarabine Injection BP 100mg/1ml Taj Pharma
Cytarabine Injection BP 500mg/5ml Taj Pharma
Cytarabine Injection BP 1000mg/10ml Taj Pharma
Cytarabine Injection BP 2000mg/20ml Taj Pharma

  1. Qualitative and quantitative composition

a) Cytarabine Injection BP 100mg/1ml
Each ml contains
Cytarabine USP                                                 100mg
Sodium Hydroxide USNF                                      q.s.
Hydrochloric Acid USNF                                        q.s.
Water for Injection USP                                         q.s.

b) Cytarabine Injection BP 500mg/5ml
Each ml contains
Cytarabine USP                                                 100mg
Sodium Hydroxide USNF                                      q.s.
Hydrochloric Acid USNF                                        q.s.
Water for Injection USP                                         q.s.

c) Cytarabine Injection BP 1000mg/10ml
Each ml contains
Cytarabine USP                                                 100mg
Sodium Hydroxide USNF                                      q.s.
Hydrochloric Acid USNF                                        q.s.
Water for Injection USP                                         q.s.

a) Cytarabine Injection BP 2000mg/20ml
Each ml contains
Cytarabine USP                                                 100mg
Sodium Hydroxide USNF                                      q.s.
Hydrochloric Acid USNF                                        q.s.
Water for Injection USP                                         q.s.

For the full list of excipients see 6.1

  1. Pharmaceutical form

Solution for injection.

  1. Clinical particulars

4.1 Therapeutic indications

Cytarabine may be used alone or in combination with other antineoplastic agents. It is indicated alone or in combination for induction of remission and/or maintenance in patients with acute myeloid leukaemia, acute non-lymphoblastic leukaemias, acute lymphoblastic leukaemias, acute lymphocytic leukaemia, erythroleukaemia, blast crises of chronic myeloid leukaemia, diffuse histiocytic lymphomas (non-Hodgkin’s lymphomas of high malignancy), meningeal leukaemia and meningeal neoplasms. Clinicians should refer to the current literature on combination therapy before initiating treatment.

4.2 Posology and method of administration

Posology

Cytarabine Injection can be diluted with Sterile Water for Injections BP, Glucose Intravenous Infusion BP or Sodium Chloride Intravenous Infusion BP. Prepared infusions, in the recommended diluents, should be used immediately. Alternatively, the diluted infusion fluids may be stored at 2-8°C, protected from light, but portions remaining unused after 24 hours must be discarded.

Remission Induction: Adults

Continuous Dosing: The usual dose in leukaemia is 2 mg/kg by rapid intravenous injection daily for ten days. If after ten days neither therapeutic response nor toxicity has been observed, the dose may be increased to 4 mg/kg until a therapeutic response or toxicity is evident. Daily blood counts should be taken. Almost all patients can be carried to toxicity with these doses.

Alternatively, 0.5 to 1 mg/kg may be infused daily in 1-24 hours for ten days, and then at a rate of 2 mg/kg/day until toxicity is observed. Continue to toxicity or until remission occurs. Results from one hour infusions have been satisfactory in the majority of patients.

Intermittent dosing: Cytarabine may be given as intermittent intravenous doses of 3-5 mg/kg daily, for five consecutive days. This course of treatment can be repeated after an interval of 2 to 9 days and repeated until the therapeutic response or toxicity is exhibited.

Evidence of bone marrow improvement has been reported to occur 7-64 days after the beginning of therapy.

In general, if a patient shows neither remission nor toxicity after a trial period, then cautiously administered higher doses can be administered. Generally patients tolerate higher doses given by rapid intravenous injection rather than slow infusion.

As a single agent for induction of remissions in patients with acute leukaemia, Cytarabine has been given in doses of 200 mg/m2 by continuous intravenous infusion for five days at approximately 2 week intervals.

Maintenance therapy: To maintain remission, doses of 1 mg/kg may be given intravenously or subcutaneously, once or twice weekly.

Leukemic Meningitis: Therapy for established meningitis employs a wide variety of dose regimens but a recommended total daily dose not exceeding 100 mg, alternating with methotrexate is recommended.

Myelosuppression, anaemia and thrombocytopenia occur almost to all patients given daily infusions or injections. Myelosuppression is biphasic and nadirs at 7-9 and 15-24 days. Evidence of bone marrow improvement may be expected 7-64 (mean 28) days after the beginning of treatment.

Paediatric population: Children appear to tolerate higher doses of Cytarabine than adults, and where the range of doses is given, children should receive the higher dose.

Elderly: No data is available to suggest that a change in dose is necessary in the elderly. However, the elderly patient is more susceptible to toxic reactions and therefore particular attention should be paid to drug induced leukopenia, thrombocytopenia and anaemia.

Method of administration

Cytarabine100 mg/1ml Injection is a ready to use injection and can be administered by the intravenous and subcutaneous routes. Cytarabine100 mg/1ml Injection should not be administered by the intrathecal route due to the slight hypertonicity of this formulation. (See section 4.8).

4.3 Contraindications

Hypersensitivity to Cytarabine or to any of the excipients listed in 6.1.

Anaemia, leukopenia and thrombocytopenia of non-malignant aetiology (e.g. bone marrow aplasia), unless the benefits outweigh the risk.

Degenerative and toxic encephalopathies, especially after the use of methotrexate or treatment with ionizing radiation.

During pregnancy, Cytarabine should only be administrated on strict indication, where the benefits of the drug to the mother should be weighed against possible hazards to the foetus.

4.4 Special warnings and precautions for use

Cytarabine is a potent bone marrow suppressant. Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression. Patients receiving the drug should be kept under close medical supervision. Leucocyte and platelet counts should be performed frequently and daily during induction. Bone marrow examinations should be performed frequently after blasts have disappeared from the peripheral blood.

Facilities should be available for management of complications, possibly fatal, of bone marrow suppression (infection resulting from granulocytopenia and other impaired body defences, and haemorrhage secondary to thrombocytopenia).

One case of anaphylaxis that resulted in cardiopulmonary arrest and necessitated resuscitation has been reported. This occurred immediately after intravenous Cytarabine was administered.

Severe and at times fatal central nervous system (CNS), gastrointestinal (GI) and pulmonary toxicity (different from that seen with conventional therapy regimens of Cytarabine) has been reported following some experimental Cytarabine dose schedules. These reactions include reversible corneal toxicity; cerebral and cerebellar dysfunction, usually reversible; somnolence; convulsion; severe gastrointestinal ulceration including pneumatisescysteroidesintestinalis, leading to peritonitis; sepsis and liver abscess; and pulmonary oedema.

The risk of CNS toxicity increases if high dose Cytarabine is given in combination with another CNS toxic treatment such as radiation therapy or in patients who have previously had CNS treatment as chemotherapy intrathecally. Rarely, neurological effects such as severe spinal cord toxicity even leading to necrotising encephalopathy, quadriplegia and paralysis and blindness have been reported with cytosine arabinoside and have been predominantly associated with intrathecal administration. Isolated cases have also been reported with high intravenous doses during combination chemotherapeutic regimens (see section 4.8).

Delayed progressive ascending paralysis resulting in death has been reported in children with AML following intravenous Cytarabine at conventional doses in combination with other drugs.

Cytarabine has been shown to be mutagenic and carcinogenic in animals. The possibility of a similar effect should be borne in mind when designing the long-term management of the patient.

Cytarabine should only be used under the constant supervision by physicians experienced in therapy with cytotoxic agents. Hyperuricemia secondary to rapid lysis of neoplastic cells may occur in patients receiving Cytarabine; serum uric acid concentrations should be monitored. The physician should be prepared to use such supportive and pharmacological measures as may be necessary to control this problem.

Periodic determinations of renal and hepatic functions and bone marrow should also be performed and the drug should be used with caution in patients with impaired hepatic function.

However, dosage reduction does not appear to be necessary in patients with impaired renal function. The human liver apparently detoxifies a substantial fraction of the administered dose. The drug should be used with caution and at a reduced dose when liver function is poor. Frequent platelet and leucocyte counts are mandatory.

Therapy should be suspended or modified when drug-induced bone marrow depression results in a platelet count of less than 50,000 or a polymorph nuclear count of under 1000 per mm3. Counts may continue to fall after the therapy has been discontinued and may reach lowest values after five to seven days. Therapy may be restarted when the bone marrow appears to be recovering on successive bone marrow studies. Therapy should not wait until the normal blood values are obtained to be re-initiated. If treatment is not resumed before blood values return to normal, the disease can get out of control.

When intravenous doses are given quickly, patients may become nauseated and may vomit for several hours afterwards. The problem tends to be less severe when infused.

Abdominal tenderness (peritonitis) and guaiac positive colitis, with concurrent neutropenia and thrombocytopenia, have been reported in patients treated with conventional doses of Cytarabine in combination with other drugs. Patients have responded to non-operative medical management.

Concurrent granulocyte-transfusion should be avoided as severe respiratory insufficiency has been reported.

Immunosuppressant effects/Increased susceptibility to infections

Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including Cytarabine, may result in serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving Cytarabine. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.

High dose therapy

Peripheral motor and sensory neuropathies after consolidation with high doses of Cytarabine, daunorubicin, and asparaginase have occurred in adult patients with acute non lymphocytic leukaemia.

Patients treated with high doses of Cytarabine should be observed for neuropathy since dose adjustments may be needed to avoid irreversible neurologic disorders.

Severe and sometimes fatal pulmonary toxicity, adult respiratory distress syndrome, and pulmonary oedema have occurred following high dose schedules with Cytarabine therapy. Cases of cardiomyopathy with subsequent death have been reported following experimental high dose therapy with Cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation.

Paediatric population

The safety of the drug has not been established in infants.

4.5 Interaction with other medicinal products and other forms of interaction

Cardiac Glycosides

GI absorption of oral digoxin tablets may be substantially reduced in patients receiving combination chemotherapy regimens (including regimens containing Cytarabine), possibly as a result of temporary damage to intestinal mucosa caused by the cytotoxic agents. Reversible decreases in steady-state plasma digoxin concentrations and renal glycoside excretion were observed in patients receiving beta-acetyl digoxin and chemotherapy regimens containing cyclophosphamide, vincristine and prednisone with or without Cytarabine or procarbazine. Limited data suggest that the extent of GI absorption of digitoxin is not substantially affected by concomitant administration of combination chemotherapy regimens known to decrease absorption of digoxin. Steady-state plasma digitoxin concentrations did not appear to change. Therefore, monitoring of plasma digoxin levels may be indicated in patients receiving similar combination chemotherapy regimens. The utilization of digitoxin for such patients may be considered as an alternative.

Anti-Infective Agents

One in vitro study indicates that Cytarabine may antagonise the activity of gentamicin against Klebsiellapneumoniae. In patients on Cytarabine being treated with gentamicin for a K.pneumoniae infection, a lack of a prompt therapeutic response may indicate the need for re-evaluation of antibacterial therapy.

5-Fluorocytosine:

5-Fluorocytosine should not be administered with Cytarabine as the therapeutic efficacy of 5-Fluorocytosine has been shown to be abolished during such therapy.

Immunosuppressive Agents

Due to the immunosuppressive action of Cytarabine, viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body, may be associated with the use of Cytarabine alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity. These infections may be mild, but can be severe and at times fatal.

4.6 Fertility, pregnancy and lactation

Pregnancy

Cytarabine is teratogenic in some animal species. It should not be used in pregnant women (especially during the first trimester) or in those who may become pregnant, unless the possible benefits outweigh the potential risks. Women who are, or who may become, pregnant during treatment with Cytarabine should be informed of the risks.

Men and women have to use effective contraception during and up to 6 months after treatment.

Breast-Feeding

It is not known if Cytarabine or its metabolite is distributed into breast milk, and it should not be used in mothers who are breastfeeding.

Fertility

Fertility studies to assess the reproductive toxicity of Cytarabine have not been conducted. Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients taking Cytarabine therapy, especially in combination with alkylating agents. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Given that Cytarabine has a mutagenic potential which could induce chromosomal damage in the human spermatozoa, males undergoing Cytarabine treatment and their partner should be advised to use a reliable contraceptive method.

4.7 Effects on ability to drive and use machines

No documented effect on ability to drive or operate machinery.

Nevertheless, patients receiving chemotherapy may have an impaired ability to drive or operate machinery and should be warned of the possibility and advised to avoid such tasks if so affected.

4.8 Undesirable effects

The following adverse events have been reported in association with Cytarabine therapy. Frequencies are defined using the following convention:

Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data)

Undesirable effects from Cytarabine are dose-dependent. Most common are gastrointestinal undesirable effects. Cytarabine is toxic to the bone marrow, and causes haematological undesirable effects.

Infections and infestations

Uncommon: Sepsis (immunosuppression)

Neoplasms benign, malignant and unspecified (including cysts and polyps)

Uncommon: Lentigo

Blood and lymphatic system disorders:

Common: Anaemia, megaloblastosis, leukopenia, thrombocytopenia

Not known: Reticulocytopenia

These appear to be more evident after high doses and continuous infusions; the severity depends on the dose of the drug and schedule of administration.

Gastrointestinal disorders

Common: Dysphagia, abdominal pain, nausea, vomiting, diarrhoea, oral/anal inflammation or ulceration

Uncommon: Oesophagitis, oesophageal ulceration, pneumatosiscystoidesintestinalis, necrotising colitis, peritonitis

Not known: Gastrointestinal haemorrhage, pancreatitis

Nausea and vomiting occur and are generally more frequent following rapid IV administration than with continuous IV infusion of the drug.

Skin and subcutaneous tissue disorders

Common: Reversible undesirable effects to the skin, such as erythema, bullous dermatitis, urticaria, vasculitis, alopecia

Uncommon: skin ulceration, pruritus, burning pain of palms and soles

Very rare: Neutrophiliceccrinehidradenitis

Not known: Rash, freckling, skin bleeding

Renal and urinary disorders

Common: Renal impairment, urinary retention

Not known: Renal dysfunction

General disorders and administration site conditions

Common: Fever, thrombophlebitis at the site of injection

Uncommon: Cellulitis at the injection site

Not known: Chest pain, irritation or sepsis at the injection site, mucosal bleeding

Cardiac disorders

Uncommon: Pericarditis

Very rare: Arrhythmia

Not Known: Sinus bradycardia

Hepatobiliary disorders

Common: Reversible effects on the liver with increased enzyme levels

Not known: Hepatic dysfunction and jaundice

Metabolism and nutrition disorders

Common: Anorexia, hyperuricemia

One case of anaphylaxis that resulted in cardiopulmonary arrest and necessitated resuscitation has been reported (see section 4.4 Special warnings and precautions for use).

Nervous system disorders

Common: At high doses cerebellar or cerebral influence with deterioration of the level of consciousness, dysarthria, nystagmus

Uncommon: Headache, peripheral neuropathy, paraplegia at intrathecal administration

Not known: Dizziness, neuritis or neural toxicity and pain, neurotoxicity rash

Eye disorders

Common: Reversible haemorrhagic conjunctivitis (photophobia, burning, visual disturbance, increased lacrimation), keratitis

Not known: Conjunctivitis

Respiratory, thoracic and mediastinal disorders

Uncommon: Pneumonia, dyspnoea, sore throat.

Musculoskeletal and connective tissue disorders

Uncommon: Myalgia, joint pain.

A Cytarabine syndrome (immunoallergic effect) is characterised by fever, myalgia, bone pain, occasionally chest pain, exanthema, maculopapular rash, conjunctivitis, nausea and malaise. It usually occurs 6-12 hours after administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are serious enough to warrant treatment, corticosteroids should be contemplated. If treatment is effective, therapy with Cytarabine may be continued.

Adverse effects due to high dose Cytarabine treatment, other than those seen with conventional doses include:

Blood and lymphatic system disorders

Hematological toxicity has been seen as profound pancytopenia which may last 15-25 days along with more severe bone marrow aplasia than that observed at conventional doses.

Nervous system disorders

After treatment with high doses of Cytarabine, symptoms of cerebral or cerebellar influence like personality changes, affected alertness, dysarthria, ataxia, tremor, nystagmus, headache, confusion, somnolence, dizziness, coma, convulsions, etc. appear in 8-37 % of treated patients. The incidence in elderly (>55 years) may be even higher. Other predisposing factors are impaired liver and renal function, previous CNS treatment (e.g., radiotherapy) and alcohol abuse. CNS disturbances are in the most cases reversible.

The risk of CNS toxicity increases if the Cytarabine treatment -given as high dose i.v.- is combined with another CNS toxic treatment such as radiation therapy or high dose of a cytotoxic agent.

Eye disorders

Reversible corneal lesion and haemorrhagic conjunctivitis have been described. These phenomena can be prevented or decreased by installation of corticosteroid eye drops.

Gastrointestinal disorders

Especially in treatment with high doses of Cytarabine, more severe reactions may appear in addition to common symptoms. Intestinal perforation or necrosis with ileus and peritonitis have been reported. Pancreatitis has also been observed after high-dose therapy.

Hepatobiliary disorders

Liver abscesses, hepatomegaly and Budd-Chiari-syndrome (hepatic venous thrombosis) have been observed after high-dose therapy.

Respiratory, thoracic and mediastinal disorders

Clinical signs as present in pulmonary oedema/ARDS may develop, particularly in high-dose therapy. The reaction is probably caused by an alveolar capillary injury. It is difficult to make an assessment of frequencies (stated as 10-26 % in different publications), since the patients usually have been in relapse where other factors may contribute to this reaction.

Reproductive system and breast disorders

Amenorrhoea and azoospermia

Others

Following Cytarabine therapy, cardiomyopathy and rhabdomyolysis have been reported.

The gastrointestinal undesirable effects are reduced if Cytarabine is administered as infusion. Local glucocorticoids are recommended as prophylaxis of haemorrhagic conjunctivitis.

One case of anaphylaxis that resulted in cardiopulmonary arrest and necessitated resuscitation has been reported (see section 4.4).

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.

4.9 Overdose

There is no specific antidote for Cytarabine overdose. Cessation of therapy followed by management of ensuing bone marrow depression including whole blood or platelet transfusion and antibiotics as required.

Twelve doses of 4.5 g/m2 by IV infusion over one hour every 12 hours induces irreversible and fatal central nervous system toxicity.

Cytarabine may be removed by haemodialysis.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Pyrimidine analogues

Mechanism of action

Cytarabine (ARA-C) is metabolised in vivo to ARA-CTP phosphorylated compound. This competitively inhibits DNA polymerase and may also inhibit certain acid kinase enzymes. Primarily the drug acts as a false nucleoside and competes for enzymes involved in the conversion of cytidine nucleotide to deoxycytidine nucleotide and also incorporation into the DNA.

Cytarabine has no effect on non-proliferating cells nor on proliferating cells unless in the S phase. It is a cell cycle specific antineoplastic drug.

5.2 Pharmacokinetic properties

Absorption

Oral administration is ineffective due to rapid deamination in the gut. Cytidinedeaminase is concentrated in the liver and intravenous doses show biphasic elimination with half-lives of approximately 10 minutes and 1-3 hours.

Elimination

After 24 hours 80% of a dose has been eliminated either as the inactive metabolite or as the unchanged Cytarabine, mostly in urine but some in bile.

Distribution

CSF levels of 50% of plasma levels are achieved with intravenous infusion. Intrathecal dosing results in slower elimination (T1/2 2-11 hours).

Cytarabine is rapidly and widely distributed into tissues, crosses the blood brain barrier and also the placenta.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

  1. Pharmaceutical particulars

6.1 List of excipients

Water for injection  q.s.

Excipients  q.s.

6.2 Incompatibilities

Solutions of Cytarabine have been reported to be incompatible with various drugs, i.e. carbenicillin sodium, cephalothin sodium, fluorouracil, gentamicin sulphate, heparin sodium, hydrocortisone sodium succinate, insulin-regular, methylprednisolone sodium succinate, nafacillin sodium, oxacillin sodium, penicillin G sodium. However, the incompatibility depends on several factors (e.g. concentrations of the drug, specific diluents used, resulting pH, temperature). Specialised references should be consulted for specific compatibility information.

6.3 Shelf life

Before use: 18 months

In use: Chemical and physical in-use stability has been demonstrated for 7 days at room temperature.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

Do not refrigerate or freeze.

Do not store above 25°C. Keep container in the outer carton, in order to protect from light.

6.5 Nature and contents of container

Clear Type I glass vial with rubber stopper

Clear Type I glass Onco-Tain® vial with rubber stopper

Clear Type I glass Onco-Vial® with rubber stopper

Pack sizes 1’s, 5’s, 10’s and 20’s.

Not all presentations and pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Prior to use, vials of Cytarabine 100mg/ml Injection must be warmed to 55°C, for 30 minutes, with adequate shaking, and allowed to cool to room temperature.

Use in the paediatric population

No special requirements.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA).

Cytarabine Injection BP 100mg/1ml Taj Pharma
Cytarabine Injection BP 500mg/5ml Taj Pharma
Cytarabine Injection BP 1000mg/10ml Taj Pharma
Cytarabine Injection BP 2000mg/20ml Taj Pharma

Package leaflet Information for the user

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

  • 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 only. 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. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

  1. What Cytarabine Injection is and what it is used for
  2. What you need to know before you use Cytarabine Injection
  3. How to use Cytarabine Injection
  4. Possible side effects
  5. How to store Cytarabine Injection
  6. Contents of the pack and other information

 

  1. What Cytarabine Injection is and what it is used for

Cytarabine Injection is an anti-cancer medicine. Treatment with an anti-cancer medicine is sometimes called cancer chemotherapy.

Cytarabine Injection is used to treat some types of leukaemia (cancer affecting the blood) and lymphomas (cancer of the lymph glands). It may be used in combination with other anti-cancer medicines.

You must talk to a doctor if you do not feel better or if you feel worse.

  1. What you need to know before you use Cytarabine Injection

Do not use Cytarabine Injection

  • if you are allergic to Cytarabine or any of the other ingredients of this medicine (listed in section 6)
  • if your blood cell count (number of cells in your blood) is very low due to some cause other than cancer (unless your doctor decides the benefits of treatment outweigh the risks)
  • if you have had severe effects on your brain (encephalopathy) after radiation treatment or treatment with another anticancer medicine such as methotrexate
  • if you are pregnant (unless your doctor considers the benefits to the mother outweigh the risks to the unborn child)

Tell your doctor if you think any of the above applies to you before this medicine is used.

Warnings and precautions

Talk to your doctor or pharmacist before taking Cytarabine Injection.

Take special care with Cytarabine Injection

  • if your blood cell count is low
  • if you have any problems with your liver including jaundice (causes yellowing of the skin)
  • if you have recently received cancer medicine treatment or radiotherapy or if you are due to have radiotherapy (the side effects of radiotherapy can be made worse by Cytarabine treatment)
  • Cytarabine strongly reduces blood cell production in the bone marrow and your blood cell numbers can continue to fall for up to a week after stopping treatment. Your doctor will test your blood regularly and examine your bone marrow if required
  • if your bone marrow is still recovering from the effects of other medicines (your doctor will only consider treatment with Cytarabine if absolutely necessary)
  • serious and sometimes life-threatening side effects can occur in the central nervous system, the bowels, the lungs or the heart especially when treated with high doses of Cytarabine
  • the levels of uric acid (showing that the cancer cells are destroyed) in your blood (hyperuricemia) may be high during treatment. Your doctor will tell you if you need to take any medicine to control this
  • during treatment with Cytarabine administration of certain vaccines is not advised. If required, consult your doctor
  • during treatment with Cytarabine, granulocyte transfusion should be avoided as severe breathing problems have been reported. Your doctor will determine if this treatment is required

Tell your doctor if either of the above applies to you before this medicine is used. Your doctor will monitor your blood to check your blood cell count, your liver and kidney functions and to monitor for raised uric acid levels.

Special care will be taken if Cytarabine is to be given to a child. Cytarabine should not be used in infants.

Other medicines and Cytarabine Injection

Tell your doctor if you are using, have recently used or might use any other medicines. Special care is needed if you are taking/using other medicines as some could interact with Cytarabine.

The effectiveness of the following medicines may be reduced or increased by Cytarabine:

  • digoxin or beta-acetyl digoxin tablets (heart medicine)
  • gentamicin (an antibiotic)
  • 5-fluorocytosine (a medicine used to treat fungal infections)
  • other medicines which decrease the activity of the immune system

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine

Avoid becoming pregnant while you or your partner is being treated with Cytarabine. As there is a risk of birth defects, women of childbearing potential or their partner should use appropriate contraception methods during and up to 6 months after treatment with Cytarabine to prevent pregnancy.

You should stop breast-feeding before starting treatment with cytarabine because this medicine may be harmful to infants being breast-fed.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Do not drive or use machines if you experience any side effect which may lessen your ability to do so.

  1. How to use Cytarabine injection

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

This medicine may be given by injection (using a syringe) under the skin (subcutaneous) or into a vein (intravenous). It may also be given by infusion (drip) into a vein. If given as an infusion, Cytarabine Injection will be diluted first.

Cytarabine100 mg/1ml Injection must not be injected intrathecally (into the spine).

Recommended Dose

Your doctor will work out the correct dose of cytarabine for you and how often it must be given.

The dose will depend on your medical condition, your size and how well your liver is working. Your doctor will tell how well your liver is working using blood tests.

You will have regular blood tests after your dose of cytarabine to check for side effects. These tests may be done more often if you are elderly, as you may be more likely to get side effects. Treatment may have to be stopped if your blood cell count drops too low.

If you use more Cytarabine Injection than you should

This medicine will be given to you in a hospital, under the supervision of a doctor. It is unlikely that you will be given too much or too little, however, tell your doctor or nurse if you have any concerns.

4 .Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any of the following happen, tell your doctor or nursing staff immediately:

  • sore mouth, particularly if you have a number of ulcers inside of the mouth
  • severe allergic reaction – you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel you are going to faint
  • symptoms of an infection, e.g. fever, chills, aches or soreness when swallowing
  • unexpected bleeding e.g. bleeding gums, blood in urine or vomit, unexpected bruises
  • black tarry stools which may indicate bleeding in the digestive system
  • severe pain in the chest and difficulty breathing (this maybe a symptom of pericarditis)
  • severe pain in the abdomen (this may be a symptom of inflammation of the pancreas)
  • loss of vision, loss of sense of touch, mental disturbance or loss of ability to move normally (this medicine may cause side effects to the brain and eyes which are usually reversible but may be very serious).

These are serious side effects. You may need urgent medical attention.

If you experience any of the following tell your doctor as soon as possible:

The side effects of cytarabine are dependent on the dose. The digestive tract is most commonly affected, but also the blood.

Common: may affect up to 1 in 10 people

  • decrease in cells responsible for providing immunity, carrying oxygen around the body and for normal blood clotting shown as a reduction in the amount of red and white cells and platelets in the blood or abnormal red blood cells, anaemia, shortness of breath, unexpected bleeding e.g. bleeding gums, blood in urine or vomit, unexpected bruises
  • loss of appetite
  • high levels of uric acid in your blood due to the breakdown of cancer cells during treatment with cytarabine (your doctor will monitor for this)
  • reduced consciousness, speaking difficulties, abnormal eye movements (nystagmus)
  • reversible effects on the eyes such as sore eyes with bleeding (haemorrhagic conjunctivitis), vision disturbance, sensitivity to light (photophobia), watery or burning eyes and inflammation of the surface of the eye (cornea) (keratitis)
  • feeling or being sick, diarrhoea, sores or ulcers in the mouth or anus (back passage), mild pain in the abdomen
  • reversible effects on the liver such as increased enzyme levels
  • reversible effects to the skin such as reddening (erythema), blistering, rash, hives, blood vessel inflammation (vasculitis)
  • hair loss
  • impaired / disturbed kidney function, problems passing urine
  • fever
  • blood clots causing inflammation at the site of injection

Uncommon: may affect up to 1 in 100 people

  • whole body infection (sepsis) seen as a fever, vomiting, confusion, dizziness, chills
  • lung infection
  • headache
  • numbness or weakness of the arms and legs, paralysis of the legs and lower body when cytarabine is given into the space surrounding the spinal cord (intrathecal)
  • inflammation of the sac that surrounds the heart
  • shortness of breath
  • sore throat
  • inflammation of the food pipe (oesophagus), ulcers in the food pipe
  • bowel cysts, severe bowel inflammation, serious infection of the membrane that lines the abdomen (peritonitis)
  • brown/black spots on the skin (lentigo), ulceration of the skin, itching
  • painful redness and blistering on the hands and the soles of the feet
  • joint and muscle pain
  • inflammation at the site of injection

Very rare: may affect up to 1 in 10,000 people

  • irregular heart beat (arrhythmia)
  • redness and itchy bumps on hands or legs, associated with inflammation of the sweat glands

Not known: frequency cannot be estimated from the available data

  • low counts of pre-stages of red cells in the blood (reticulocytopenia)
  • dizziness, inflammation of a nerve or part of the nervous system, damage to nerve tissues and pain
  • sore or itchy eyes
  • black tarry stools which may indicate bleeding in the digestive system
  • impaired liver function
  • yellowing of the skin or yellowing of the whites of the eyes (jaundice)
  • skin rash, pigmented spots on the skin (freckles), skin bleeding
  • kidneys may not work properly
  • lack of periods and low sperm count (amenorrhoea and azoospermia)
  • chest pain
  • irritation or infection at the site of injection
  • bleeding of the lining of the mouth
  • slower heartbeat

The side effects on the digestive tract are less if cytarabine is given by infusion rather than by bolus injection. Your doctor may prescribe local steroids (anti-inflammatory medicines) to reduce effects on the eyes such as sore eyes with bleeding (haemorrhagic conjunctivitis).

Cytarabine may lead to changes in your blood cells. Your doctor will take blood samples to monitor for these and also to check how well your liver and kidneys are working.

Sometimes the following side effects can occur together, usually 6-12 hours after receiving cytarabine:

  • feeling generally unwell with a high temperature
  • pain in bone, muscle and occasionally the chest
  • rash
  • sore eyes

This is known as ‘cytarabine syndrome’ and it can be treated. If you experience these side effects please tell your doctor or nurse as soon as possible.

Side effects after high dose cytarabine treatment:

Severe and at times fatal side effects on the blood, eyes, lungs, nervous system, liver, digestive or genital system have been reported after using experimental dose schedules. The side effects have included severe bone marrow suppression, reversible effects on the cornea (surface of the eye), effects on the brain (usually reversible), drowsiness and convulsion, ulcers in the digestive system which may lead to infection of your abdominal lining (peritonitis), inflammation of the pancreas, liver abscess or enlargement, blood clots in the vein in the liver, blood infection, fluid in the lungs, absence of menstrual periods in women or complete lack of sperm in the ejaculate in men, heart muscle disease or abnormal muscle breakdown, which may lead to kidney problems (rhabdomyolysis).

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

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.By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Cytarabine Injection

Keep this medicine out of the reach and sight of children

Expiry

Do not use this medicine after the expiry date which is stated on the vial and carton after ‘EXP’. Where only a month and year is stated, 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.

Storage

Do not store above 25°C .Keep the vial in the outer carton in order to protect from light. Do not refrigerate or freeze.

  1. Contents of the pack and other information

What Cytarabine Injection contains

Active substance is Cytarabine. It contains  500mg, 1000mg or 2000mg Cytarabine USP.

What Cytarabine Injection looks like and contents of the pack

Cytarabine Injection is a clear, colourless solution for injection which comes in glass containers called vials.

It may be supplied in packs containing:

  • 1, 5, 10 or 20 x 100 mg/1 ml vials
  • 1, 5, 10 or 20 x 500 mg/5 ml vials
  • 1, 5, 10 or 20 x 1000 mg/10 ml vials
  • 1, 5, 10 or 20 x 2000 mg/20 ml vials

Not all packs may be marketed.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA).

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Taj Generics (Taj Pharma) provides a wide range of products to the Indian market, including an extensive range of generics and specialty products; Our products cover a vast array of therapeutic categories, and we offer an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products. Our Generics portfolio offers over 1500 products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, anti-infectives, paediatrics and dermatology.