Drugs List

Therapeutic Indications

Uses

Leukaemia
Monotherapy or adjunct in diffuse histiocytic lymphomas

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

Administration

By intravenous infusion or injection, or subcutaneous injection.

Some brands of the 20 mg/ml presentation are also suitable for intrathecal use (refer to individual manufacturers information).

Higher doses may be better tolerated when given by rapid injection rather than slow infusion because of the rapid clearance of cytarabine. However, rapid injection may be more emetogenic.

Contraindications

Breastfeeding
Encephalopathy
Pregnancy

Precautions and Warnings

Children under 18 years
History of intrathecal chemotherapy
History of radiotherapy
Patients over 60 years
Dehydration
Hepatic impairment
Myelosuppression
Renal impairment

Administration of live vaccines is not recommended
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Maintain adequate hydration of patient prior / during treatment
Not all available brands are licensed for all routes of administration
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Monitor closely patient with pre-existing hepatic impairment
Monitor for signs of bone marrow depression
Monitor haematological parameters daily throughout therapy
Monitor hepatic function regularly
Monitor patients for signs of tumour lysis syndrome
Monitor patients for symptoms of neuropathy
Monitor renal function regularly
Monitor uric acid levels
Perform bone marrow examinations frequently after blasts have disappeared
Advise patient to report abdominal pain or tenderness, fever or diarrhoea
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider dose/ schedule adjustment if neuropathy occurs
Risk of cardiomyopathy increases with high cumulative dosage
Suspend or modify therapy if platelet count less than 50,000 per cubic mm
Suspend or modify therapy if polymorphonuclear count < 1000 per cubic mm
May cause impaired fertility
Male & female: Contraception required during & for 6 months after treatment
Advise patients of possible adverse reactions

Myelosuppression, anaemia and thrombocytopenia occur in almost all patients given daily infusions or injections. Myelosuppression is biphasic with nadirs at days 7 to 9 and days 15 to 24 with evidence of bone marrow improvement expected after a mean of 28 days.

Rarely neurological effects such as severe spinal cord toxicity leading to necrotising encephalopathy, quadriplegia, paralysis and blindness have occurred. These have occurred predominantly with intrathecal administration but isolated cases have been reported with high intravenous doses during combination regimens.

Pregnancy and Lactation

Pregnancy

Cytarabine is contraindicated during pregnancy.

At the time of writing there is limited data on the use of cytarabine in pregnancy, cases of intrauterine death and foetal abnormalities have been reported. Animal studies have shown teratogenicity.

The effect of concurrent therapies must also be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Cytarabine is contraindicated during breastfeeding.

It is not known whether cytarabine is excreted in human breast milk, a risk to neonates cannot be excluded. Some sources suggest withholding breastfeeding for 24 to 48 hours will minimise the risks.

The effect of concurrent therapies must also be considered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Adult respiratory distress syndrome
Alopecia
Anaemia
Anal ulceration
Anaphylaxis
Anorexia
Arrhythmias
Ataxia
Blindness
Bone marrow depression
Bone pain
Bowel necrosis
Budd-Chiari syndrome
Bullous reactions
Burning sensation in hands and feet
Cardiomyopathy
Cellulitis (injection site)
Cerebellar dysfunction
Cerebral dysfunction
Chest pain
CNS toxicity
Coma
Confusion
Conjunctivitis
Convulsions
Corneal toxicity
Cytarabine reaction syndrome
Diarrhoea
Dizziness
Dysarthria
Dysphagia
Dyspnoea
Erythema
Exanthema
Fever
Freckling
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal toxicity
Gastro-intestinal ulceration
Granulocytopenia
Headache
Hepatic abscess
Hepatic impairment
Hepatomegaly
Hyperuricaemia
Increased lacrimation
Infections
Injection site reactions
Jaundice
Joint pain
Keratitis
Lentigo
Leucopenia
Maculopapular rash
Malaise
Megaloblastosis
Mouth ulcers
Myalgia
Nausea
Necrotising encephalopathy
Necrotising enterocolitis
Neuritis
Neurotoxicity
Nystagmus
Oedema
Oesophagitis
Pancreatitis has been observed with the induction of cytarabine
Paralysis
Pericarditis
Peripheral neuropathy
Peritonitis
Personality change
Photophobia
Pneumatosis cystoides intestinalis
Pneumonia
Pruritus
Pulmonary oedema
Pulmonary toxicity
Rash
Reduction in reticulocytes
Refractive changes
Renal impairment
Rhabdomyolysis
Sepsis
Skin and mucosal bleeding
Skin ulcer
Somnolence
Sore throat
Thrombocytopenia
Thrombophlebitis (injection site)
Tremor
Tumour lysis syndrome
Urinary retention
Urticaria
Vasculitis
Visual disturbances
Vomiting

Presentation

Infusions containing cytarabine

Drugs List

Therapeutic Indications

Uses

Leukaemia
Monotherapy or adjunct in diffuse histiocytic lymphomas

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

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Patients with Renal Impairment

Administration

By intravenous infusion or injection, or subcutaneous injection.

Some brands of the 20 mg/ml presentation are also suitable for intrathecal use (refer to individual manufacturers information).

Higher doses may be better tolerated when given by rapid injection rather than slow infusion because of the rapid clearance of cytarabine. However, rapid injection may be more emetogenic.

Contraindications

Breastfeeding
Encephalopathy
Pregnancy

Precautions and Warnings

Children under 18 years
History of intrathecal chemotherapy
History of radiotherapy
Patients over 60 years
Dehydration
Hepatic impairment
Myelosuppression
Renal impairment

Administration of live vaccines is not recommended
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Maintain adequate hydration of patient prior / during treatment
Not all available brands are licensed for all routes of administration
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Monitor closely patient with pre-existing hepatic impairment
Monitor for signs of bone marrow depression
Monitor haematological parameters daily throughout therapy
Monitor hepatic function regularly
Monitor patients for signs of tumour lysis syndrome
Monitor patients for symptoms of neuropathy
Monitor renal function regularly
Monitor uric acid levels
Perform bone marrow examinations frequently after blasts have disappeared
Advise patient to report abdominal pain or tenderness, fever or diarrhoea
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider dose/ schedule adjustment if neuropathy occurs
Risk of cardiomyopathy increases with high cumulative dosage
Suspend or modify therapy if platelet count less than 50,000 per cubic mm
Suspend or modify therapy if polymorphonuclear count < 1000 per cubic mm
May cause impaired fertility
Male & female: Contraception required during & for 6 months after treatment
Advise patients of possible adverse reactions

Myelosuppression, anaemia and thrombocytopenia occur in almost all patients given daily infusions or injections. Myelosuppression is biphasic with nadirs at days 7 to 9 and days 15 to 24 with evidence of bone marrow improvement expected after a mean of 28 days.

Rarely neurological effects such as severe spinal cord toxicity leading to necrotising encephalopathy, quadriplegia, paralysis and blindness have occurred. These have occurred predominantly with intrathecal administration but isolated cases have been reported with high intravenous doses during combination regimens.

Pregnancy and Lactation

Pregnancy

Cytarabine is contraindicated during pregnancy.

At the time of writing there is limited data on the use of cytarabine in pregnancy, cases of intrauterine death and foetal abnormalities have been reported. Animal studies have shown teratogenicity.

The effect of concurrent therapies must also be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Cytarabine is contraindicated during breastfeeding.

It is not known whether cytarabine is excreted in human breast milk, a risk to neonates cannot be excluded. Some sources suggest withholding breastfeeding for 24 to 48 hours will minimise the risks.

The effect of concurrent therapies must also be considered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Adult respiratory distress syndrome
Alopecia
Anaemia
Anal ulceration
Anaphylaxis
Anorexia
Arrhythmias
Ataxia
Blindness
Bone marrow depression
Bone pain
Bowel necrosis
Budd-Chiari syndrome
Bullous reactions
Burning sensation in hands and feet
Cardiomyopathy
Cellulitis (injection site)
Cerebellar dysfunction
Cerebral dysfunction
Chest pain
CNS toxicity
Coma
Confusion
Conjunctivitis
Convulsions
Corneal toxicity
Cytarabine reaction syndrome
Diarrhoea
Dizziness
Dysarthria
Dysphagia
Dyspnoea
Erythema
Exanthema
Fever
Freckling
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal toxicity
Gastro-intestinal ulceration
Granulocytopenia
Headache
Hepatic abscess
Hepatic impairment
Hepatomegaly
Hyperuricaemia
Increased lacrimation
Infections
Injection site reactions
Jaundice
Joint pain
Keratitis
Lentigo
Leucopenia
Maculopapular rash
Malaise
Megaloblastosis
Mouth ulcers
Myalgia
Nausea
Necrotising encephalopathy
Necrotising enterocolitis
Neuritis
Neurotoxicity
Nystagmus
Oedema
Oesophagitis
Pancreatitis has been observed with the induction of cytarabine
Paralysis
Pericarditis
Peripheral neuropathy
Peritonitis
Personality change
Photophobia
Pneumatosis cystoides intestinalis
Pneumonia
Pruritus
Pulmonary oedema
Pulmonary toxicity
Rash
Reduction in reticulocytes
Refractive changes
Renal impairment
Rhabdomyolysis
Sepsis
Skin and mucosal bleeding
Skin ulcer
Somnolence
Sore throat
Thrombocytopenia
Thrombophlebitis (injection site)
Tremor
Tumour lysis syndrome
Urinary retention
Urticaria
Vasculitis
Visual disturbances
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 9 September 2015.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 9 September 2015.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

Summary of Product Characteristics: Cytarabine 100mg/ml. Accord healthcare. Revised September 2014.
Summary of Product Characteristics: Cytarabine 20mg/ml. Pfizer Ltd. Revised July 2014.
Summary of Product Characteristics: Cytarabine 100mg/ml. Pfizer Ltd. Revised July 2014.
Summary of Product Characteristics: Cytarabine 20mg/ml. Hospira UK Ltd. Revised June 2015.
Summary of Product Characteristics: Cytarabine 100mg/ml. Hospira UK Ltd. Revised June 2015.