Clofarabine parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of clofarabine.
Drugs List
Therapeutic Indications
Uses
Acute lymphoblastic leukaemia in relapsed or refractory paediatric patients
Treatment of acute lymphoblastic leukaemia (ALL) in paediatric patients (aged 1 to 21 years at initial diagnosis), who have relapsed or are refractory after receiving at least two prior regimens.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Children
Children aged 1 to 21 years at initial diagnosis:
The recommended dose is 52mg/metre squared of body surface area daily for 5 consecutive days.
Body surface area must be accurately calculated using actual height and weight of the patient before the start of each cycle.
Cycles should be repeated every 2 to 6 weeks following recovery to normal haematopoiesis (absolute neutrophil count (ANC) equal to or greater than 0.75 x 10 to the power of 9 per litre) and a return to baseline organ function. Most patients will respond after 1 or 2 cycles of treatment. The benefits and risks of continuing treatment after 2 cycles in patients who have not responded should be assessed by the treating physician. There is limited data on safety and efficacy when administered for more than 3 cycles.
Patients with Renal Impairment
Creatinine clearance greater than 60ml/minute:
Dose as normal.
Creatinine clearance between 30 and 60ml/minute:
Reduce dose by 50%.
Creatinine clearance less than 30ml/minute:
Not recommended.
Additional Dosage Information
Dose modifications for haematological toxicity
Absolute neutrophil count (ANC) remains below 0.75 x 10 to the power of 9 per litre 6 weeks from the start of treatment cycle:
Perform bone marrow aspirate/ biopsy to determine possible refractory disease.
If persistent leukaemia is not evident, reduce dose for next cycle by 25%.
Absolute neutrophil count (ANC) remains below 0.5 x 10 to the power of 9 per litre for more than 4 weeks from the start of treatment cycle:
Reduce dose for next cycle by 25%.
Dose modifications for non-haematological toxicity
Grade 3 non-haematological toxicity (excluding nausea and vomiting):
First occurrence:
Interrupt until toxicity resolves to baseline, or to a tolerable level where the benefit of restarting treatment outweighs any risks. Reduce dose by 25%.
Second occurrence:
Interrupt until toxicity resolves to baseline, or to a tolerable level where the benefit of restarting treatment outweighs any risks. Reduce dose by a further 25%.
Third occurrence:
Discontinue treatment.
Grade 4 non-haematological toxicity:
Discontinue treatment.
Dose modifications due to infection
First occurrence:
Interrupt until infection is controlled. Restart at previous dose.
Second occurrence:
Interrupt until infection is controlled. Reduce dose by 25%.
Administration
For intravenous infusion only.
Administer over 2 hours. For patients weighing less than 20kg increase the infusion time.
Contraindications
Children under 1 year
Patients over 21 years
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Precautions and Warnings
Children weighing less than 20kg
History of progenitor cell transplantation
Infection
Neutrophil count below 0.75 x 10 to the power of 9 / L
Restricted sodium intake
Cardiovascular disorder
Dehydration
Mild hepatic impairment
Renal impairment - creatinine clearance 30-90 ml/minute
Contains more than 1 mmol (23 mg) sodium per dose
Reduce dose in patients with creatinine clearance of 30-60ml/min
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider premedication with a corticosteroid
Consider premedication with hypouricaemic agent
Give IV fluids throughout 5-day administration period
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor fluid balance
Monitor for signs and symptoms of colitis
Monitor full blood count regularly
Monitor patients for signs of tumour lysis syndrome
Monitor patients with cardiac disorders
Monitor respiratory function
Monitor weight and blood pressure
Reduce dose if neutrophil count <500cells/cubic mm for more than 4 weeks
Advise patient to report symptoms of infection immediately
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patient to seek medical advice if symptoms of dehydration occur
Advise patients to report bleeding episodes
Consider the use of anti-emetics before and during therapy
Discontinue treatment if Stevens-Johnson Syndrome suspected
Discontinue treatment if toxic epidermal necrolysis is suspected
May affect immune response to live vaccines
Potentially hepatotoxic
Risk of developing opportunistic infections
Discontinue if grade 3 toxicity recurs for 3rd time
Discontinue if hypotension occurs, restart at lower dose and monitor
Discontinue if patients show signs of SIRS/capillary leak syndrome
Discontinue if serum creatinine increases
Discontinue if severe skin reaction occurs
Discontinue if substantial increase in bilirubin occurs
Discontinue if there is a rise in liver enzymes
Interrupt treatment and/or reduce dose for any grade 3 toxicity
Interrupt treatment if severe infection develops
Interrupt treatment if grade 4 non-haematological toxicity occurs
Male & female: May cause infertility
Male & female: Ensure adequate contraception during treatment
Advise patient of risk of bleeding
If hypotension develops (for any reason) during the 5 days of administration, treatment should be discontinued until baseline organ function has returned at which time clofarabine treatment can be restarted at a lower dose.
Patients who have previously received a haematopoietic stem cell transplant (HSCT) may be at higher risk for hepatotoxicity suggestive of veno-occlusive disease (VOD) following treatment with clofarabine (40 mg/metre squared) when used in combination with etoposide and cyclophosphamide.
The concomitant use of medicinal products that have been associated with hepatotoxicity should be avoided wherever possible.
Pregnancy and Lactation
Pregnancy
Clofarabine is contraindicated during pregnancy.
The manufacturer recommends that clofarabine should not be used during pregnancy. There are no data for the use of clofarabine in pregnant women. Animal studies have shown reproductive toxicity including teratogenicity. However, Briggs (2015) suggests that as lymphoblastic leukaemia is a potentially fatal disease, if considered essential, the teratogenic risk of clofarabine should be discussed with the patient and if informed consent is obtained treatment should not be withheld.
Lactation
Clofarabine is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued prior to, during and following treatment with clofarabine. It is unknown if clofarabine is excreted in human breast milk. Based on its molecular weight, plasma protein binding and elimination half life presence in human breast milk is possible. Due to the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued prior to, during and following treatment with clofarabine.
Side Effects
Abdominal pain
Acute renal failure
Agitation
Alopecia
Anaemia
Anorexia
Anxiety
Arthralgia
Bacteraemia
Bone pain
Caecitis
Candidiasis (mouth or throat)
Capillary leak syndrome
Colitis
Contusion
Cough
Decreased appetite
Dehydration
Diarrhoea
Dizziness
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Epistaxis
Erythema
Erythematous rash
Exfoliative dermatitis
Extremity pain
Fatigue
Febrile neutropenia
Feeling abnormal
Flushing
Haematemesis
Haematoma
Haematuria
Haemorrhage
Headache
Hepatic failure
Hepatitis
Hepatobiliary disorders
Herpes simplex
Herpes zoster
Hyperbilirubinaemia
Hyperpigmentation of skin
Hypersensitivity reactions
Hypoacusis
Hyponatraemia
Hypotension
Increase in serum ALT/AST
Increased sweating
Infections
Infertility
Irritability
Jaundice
Leucopenia
Lymphopenia
Maculopapular rash
Mental status changes
Mouth ulcers
Mucosal inflammation
Multiorgan failure
Myalgia
Nausea
Neutropenia
Neutropenic colitis
Oedema
Pain
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Paraesthesia
Pericardial effusion
Peripheral neuropathy
Peripheral oedema
Petechiae
Pneumonia
Proctalgia
Pruritic rash
Pruritus
Pyrexia
Rash
Renal failure
Respiratory distress
Restlessness
Sepsis
Septic shock
Serum creatinine increased
Skin disorder
Somnolence
Stevens-Johnson syndrome
Stomatitis
Systemic inflammatory response syndrome (SIRS)
Tachycardia
Tachypnoea
Thrombocytopenia
Toxic epidermal necrolysis
Tremor
Tumour lysis syndrome
Veno-occlusive disease
Vomiting
Weight loss
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 2019
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G. and Freeman, R., Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Clofarabine 1mg/ml concentrate for solution for infusion. Consilient Health Ltd. Revised January 2021.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 18 November 2021
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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