Clofarabine
Generic name
Clofarabine
Brand name
ATC Code
L01BB06
- Dosages
- Side effects in children
- Warnings & precautions in children
- Contra-indications in children
-
Interactions - PK
- Renal impairment
- References
Pharmacokinetics in children
The following kinetic parameters were found in 40 children 2-19 years of age after they had been given multiple doses:
Vd = 172 l/m².
T½ clofarabine = 5.2 hours;
T½ clofarabine triphosphate > 24 hours.
Cl = 28.8 l/hour/m².
dose recommendation of formulary compared to licensed use (on-label versus off-label)
No information is present at this moment.
Available formulations
No information is present at this moment.
Dosages
| Conditioning for SCT in AML/ALL |
|---|
|
Renal impaiment in children > 3 months
Adjustment in renal impairment as specified:
GFR 50-80 ml/min/1.73 m2
Dose adjustment is not requiredGFR 30-50 ml/min/1.73 m2
50 percentage of single dose and dosing interval : 24 uurGFR 10-30 ml/min/1.73 m2
ContraindicatedGFR < 10 ml/min/1.73 m2
ContraindicatedClinical consequences
There is no data available about the use of clofarabine in patients with reduced renal function. In a study of 23 patients (aged 2-19 years) with creatinine clearances of 90-200 ml/min who received multiple doses of intravenous clofarabine, the smaller the creatinine clearance was, the more the AUC increased. Possible symptoms of overdose are nausea, vomiting, diarrhoea and severe bone marrow depression
Patients on dialysis
No generalized recommendations are given.
The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here
Side effects in children
Very common (> 10%): febrile neutropenia. Fear, anxiety. Fever, headache, fatigue. Mucositis, nausea, vomiting, diarrhea. To blush. Itching, hand–foot syndrome.
Common (1-10%): tumor lysis syndrome. Pericardial effusion, tachycardia. Capillary leak syndrome, hypotension, hematoma. Pneumonia, tachypnea, epistaxis, dyspnea, cough. Septic shock, sepsis, bacteremia, herpes zoster, herpes simplex. Hypersensitivity reaction. Agitation, altered mental state. Peripheral neuropathy, paresthesia, somnolence, dizziness, tremor. Hearing loss. Anorexia, weight loss, dehydration. Stomatitis, oral candidiasis, mouth bleeding incl. gum bleeding, mouth ulcers, hematemesis, (upper) abdominal pain, proctalgia. Jaundice, liver failure, hepatic veno-occlusive disease. Multiple organ dysfunction syndrome (MODS), systemic inflammatory response syndrome (SIRS), chills, (peripheral) oedema, feeling very warm (hot). Generalized rash such as maculopapular rash, scaling or erythematous rash, skin hyperpigmentation, dry skin, increased sweating, alopecia, petechiae. Myalgia, arthralgia, bone pain, chest wall pain, neck and back pain, limb pain. Hematuria, (acute) renal failure. Neutropenia. Increase in creatinine concentration, AST and ALT, hyperbilirubinemia.
Uncommon (0.1–1%): hepatitis.
Furthermore, bleeding in the brain, gut or lungs have been reported. Colitis caused by Clostridioides difficile, neutropenic colitis, other enterocolitis, caecitis, elevations in serum amylase and lipase due to pancreatitis, cholecystitis, cholelithiasis. Stevens-Johnson syndrome, toxic epidermal necrolysis. Hyperuricemia. hyponatremia.
The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here
Contra-indications in children
Severely disrupted hepatic or renal function.
The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here
Warnings & precautions in children
In children of < 20 kg, consider an infusion time of greater than 2 hours in order to reduce symptoms of anxiety and irritability.
If prophylaxis with an azole is needed, stop it while clofarabine is being used and restart at least 5 days after the last dose of clofarabine. This is because of the potential for liver intoxication [SKION].
Myelotoxicity: Bone marrow suppression is usually reversible and appears to be dose dependent. Severe bone marrow suppression occurs with neutropenia, anemia and/or thrombocytopenia possibly leading to serious (opportunistic) infections and/or bleeding (including cerebral, gastrointestinal and pulmonary haemorrhages, sometimes fatal). However, these abnormalities can also occur at the beginning of the treatment (partly) as a result of the leukaemia. Regularly check the complete blood count including platelet count and also check for (first) signs and symptoms of infections. Treat the infections promptly, as a serious course is possible in immunocompromised patients and neutropenia.
Cardiovascular system: monitor the patient carefully if there is any pre-existing cardiac disease and if there is any concomitant medication that affects blood pressure or heart function. Interrupt treatment if hypotension develops within the 5 days of clofarabine administration; possibly resume treatment after recovery, usually at a lower dose.
Systemic inflammatory response syndrome (SIRS), capillary leak syndrome and/or multiple organ dysfunction syndrome (MODS) may be caused by release of cytokines after administration. At the first signs of these syndromes, discontinue administration immediately and take supportive measures. Consider prophylactic use of steroids (e.g. 100 mg/m2 hydrocortisone during days 1 to 3) to prevent SIRS or capillary leakage. If necessary, resume treatment after recovery, at a lower dose.
Hepatotoxicity: clofarabine is potentially hepatotoxic, including hepatitis and liver failure. Check liver function regularly. There are no data on use in hepatic impairment with bilirubin > 1.5 × upper limit of normal (ULN) and AST and ALT > 5 × ULN. The risk of hepatotoxicity is increased with the use of other hepatotoxic drugs and also after a previous haematopoietic stem cell transplantation, in which clofarabine (40 mg/m2) has been used in combination with etoposide (100 mg/m2) and cyclophosphamide (440 mg/m2). Serious side effects on the liver have been seen due to veno-occlusive disease (VOD). Often a preparatory treatment is therefore done with busulfan, melphalan and/or the combination of cyclophosphamide and radiation of the whole body.
Interactions
The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here
ANTIMETABOLITES
This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.
| Purine analogues | ||
|---|---|---|
| L01BB05 | ||
| L01BB02 | ||
| L01BB07 | ||
| L01BB03 | ||
| Pyrimidine analogues | ||
|---|---|---|
| L01BC01 | ||
| L01BC52 | ||
| L01BC05 | ||
References
- Cooper TM et al., AAML0523: a report from the Children's Oncology Group on the efficacy of clofarabine in combination with cytarabine in pediatric patients with recurrent acute myeloid leukemia., Cancer., 2014, Aug 15;120(16):, 2482-9
- Genzyme Europe B.V., SPC Evoltra (EU/1/06/334/001-5) 27-4-2015., www.geneesmiddeleninformatiebank.nl
- Jeha S et al., Phase II study of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia., J Clin Oncol., 2009, Sep 10;27(26):, 4392-7
- SKION., Behandelschemas ALL11., www.skion.nl
Changes
Therapeutic Drug Monitoring
Overdose
