pharmacopeia
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/api/v1/drug/clofarabine

Mechanism of action

Sourced from openFDA

Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phospho-kinases to the active 5’-triphosphate metabolite. Clofarabine has affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine.

KinaseNucleic Acid Synthesis

Indications

Sourced from openFDA
  • Clofarabine injection is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. Clofarabine injection is a nucleoside metabolic inhibitor indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens.ICD-10: C95.90

Contraindications

Sourced from openFDA
  • None. None.contraindicated

Dosage & administration

Sourced from openFDA

Administer the recommended pediatric dose of 52 mg/m 2 as an intravenous infusion over 2 hours daily for 5 consecutive days of a 28-day cycle. Repeat cycles every 2 to 6 weeks. (2.1) Provide supportive care, such as intravenous infusion fluids, antihyperuricemic treatment, and alkalinization of urine throughout the 5 days of clofarabine injection administration to reduce the risk of tumor lysis and other adverse reactions. (2.1) Discontinue clofarabine injection if hypotension develops during the 5 days of administration. ( 2.1 ) Reduce the dose in patients with renal impairment. (2.2) Use dose modification for toxicity. (2.4) 2.1 Recommended Dosage Administer the recommended pediatric dose of 52 mg/m 2 as an intravenous infusion over 2 hours daily for 5 consecutive days. Repeat treatment cycles following recovery or return to baseline organ function, approximately every 2 to 6 weeks. Base dosage on the patient’s body surface area (BSA), calculated using the actual height and weight before the start of each cycle. To prevent drug incompatibilities, do not administer other medications through the same intravenous line. Administer subsequent cycles no sooner than 14 days from the starting day of the previous cycle and provided the patient’s ANC is ≥ 0.75 × 10 9 /L. Provide supportive care, such as intravenous fluids, antihyperuricemic treatment, and alkalinize urine throughout the 5 days of clofarabine injection administration to reduce the effects of tumor lysis and other adverse reactions.

Warnings & precautions

Sourced from openFDA

Myelosuppression: May be severe and prolonged. Monitor complete blood counts and platelet counts during clofarabine therapy. (5.1) Hemorrhage: Serious and fatal cerebral, gastrointestinal and pulmonary hemorrhage. Monitor platelets and coagulation parameters and treat accordingly. (5.2) Infections: Severe and fatal sepsis as a result of bone marrow suppression. Monitor for signs and symptoms of infection; discontinue clofarabine and treat promptly. (5.3) Tumor Lysis syndrome: Anticipate, monitor for signs and symptoms and treat promptly. (5.4) Systemic Inflammatory Response Syndrome (SIRS) or Capillary Leak Syndrome: Monitor for and discontinue clofarabine immediately if suspected. (5.5) Venous Occlusive Disease of the Liver: Monitor for and discontinue clofarabine if suspected. (5.6) Hepatotoxicity: Severe and fatal hepatotoxicity. Monitor liver function, for signs and symptoms of hepatitis and hepatic failure. Discontinue clofarabine immediately for Grade 3 or greater liver enzyme and/or bilirubin elevations. (5.7) Renal Toxicity: Increased creatinine and acute renal failure; monitor renal function and interrupt or discontinue clofarabine. (5.8) Enterocolitis: Serious and fatal enterocolitis, occurring more frequently within 30 days of treatment and with combination chemotherapy. Monitor patients for signs and symptoms of enterocolitis and treat promptly. (5.9) Skin Reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal cases. Discontinue for exfoliative or bullous rash, or if SJS or TEN is suspected.

Adverse reactions

Sourced from openFDA

The following clinically significant adverse reactions are discussed in greater detail in other sections of the label: Myelosuppression [see Warnings and Precautions (5.1) ] Hemorrhage [see Warnings and Precautions (5.2) ] Serious Infections [see Warnings and Precautions (5.3) ] Hyperuricemia (tumor lysis syndrome) [see Warnings and Precautions (5.4) ] Systemic Inflammatory Response Syndrome (SIRS) and Capillary Leak Syndrome [see Warnings and Precautions (5.5) ] Venous Occlusive Disease of the Liver [see Warnings and Precautions (5.6) ] Hepatotoxicity [see Warnings and Precautions (5.7) ] Renal Toxicity [see Warnings and Precautions (5.8) ] Enterocolitis [see Warnings and Precautions (5.9) ] Skin Reactions [see Warnings and Precautions (5.10) ] Most common adverse reactions (≥ 25%): vomiting, nausea, diarrhea, febrile neutropenia, pruritus, headache, bacteremia, pyrexia, rash, tachycardia, abdominal pain, chills, fatigue, anorexia, pain in extremity, hypotension, epistaxis, and petechiae. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Use in specific populations

Sourced from openFDA

Lactation: Advise not to breastfeed. (8.2) 8.1 Pregnancy Risk Summary In animal reproduction studies, intravenous administration of clofarabine to pregnant rats and rabbits during organogenesis at doses approximately 0.2 to 1-times the maximum recommended human dose of 52 mg/m 2 based on body surface area (BSA) resulted in embryo-fetal mortality, alterations to growth, and structural abnormalities (see Data) . Advise pregnant women of the potential risk to a fetus. There are no available data on clofarabine use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Clofarabine should be used during pregnancy only if the potential benefits to the mother outweigh the potential risks, including those to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Pharmacokinetics

Sourced from openFDA
Metabolism
The population pharmacokinetics of clofarabine were studied in 40 pediatric patients aged 2 to 19 years (21 males/19 females) with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). At the given 52 mg/m 2 dose, similar concentrations were obtained over a wide range of body surface areas (BSAs).

Overdosage

Sourced from openFDA

There were no known overdoses of clofarabine. The highest daily dose administered to a human to date (on a mg/m 2 basis) has been 70 mg/m 2 /day × 5 days (2 pediatric ALL patients). The toxicities included in these 2 patients included Grade 4 hyperbilirubinemia, Grade 2 and 3 vomiting, and Grade 3 maculopapular rash. In a Phase 1 study of adults with refractory and/or relapsed hematologic malignancies, the recommended pediatric dose of 52 mg/m 2 /day was not tolerated.

Approval history

Sourced from openFDA
  • May 9, 2017ANDAANDA204029Abon Pharms Llc
  • Nov 6, 2017ANDAANDA208857Amneal
  • Nov 6, 2017ANDAANDA205375Dr Reddys
  • Oct 31, 2018ANDAANDA207831Gland
  • Oct 23, 2020ANDAANDA213461Meitheal
  • Oct 3, 2022ANDAANDA212457Eugia Pharma

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
2,254 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Febrile Neutropenia27012%
  2. 2Off Label Use23410%
  3. 3Pyrexia2059.1%
  4. 4Drug Ineffective1938.6%
  5. 5Sepsis1587.0%
  6. 6Mucosal Inflammation1215.4%
  7. 7Neutropenia1215.4%
  8. 8Nausea1114.9%
  9. 9Death1044.6%
  10. 10Vomiting1014.5%
  11. 11Pancytopenia1004.4%
  12. 12Blood Bilirubin Increased974.3%
  13. 13Product Use In Unapproved Indication964.3%
  14. 14Pneumonia924.1%
  15. 15Multiple Organ Dysfunction Syndrome893.9%

Literature

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Recent PubMed references pinned to Clofarabine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 185 ClinicalTrials.gov registrations naming Clofarabine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Clofarabine work?
Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phospho-kinases to the active 5’-triphosphate metabolite. Clofarabine has affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine.
What is Clofarabine used for?
According to FDA labeling, Clofarabine carries indications including: Clofarabine injection is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. Clofarabine injection is a nucleoside metabolic inhibitor indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Clofarabine?
Clofarabine is classified as Purine analogues, Nucleoside Metabolic Inhibitor, Kinase Inhibitors, Nucleic Acid Synthesis Inhibitors, Decreased Cell Membrane Integrity, Decreased DNA Integrity, Decreased DNA Replication, Increased Cellular Death.
What are the brand names for Clofarabine?
Clofarabine is marketed under brand names including Clolar.
What are the contraindications for Clofarabine?
Clofarabine labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.
Note. Data for clofarabine is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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