Clofarabine

303.68

303.68

2017-001-1

762RDY0Y2H

DTXSID5046437

C26638

L01BB06|L - Antineoplastic and immunomodulating agents

29349990

119

0

white Powder

1.4804 (estimate)

225-227 °C @ Solvent: Ethanol, Water

550.0±60.0 °C(Predicted)

286.4ºC

1.843

DMSO: >10mg/mL

Desiccate at +4°C

3.19E-15mmHg at 25°C

Combustible; Fire site decomposes toxic nitrogen oxides; Fluoride and chloride fumes

Ⅲ

6.1

UN 2811 6.1 / PGIII

2

25

45

UD7473000

T

The warehouse is low-temperature, ventilated and dry

P201, P202, P260, P264, P270, P281, P301+P310, P308+P313, P314, P321, P330, P405, P501

H300

|Danger|H300 (84.78%): Fatal if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P264, P270, P281, P301+P310, P308+P313, P314, P321, P330, P405, and P501|Aggregated GHS information provided by 46 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

There were no known overdoses of clofarabine. The highest daily dose administered to a human to date (on a mg/m2 basis) has been 70 mg/m2/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 clinical trials, serum enzymes elevations occurred in up to 75% of patients treated with clofarabine as monotherapy for refractory or relapsed acute leukemia. These elevations usually arose within 5 to 10 days of starting therapy and were generally transient and asymptomatic. The elevations rarely required dose adjustment or delay in therapy. Cases of clinically apparent liver injury due to clofarabine have been reported to occur, but few details were available and most patients were receiving other cancer chemotherapeutic agents. A single case report of toxic epidermal necrosis and fulminant hepatic failure in a child with ALL receiving clofarabine has been published. In high doses, clofarabine has been associated with very high rates of serum enzyme elevations and hyperbilirubinemia that are dose limiting. Instances of capillary leak syndrome and possibly sinusoidal obstruction syndrome have also been reported.

47% bound to plasma proteins, predominantly to albumin.

For the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use.|FDA Label|Treatment of acute lymphoblastic leukaemia (ALL) in paediatric patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response. Safety and efficacy have been assessed in studies of patients ≤ 21 years old at initial diagnosis.|Drug: Clofarabine

Clofarabine is a purine analogue and antineoplastic agent used in the therapy of acute lymphoblastic leukemia (ALL) in children. Clofarabine is associated with frequent transient serum enzyme elevations during therapy, but they are usually asymptomatic and transient and it has only rarely been implicated in causing clinically apparent acute liver injury with jaundice.

Antineoplastic Agents

Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells.

Antimetabolites that are useful in cancer chemotherapy. (See all compounds classified as Antimetabolites, Antineoplastic.)

Based on 24-hour urine collections in the pediatric studies, 49 - 60% of the dose is excreted in the urine unchanged.|172 L/m2|28.8 L/h/m2 [Pediatric patients (2 - 19 years old) with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) receiving 52 mg/m2 dose]

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

The terminal half-life is estimated to be 5.2 hours.

Clofarabine is metabolized intracellularly to the active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death.

2 Chloro 2' arabino fluoro 2' deoxyadenosine

Human drugs -> Ivozall -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human drugs -> Evoltra -> EMA Drug Category|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients