Clolar

Clolar - General Information

Clolar is a substance that is being studied in the treatment of cancer. It is a purine nucleoside antimetabolite. It is marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra.
It is used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), only after at least two other types of treatment have failed. It is not known if extends life expectancy. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out.

Pharmacology of Clolar

Clolar is a purine nucleoside antimetabolite. Clolar seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells also may be affected by clofarabine, other effects also occur. Clolar prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells.

Clolar for patients

Physicians are advised to discuss the following with patients to whom CLOLARÔ will be administered and patient caregivers, as appropriate.

Dehydration/Hypotension

Patients receiving CLOLARÔ may experience vomiting and diarrhea; they should therefore be advised regarding appropriate measures to avoid dehydration. Patients should be instructed to seek medical advice if they experience symptoms of dizziness, lightheadedness, fainting spells, or decreased urine output. CLOLARÔ administration should be stopped if the patient develops hypotension for any reason during the 5 days of administration. If hypotension is transient and resolves without pharmacological intervention, CLOLARÔ treatment can be re-instituted, generally at a lower dose.

Concomitant Medications

Since CLOLARÔ is excreted primarily by the kidneys, drugs with known renal toxicity should be avoided during the 5 days of CLOLARÔ administration. In addition, since the liver is a known target organ for CLOLARÔ toxicity, concomitant use of medications known to induce hepatic toxicity should also be avoided. Patients taking medications known to affect blood pressure or cardiac function should be closely monitored during administration of CLOLARÔ.

Pregnancy/Nursing

All patients should be advised to use effective contraceptive measures to prevent pregnancy. Female patients should be advised to avoid breast feeding during treatment with CLOLARÔ.

Clolar Interactions

Although no clinical drug-drug interaction studies have been conducted to date, on the basis of the in vitro studies, cytochrome p450 inhibitors and inducers are unlikely to affect the metabolism of clofarabine. The effect of clofarabine on the metabolism of cytochrome p450 substrates has not been studied.

Drug/Laboratory Tests Interactions

There are no known clinically significant interactions of CLOLARÔ with other medications or laboratory tests. No formal drug/laboratory test interaction studies have been conducted with CLOLARÔ.

Clolar Contraindications

Contraindicated in pregnancy or planned pregnancy, breast-feeding, liver problems, and kidney problems.

Additional information about Clolar

Clolar Indication: For the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens.
Mechanism Of Action: Clolar is metabolized intracellularly to the active 5’-triphosphate metabolite. This metabolite inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through incorporation into the DNA chain by competitive inhibition of DNA polymerases. 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. Clolar 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.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Clofarabine
Synonyms: Not Available
Drug Category: Antineoplastic Agents; Antimetabolites; Purine analogues
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Clofarabine: Clolar;
Absorption: Not Available
Toxicity (Overdose): 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.
Protein Binding: 47% bound to plasma proteins, predominantly to albumin.
Biotransformation: 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.
Half Life: The terminal half-life is estimated to be 5.2 hours.
Dosage Forms of Clolar: Injection, solution Intravenous drip
Chemical IUPAC Name: (2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
Chemical Formula: C10H11ClFN5O3
Clofarabine on Wikipedia: https://en.wikipedia.org/wiki/Clofarabine
Organisms Affected: Humans and other mammals