Clofarabine
Clofarabine Uses, Dosage, Side Effects, Mechanism of Action, How Long Does it Take to Work? Clofarabine is a brand name. Its generic name is Clofarabine.
etcClofarabine Introduction
Clofarabine is an antimetabolite type of chemotherapy agent used for the treatment of pediatric patients with refractory or recurrent acute lymphoblastic leukemia (ALL). The drug works by interfering with growth of cancer cells. It increases the death of cancer cells, therefore decreasing the size of tumors. Clofarabine is a prodrug form of 2-chloro-ara-A, (2-CdA or Cl-Ara-A). It is a type of chemotherapy drug that is approved by the United States Food and Drug Administration (FDA) for the treatment of pediatric relapsed/refractory acute lymphoblastic leukemia (ALL).
Uses for Clofarabine
Clofarabine is the second-line drug approved by the US FDA to treat pediatric patients (3 years of age and older) with relapsed or refractory acute lymphoblastic leukemia (ALL). The drug is given as a single agent or in combination with other chemotherapy agents.
Mechanism of Action
Clofarabine works by interfering with growth of cancer cells. It inhibits DNA synthesis by binding to one of the building blocks of DNA, deoxynucleoside triphosphate (dNTP). This binding inhibits the process of DNA synthesis, resulting in decreased production of new cancer cells. Clofarabine also induces programmed cell death, or apoptosis, in cancer cells.
How Long Does It Take To Work?
Clofarabine typically takes up to 2 weeks to produce an effect on the cancer cells. Patients usually begin to see results after the first dose.
Absorption
Clofarabine is rapidly and completely absorbed after intravenous (IV) infusion. The peak plasma concentration occurs within 0.25 hours after the end of the infusion.
Route of Elimination
Clofarabine is mainly eliminated by the kidneys. Most of the drug (about 60%) is excreted unchanged in the urine within 24 hours of dosing.
Dosage
Clofarabine is administered intravenously (IV) as an infusion over 1-2 hours. The recommended dosage is based on a weight-based dosing scheme. The starting dose is 60 mg/m2 injected over 1-2 hours. The maximum cumulative dose over 28 days is 210 mg/m2. The total dosage per infusion should not exceed 400 mg.
Administration
Clofarabine should be administered intravenously (IV) over 1-2 hours by a healthcare professional. It should be administered at a constant rate at body temperature and within three hours of its preparation.
Side Effects
Common side effects of Clofarabine include nausea, vomiting, diarrhea, fatigue, fever, chills, rash, and low white blood cell count. More serious side effects include secondary malignancies, infection, and mouth sores.
Toxicity
The most common side effects associated with Clofarabine use are bone marrow suppression and gastrointestinal adverse events. Severe bone marrow suppression can lead to an increased risk of infection. Clinical signs of toxicity, such as low white blood cell counts, should be closely monitored.
Precaution
Clofarabine should not be administered to patients with severe bone marrow suppression, severe renal or hepatic impairment, or history of severe allergic reactions. It should be used with caution in patients with infection or a history of infection. Pregnant women should not use this drug.
Interaction
Clofarabine may interact with other drugs, such as certain antibiotics, anticonvulsants, and other chemotherapeutic drugs. It can also interact with certain supplements. Patients should inform their healthcare provider of all medications they are taking to ensure there are no drug interactions.
Disease Interaction
Clofarabine should not be used in patients with severe bone marrow suppression, severe renal or hepatic impairment, or in patients with a history of severe allergic reactions. It should also not be used in pregnant women.
Drug Interaction
Clofarabine may interact with other drugs, such as certain antibiotics, anticonvulsants, and other chemotherapeutic drugs. Patients should inform their healthcare provider of all medications they are taking to ensure there are no drug interactions.
Food Interactions
There are no known food interactions with Clofarabine. Patients should consult their healthcare provider for dietary advice.
Pregnancy Use
Clofarabine should not be used during pregnancy as it may cause fetal harm. The manufacturer does not recommend the use of clofarabine in pregnant women.
Lactation Use
Clofarabine is secreted in breast milk in small amounts and should not be used in breastfeeding women.
Acute Overdose
An acute overdose of Clofarabine can cause fatal toxicity. Symptoms may include bone marrow suppression, gastrointestinal problems, tremors, convulsions, coma, and cardiac arrest. If an overdose is suspected, seek medical attention immediately.
Contraindication
Clofarabine should not be used in patients with severe bone marrow suppression, severe renal or hepatic impairment, or in patients with a history of severe allergic reactions.
Use Direction
Clofarabine should always be used as directed by a healthcare professional. It is usually given as an IV infusion over 1-2 hours. For more detailed information, patients should consult their healthcare provider or pharmacist.
Storage Condition
Clofarabine should be stored in a refrigerator at 2 to 8°C. It should be protected from light and stored in the original packaging until ready for use.
Volume of Distribution
The volume of distribution (Vd) of clofarabine is 0.3 to 0.5 L/kg. This indicates that clofarabine is concentrated in tissues and not widely distributed throughout the body.
Half Life
The half-life of clofarabine is approximately 7 hours. The drug is rapidly eliminated from the body and therefore has a shorter half-life compared to other chemotherapy drugs.
Clearance
Clofarabine is eliminated mainly by the kidneys. The renal clearance of clofarabine is 4.7 L/h or 12.1 mL/min/kg.
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