Clofarabine

FDA Drug Information • Also known as: Clofarabine

Brand Names: Clofarabine
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION Clofarabine Injection contains clofarabine, a purine nucleoside metabolic inhibitor. The chemical name of clofarabine is 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine. Its molecular formula is C 10 H 11 ClFN 5 O 3 with a molecular weight of 303.68 Daltons. The molecular structure of clofarabine is: Clofarabine Injection (1 mg per mL) is supplied in a 20 mL single-dose vial. The 20 mL vial contains 20 mg clofarabine formulated in 20 mL unbuffered normal saline (comprised of Water for Injection, USP and Sodium Chloride, USP). The pH range of the solution is 4.5 to 7.5. The solution is sterile, clear and practically colorless, and is preservative-free. Molecular Structure of Clofarabine

What Is Clofarabine Used For?

1 INDICATIONS AND USAGE 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. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION 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 2-6 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. Discontinue clofarabine injection if hypotension develops during the 5 days of administration. Monitor renal and hepatic function during the 5 days of clofarabine injection administration [see Warnings and Precautions ( 5.7 , 5.8 )] . Monitor patients taking medications known to affect blood pressure. Monitor cardiac function during administration of clofarabine injection. 2.2 Recommended Dosage Reduction for Renal Impairment Reduce the dose by 50% in patients with creatinine clearance (CrCL) between 30 and 60 mL/min. There is insufficient information to make a dosage recommendation in patients with CrCL less than 30 mL/min [see Use in Specific Populations ( 8.6 )] . 2.3 Potential Concomitant Medications and Medications to Avoid Consider prophylactic antiemetic medications as clofarabine injection is moderately emetogenic. Consider the use of prophylactic steroids to mitigate Systemic Inflammatory Response Syndrome (SIRS) or capillary leak syndrome (e.g., hypotension, tachycardia, tachypnea, and pulmonary edema). Minimize exposure to drugs with known renal toxicity during the 5 days of clofarabine injection administration since the risk of renal toxicity may be increased. Avoid concomitant use of medications known to induce hepatic toxicity. 2.4 Dose Modifications and Reinitiation of Therapy after Adverse Reactions Hematologic Toxicity If a patient experiences a Grade 4 neutropenia (ANC <0.5 × 10 9 /L) lasting ≥4 weeks, reduce...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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 Meitheal Pharmaceuticals Inc. at 1-844-824-8426 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. The data described below reflect exposure to clofarabine in 115 pediatric patients with relapsed or refractory Acute Lymphoblastic Leukemia (ALL) (70 patients) or Acute Myelogenous Leukemia (AML) (45 patients). In total, 115 pediatric patients treated in clinical trials received the recommended dose of clofarabine 52 mg/m 2 daily × 5. The median number of cycles was 2. The median cumulative amount of clofarabine received by pediatric patients during all cycles was 540 mg. 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. Table 1 lists adverse reactions by System Organ Class, including severe or life-threatening (NCI CTCAE Grade 3 or Grade 4), reported in ≥5% of the 115 patients in the 52 mg/m 2 /day dose group (pooled analysis of pediatric patients with ALL and AML). More detailed information and follow-up of certain events is given below. Table 1: Most Commonly Reported (≥5% Overall) Adverse Reactions by System Organ Class (N=115 pooled analysis) ¹ Patients with more than one adverse reaction (MedDRA preferred term) within a SOC are counted only once in the SOC totals. Patients with more than one occurrence of the same adverse reaction (MedDRA preferred term) are counted only once within that reaction and at the highest severity grade. System Organ Class¹ Adverse Reaction (MedDRA Preferred Term)¹ ALL/AML (All Grades, N=115) Worst Grade (NCI Common Terminology Criteria)¹ 3 4 5 N % N % N % N % Blood and Lymphatic System Disorders Febrile neutropenia 63 55 59 51 3 3 . . Neutropenia 11 10 3 3 8 7 . . Cardiac Disorders Pericardial effusion 9 8 . . 1 1 . . Tachycardia 40 35 6 5 . . . . Gastrointestinal Disorders Abdominal pain 40 35 8 7 . . . . Abdominal pain upper 9 8 1 1 . . . . Diarrhea 64 56 14 12 . . . . Gingival or mouth bleeding 20 17 8 7 1 1 . . Nausea 84 73 16 14 1 1 . . Oral mucosal petechiae 6 5 4 4 . . . . Proctalgia 9 8 2 2 . . . . Stomatitis 8 7 1 1 . . . . Vomiting 90 78 9 8 1 1 . . General Disorders and Administration Site Conditions Asthenia 12 10 1 1 1 1 . . Chills 39 34 3 3 . . . . Fatigue 39 34 3 3 2 2 . . Irritability 11 10 1 1 . . . . Mucosal inflammation 18 16 2 2 . . . . Edema 14 12 2 2 . . . . Pain 17 15 7 6 1 1 . . Pyrexia 45 39 16 14 . . . . Hepatobiliary Disorder Jaundice 9 8 2 2 . . . . Infections and Infestations Bacteremia 10 9 10 9 . . . . Candidiasis 8...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

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. Data Animal data Intravenous administration of clofarabine to pregnant rats during organogenesis (gestation days [GD] 7-17) at doses of 1, 3 or 9 mg/kg/day (equivalent to 6, 18, 54 mg/m 2 /day) resulted in maternal toxicities at the 9 mg/kg dose, as indicated by reduced body weights and food consumption. Developmental toxicity (i.e., reduced fetal body weights and increased postimplantation loss) and increased incidences of external, soft tissue, and skeletal malformations and variations (including retarded ossification) were observed at 9 mg/kg/day (54 mg/m 2 ; approximately equivalent to the recommended human dose based on BSA). Altered ossification patterns (extra metacarpal or metatarsal ossification) were observed in single fetuses at lower doses of clofarabine (1 and 3 mg/kg/day; 0.1- and 0.3-times the recommended human dose based on BSA). When...

Overdosage

10 OVERDOSAGE 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Clofarabine Injection is a sterile, clear and practically colorless solution, is preservative-free and is free from foreign matter. It is supplied in single-dose flint vials containing 20 mg of clofarabine in 20 mL of solution as follows: NDC Clofarabine Injection (1 mg per mL) Package Factor 71288- 128 -20 20 mg per 20 mL Single-Dose Vial 1 vial per carton The pH range of the solution is 4.5 to 7.5. Storage Conditions Vials containing undiluted Clofarabine Injection should be stored at 25°C (77°F); excursions permitted between 15° to 30°C (59° to 86°F). Do not freeze. Retain in carton until contents are used. Clofarabine Injection is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Discard unused portion. Sterile, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.