DrugindexOnline^{2nd edition}

Pronouncation: (kloe-FER-ah-bean)
Class: Purine analog

Trade Names:
Clolar
- Solution for injection 1 mg/mL

Mechanism of Action

Pharmacology

Inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools by 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.

Pharmacokinetics

Distribution

Plasma protein binding, predominantly to albumin, is 47%. Steady state Vd is 172 L/m ² .

Elimination

Systemic CL is 28.8 L/h/m ² and the terminal t _½ is about 5.2 h. Based on the 24-h urine collection in pediatrics, 49% to 60% of the dose is excreted unchanged in the urine.

Indications and Usage

Treatment of patients 1 to 21 yr of age with relapsed or refractory acute lymphoblastic leukemia after at least 2 prior regimens.

Contraindications

Standard considerations.

Dosage and Administration

Patients 1 to 21 yr of age

IV Recommended dose is 52 mg/m ² infused over 2 h/day for 5 days. Treatment cycles are repeated following recovery or return to baseline organ function, approximately every 2 to 6 wk.

General Advice

• For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, intra-arterial, or oral administration.
• Diligently follow institutional and National Institutes of Health procedures for handling, administration, and disposal of anticancer drugs. Wear appropriate protective equipment when preparing and administering clofarabine.
• Continuously administer IV fluids as ordered throughout the 5 days of clofarabine administration to reduce the effects of tumor lysis and other adverse reactions.
• Administer prophylactic corticosteroids (eg, hydrocortisone 100 mg/m ² on days 1 to 3) as ordered to help prevent signs or symptoms of systemic inflammatory response syndrome or capillary leak.
• Ensure clofarabine dose is accurately determined before each cycle using body surface area calculated using the actual height and weight of the patient determined just prior to each cycle.
• Prior to administration, further dilute solution for injection by filtering prescribed dose through 0.2 mcm syringe filter and adding to prescribed volume of dextrose 5% or sodium chloride 0.9% injection.
• Do not administer if particulate matter, cloudiness, or discoloration is noted.
• Do not administer any other medications through same IV line.

Storage/Stability

Store unopened vials of solution for injection at controlled room temperature (59° to 86°F). Diluted infusion solution contains no preservative and must be administered within 24 h of preparation if stored at room temperature.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Pericardial effusion (35%); tachycardia (34%); hypotension (29%); left ventricular systolic dysfunction (27%); hypertension (11%).

CNS

Headache (46%); pyrexia (41%); fatigue (36%); anxiety (22%); dizziness (16%); depression, irritability (11%); somnolence, tremor (10%).

Dermatologic

Pruritus (47%); dermatitis (41%); petechiae (29%); erythema, flushing (18%); palmar-plantar erythrodysethesia syndrome (13%); contusion (11%); dry skin (10%).

EENT

Epistaxis (31%).

GI

Vomiting (83%); nausea (75%); diarrhea (53%); abdominal pain (36%); anorexia (31%); constipation (21%); gingival bleeding (15%); sore throat (14%); oral candidiasis (13%); decreased appetite (11%).

Genitourinary

Hematuria (17%).

Hematologic-Lymphatic

Febrile neutropenia (57%); neutropenia, transfusion reaction (10%).

Hepatic

Hepatomegaly, jaundice (15%).

Lab Tests

Elevated ALT (44%); elevated AST (38%); elevated bilirubin (15%); elevated creatinine (6%).

Local

Injection site pain (14%).

Metabolic-Nutritional

Decreased weight (10%).

Musculoskeletal

Rigors (38%); limb pain (29%); myalgia (14%); back pain (13%); arthralgia (11%).

Respiratory

Cough (19%); respiratory distress (14%); dyspnea (13%); pleural effusion, pneumonia (10%).

Miscellaneous

Edema (20%); pain (19%); mucosal inflammation (18%); sepsis (15%); staphylococcal infections (13%); cellulitis, herpes simplex (11%); bacteremia (10%).

Precautions

Monitor BP Monitor BP frequently during the 5 days of clofarabine administration. Stop therapy if patient develops hypotension for any reason. If hypotension is transient and resolves without pharmacologic intervention, consider reinstituting therapy at a lower dose. CBC Ensure CBC with differential and platelet count are evaluated before starting therapy and then at regular intervals during clofarabine. Notify health care provider of any significant cytopenia. Monitor blood and platelet counts more frequently if cytopenia develops. Hyperuricemia Ensure risk of developing hyperuricemia is evaluated before starting therapy and that hypouricemic therapy, including adequate fluid intake and administration of allopurinol, and monitoring of uric acid, is initiated before starting treatment in patient determined to be at risk for developing hyperuricemia and urate precipitation. Renal/Hepatic function Ensure renal and hepatic function are monitored closely during the 5 days of clofarabine administration. Discontinue therapy and notify health care provider if substantial increases in creatinine or bilirubin are noted. Consider reinstituting clofarabine at a lower dose when patient is stable and organ function has returned to normal. Tumor lysis syndrome/Cytokine release Monitor patient closely for signs or symptoms of tumor lysis syndrome and cytokine release (eg, tachypnea, tachycardia, hypotension, pulmonary edema) that could develop into systemic inflammatory response syndrome, capillary leak, and organ dysfunction. Immediately discontinue infusion and inform health care provider if systemic inflammatory response syndrome or capillary leak syndrome noted or suspected. Be prepared to provide supportive measures (eg, corticosteroids, diuretics, albumin). Consider reinstituting clofarabine at a lower dose when patient is stable. WBC Implement infection control measures if WBC drops; implement bleeding precautions if platelet count drops.

Pregnancy

Category D .

Lactation

Undetermined.

Adults

Safety and efficacy not established.

Bone marrow suppression

Should be anticipated; anemia, neutropenia, and thrombocytopenia have been reported.

Breastfeeding mother

Ensure woman who is breastfeeding discontinues breastfeeding during treatment with clofarabine.

Concurrent medications

Because clofarabine primarily is excreted by the kidneys, avoid renal toxic drugs during the 5 days of clofarabine administration.

Dehydration/hypotension

Patients may experience vomiting and diarrhea; therefore, appropriate measures should be taken to avoid dehydration.

Hepatic/renal function impairment

Use with caution.

Overdosage

Symptoms

Vomiting, maculopapular rash, hyperbilirubinemia.

Patient Information

• Explain name, action, and potential side effects of the treatment regimen. Review the treatment regimen including dosing schedule, duration of treatment, and monitoring that will be required.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care providers in a health care setting.
• Advise patient, family, or caregiver that medication may be used in combination with other agents, to achieve max benefit possible.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; rapid or difficult breathing; rapid heart beat; dizziness; light-headedness; fainting spells; decreased urination; fever, chills, or other signs of infection; bleeding or unusual bruising; sores in mouth; dark urine; yellowing of skin or eyes; pain, redness, or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness.
• Instruct patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Caution woman of childbearing potential to avoid becoming pregnant during therapy.