clofarabine

Action

Inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools through inhibitory action on ribonucleotide reductase, terminating DNA chain elongation, and inhibiting repair through incorporation into DNA chain by competitive inhibition of DNA polymerases. Drug is cytotoxic to rapidly proliferating and quiescent cancer cell types in vitro.

Availability

Solution for injection: 1 mg/ml (20 mg in 20-ml flint vials)

Indications and dosages

➣ Relapsed or refractory acute lymphoblastic leukemia after at least two previous regimens

Children and adults ages 1 to 21: 52 mg/m²/day by I.V. infusion over 2 hours daily for 5 consecutive days every 2 to 6 weeks, depending on toxicity and response

Dosage adjustment

• Hypotension

• Systemic inflammatory response syndrome (SIRS)

• Capillary leak syndrome (CLS)

• Substantial creatinine and bilirubin elevations

Contraindications

None

Precautions

Use cautiously in:

• renal or hepatic impairment, active infection, dehydration, hypotension

• adults older than age 21

• pregnant or breastfeeding patients.

Administration

• Filter through sterile 0.2-micron syringe filter, and dilute further with D₅W or normal saline solution for injection before I.V. infusion. Resulting admixture may be stored at room temperature but must be used within 24 hours of preparation.

• To prevent incompatibilities, don't give other drugs through same I.V. line.

• Administer continuous I.V. fluids throughout 5 days of treatment to reduce effects of tumor lysis and other adverse events. Give allopurinol, as ordered, if hyperuricemia is expected.

• Prophylactic steroids (such as 100 mg/m² hydrocortisone on days 1 through 3) may help prevent SIRS and CLS. If early signs or symptoms of these life-threatening syndromes occur, stop drug immediately and start appropriate supportive measures.

• Withdraw drug immediately if patient develops significant signs or symptoms of SIRS or CLS (such as hypotension); consider giving steroids, diuretics, and albumin. Drug may be reinstituted (generally at lower dosage) when patient is stable.

• Stop drug if hypotension occurs during 5 days of treatment. If hypotension is transient and resolves without pharmacologic intervention, reinstitute drug (generally at lower dosage).

• If creatinine or bilirubin level rises substantially, discontinue drug. Drug may be reinstituted (possibly at lower dosage) when patient is stable and organ function returns to baseline.

• Know that after recovery or return to baseline organ function, treatment cycles are repeated about every 2 to 6 weeks. Dosage is based on body surface area, calculated using actual height and weight before start of each cycle.

• Avoid concurrent administration of hepatotoxic or renotoxic drugs during 5 days of treatment.

Adverse reactions

CNS: dizziness, headache, somnolence, tremor, anxiety, depression, lethargy, fatigue, irritability, rigors

CV: tachycardia, flushing, hypertension, hypotension

EENT: sore throat, epistaxis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, anorexia, gingival bleeding, oral candidiasis

GU: hematuria

Hematologic: febrile neutropenia, neutropenia, anemia, thrombocytopenia

Hepatic: hepatomegaly, jaundice

Musculoskeletal: arthralgia, back pain, myalgia, limb pain

Respiratory: pneumonia, cough, dyspnea, pleural effusion, respiratory distress

Skin: contusion, dermatitis, herpes simplex, dry skin, erythema, palmarplantar erythrodysesthesia, petechiae, pruritus, cellulitis

Other: decreased appetite, weight loss, edema, injection site pain, mucosal inflammation, pain, fever, bacteremia, sepsis, staphylococcal infection, transfusion reaction

Interactions

Drug-drug. Hepatotoxic or renotoxic drugs: additive toxicity

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin: increased

Drug-herbs. Alpha-lipoic acid, coenzyme Q10: decreased chemotherapeutic efficacy

Glutamine: possible increase in tumor growth

Patient monitoring

• Assess hepatic and renal function before and during therapy.

• Closely monitor respiratory status and blood pressure during infusion.

• Monitor hematologic status carefully during therapy; drug may cause severe bone marrow depression, resulting in neutropenia, anemia, and thrombocytopenia.

• Monitor for signs and symptoms of tumor lysis syndrome or cytokine release (such as tachypnea, tachycardia, hypotension, and pulmonary edema), which could progress to SIRS, CLS, or organ dysfunction.

• Closely monitor patients receiving drugs that affect blood pressure or cardiac function.

Patient teaching

• Teach patient about appropriate measures to avoid dehydration caused by vomiting and diarrhea. Tell patient to seek medical advice if signs and symptoms of dehydration occur (such as dizziness, light-headedness, fainting spells, or decreased urine output).

• Advise female with childbearing potential to avoid pregnancy during therapy.

• Caution breastfeeding patient to discontinue breastfeeding during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.