clofarabine

Therapeutic Classification: antineoplastics

Pharmacologic Classification: antimetabolites

High Alert

Refractory or relapsed acute lymphoblastic leukemia after ≥2 previous regimens.

Converted intracellularly to the active 5'-triphosphate metabolite, which acts as a purine nucleoside antimetabolite; net result is inhibition of DNA synthesis.
Produces a rapid reduction of peripheral leukemia cells.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: 46–60% excreted unchanged in urine.

Half-Life: 5.2 hr.

(effect on WBCs)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	unknown	2–6 wk

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment;
Hepatic impairment;
Infection, sepsis, or tumor lysis syndrome (↑ risk of acute renal failure).

CV: pericardial effusion, tachycardia, edema

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: pharyngitis

F and E: dehydration

GI: diarrhea, nausea, abdominal pain, constipation, ENTEROCOLITIS, HEPATOTOXICITY, mucositis, vomiting

GU: hematuria, acute renal failure

Hemat: bleeding, neutropenia, anemia, thrombocytopenia

Local: injection site pain

Neuro: fatigue

Misc: infection, chills, fever, SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS), TUMOR LYSIS SYNDROME

Drug-drug:

Concurrent use of hepatotoxic or nephrotoxic drugs↑ risk of hepatotoxicity and nephrotoxicity and should be avoided for the 5-day treatment period.

IV (Children 1–21 yr): 52 mg/m² daily for 5 days; cycle may be repeated every 2–6 wk.

(Generic available)

Solution for injection: 1 mg/mL

Monitor respiratory status and BP during clofabarine infusion.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. If a clinically significant infection occurs, withhold therapy until infection is controlled; then restart at full dose. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Monitor for signs and symptoms of tumor lysis syndrome and cytokine release (tachypnea, tachycardia, hypotension, pulmonary edema) that could develop into SIRS, capillary leak syndrome (pleural and pericardial effusions), and organ dysfunction. Administer continuous IV fluids during 5 days of therapy to reduce effects of tumor lysis syndrome and other adverse drug reactions. Administer prophylactic corticosteroids (hydrocortisone 100 mg/m² of Days 1 and 3) and allopurinol if hyperuricemia is expected. If significant signs or symptoms of SIRS or capillary leak syndrome occur, discontinue clofarabine immediately; diuretics and albumin may be used; may be fatal. Clofarabine may be reinstituted, with a 25% dose reduction, when the patient is stable.
Assess for nausea and diarrhea. Prevent dehydration. Discontinue clofarabine administration if hypotension occurs during 5 days of therapy. If hypotension resolves without pharmacological intervention, clofarabine may be reinstituted, usually at a lower dose.
Monitor for signs and symptoms of enterocolitis (abdominal pain, nausea, vomiting, diarrhea), especially during first 30 days of therapy. Treat promptly.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor CBC and platelet counts at regular intervals during therapy and more frequently if levels are abnormal. May cause anemia, leukopenia, thrombocytopenia, neutropenia, febrile neutropenia, and infection. If Grade 4 neutropenia (ANC <0.5 X 10⁹/L) occurs and lasts ≥4 wk, ↓ dose by 25% for next cycle.
- Monitor hepatic and renal function frequently during therapy. May cause ↑ AST, ALT, and bilirubin; usually occur within 1 wk of administration and return to baseline within several days. If bilirubin ↑≥Grade 3, discontinue clofarabine and restart with a 25% dose reduction when stable and organ function returned to baseline.
- May cause ↑ serum creatinine. If ≥Grade 3 renal toxicity occurs, discontinue clofarabine and restart with a 25% dose reduction when stable and organ function returned to baseline.

IV Administration:

Intermittent Infusion: Diluent: Dilute with 50 mL of 5% D5W or 0.9% NaCl and filter through a sterile 0.2-micron syringe filter. Solution is clear and practically colorless. Concentration: 0.4 mg/mL. Store at room temperature; use within 24 hr of preparation.
Rate: Administer over 2 hr daily for 5 consecutive days.
Y-Site Incompatibility: Do not administer other medications through same IV line.

Explain purpose of clofarabine to patient.
Advise patient to notify health care professional if signs and symptoms of hematologic toxicity (weakness, fatigue, pallor, shortness of breath, easy bruising, petechiae, purpura, fever), infection (fever), SIRS/capillary leak syndrome (fever, tachycardia, tachypnea, dyspnea, hypotension), and rash occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 mo after last dose and to avoid breastfeeding during and for at least 2 wk after last dose of therapy. Advise males with female partners of reproductive potential to use effective contraception during and for at least 3 mo after last dose of therapy. May impair female and male fertility.

Rapid reduction in peripheral leukemia cells.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆