clofarabine

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clofarabine

Clolar, Evoltra (UK)

Pharmacologic class: Purine nucleoside antimetabolite

Therapeutic class: Antineoplastic

Pregnancy risk category D

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.

clofarabine

(klo-far-a-been) ,

Clolar

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antimetabolites
Pregnancy Category: D

Indications

Refractory/relapsed acute lymphoblastic leukemia in children 1–21 yr.

Action

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.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: 46–60% excreted unchanged in urine.
Half-life: 5.2 hr.

Time/action profile (effect on WBCs)

ROUTEONSETPEAKDURATION
IVrapidunknown2–6 wk

Contraindications/Precautions

Contraindicated in: None; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Hepatic or renal impairment;Concurrent use of nephrotoxic or hepatotoxic drugs.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue

Respiratory

  • pharyngitis

Cardiovascular

  • pericardial effusion (most frequent)
  • tachycardia (most frequent)
  • edema

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • abdominal pain
  • constipation
  • mucositis
  • vomiting

Fluid and Electrolyte

  • dehydration

Hematologic

  • neutropenia
  • anemia
  • thrombocytopenia

Local

  • injection site pain

Miscellaneous

  • systemic inflammatory response syndrome (life-threatening)
  • tumor lysis syndrome (life-threatening)
  • infections (most frequent)
  • fever
  • chills

Interactions

Drug-Drug interaction

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

Route/Dosage

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

Availability

Solution for injection : 20 mg/20 mL vials

Nursing implications

Nursing assessment

  • 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. 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 systemic inflammatory response syndrome (SIRS), capillary leak syndrome (pleural and pericardial effusions) and organ dysfunction. Administer continuous IV fluids throughout the 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, usually at a lower dose, 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.
  • Lab Test Considerations: 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.
    • 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. May cause ↑ serum creatinine.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • Administer under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.
  • Intravenous Administration
  • pH: 4.5–7.5.
  • 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.

Patient/Family Teaching

  • Advise patient to consult health care professional if dizziness, fainting spells, or decreased urine output occur during therapy.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.

Evaluation/Desired Outcomes

  • Rapid reduction in peripheral leukemia cells.
References in periodicals archive ?
Evoltra achieves durable responses with a notable survival advantage for the responders".
In addition study results were presented at the plenary sessions of SIOP and at a dedicated Evoltra satellite symposium.
Evoltra is currently indicated for the treatment of acute lymphoblastic leukemia (ALL) in pediatric patients who have relapsed or are refractory to at least two prior regimens.
Evoltra is currently approved in Europe for the treatment of acute lymphoblastic leukemia (ALL) in pediatric patients who have relapsed or are refractory to at least two prior regimens and where there is no other treatment option anticipated to result in a durable response.
Topics Covered Executive Summary Introduction Manufacturing sites Manufacturing site review, 2006 Products Leading Mayne Pharma Products, August 2006 Mayne Pharma ANDA approvals, 2002-06 Faulding Pharmaceutical ANDA approvals, 2002-03 Product Pipeline Innovative Product Distribution Deals Mayne acquires SuperGen's North American oncology products Mayne signs deal with Bioenvision for Evoltra Recent product approvals Recent Product Launches/Approvals Oxaliplatin approved in Germany Epirubicin injection Mitoxantrone injection Carboplatin Fluconazole injection Mayne launches paclitaxel in the EU Financial results Latest Yearly Results Financial Results, Fiscal 2005-06 Sales by Category, 2006 Major developments Mergers, acquisitions and agreements Hospira completes A$2.