Dosing and uses of Clolar (clofarabine)
Adult dosage forms and strengths
injectable solution
- 1mg/mL (20mg vial)
Refractory or Relapsed Acute Lymphoblastic Leukemia
<21 years: 52 mg/m² IV over 2 hr qDay for 5 consecutive days
Treatment cycles repeated q2-6wk following recovery or return to baseline organ function
>21 years: Not indicated for this age group
Acute Myelogenous Leukemia (Orphan)
Orphan indication sponsor
- Genzyme Corporation; 4545 Horizon Hill Blvd; San Antonio, TX 78229-2263
Dosage modifications
Discontinue if hypotension develops during 5 days of treatment
Hepatic impairment: Not studied
Renal impairment
- CrCl 30-60 mL/min: Decrease dose by 50%
- CrCl <30 mL/min: Insufficient data to make recommendation
Monitor
Respiratory status & BP during infusion
Renal & hepatic function during administration
Hematologic status
Pediatric dosage forms and strengths
injectable solution
- 1mg/mL (20mg vial)
Refractory or Relapsed Acute Lymphoblastic Leukemia
52 mg/m² IV over 2 hr daily for 5 consecutive days
Treatment cycles repeated q2-6wk following recovery or return to baseline organ function
Dosage modifications
Discontinue if hypotension develops during 5 days of treatment
Hepatic impairment: Not studied
Renal impairment
- CrCl 30-60 mL/min: Decrease dose by 50%
- CrCl <30 mL/min: Insufficient data to make recommendation
Monitor
Respiratory status & BP during infusion
Renal & hepatic function during administration
Hematologic status
Clolar (clofarabine) adverse (side) effects
>10%
Infection: bacterial, viral, & fungal (83%)
Vomiting (83%)
Nausea (75%)
Anemia (83%)
Leukopenia (88%)
Lymphopenia (82%)
Febrile neutropenia (57%)
Thrombocytopenia (81%)
Diarrhea (53%)
Abdominal pain (8-35%)
Anorexia (30%)
Dermatitis
Pruritus (43%)
Fatigue (34%)
Headache (43%)
Pyrexia (39%)
Edema (12%)
Flushing (19%)
HTN (13%)
Hypotension (29%)
Anxiety (21%)
Pain (15%)
Erythema (11%)
Petechiae (26%)
Palmar-plantar erythrodysesthesia syndrome (16%)
Gingival bleeding (14%)
Mucositis (16%)
Oral candidiasis (11%)
Cough
Dyspnea (13%)
Pleural effusion (12%)
Hepatobiliary disorder
Hematuria (13%)
Limb pain (30%)
Myalgia (14%)
Contusion
Injection site pain
Transfusion reaction
1-10%
Back pain (10%)
Bacteremia (10%)
Herpes simplex infections (10%)
Sepsis (10%)
Irritability (10%)
Lethargy (10%)
Somnolence (10%)
Cellulitis (8%)
Agitation (5%)
Postmarketing Reports
Gastrointestinal disorders: Gastrointestinal hemorrhage including fatalities
Skin and subcutaneous tissue disorders: Occurrences of Stevens-Johnson Syndrome and toxic epidermal necrolysis
Metabolism and nutrition disorders: Hyponatremia
Hepatitis and hepatic failure
Warnings
Contraindications
Hypersensitivity
Cautions
Expect typical chemotherapeutic adverse events (diarrhea, nausea/vomiting, bone marrow suppression, risk of tumor lysis syndrome)
Discontinue immediately if clinically significant systemic inflammatory response synd or capillary leak synd develops (may be prevented with prophylactic steroids)
Myelosuppression may be severe and prolonged; monitor complete blood and platelet counts
Serious and fatal cerebral, gastrointestinal and pulmonary hemorrhage; monitor platelets and coagulation parameters and treat accordingly
Monitor for signs and symptoms of infection; severe and fatal sepsis as a result of bone marrow suppression; discontinue therapy promptly if infection occur
Monitor for and discontinue promptly if systemic inflammatory response or capillary leak syndrome suspected
Anticipate and monitor for signs and symptoms of tumor lysis syndrome occur; treat promptly
Monitor for and discontinue if venous occlusive disease of the liver suspected
Monitor liver enzymes and discontinue therapy at first signs of severe hepatotoxicity; discontinue therapy, immediately, for Grade 3 or greater liver enzyme and/or bilirubin elevations; fatal hepatotoxicity may occur
Monitor renal function and interrupt or discontinue if creatinine levels increase or acute renal failure occur
Monitor for signs and symptoms of enterocolitis and treat promptly
Discontinue therapy if exfoliative or bullous rash suspected or if Stevens-Johnson syndrome or toxic epidermal necrolysis suspected
Avoid pregnancy
Hepatitis and hepatic failure reported
Renal impairment
Pregnancy and lactation
Pregnancy category: d
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Clolar (clofarabine)
Half-Life: 5.2 hr
Protein Bound: 47%
Vd: 172 L/sq.meter
Metabolism: metabolized intracellularly to active triphosphate derivative by kinases & phosphokinases
Clearance: 28.8 L/h/sq.meter
Excretion: urine 49-60%
Mechanism of action
Purine nucleoside analog, inhibits ribonucleotide reductase & DNA polymerases
May also promote mitochondria-mediated apoptosis
Administration
IV Preparation
Filter through 0.2 micron syringe filter
Dilute in D5W or Ns
May store at room temp for <24 hr
IV Administration
Infuse over 2 hr
Do not administer other drugs in same IV line
Continuous IV fluids are recommended during the 5 days of Tx to reduce effects of tumor lysis syndrome
