(KLA dri been)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Leustatin: 1 mg/mL (10 mL [DSC])
Generic: 1 mg/mL (10 mL [DSC])
Solution, Intravenous [preservative free]:
Generic: 1 mg/mL (10 mL)
Brand Names: U.S.
- Leustatin [DSC]
- Antineoplastic Agent, Antimetabolite
- Antineoplastic Agent, Antimetabolite (Purine Analog)
A purine nucleoside analogue; prodrug which is activated via phosphorylation by deoxycytidine kinase to a 5'-triphosphate derivative (2-CaAMP). This active form incorporates into DNA to result in the breakage of DNA strand and shutdown of DNA synthesis and repair. This also results in a depletion of nicotinamide adenine dinucleotide and adenosine triphosphate (ATP). Cladribine is cell-cycle nonspecific.
Vd: Children 8 months to 18 years: 12.7 ± 8.5 L/kg; penetrates CSF (CSF concentrations are ~18% of plasma concentration) (Kearns, 1994); Adults: ~9 L/kg; penetrates CSF (CSF concentrations are ~25% of plasma concentrations)
Children 8 months to 18 years: 19.7 ± 3.4 hours (Kearns, 1994) ; Adults: After a 2-hour infusion (with normal renal function): 5.4 hours
Use: Labeled Indications
Treatment of active hairy cell leukemia
Treatment of acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphomas (mantle cell), Waldenström’s macroglobulinemia, refractory Langerhans cell histiocytosis
Hypersensitivity to cladribine or any component of the formulation
Acute myeloid leukemia (off-label use): 8.9 mg/m2/day continuous infusion for 5 days for 1 or 2 courses (Krance, 2001) or 9 mg/m2/day over 30 minutes for 5 days for 1 course (in combination with cytarabine) (Crews, 2002; Rubnitz, 2009)
Langerhans cell histiocytosis, refractory (off-label use): 5 mg/m2/day over 2 hours for 5 days every 21 days for up to 6 cycles (Weitzman, 2009)
Adults: Details concerning dosing in combination regimens should also be consulted.
Hairy cell leukemia: IV: 0.09 mg/kg/day continuous infusion for 7 days for 1 cycle or (off-label dosing) 0.1 mg/kg/day continuous infusion for 7 days for 1 cycle (Goodman, 2003; Saven, 1998)
Acute myeloid leukemia, induction (off-label use): IV: CLAG or CLAG-M regimen: 5 mg/m2/day over 2 hours for 5 days; a second induction may be administered if needed (Robak, 2000; Wierzbowska, 2008; Wrzesień-Kuś, 2003)
Chronic lymphocytic leukemia (off-label use): IV: 0.1 mg/kg/day continuous infusion for 7 days every 4-5 weeks (Saven, 1995) or 0.14 mg/kg/day over 2 hours for 5 days every 28 days for 3-6 cycles (Byrd, 2003)
Mantle cell lymphoma (off-label use): IV: 5 mg/m2/day over 2 hours for 5 days every 4 weeks for 2-6 cycles (Inwards, 2008; Rummel, 1999) or 5 mg/m2/day over 2 hours for 5 days every 4 weeks for 2-6 cycles (in combination with rituximab) (Inwards, 2008)
Waldenström’s macroglobulinemia (off-label use):
IV: 0.1 mg/kg/day continuous infusion for 7 days every 4 weeks for 2 cycles (Dimopoulos, 1994)
SubQ: 0.1 mg/kg/day for 5 consecutive days every month for 4 cycles (in combination with rituximab) (Laszlo, 2010)
Dosing adjustment in renal impairment: No dosage adjustment provided in the manufacturer’s labeling (due to inadequate data); use with caution. The following adjustments have been used (Aronoff, 2007):
CrCl 10-50 mL/minute: Administer 50% of dose
CrCl <10 mL/minute: Administer 30% of dose
Hemodialysis: Administer 30% of dose
Continuous renal replacement therapy (CRRT): Administer 50% of dose
CrCl 10-50 mL/minute: Administer 75% of dose
CrCl <10 mL/minute: Administer 50% of dose
Continuous ambulatory peritoneal dialysis (CAPD): Administer 50% of dose
Dosing adjustment in hepatic impairment: No dosage adjustment provided in the manufacturer’s labeling (due to inadequate data); use with caution.
Dosing in obesity: ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
A precipitate may develop at low temperatures and may be resolubilized at room temperature or by shaking the solution vigorously. Inadvertent freezing does not affect the solution; if freezing occurs prior to dilution, allow to thaw naturally; do not heat or microwave; do not refreeze.
To prepare a 24-hour continuous infusion: Dilute in 500 mL NS. The manufacturer recommends filtering with a 0.22 micron hydrophilic syringe filter prior to adding to infusion bag.
To prepare a 7-day continuous infusion: Dilute to a total volume of 100 mL in a CADD medication cassette reservoir using bacteriostatic NS. Filter diluent and cladribine with a 0.22 micron hydrophilic filter prior to adding to cassette/reservoir.
IV: Administer as a continuous infusion. May also be administered over 30 minutes or over 2 hours (off-label administration rates) depending on indication and/or protocol.
SubQ (off-label route): May also be administered SubQ (Laszlo, 2010)
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Stable in NS; incompatible with D5W.
Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F). Protect from light. A precipitate may develop at low temperatures and may be resolubilized at room temperature or by shaking the solution vigorously. Inadvertent freezing does not affect the solution; if freezing occurs prior to dilution, allow to thaw naturally prior to reconstitution; do not heat or microwave; do not refreeze.
24-hour continuous infusion: Dilutions for infusion should be used promptly; if not used promptly, the 24-hour infusion may be stored refrigerated for up to 8 hours prior to administration.
7-day continuous infusion: Dilutions for infusion should be used promptly; if not used promptly, the 7-day infusion may be stored refrigerated for up to 8 hours prior to administration. Reconstituted solution is stable for 7 days (when diluted in bacteriostatic NS) in a CADD® medication cassette reservoir. For patients weighing >85 kg, the effectiveness of the preservative in the bacteriostatic diluent may be reduced (due to dilution).
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Central nervous system: Fever (33% to 69%; ≥100°F: 67%; ≥104°F: 11%), fatigue (11% to 45%), headache (7% to 22%)
Dermatologic: Rash (10% to 27%)
Gastrointestinal: Nausea (22% to 28%), appetite decreased (8% to 17%), vomiting (9% to 13%)
Hematologic: Neutropenia (grade 4: 70%; recovery: by week 5); anemia (1% to 37%; recovery: by week 8); myelosuppression (34%; prolonged), neutropenic fever (8% to 47%; severe: 32%), thrombocytopenia (grade 4: 12%; recovery: by day 12)
Local: Injection site reactions (9% to 19%)
Respiratory: Abnormal breath sounds (4% to 11%)
Miscellaneous: Infection (month 1: 28% [serious: 6%]; month 2: 6%)
1% to 10%:
Cardiovascular: Edema (2% to 6%), tachycardia (2% to 6%), thrombosis (2%)
Central nervous system: Chills (2% to 9%), dizziness (6% to 9%), insomnia (3% to 7%), malaise (5% to 7%), pain (6%), anxiety (1%)
Dermatologic: Purpura (10%), petechiae (2% to 8%), pruritus (2% to 6%), erythema (6%), hyperhidrosis (3%), bruising (1% to 2%)
Gastrointestinal: Diarrhea (7% to 10%), constipation (4% to 9%), abdominal pain (4% to 6%), flatulence (1%)
Local: Phlebitis (2%)
Neuromuscular & skeletal: Weakness (6% to 9%), myalgia (6% to 7%), arthralgia (3% to 5%), muscle weakness (1%)
Respiratory: Cough (7% to 10%), abnormal chest sounds (9%), dyspnea (5% to 7%), epistaxis (5%), rales (1%)
Miscellaneous: Diaphoresis (9%)
<1% (Limited to important or life-threatening): Aplastic anemia, bacteremia, CD4 lymphocytopenia (nadir: 4-6 months), cellulitis, consciousness decreased, conjunctivitis, hemolytic anemia, hypereosinophilia, hypersensitivity, myelodysplastic syndrome, opportunistic infections (cytomegalovirus, fungal infections, herpes virus infections, listeriosis, Pneumocystis jirovecii), pancytopenia (prolonged), paraparesis, pneumonia, polyneuropathy (with high doses), progressive multifocal leukoencephalopathy (PML), pulmonary interstitial infiltrates, quadriparesis (reported at high doses); renal dysfunction (with high doses), renal failure, septic shock, Stevens-Johnson syndrome, stroke, toxic epidermal necrolysis, tuberculosis reactivation, tumor lysis syndrome
Concerns related to adverse effects:
• Bone marrow suppression: [U.S. Boxed Warning]: Dose-dependent myelosuppression (neutropenia, anemia, and thrombocytopenia) is common and generally reversible. Use with caution in patients with preexisting hematologic or immunologic abnormalities. Monitor blood counts, especially during the first 4-8 weeks after treatment.
• Fever: Treatment is associated with fever (>100°F), with or without neutropenia, observed more commonly in the first month.
• Infection: Infections (bacterial, viral, and fungal) were reported more commonly in the first month after treatment (generally mild or moderate in severity, although serious infections including sepsis have been reported); the incidence is reduced in the second month. Due to neutropenia and T-cell depletion, risk versus benefit of treatment should be evaluated in patients with active infections.
• Neurotoxicity: [U.S. Boxed Warning]: Serious, dose-related neurologic toxicity (including irreversible paraparesis and quadriparesis) has been reported with continuous infusions of higher doses (4-9 times the FDA-approved dose); may also occur at approved doses (rare). Neurotoxicity may be delayed and may present as progressive, irreversible weakness; diagnostics with electromyography and nerve conduction studies were consistent with demyelinating disease.
• Renal toxicity: [U.S. Boxed Warning]: Acute nephrotoxicity (eg, acidosis, anuria, increased serum creatinine), possibly requiring dialysis, has been reported with high doses (4-9 times the FDA-approved dose), particularly when administered with other nephrotoxic agents.
• Tumor lysis syndrome: With high tumor burden, tumor lysis syndrome and subsequent hyperuricemia may occur (rare); consider allopurinol and hydrate accordingly.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Weekly (7-day) infusion preparation recommends further dilution with bacteriostatic normal saline which contains benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.
• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• Vaccines: Administration of live vaccines is not recommended during treatment with cladribine (may increase the risk of infection due to immunosuppression).
CBC with differential (particularly during the first 4-8 weeks post-treatment), renal and hepatic function; bone marrow biopsy (after CBC has normalized, to confirm treatment response); monitor for fever; monitor for signs/symptoms of neurotoxicity
Pregnancy Risk Factor
Teratogenic effects and fetal mortality were observed in animal reproduction studies. May cause fetal harm if administered during pregnancy. Women of reproductive potential should use highly effective contraception during treatment.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience dizziness, headache, cough, muscle pain, or lack of appetite. Have patient report immediately to prescriber signs of infection, signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), numbness, tingling, or weakness in arms or legs, tachycardia, arrhythmia, bruising, bleeding, shortness of breath, severe nausea, vomiting, severe diarrhea, dark urine, jaundice, severe skin irritation, loss of strength and energy, severe injection site irritation, or signs of tumor lysis syndrome (fast heartbeat or abnormal heartbeat; any passing out; trouble passing urine; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feel sluggish) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about cladribine
- Other brands: Leustatin