AHFS Class:

• Antineoplastic Agents 10:00

Generic Name(s):

• Cladribine

Cladribine, a synthetic purine nucleoside, is an antimetabolite antineoplastic agent.1,2,3,4,5,6,7,9

For oral use of cladribine in the treatment of multiple sclerosis, see Cladribine 92:20.

Hairy Cell Leukemia

Cladribine injection is used for the treatment of active hairy cell leukemia (leukemic reticuloendotheliosis).1,30,31 Active hairy cell leukemia is defined as disease involving clinically important anemia, neutropenia, thrombocytopenia, or other disease-related symptoms.1 Cladribine is designated an orphan drug by FDA for treatment of hairy cell leukemia.101 Safety and efficacy of cladribine in hairy cell leukemia are based principally on data from open-label studies.1

Clinical Experience

Efficacy and safety of cladribine injection in the treatment of hairy cell leukemia were established in 2 single-center, open-label studies in patients with evidence of active disease requiring therapy.1 During these open-label studies, overall response (complete, good partial, or partial responses) was observed in approximately 88% of patients across both studies combined.1

A complete response to cladribine therapy generally was defined as clearing of the peripheral blood and bone marrow of hairy cells and recovery of hemoglobin concentration to at least 12 g/dL, platelet count to at least 100,000/mm³, and absolute neutrophil count (ANC) to at least 1500/mm³.1 For evaluation of the data using intent-to-treat analysis, an additional criterion for complete response was absence of evidence of splenomegaly indicated by absence of palpable spleen on physical examination and spleen size not exceeding 13 cm on CT scan.1 A good partial response was defined as a decrease to fewer than 5% hairy cells in bone marrow; hematologic parameters for a good partial response were the same as those for a complete response.1 A partial response was defined as a decrease of at least 50% in the number of hairy cells in bone marrow; hematologic parameters for a partial response also were the same as those for a complete response.1

A pathologic relapse was defined as an increase in the number of hairy cells in bone marrow to at least 25% of pretreatment levels.1 A clinical relapse was defined as the recurrence of cytopenias, specifically, decreases in hemoglobin concentration of at least 2 g/dL, decreases in ANC of at least 25%, and/or decreases in platelet count of at least 50,000/mm³.1 Patients who met the criteria for a complete response but subsequently were found to have evidence of hairy cells in bone marrow (less than 25% of pretreatment levels) were reclassified as exhibiting partial responses and were not considered to exhibit complete responses with relapse.1

Complete responses to cladribine were observed in 65-68% of evaluable patients but in only 54% of patients when determined according to intent-to-treat analysis.1 The median time to response in these patients reportedly was about 4 months.1 The median duration of complete response to cladribine therapy exceeded 8 months and in some patients ranged to longer than 25 months.1

In these studies, 60% of patients had not received prior chemotherapy for hairy cell leukemia or had undergone splenectomy as the only prior treatment and were receiving cladribine as initial systemic antineoplastic therapy.1 The remaining 40% of the patients had been treated previously with other agents, including interferon alfa and/or pentostatin.1 The overall response rate for patients without prior chemotherapy was 92% compared with 84% for previously treated patients.1

In a large case series, long-term follow-up of 358 patients receiving cladribine for hairy cell leukemia showed an overall response rate of 95% and a complete response rate of 89% according to intention-to-treat analysis at a median follow-up of approximately 4 years.21 An increased risk of secondary malignancies (observed to expected ratio of 1.88) was reported in this series.21 Under a group C protocol, follow-up of 979 patients receiving cladribine for hairy cell leukemia for at least 4 years showed an overall response rate of 76% and a complete response rate of 44% according to intention-to-treat analysis.9 A high rate of secondary malignancies was also observed in this protocol.9 It is unclear whether the high rate of secondary malignancy associated with cladribine therapy is attributable to the drug or to the underlying disease.31,43,44

Additional data from other case series or open-label studies in small numbers of patients with hairy cell leukemia receiving cladribine demonstrate a consistently high rate of response to the drug.22,23,24,25,42 Although durable complete responses to cladribine therapy have been observed in many patients, longer follow-up is needed to determine the curative potential of the drug.20,31,42 To date, extended follow-up shows high rates of overall survival in a subset of 207 patients from a large case series (97% at 9 years),45 in a case series of 34 patients (100% at 10 years),104 and in a case series of 86 patients (87% at 12 years).46

Clinical Perspective

The American Society of Hematology (ASH) has issued guidelines on the treatment of classic hairy cell leukemia.102 The guidelines recommend that in the absence of renal impairment or active infection, first-line therapy of classic hairy cell leukemia should consist of a standard regimen of a purine nucleoside analog (either cladribine or pentostatin).102 Similar response rates have been reported for cladribine and pentostatin, but the comparative efficacy and safety of these agents have not been studied in phase 3 randomized trials.9,31,104 Some evidence suggests that prior treatment with splenectomy and/or interferon alfa, or with pentostatin, does not alter response to cladribine in patients with hairy cell leukemia;20,21,22,23 however, conflicting data exist.1,20,24

Other Uses

Cladribine has been used in the treatment of chronic lymphocytic leukemia†, low-grade non-Hodgkin's lymphoma,† and cutaneous T-cell lymphoma.†30

General

Pretreatment Screening

• Assess the risks and benefits of cladribine therapy in patients with active infections.1

Patient Monitoring

• Monitor hematologic parameters, particularly during the first 4-8 weeks after treatment.1
• After peripheral counts have normalized, perform bone marrow aspiration and biopsy to confirm response to treatment.1
• Monitor for fever, especially during the first month of therapy.1
• Monitor renal and hepatic function, especially in patients with underlying kidney or liver dysfunction, and in patients receiving other potentially nephrotoxic agents.1,33
• Observe patients closely for signs of hematologic and nonhematologic toxicity.1

Dispensing and Administration Precautions

• Cladribine is a hazardous drug.115 Use disposable gloves and protective garments when handling and disposing of cladribine.1
• If the drug comes in contact with the skin or mucous membranes, immediately wash the involved surface with large amounts of water.1
• Cladribine injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy.1

Administration

Administer cladribine by continuous IV infusion as a single course of therapy given over 7 consecutive days.1,5 Cladribine injection concentrate must be diluted prior to IV infusion. 1 The drug also has been administered subcutaneously†.102

To dilute the drug, add the calculated single daily dose of cladribine injection concentrate through a sterile 0.22-µm disposable hydrophilic syringe filter to an infusion bag containing 500 mL of 0.9% sodium chloride injection.1 Repeat daily for a total of 7 consecutive days.1 Admixtures of cladribine injection are chemically and physically stable for at least 24 hours at room temperature under normal room fluorescent light in Baxter Viaflex PVC infusion containers.1 Do not use dextrose 5% injection because cladribine degradation is accelerated in this diluent.1 Infuse diluted solution by continuous IV infusion over 24 hours.1

Alternatively, if the entire 7-day course of cladribine is to be administered as a single continuous IV infusion, the manufacturer recommends that the entire dose for this period only be diluted with bacteriostatic 0.9% sodium chloride injection containing benzyl alcohol as a preservative.1 To further minimize the risk of microbial contamination, first the calculated 7-day dose of cladribine concentrate for injection (0.63 mg/kg total) and then the calculated amount of diluent needed to bring the total volume of the solution to 100 mL should be passed through a sterile 0.22-µm disposable hydrophilic syringe filter as each solution is being introduced into the infusion reservoir.1 Solutions of cladribine prepared with bacteriostatic sodium chloride injection for individuals weighing more than 85 kg may have reduced preservative effectiveness because of greater dilution of the benzyl alcohol.1 Admixtures for the 7-day infusion have demonstrated acceptable chemical and physical stability for at least 7 days in the SIMS Deltec Medication Cassette Reservoir.1 Infuse diluted solution continuously over 7 days.1

Cladribine IV infusion solutions that have been prepared with bacteriostatic sodium chloride injection containing benzyl alcohol should not be used in neonates.1

Consult the manufacturer's labeling for additional information on proper techniques for dilution, storage, and administration of cladribine as well as measures to avoid precipitation of the drug.1

Store cladribine injection in the refrigerator at 2-8ºC, protected from light until time of use.1 Once diluted, administer solutions of cladribine injection promptly or store at 2-8ºC for no more than 8 hours before the start of administration.1

Dosage

Hairy Cell Leukemia

The adult dosage of cladribine provided in the FDA-approved labeling for the treatment of active hairy cell leukemia is a single course given by continuous IV infusion for 7 consecutive days at a dosage of 0.09 mg/kg daily.1 The manufacturer states that if the patient fails to respond to the initial course of therapy, additional courses of cladribine are unlikely to provide any benefit.1 The manufacturer states that deviations from this dosage regimen are not advised.1

Cladribine has been administered in various dosage schedules and by different routes of administration (e.g., IV continuous infusion for 7 days, IV infusion over 2 hours for a 5-day regimen†, or alternatively subcutaneously on a once-per-day or once-per-week regimen†.1,9,21,42,45,46,47,102 The American Society of Hematology (ASH) recommends regimens of cladribine as a continuous IV infusion of 0.1 mg/kg daily for 7 days†102 , or 0.14 mg/kg daily IV over 2 hours once per day for 5 days†102 , 0.14 mg/kg IV over 2 hours once per week for 5 or 6 weeks†102,103 , or 0.1-0.14 mg/kg daily subcutaneously once per day for 5 days†.102

Because cladribine is a highly toxic drug (consult the manufacturer's labeling), patients undergoing therapy should be observed closely for signs of hematologic and nonhematologic toxicity.1 Discontinuance or interruption of cladribine therapy should be considered in patients who experience neurotoxicity and/or renal toxicity.1

Special Populations

Hepatic Impairment

The manufacturer makes no specific recommendations for dosage adjustment in patients with hepatic impairment.1

Renal Impairment

The manufacturer makes no specific recommendations for dosage adjustment in patients with renal impairment.1

Geriatric Patients

While other clinical experience has not revealed age-related differences in response, drug dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range.1 The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered.1

Contraindications

• Known hypersensitivity to the drug or any of its components.1

Warnings/Precautions

Warnings

Experience of Supervising Clinician

A boxed warning included in the prescribing information for cladribine injection states to use the drug only under the supervision of a qualified physician experienced in the use of antineoplastic therapy.1

Hematologic Effects

A boxed warning about the risk of severe bone marrow suppression resulting in neutropenia, anemia, and thrombocytopenia is included in the prescribing information for cladribine.1 Severe bone marrow suppression resulting in neutropenia, anemia, and thrombocytopenia occurs frequently in patients with hairy cell leukemia receiving cladribine,1,5,22,24 especially at high doses1 or in patients with preexisting pancytopenia.32 Most patients with hairy cell leukemia receiving cladribine in clinical trials had hematologic impairment as a manifestation of the disease.1,5,22,24 Following cladribine treatment, further hematologic impairment occurred before recovery of peripheral blood counts began.1 Prolonged pancytopenia1,20,35,36 including aplastic anemia and hemolytic anemia (reported in patients with lymphoid malignancies1,37 within the first few weeks following cladribine therapy) has been reported in postmarketing surveillance of patients usually receiving multiple courses of the drug.1

Myelosuppression occurred frequently during the first month after initiation of cladribine therapy in patients with hairy cell leukemia in clinical trials; 44% of patients received red blood cell transfusions and 14% received platelet transfusions.1 During the first 2 weeks after treatment was initiated, mean platelet count, absolute neutrophil count (ANC), and hemoglobin concentration declined and subsequently increased with normalization of mean counts by day 12, week 5, and week 8, respectively.1 Platelet recovery may be delayed in patients with severe baseline thrombocytopenia.1 During the first month after treatment initiation, severe neutropenia (ANC less than 500/mm³) occurred in 70% of patients; it was present in 26% of patients before treatment.1 The time of maximum cladribine-induced neutropenia appears to correspond with an increased risk of serious infection.20,24,26

Severe anemia (hemoglobin less than 8.5 g/dL), which was present in 10% of patients before treatment, developed in 37% of patients, and thrombocytopenia (platelet count less than 20,000/mm³), which was present in 4% of patients before treatment, developed in 12% of patients.1 Hematologic function must be monitored carefully in patients receiving cladribine, particularly during the first 4-8 weeks after therapy is initiated.1 Multiple cycles of cladribine therapy may be associated with cumulative myelotoxicity and prolonged thrombocytopenia.20 Thrombocytopenia was the limiting toxicity in 20-30% of patients with chronic lymphocytic leukemia† or lymphomas† after repeated courses of cladribine therapy.32

Prolonged bone marrow hypocellularity was observed in patients with hairy cell leukemia treated with cladribine in clinical trials, but its clinical importance is not known.1 Bone marrow hypocellularity of less than 35% was observed after 4 months in 34% of patients and was observed as late as 33 months after treatment was initiated.1 It is not known whether the hypocellularity results from disease-related marrow fibrosis or cladribine toxicity.1 No apparent clinical effect on peripheral blood counts was observed.1

Purpura was reported in 10%, petechiae in 8%, and epistaxis in 5% of patients with hairy cell leukemia during the first 2 weeks after initiation of cladribine therapy in clinical trials.1 Erythroid macrocytosis that persisted for 6 months or longer in patients with cutaneous T-cell lymphomas† who received as many as 6 courses of cladribine therapy also has been reported.32

In patients with normal bone marrow function, only lymphopenia and transient profound monocytopenia as well as neutropenia and thrombocytopenia may be observed after cladribine therapy.33,40

Based on analysis of lymphocyte subsets from patients with hairy cell leukemia, cladribine therapy is associated with prolonged depression of helper/inducer (CD4⁺, T4⁺) T-cell counts.1,24 Prior to treatment, the mean CD4⁺ T-cell count was 766/mm³; the mean CD4⁺ T-cell count nadir, which occurred 4-6 months following treatment, was 272/mm³.1 Fifteen months after treatment, mean CD4⁺ T-cell counts remained below 500/mm³.1 The effect on cytotoxic/suppressor (CD8⁺, T8⁺) T-cell counts was similar, although increasing counts were observed after 9 months.1 The clinical importance of the prolonged depression of the helper/inducer (CD4⁺, T4⁺) T-cell subset is not known.1 No associated opportunistic infections were reported during this period.1

Neurologic Effects

A boxed warning about the risk of neurological toxicity is included in the prescribing information for cladribine.1 Serious neurological toxicity (including irreversible paraparesis and quadriparesis) has been reported in patients treated with cladribine injection by continuous infusion at high doses (4-9 times the recommended dose for hairy cell leukemia) as part of a bone marrow transplant conditioning regimen, which also included high dose cyclophosphamide and total body irradiation.1,33 Neurologic toxicity appears to demonstrate a dose relationship; however, severe neurological toxicity has been reported rarely following treatment with standard cladribine dosing regimens.1,33

Severe neurologic toxicity also has been observed with high doses of another drug in the same class as cladribine.1 Similar neurotoxicity has been reported rarely in patients with hairy cell leukemia receiving the currently recommended cladribine dosage regimen (0.09 mg/kg daily for 7 consecutive days).1 Axonal peripheral polyneuropathy was observed in a dose-escalation study at the highest dose levels (about 4 times the currently recommended dose for hairy cell leukemia) in patients not receiving cyclophosphamide or total body irradiation therapy.1 Mild neurotoxicity has been reported in postmarketing surveillance of patients usually receiving multiple courses of the drug.1

Renal Effects

A boxed warning about the risk of acute nephrotoxicity is included in the prescribing information for cladribine.1 Acute nephrotoxicity has been observed with high doses of cladribine injection (4-9 times the recommended dose for hairy cell leukemia), in conjunction with cyclophosphamide and total body irradiation as preparation for bone marrow transplantation, in patients within 1-2 weeks after starting treatment.1,33 Several of the patients also were receiving other potentially nephrotoxic drugs.1 Most of the patients developing acute renal insufficiency required dialysis.1,33 Renal dysfunction was reversible in some of the patients.1,33 In several patients in whom renal function had not recovered by the time of death, evidence of renal tubular damage was found.1 Similar nephrotoxicity has not been reported in patients with hairy cell leukemia receiving the currently recommended cladribine dosage regimen (0.09 mg/kg daily for 7 consecutive days).1

Other Warnings and Precautions

Infectious Complications

Infectious complications,1,22,24,25 including those associated with immunosuppression (e.g., fungal, viral), were documented in 28% of patients with hairy cell leukemia during the first month after initiation of cladribine treatment and in 6% of patients during the second month after initiation of treatment in clinical trials.1 Opportunistic infections also have been reported in postmarketing surveillance of patients usually receiving multiple courses of the drug.1 Serious infections (e.g., septicemia, pneumonia)1,21,24 were reported in 6% of patients and occurred only during the first month after initiation of cladribine treatment; the remaining infections were mild or moderate in severity.1 Several deaths were attributed to infection and/or complications related to the underlying disease.1,24,25,26 During the second month, documented infections were mild to moderate in severity and no severe systemic infections occurred.1 Approximately 10% of the patients with hairy cell leukemia in clinical trials had a documented infection in the month prior to cladribine treatment.1 After the third month, the incidence of monthly infections was less than or equal to that of the months immediately preceding cladribine therapy.1 This trend toward a reduced incidence of infection corresponded to normalization of the ANC.1

Of the documented infections occurring in the first month following cladribine therapy, 42% were bacterial, 20% were fungal, and 20% were viral.1 The most frequently reported infection associated with a fatal outcome following cladribine therapy was Candida sepsis, although a number of other bacterial, fungal, and viral infections were reported.20,24,25,26 Most of the documented episodes of herpes zoster infections occurred during the first month following treatment, and almost all of the documented fungal infections occurred during the first 2 months after treatment.1

During the first 2 weeks after initiation of cladribine treatment in clinical trials, approximately two-thirds of patients with hairy cell leukemia developed fever,1,5,21,22,24 and during the first month, 11% of patients developed severe fever (temperature greater than or equal to 40°C); virtually all patients developing fever were treated empirically with parenteral anti-infectives.1 Overall, 47% of patients had fever in the presence of neutropenia (ANC less than or equal to 1000/mm³), including 32% with severe neutropenia (ANC less than or equal to 500/mm³).1 Less than one-third of the febrile events were associated with documented infection.1,5,21,22,24 In many cases, fever probably was related to the release of pyrogens from tumor cells.5,32

Fever

Because fever occurs frequently during the first month of cladribine therapy, mainly in neutropenic patients, patients receiving the drug should be monitored carefully during this period.1 Febrile episodes should be evaluated with appropriate laboratory and radiologic studies, and empiric anti-infective therapy should be initiated as clinically indicated.1 Because of the myelosuppressive effects of cladribine, clinicians should weigh carefully the risks and benefits of administering the drug to patients with active infections.1 In addition, caution should be exercised if cladribine is administered before, after, or in conjunction with other drugs known to cause immunosuppression or myelosuppression.1

Tumor Lysis Syndrome

The possibility of tumor lysis syndrome and hyperuricemia, which have been reported rarely in patients with large tumor burdens receiving cladribine,40 should be considered.1,34,40 Empiric therapy with allopurinol appears to reduce the risk of tumor lysis syndrome in cladribine-treated patients with active hairy cell leukemia.1,5,22

Vaccinations

Due to the increased risk of infection with immunosuppression with chemotherapy including cladribine, it is recommended not to administer live attenuated vaccines to patients receiving cladribine injection.1

Specific Populations

Pregnancy

Cladribine can cause fetal harm when administered to pregnant females.1 Although there is no evidence of teratogenicity in humans caused by cladribine, other drugs that inhibit DNA synthesis (e.g., methotrexate, aminopterin) have been reported to be teratogenic in humans,1 and cladribine has been shown to be teratogenic in mice and rabbits.1

Cladribine should not be used during pregnancy.1 If the drug is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.1 (See Females and Males of Reproductive Potential under Cautions.)

Lactation

It is not known whether cladribine is distributed into human milk.1 Because of the potential for serious adverse reactions to cladribine in nursing infants if the drug were distributed into milk, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the patient.1

Females and Males of Reproductive Potential

Females of childbearing potential should be advised to avoid becoming pregnant while receiving cladribine.1 Such females should use highly effective contraception during treatment with the drug.1

Following IV administration in cynomolgus monkeys, cladribine has been shown to cause suppression of rapidly generating cells, including testicular cells.1 The effect of the drug on fertility in humans is not known.1

Pediatric Use

Safety and efficacy of cladribine in children have not been established.1 When cladribine was administered by continuous IV infusion at dosages of 3-10.7 mg/m² daily for 5 days in patients 1-21 years of age with relapsed acute leukemia, the dose-limiting toxicity was severe myelosuppression with profound neutropenia and thrombocytopenia.1,39 At the highest dosage, several patients developed irreversible myelosuppression and fatal systemic bacterial or fungal infections.1,39 No unique toxicities were reported in these patients.1 Children may tolerate cladribine better than adults.39

Cladribine IV infusion solutions that have been prepared with bacteriostatic sodium chloride injection containing benzyl alcohol should not be used in neonates.1 Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates.1,12,13,14,15,16,17

Geriatric Use

Clinical studies of cladribine did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.1 While other clinical experience has not revealed age-related differences in response, drug dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range.1 The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered.1

Hepatic Impairment

The effects of hepatic impairment on the elimination of cladribine have not been elucidated.1 The manufacturer recommends monitoring of hepatic function during cladribine therapy, especially in patients with hepatic impairment, but makes no specific dosage adjustment.1 Cladribine should be used with caution in patients with known or suspected hepatic insufficiency.1,20

Renal Impairment

The effects of renal impairment on the elimination of cladribine have not been elucidated.1 The manufacturer recommends monitoring renal function during cladribine therapy, especially in patients with renal impairment, but makes no specific recommendations for dosage adjustment.1 Cladribine should be used with caution in patients with known or suspected renal insufficiency.1,20

Common Adverse Effects

The most frequent adverse effects of cladribine include pyrexia (33%), fatigue (31%), nausea (22%), rash (16%), and headache (14%).1

There are no known drug interactions with cladribine.1

Immunosuppressive and Myelosuppressive Drugs

Caution should be exercised if cladribine injection is administered before, after, or in conjunction with other drugs known to cause immunosuppression or myelosuppression.1

Nephrotoxic Drugs

Concomitant nephrotoxic drugs may increase the risk of acute nephrotoxicity.1

Vaccinations

Due to the increased risk of infection with immunosuppression with chemotherapy including cladribine, it is recommended not to administer live attenuated vaccines to patients receiving cladribine.1

Description

Cladribine (chlorodeoxyadenosine, 2-CdA), a synthetic purine nucleoside, is an antineoplastic agent.1,2,3,4,5,6,7,9 Cladribine differs structurally from deoxyadenosine only by the presence of a chlorine atom at position 2 of the purine ring, which results in resistance to enzymatic degradation by adenosine deaminase.2,3,4,7 Because of its resistance to deamination, cladribine exhibits a more prolonged cytotoxic effect than deoxyadenosine against resting and proliferating lymphocytes.2,3,6

The precise mechanism(s) of antileukemic action of cladribine has not been fully elucidated.1,3,6,7,8 Cladribine is phosphorylated by deoxycytidine kinase to the nucleotide cladribine triphosphate (CdATP; 2-chloro-2'-deoxyadenosine 5'-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that have high levels of deoxycytidine kinase and low levels of deoxynucleotidase. 1,2,7 High intracellular concentrations of cladribine triphosphate appear to inhibit ribonucleotide reductase, causing an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death.1,3,6,7,8 Incorporation of accumulated cladribine triphosphate into DNA also may contribute to DNA strand breakage and inhibition of DNA synthesis and repair. 1,2,3,7,8 Unlike other commonly used antineoplastic drugs that affect purine and pyrimidine metabolism, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes and monocytes.1,2,4,7,20

Advice to Patients

• Advise patients that they are more susceptible to infections while receiving cladribine and to immediately report any signs or symptoms of infection (e.g., fever, chills, constant cough, dysuria) to their healthcare provider.1
• Advise patients of the risk of lymphopenia and other hematologic toxicity and the need to monitor complete blood cell counts during therapy.1
• Advise patients of the risk of nephrotoxicity and neurotoxicity and to immediately report signs and symptoms to their healthcare provider.1
• Advise patients to avoid the use of live attenuated vaccines during treatment with cladribine.1
• Advise females of reproductive potential of the potential risk to a fetus and to use highly effective contraception during treatment with cladribine.1
• Advise females to inform their clinician if they are breastfeeding or plan to breastfeed.1
• Advise patients to inform their healthcare provider about all concomitant medications, including prescription medicine, over the counter drugs, vitamins, and herbal products, as well as any concomitant illnesses.1
• Advise patients to inform their healthcare provider of other important precautionary information.1 (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Fresenius Kabi. Cladribine injection for intravenous infusion only prescribing information. Lake Zurich, IL; 2016 Aug.

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