Class: Antineoplastic Agents
- Antibody-fusion Proteins
Chemical Name: Disulfide with anti-(human CD22 (antigen)) (synthetic Mus musculus CAT-8015 heavy chain variable region fragment) fusion protein with exotoxin PE38 (Pseudomonas fragment), immunoglobulin
Molecular Formula: C2804H4339N783O870S14
CAS Number: 1020748-57-5
- Capillary Leak Syndrome
Capillary leak syndrome, sometimes life-threatening, reported. (See Capillary Leak Syndrome under Cautions.)
Temporary interruption of therapy or drug discontinuance may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration.)
- Hemolytic Uremic Syndrome
Hemolytic uremic syndrome, sometimes life-threatening, reported. (See Hemolytic Uremic Syndrome under Cautions.)
Institute appropriate prophylactic measures (e.g., adequate hydration, low-dose aspirin). (See General under Dosage and Administration.)
Discontinuance of therapy may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration.)
Antineoplastic agent; a CD22-directed antibody-fusion protein consisting of a recombinant murine monoclonal antibody (moxetumomab) covalently linked to a cytotoxic bacterial protein toxin (Pseudomonas exotoxin [PE38]).
Uses for Moxetumomab Pasudotox-tdfk
Hairy Cell Leukemia
Treatment of relapsed or refractory hairy cell leukemia in patients who previously received ≥2 systemic therapies, including a purine nucleoside analog (e.g., cladribine, pentostatin). Efficacy determined based on durable (lasting >180 days) complete response rate in a noncomparative, open-label, multicenter phase 3 study in patients with relapsed or refractory hairy cell leukemia or hairy cell leukemia-variant previously treated with ≥2 systemic therapies.
Designated an orphan drug by FDA for treatment of hairy cell leukemia.
Moxetumomab Pasudotox-tdfk Dosage and Administration
To minimize risk of infusion-related reactions, premedicate with an antihistamine (e.g., diphenhydramine, hydroxyzine), acetaminophen, and a histamine H2-receptor antagonist (e.g. ranitidine, famotidine, cimetidine) 30–90 minutes prior to each infusion. Consider an oral antihistamine and acetaminophen for ≤24 hours after each infusion.
To minimize risk of hemolytic uremic syndrome, administer 1 L (for patients weighing ≥50 kg) or 500 mL (for patients weighing <50 kg) of 5% dextrose injection in 0.45% sodium chloride injection, 5% dextrose in 0.9% sodium chloride injection, or an appropriate isotonic IV solution by IV infusion over 2–4 hours before and after each dose of moxetumomab pasudotox. Also maintain adequate oral hydration on days 1–8 of each 28-day cycle with up to 12 glasses (3 L) of fluids (e.g., water, milk, juice) for patients weighing ≥50 kg or 8 glasses (2 L) for patients weighing <50 kg. (See Hemolytic Uremic Syndrome under Cautions.)
Consider thromboprophylaxis with low-dose aspirin (81 mg daily) on days 1–8 of each 28-day cycle.
To reduce incidence and/or severity of nausea and vomiting, administer an oral corticosteroid (e.g., dexamethasone 4 mg) after each dose of moxetumomab pasudotox.
For solution compatibility information, see Compatibility under Stability.
Administer by IV infusion over 30 minutes. To ensure administration of a full dose of the drug, flush IV administration line with 0.9% sodium chloride injection after each dose using same infusion rate.
Must reconstitute powder for injection and dilute prior to administration. (See Storage under Stability.)
Do not admix with or infuse simultaneously through the same IV line with any other drugs.
Vials containing moxetumomab pasudotox-tdfk and vials containing the IV solution stabilizer are intended for single use only; discard any partially used vials.
Reconstitute appropriate number of vials containing 1 mg of moxetumomab pasudotox-tdfk to achieve desired dose; do not round dose down for partial vials.
Reconstitute each vial containing 1 mg of moxetumomab pasudotox-tdfk with 1.1 mL of sterile water for injection to provide a solution containing 1 mg/mL. Direct diluent toward the wall of the vial. Gently swirl and invert vial to dissolve the cake or powder. Do not shake reconstituted solution.
Reconstituted solution should be clear to slightly opalescent, colorless to slightly yellow, and free of visible particulates. Discard solution if it is cloudy, discolored, or contains precipitates.
Dilute reconstituted solution immediately.
Add 1 mL of the IV solution stabilizer to a 50-mL infusion bag containing 0.9% sodium chloride injection; must be added to the infusion bag prior to adding the reconstituted moxetumomab pasudotox-tdfk solution. Only one vial of the IV solution stabilizer is necessary for each infusion of the drug. Gently invert infusion bag to mix solution; do not shake. Do not use the IV solution stabilizer to reconstitute moxetumomab pasudotox-tdfk powder for injection.
To prepare final diluted solution for infusion, add appropriate volume of the appropriate number of vials of reconstituted moxetumomab pasudotox-tdfk solution to the infusion bag containing 0.9% sodium chloride injection and IV solution stabilizer. Gently invert infusion bag to mix final diluted solution.
Immediate administration recommended. If necessary, may store diluted infusion solution according to manufacturer's storage instructions. (See Storage under Stability.) If diluted solution was previously refrigerated, allow infusion bag to stand at room temperature for ≤4 hours prior to administration.
Rate of Administration
Administer by IV infusion over 30 minutes.
Hairy Cell Leukemia
0.04 mg/kg on days 1, 3, and 5 of each 28-day cycle. Continue for a maximum of 6 cycles or until disease progression or unacceptable toxicity occurs.
Calculate dosage based on actual body weight at baseline prior to initiation of therapy. Do not adjust dose during treatment cycle based on changes in body weight. However, if body weight increases >10% from baseline, may adjust dose based on current weight before starting next treatment cycle.
Dosage Modification for Toxicity
Capillary Leak SyndromeIV
If symptomatic grade 2 capillary leak syndrome requiring medical management occurs, interrupt therapy until toxicity resolves. (See Capillary Leak Syndrome under Cautions.)
If grade 3 or 4 capillary leak syndrome requiring medical management occurs, permanently discontinue drug.
Hemolytic Uremic SyndromeIV
If hemolytic uremic syndrome occurs, discontinue drug.
If grade 2 or greater (>1.5 times baseline values or the ULN) elevations of Scr concentrations occur in patients with baseline Scr concentrations within the normal range, interrupt therapy until Scr concentrations resolve to grade 1 or less (≤1.5 times baseline values or the ULN).
If grade 3 or greater (>3 times baseline values or the ULN) elevations of Scr concentrations occur in patients with baseline grade 1 or 2 elevations of Scr concentrations, interrupt therapy until Scr resolves to baseline or less.
If severe infusion-related reactions occur, interrupt infusion and provide appropriate treatment. (See Infusion-related Reactions under Cautions.)
Hairy Cell Leukemia
Maximum of 6 28-day cycles.
No dosage adjustment necessary. (See Hepatic Impairment under Cautions.)
Mild or moderate renal impairment (Clcr ≥30 mL/minute): No dosage adjustment necessary. (See Renal Impairment under Cautions.)
Severe renal impairment (Clcr ≤29 mL/minute): Not recommended. (See Renal Effects under Cautions.)
No specific dosage recommendations. (See Geriatric Use under Cautions.)
Cautions for Moxetumomab Pasudotox-tdfk
No known contraindications.
Capillary Leak Syndrome
Capillary leak syndrome (characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration), sometimes life-threatening, reported. May occur at any time during a treatment cycle; generally occurs within 8 days (range: 1–19 days) following the initial dose of a cycle. Median time to resolution 12 days (range: 1–53 days).
Assess BP and weight prior to each infusion and as clinically indicated during therapy. Monitor for manifestations of capillary leak syndrome (e.g., weight gain, hypotension, peripheral edema, shortness of breath, cough, pulmonary edema, serosal effusions, hypoalbuminemia, elevated hematocrit, leukocytosis, thrombocytosis).
Promptly evaluate patients experiencing hypotension and weight gain (i.e., increase in weight of 2.5 kg or ≥5% from day 1 of current cycle) for peripheral edema, hypoalbuminemia, and respiratory symptoms (i.e., shortness of breath, cough). If capillary leak syndrome is suspected, assess oxygen saturation and assess for manifestations of pulmonary edema and/or serosal effusions.
Capillary leak syndrome may be life-threatening if treatment is delayed. If grade 2 or greater capillary leak syndrome occurs, monitor weight, BP, serum albumin concentrations and initiate symptomatic treatment (i.e., oral or IV corticosteroids), until toxicity resolves; hospitalization may be necessary. Temporary interruption of therapy or drug discontinuance may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration.)
Hemolytic Uremic Syndrome
Hemolytic uremic syndrome (characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and progressive renal failure) reported. May occur at any time during a treatment cycle; generally occurs within 9 days (range: 1–16 days) following the initial dose of a cycle. Median time to resolution 11.5 days (range: 2–44 days).
Avoid use in patients with history of severe thrombotic microangiopathy or hemolytic uremic syndrome.
Administer appropriate prophylactic measures (e.g., adequate hydration, low-dose aspirin). (See General under Dosage and Administration.) Monitor patients for fluid overload, thrombosis, and electrolyte abnormalities.
Monitor CBCs (including hemoglobin concentrations and platelet counts) and blood chemistries (i.e., Scr concentrations) prior to each dose and on day 8 of each cycle; additional monitoring on day 14 of each cycle is recommended.
Consider possible diagnosis of hemolytic uremic syndrome if hemolytic anemia, sudden onset or worsening of thrombocytopenia, elevated Scr concentrations, elevated serum bilirubin and/or LDH concentrations, or evidence of microangiopathic hemolytic anemia (presence of schistocytes on peripheral blood smear) occur.
Hemolytic urine syndrome may be life-threatening and/or result in renal failure requiring dialysis if treatment is delayed. If hemolytic uremic syndrome is suspected, monitor hemodynamic parameters, peripheral blood smear, serum LDH concentrations, and indirect bilirubin concentrations, and initiate supportive treatment (i.e., hydration), until toxicity resolves; hospitalization may be necessary. If hemolytic uremic syndrome is confirmed, discontinue drug and initiate supportive treatment (i.e., hydration) and monitoring (i.e., renal function, CBCs, blood chemistries) until toxicity resolves.
Other Warnings and Precautions
Renal toxicity (e.g., acute kidney injury, renal failure, deterioration of renal function, laboratory abnormalities), generally mild to moderate in severity, reported.
Increased risk in patients who develop hemolytic uremic syndrome, those with baseline renal impairment, and in those ≥65 years of age. (See Geriatric Use under Cautions.) Do not use in patients with severe renal impairment (Clcr 29 mL/minute).
Monitor renal function prior to each dose and as clinically indicated during therapy. If elevations of Scr occur, temporary interruption of therapy may be necessary. (See Dosage Modification for Toxicity under Dosage and Administration.)
Infusion-related reactions (e.g., nausea, pyrexia, chills, vomiting, headache, cough, wheezing, dizziness, dyspnea, feeling hot, flushing, hypertension, hypotension, myalgia, tachycardia) reported; may occur during any treatment cycle.
Premedicate with acetaminophen, an antihistamine, and a histamine H2-receptor antagonist prior to each infusion of the drug. (See General under Dosage and Administration.)
If severe infusion-related reactions occur, interrupt infusion and initiate appropriate treatment. Administer an oral or IV corticosteroid approximately 30 minutes prior to resuming infusion and 30 minutes prior to subsequent infusions. (See Infusion-related Reactions under Dosage and Administration.)
Electrolyte abnormalities (i.e., hypocalcemia) reported; generally occurred in the same treatment cycle as capillary leak syndrome, hemolytic uremic syndrome, fluid retention, or renal toxicity.
Monitor serum electrolytes prior to each dose and on day 8 of each cycle; manufacturer also recommends monitoring on day 14 of each cycle.
Potential for immunogenicity. Development of binding and neutralizing antibodies to moxetumomab pasudotox reported.
In patients with high titers of antimoxetumomab pasudotox antibodies, peak plasma concentrations of moxetumomab pasudotox substantially decreased during cycle 3 and beyond; durable complete response rates were lower in such patients in cycle 5 compared with those with lower antimoxetumomab pasudotox antibody titers.
May cause fetal and maternal harm. No data regarding use in pregnant women.
Confirm pregnancy status prior to initiating therapy. Avoid pregnancy during therapy. Women of reproductive potential should use an effective method of contraception while receiving moxetumomab pasudotox and for ≥30 days after the last dose of the drug.
If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.
Not known whether moxetumomab pasudotox distributes into human milk, affects the breast-fed infant, or affects milk production.
Consider benefits of breast-feeding and woman’s clinical need for the drug along with any potential adverse effects on breast-fed infant from the drug or underlying maternal condition.
Safety and efficacy not established.
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.
Older age is associated with an increased risk of developing renal toxicity or adverse effects requiring discontinuance of therapy. (See Renal Effects under Cautions.)
Pharmacokinetics not substantially affected by mild hepatic impairment (total bilirubin concentrations not exceeding the ULN and AST concentrations exceeding the ULN, or total bilirubin concentrations exceeding the ULN, but <1.5 times the ULN, with any AST concentration).
Not studied in patients with moderate or severe hepatic impairment (total bilirubin concentrations >1.5 times the ULN).
Pharmacokinetics not substantially affected by mild or moderate renal impairment (Clcr 30–89 mL/minute).
Not studied in patients with severe renal impairment (Clcr ≤29 mL/minute); do not use in patients with severe renal impairment.
Moxetumomab pasudotox may worsen renal function in patients with baseline renal impairment. (See Renal Effects under Cautions.)
Common Adverse Effects
Infusion-related reactions, peripheral edema, nausea, fatigue, headache, pyrexia, constipation, anemia, diarrhea, elevated Scr concentrations, elevated AST and/or ALT concentrations, hypoalbuminemia, hypocalcemia, hypophosphatemia, decreased hemoglobin concentrations, neutropenia, hyponatremia, elevated bilirubin concentrations, hypokalemia, elevated γ-glutamyltransferase (γ-glutamyltranspeptidase, GGT, GGTP) concentrations, hypomagnesemia, thrombocytopenia, hyperuricemia, elevated serum alkaline phosphatase concentrations, decreased lymphocyte concentrations.
Interactions for Moxetumomab Pasudotox-tdfk
No formal drug interaction studies to date.
Moxetumomab Pasudotox-tdfk Pharmacokinetics
Systemic exposure is dose proportional over dosage range of 0.005–0.05 mg/kg. Systemic accumulation does not occur following IV administration on days 1, 3, and 5 of a 28-day cycle.
Mild hepatic impairment (total bilirubin concentrations not exceeding the ULN with AST concentrations exceeding the ULN, or total bilirubin concentrations exceeding the ULN, but not >1.5 times the ULN, with any AST concentration) does not affect pharmacokinetics.
Mild or moderate renal impairment (Clcr 30–89 mL/minute) does not affect pharmacokinetics.
Not studied in patients with severe hepatic impairment (total bilirubin concentrations >1.5 times the ULN) or severe renal impairment (Clcr <29 mL/minute).
Age (range of 36–84 years), sex, race (white versus non-white), and body weight (42–152 kg) do not have meaningful effects on pharmacokinetics of moxetumomab pasudotox.
Not known whether moxetumomab pasudotox is distributed into human milk.
Not characterized. Expected to be degraded into small peptides and amino acids via catabolic pathways.
Clearance decreases over time following initial dose suggesting target-mediated drug disposition.
Powder for Injection
Vials of lyophilized moxetumomab pasudotox and vials of IV solution stabilizer: 2–8°C in original carton to protect from light. Do not freeze or shake.
Reconstituted drug: Dilute immediately; do not store reconstituted solution.
Diluted infusion solution: Should be administered immediately after dilution, but may be stored at 20–25°C for ≤4 hours or 2–8°C for ≤24 hours after dilution. If refrigerated, allow infusion bag to stand at room temperature for ≤4 hours. Diluted solutions must be administered ≤24 hours after reconstitution. Protect from light. Do not freeze or shake.
For information on systemic interactions resulting from concomitant use, see Interactions.
Sodium chloride 0.9%
A CD22-directed antibody-fusion protein consisting of a recombinant murine monoclonal antibody (moxetumomab) covalently linked to a cytotoxic bacterial protein toxin (Pseudomonas exotoxin [PE38]).
Produced by recombinant DNA technology in Escherichia coli.
Following binding to CD22-expressing tumor cells, the resultant complex is internalized by the cell and the bacterial toxin PE38 then inactivates adenosine diphosphate (ADP)-ribosylation of elongation factor 2 causing inhibition of protein synthesis and subsequent apoptosis.
In patients with hairy cell leukemia, reduces CD19+ B-cell counts (surrogate marker for peripheral B-cells) by 89% on day 8 of the first treatment cycle. Decreased B-cell counts persist for ≥1 month following discontinuance of drug.
Reduces median CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and CD16+/CD56 natural killer cell counts by 21, 20, 23, and 47%, respectively, on day 8 of first treatment cycle and returns to or remains above baseline values on day 29 and thereafter.
Advice to Patients
Importance of advising patients to read the manufacturer's medication guide before beginning treatment and each time moxetumomab pasudotox-tdfk is administered.
Risk of capillary leak syndrome. Importance of informing clinician immediately if manifestations of capillary leak syndrome (e.g., hypotension, generalized edema, dyspnea, rapid weight gain) occur.
Risk of hemolytic uremic syndrome. Importance of monitoring blood chemistries frequently. Importance of informing clinician immediately if manifestations of hemolytic uremic syndrome (e.g., decreased urination, hematuria, unusual bleeding or bruising, stomach pain, vomiting, fever, fatigue, mood or behavior changes, confusion, seizures, difficulty breathing, tachycardia) occur. Importance of advising patients to maintain adequate hydration during moxetumomab pasudotox therapy. (See General under Dosage and Administration.)
Risk of infusion-related reactions. Importance of informing clinician immediately if signs or symptoms of such reactions, including fever, chills, difficulty breathing, wheezing, cough, dizziness, flushing, tachycardia, headache, BP changes, muscle pain, nausea, or vomiting, occur during infusion of moxetumomab pasudotox-tdfk.
Risk of renal impairment. Importance of informing clinician if changes in urination occur.
Risk of electrolyte abnormalities (e.g., hypokalemia). Importance of informing clinician immediately if symptoms of electrolyte abnormalities (e.g., seizure, irregular or fast heartbeat, muscle cramping, paresthesia, nausea) occur.
Risk of fetal harm. Necessity of advising women of reproductive potential that they should use an effective method of contraception while receiving the drug and for at least 30 days after the last dose of the drug. Importance of women informing clinicians if they are or plan to become pregnant. If pregnancy occurs, advise pregnant women of potential risk to the fetus.
Importance of advising women to avoid breast-feeding during moxetumomab pasudotox therapy.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., renal impairment).
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
For injection, for IV infusion only
AHFS DI Essentials™. © Copyright 2021, Selected Revisions March 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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