INDICATION
ELITEK is indicated for the initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid. ELITEK is indicated only for a single course of treatment.
IMPORTANT SAFETY INFORMATION
WARNING: HYPERSENSITIVITY REACTIONS, HEMOLYSIS, METHEMOGLOBINEMIA, AND INTERFERENCE WITH URIC ACID MEASUREMENTS
- Hypersensitivity Reactions: ELITEK can cause serious and fatal hypersensitivity reactions including anaphylaxis. Immediately and permanently discontinue ELITEK in patients who experience a serious hypersensitivity reaction.
- Hemolysis: Do not administer ELITEK to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Immediately and permanently discontinue ELITEK in patients developing hemolysis. Screen patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to starting ELITEK.
- Methemoglobinemia: ELITEK can result in methemoglobinemia in some patients. Immediately and permanently discontinue ELITEK in patients developing methemoglobinemia.
- Interference with Uric Acid Measurements: ELITEK enzymatically degrades uric acid in blood samples left at room temperature. Collect blood samples in pre-chilled tubes containing heparin and immediately immerse and maintain sample in an ice water bath. Assay plasma samples within 4 hours of collection.
- Among the 347 (265 pediatric; 82 adult) patients for whom all adverse reactions (ARs) regardless of severity were assessed in Studies 1, 2 and 3, as well as an uncontrolled safety trial, the most frequently observed ARs (incidence ≥10%) were vomiting (50%), fever (46%), nausea (27%), headache (26%), abdominal pain (20%), constipation (20%), diarrhea (20%), mucositis (15%), and rash (13%).
- Among the 275 adult patients in Study 4, hypersensitivity reactions occurred in 4.3% of patients treated with ELITEK alone and 1.1% of patients treated with the ELITEK/oral allopurinol combination. Hypersensitivity reactions included arthralgia, injection site irritation, peripheral edema, and rash. The most common Grade 3 or 4 ARs regardless of relationship to study drug in the 3 arms of Study 4 (ELITEK alone; ELITEK combined with oral allopurinol; oral allopurinol alone) were sepsis (5.4%; 6.5%; 4.4%), hypophosphatemia (4.3%; 6.5%; 6.6%), anxiety (3.3%; 0%; 0%), abdominal pain (3.3%; 4.3%; 2.2%), hyperbilirubinemia (3.3%; 2.2%; 4.4%), and increased alanine aminotransferase (3.3%; 4.3%; 2.2%), respectively.
- The following serious ARs occurred with a difference in incidence of greater than or equal to 2% in patients receiving ELITEK compared to patients receiving oral allopurinol in randomized studies (Study 1 and Study 4): pulmonary hemorrhage, respiratory failure, supraventricular arrhythmias, ischemic coronary artery disorders, and abdominal and gastrointestinal infections.
Please see full Prescribing Information, including Boxed WARNING.
INDICATION
JEVTANA is a microtubule inhibitor indicated in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing regimen.
IMPORTANT SAFETY INFORMATION
WARNING: NEUTROPENIA AND HYPERSENSITIVITY
- Neutropenic deaths have been reported. Obtain frequent blood counts to monitor for neutropenia. JEVTANA is contraindicated in patients with neutrophil counts of ≤1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.
- Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of the JEVTANA infusion and administration of appropriate therapy. Patients should receive premedication. JEVTANA is contraindicated in patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80.
CONTRAINDICATIONS
JEVTANA is contraindicated in patients with neutrophil counts of ≤1,500/mm3, patients with a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80, patients with severe hepatic impairment (total bilirubin >3x upper limit of normal (ULN)), and in pregnant women (JEVTANA can cause fetal harm and potential loss of pregnancy).
WARNINGS AND PRECAUTIONS
Bone Marrow Suppression (BMS): BMS manifested as neutropenia, anemia, thrombocytopenia and/or pancytopenia may occur. Neutropenic deaths have been reported. Monitor blood counts frequently to determine if initiation of G-CSF and/or dosage modification is needed. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features. Monitoring of complete blood counts is essential on a weekly basis during cycle 1 and before each treatment cycle thereafter so that the dose can be adjusted if needed. Caution is recommended in patients with hemoglobin <10 g/dl.
Increased Toxicities in Elderly Patients: Patients ≥65 years of age were more likely to experience fatal outcomes not related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia. Monitor closely.
Hypersensitivity Reactions: Severe hypersensitivity reactions can occur. Premedicate all patients with antihistamines, corticosteroids and H2 antagonists prior to JEVTANA. Observe patients closely, especially during the first and second infusions. Discontinue JEVTANA immediately if severe hypersensitivity occurs and treat as indicated.
Gastrointestinal (GI) Adverse Reactions: Nausea, vomiting and severe diarrhea may occur. Death related to diarrhea and electrolyte imbalance occurred in the clinical trial and mortality related to diarrhea has been reported. Intensive measures may be required for severe diarrhea and electrolyte imbalance. Rehydrate and treat with antiemetics and antidiarrheals as needed. If experiencing grade ≥3 diarrhea, dosage should be modified.
GI hemorrhage and perforation, ileus, enterocolitis, neutropenic enterocolitis, including fatal outcome, have been reported. Risk may be increased with neutropenia, age, steroid use, concomitant use of NSAIDs, antiplatelet therapy or anticoagulants, and prior history of pelvic radiotherapy, adhesions, ulceration and GI bleeding. Abdominal pain and tenderness, fever, persistent constipation, diarrhea, with or without neutropenia, may be early manifestations of serious GI toxicity and should be evaluated and treated promptly. JEVTANA treatment delay or discontinuation may be necessary.
Renal Failure: Cases, including those with fatal outcomes, have been reported. Identify cause and manage aggressively.
Urinary Disorders including Cystitis: Cystitis, radiation cystitis, and hematuria, including that requiring hospitalization, has been reported with JEVTANA in patients who previously received pelvic radiation. Cystitis from radiation recall may occur late in treatment with JEVTANA. Monitor patients who previously received pelvic radiation for signs and symptoms of cystitis while on JEVTANA. Interrupt or discontinue JEVTANA in patients experiencing severe hemorrhagic cystitis. Medical and/or surgical supportive treatment may be required to treat severe hemorrhagic cystitis.
Respiratory Disorders: Interstitial pneumonia/pneumonitis, interstitial lung disease and acute respiratory distress syndrome have been reported and may be associated with fatal outcome. Patients with underlying lung disease may be at higher risk for these events. Acute respiratory distress syndrome may occur in the setting of infection. Interrupt JEVTANA if new or worsening pulmonary symptoms develop. Closely monitor, promptly investigate, and appropriately treat patients receiving JEVTANA. Consider discontinuation. The benefit of resuming JEVTANA treatment must be carefully evaluated.
Use in Patients with Hepatic Impairment: JEVTANA dose should be reduced for patients with mild (total bilirubin >1 to ≤1.5 x ULN or AST >1.5 x ULN) and moderate (total bilirubin >1.5 to ≤3.0 x ULN and any AST) hepatic impairment, based on tolerability data in these patients. Administer JEVTANA 20 mg/m2 for mild hepatic impairment. Administer JEVTANA 15 mg/m2 for moderate hepatic impairment. Monitor closely.
ADVERSE REACTIONS (ARs)
Deaths due to causes other than disease progression within 30 days of last JEVTANA dose were reported in 22 (3.8%) patients in the 20 mg/m2 arm and 32 (5.4%) patients in the 25 mg/m2 arm. The most common fatal ARs were related to infections, and these occurred more commonly with 25 mg/m2(n=15) vs. 20 mg/m2 (n=8).
The most common 1-4 grade ARs and laboratory abnormalities (≥10%) with JEVTANA 20 mg/m2 or 25 mg/m2 were neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, and anorexia.
Grade 3-4 ARs occurring ≥5% more commonly with 25 mg/m2 versus 20 mg/m2 were leukopenia, neutropenia, and febrile neutropenia.
Please see full Prescribing Information, including Boxed WARNING.
INDICATION
ZALTRAP®, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for
patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed
following an oxaliplatin-containing regimen.
IMPORTANT SAFETY INFORMATION
WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, COMPROMISED WOUND HEALING
Severe and sometimes fatal hemorrhage, including gastrointestinal (GI) hemorrhage, has been reported in the patients who have received ZALTRAP in combination with FOLFIRI. Monitor patients for signs and symptoms of GI bleeding and other severe bleeding. Do not administer ZALTRAP to patients with severe hemorrhage.
GI perforation including fatal GI perforation can occur in patients receiving ZALTRAP. Discontinue ZALTRAP therapy in patients who experience GI perforation.
Severe compromised wound healing can occur in patients receiving ZALTRAP/FOLFIRI. Discontinue ZALTRAP in patients with compromised wound healing. Suspend ZALTRAP for at least 4 weeks prior to elective surgery, and do not resume ZALTRAP for at least 4 weeks following major surgery and until the surgical wound is fully healed.
WARNINGS AND PRECAUTIONS
- Patients treated with ZALTRAP have an increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events.
- Bleeding/hemorrhage (all grades) occurred in 38% of ZALTRAP/FOLFIRI patients vs. 19% of placebo/FOLFIRI patients. Grade 3–4 hemorrhagic events, including GI hemorrhage, hematuria, and post–procedural hemorrhage, occurred in 3% of ZALTRAP/FOLFIRI patients vs. 1% of placebo/FOLFIRI patients. Severe intracranial hemorrhage and pulmonary hemorrhage/hemoptysis including fatal events have occurred in patients receiving ZALTRAP.
- Monitor patients for signs and symptoms of bleeding. Do not initiate ZALTRAP in patients with severe hemorrhage. Discontinue ZALTRAP in patients who develop severe hemorrhage.
- GI perforation including fatal GI perforation can occur in patients receiving ZALTRAP.
- Across three clinical trials (colorectal, pancreatic, and lung cancer), GI perforation (all grades/Grade 3–4) occurred in 0.8% /0.8% of Zaltrap patients and 0.3% /0.2% for placebo patients.
- Monitor patients for signs and symptoms of GI perforation. Discontinue ZALTRAP in patients who experience GI perforation.
- ZALTRAP impairs wound healing in animal models. Grade 3 compromised wound healing occurred in 2 patients (0.3%) treated with ZALTRAP/FOLFIRI and none of the patients treated with placebo/FOLFIRI.
- Discontinue ZALTRAP in patients with compromised wound healing.
- Suspend ZALTRAP for at least 4 weeks prior to elective surgery and do not initiate/resume ZALTRAP until at least 4 weeks after major surgery and surgical wound is fully healed.
- For minor surgery such as central venous access port placement, biopsy, and tooth extraction, ZALTRAP may be initiated/resumed once the surgical wound is fully healed.
- Fistula formation involving GI and non–GI sites occurs at a higher incidence in patients treated with ZALTRAP. Fistulas (anal, enterovesical, enterocutaneous, colovaginal, intestinal sites) were reported in 1.5% (9/611) of ZALTRAP/FOLFIRI treated patients and 0.5% (3/605) of placebo/FOLFIRI patients. Grade 3 GI fistula formation occurred in 2 patients treated with Zaltrap (0.3%) and 1 placebo–treated patient (0.2%). Discontinue ZALTRAP therapy in patients who develop fistula.
- An increased risk of Grade 3–4 hypertension has been observed in patients receiving ZALTRAP.
- There is no clinical trial experience administering ZALTRAP to patients with NYHA class III or IV heart failure. In patients with mCRC, Grade 3 hypertension (defined as requiring adjustment in existing anti–hypertensive therapy or treatment with more than one drug) was reported in 1.5% of patients treated with placebo/FOLFIRI and 19% treated with ZALTRAP/FOLFIRI. Grade 4 hypertension (hypertensive crisis) was reported in 1 patient (0.2%) treated with ZALTRAP/FOLFIRI. Of patients treated with ZALTRAP/FOLFIRI who developed Grade 3–4 hypertension, 54% had onset during the first two cycles of treatment.
- Monitor blood pressure at least every two weeks, treat with appropriate anti–hypertensive therapy, and continue monitoring blood pressure regularly during ZALTRAP treatment. Temporarily suspend ZALTRAP until hypertension is controlled, and reduce ZALTRAP dose to 2 mg/kg for subsequent cycles. Discontinue ZALTRAP in patients with hypertensive crisis or hypertensive encephalopathy.
- Arterial thromboembolic events (ATE), including transient ischemic attack, cerebrovascular accident, and angina pectoris, occurred more frequently in patients who have received ZALTRAP. ATE occurred in 2.6% of ZALTRAP/FOLFIRI patients and 1.7% of placebo/FOLFIRI patients. Grade 3–4 events occurred in 11 patients (1.8%) treated with ZALTRAP/FOLFIRI and 4 patients (0.7%) treated with placebo/FOLFIRI. Discontinue ZALTRAP in patients who experience an ATE.
- Severe proteinuria, nephrotic syndrome, and thrombotic microangiopathy (TMA) occurred more frequently in patients treated with ZALTRAP.
- Proteinuria was reported in 62% of ZALTRAP/FOLFIRI patients compared to 41% of placebo/FOLFIRI patients. Grade 3–4 proteinuria occurred in 8% of ZALTRAP/FOLFIRI patients compared to 1% of placebo/FOLFIRI patients. Nephrotic syndrome occurred in 2 patients (0.5%) treated with ZALTRAP/FOLFIRI compared to none of the patients treated with placebo/FOLFIRI. TMA was reported in 3 of 2258 patients with cancer enrolled across completed studies.
- Monitor proteinuria by urine dipstick analysis and/or urinary protein creatinine ratio (UPCR) for the development or worsening of proteinuria. Obtain a 24-hour urine collection in patients with a dipstick of ≥2+ for protein or UPCR ˃1.
- Suspend ZALTRAP when proteinuria ≥2 grams/24 hours and resume ZALTRAP when proteinuria <2 grams/24 hours.
- If recurrent, suspend until proteinuria <2 grams/24hours and then reduce ZALTRAP dose to 2 mg/kg.
- Discontinue ZALTRAP if nephrotic syndrome or TMA develops.
- A higher incidence of neutropenic complications (febrile neutropenia and neutropenic infection) occurred in patients receiving ZALTRAP.
- Grade 3–4 neutropenia occurred in 37% of ZALTRAP/FOLFIRI patients compared to 30% of placebo/FOLFIRI patients. Grade 3–4 febrile neutropenia occurred in 4% of ZALTRAP/FOLFIRI patients compared to 2% of placebo/FOLFIRI patients. Grade 3–4 neutropenic infection/sepsis occurred in 1.5% of ZALTRAP/FOLFIRI patients compared to 1.2% of placebo/FOLFIRI patients.
- Monitor CBC with differential count at baseline and prior to initiation of each cycle of ZALTRAP. Delay administration of ZALTRAP/FOLFIRI until neutrophil count is ≥1.5 x 109/L.
- Incidence of severe diarrhea and dehydration is increased in patients treated with ZALTRAP/FOLFIRI.
- Grade 3–4 diarrhea was reported in 19% of ZALTRAP/FOLFIRI patients compared to 8% of placebo/FOLFIRI patients. Grade 3–4 dehydration was reported in 4% of ZALTRAP/FOLFIRI patients compared to 1% of placebo/FOLFIRI patients.
- The incidence of diarrhea is increased in patients ≥65 years of age compared to patients <65 years of age. Monitor closely.
- RPLS (also known as posterior reversible encephalopathy syndrome) was reported in 0.5% of 3795 patients treated with ZALTRAP monotherapy or in combination with chemotherapy. Confirm diagnosis of RPLS with MRI and discontinue ZALTRAP in patients who develop RPLS. Symptoms usually resolve or improve within days, although some patients have experienced ongoing neurologic sequelae or death.
ADVERSE REACTIONS
- The most common adverse reactions (all grades, ≥20% incidence) reported at a higher incidence (2% or greater between–arm difference) in the ZALTRAP/FOLFIRI arm, in order of decreasing frequency, were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
- The most common Grade 3–4 adverse reactions (≥5%) reported at a higher incidence (2% or greater between–arm difference) in the ZALTRAP/FOLFIRI arm, in order of decreasing frequency, were neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia.
- Infections occurred at a higher frequency in patients receiving ZALTRAP/FOLFIRI (46%, all grades; 12%, Grade 3–4) than in patients receiving placebo/FOLFIRI (33%, all grades; 7%, Grade 3–4), including urinary tract infection, nasopharyngitis, upper respiratory tract infection, pneumonia, catheter site infection, and tooth infection.
- In patients with mCRC, venous thromboembolic events (VTE), consisting primarily of deep venous thrombosis and pulmonary embolism, occurred in 9% of patients treated with ZALTRAP/FOLFIRI and 7% of patients treated with placebo/FOLFIRI.
PREGNANCY AND NURSING MOTHERS
- ZALTRAP should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Females and males of reproductive potential should use highly effective contraception during and up to a minimum of 3 months after the last dose of treatment.
- It is not known whether ZALTRAP is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Please see full Prescribing Information, including Boxed WARNING.
INDICATION
Mozobil (plerixafor injection) is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM).
IMPORTANT SAFETY INFORMATION
- Mozobil is contraindicated in patients with a history of hypersensitivity to Mozobil.
- Anaphylactic shock and serious hypersensitivity reactions, some of which have been life-threatening, have occurred in patients receiving Mozobil. Observe patients for signs and symptoms of hypersensitivity during and after Mozobil administration for at least 30 minutes and until clinically stable. Only administer Mozobil when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions.
- Mozobil may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, Mozobil is not intended for HSC mobilization and harvest in patients with leukemia.
- Mozobil in conjunction with G-CSF increases circulating leukocytes and HSC populations. White blood cell counts should be monitored during treatment.
- Thrombocytopenia has been observed in patients receiving Mozobil. Platelet counts should be monitored in patients who receive Mozobil and then undergo apheresis.
- In patients treated with Mozobil in combination with G-CSF for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
- Postmarketing cases of splenic enlargement and/or rupture have been reported following administration of Mozobil in conjunction with growth factor G-CSF. Individuals receiving Mozobil in combination with G-CSF who report left upper abdominal pain and/or scapular or shoulder pain should be evaluated for splenic integrity.
- Mozobil may cause fetal harm when administered to a pregnant woman. Plerixafor is teratogenic in animals. There are no adequate and well-controlled studies in pregnant women using Mozobil. Advise women of childbearing potential to avoid becoming pregnant while receiving treatment with Mozobil.
- The most common adverse reactions (≥10%) during HSC mobilization and apheresis were: diarrhea (37%), nausea (34%), fatigue (27%), injection site reactions (34%), headache (22%), arthralgia (13%), dizziness (11%), and vomiting (10%). The majority of these adverse reactions were Grade 1 or 2.
Please see full Prescribing Information.
INDICATION
Thymoglobulin® (anti-thymocyte globulin (rabbit)) is indicated for the prophylaxis and treatment of acute rejection in patients receiving a kidney transplant. Thymoglobulin is to be used in conjunction with concomitant immunosuppression.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNOSUPPRESSION. Thymoglobulin should only be used by physicians experienced in immunosuppressive therapy in transplantation.
- Contraindications. Thymoglobulin is contraindicated in patients with a history of allergy or anaphylaxis to rabbit proteins or to any product excipients, or who have active acute or chronic infections which contraindicate any additional immunosuppression.
- Management of Immunosuppression. To prevent over-immunosuppression, physicians may wish to decrease the dose of the maintenance immunosuppression regimen during the period of Thymoglobulin use. Dosing for Thymoglobulin is different from dosing for other ATG products, because protein composition and concentrations vary depending on the source of ATG. Thymoglobulin should be used under strict medical supervision in a hospital setting, and patients should be carefully monitored during the infusion.
- Immune Mediated Reactions. Serious immune-mediated reactions, including anaphylaxis or severe cytokine release syndrome (CRS), have been reported with the use of Thymoglobulin. Fatal anaphylaxis has been reported. If an anaphylactic reaction occurs, the infusion should be terminated immediately.
- Infusion-Associated Reactions. Cases consistent with cytokine release syndrome (CRS) have been reported with rapid infusion rates. CRS is attributed to the release of cytokines by activated monocytes and lymphocytes. Severe acute CRS can cause serious cardiorespiratory events and/or death. Close compliance with the recommended dosage and infusion time may reduce the incidence and severity of infusion-associated reactions (IARs). Slowing the infusion rate may minimize many of these IARs. Reactions at the infusion site may include pain, swelling, and redness of the skin.
- Hematologic Effects. Low counts of platelets and white blood cells (including low counts of lymphocytes and neutrophils) have been identified and are reversible following dose adjustments. Total white blood cell and platelet counts should be monitored.
- Infection and Malignancy. Infections, reactivation of infection, febrile neutropenia, sepsis, malignancies including lymphoproliferative disorders (LPD) and other lymphomas as well as solid tumors have been reported after Thymoglobulin administration in combination with multiple immunosuppressive agents. These events can be fatal.
- Immunization.The safety of immunization with attenuated live vaccines following Thymoglobulin therapy has not been studied; therefore, immunization with attenuated live vaccines is not recommended for patients who have recently received Thymoglobulin.
- Overdosage. Thymoglobulin overdosage may result in leukopenia (including lymphopenia and neutropenia) and/or thrombocytopenia, which can be managed with dose reduction.
- Adverse Reactions. The most common adverse reactions and laboratory abnormalities (incidence >5% higher than comparator) are urinary tract infection, abdominal pain, hypertension, nausea, shortness of breath, fever, headache, anxiety, chills, increased potassium levels in the blood, and low counts of platelets and white blood cells.
- During post-marketing surveillance, arthralgia/myalgia, lymphadenopathy, proteinuria, and decreased oxygen saturation tend to occur 5 to 15 days after Thymoglobulin infusion and are consistent with serum sickness. Symptoms are manageable with corticosteroid treatment.
Please see full Prescribing Information, including Boxed WARNING.
INDICATION
SARCLISA (isatuximab-irfc) is indicated, in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Infusion-related reactions (IRRs) have been observed in 39% of patients treated with SARCLISA. All IRRs started during the first SARCLISA infusion and resolved on the same day in 98% of the cases. The most common symptoms of an IRR included dyspnea, cough, chills, and nausea. The most common severe signs and symptoms included hypertension and dyspnea.
To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone. Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade 1 or 2 reactions, interrupt SARCLISA infusion and provide appropriate medical support. If symptoms improve, restart SARCLISA infusion at half of the initial rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally. In case symptoms do not improve or recur after interruption, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if a grade 3 or higher IRR occurs and institute appropriate emergency medical management.
Neutropenia
SARCLISA may cause neutropenia. Neutropenia (reported as laboratory abnormality) occurred in 96% of patients and grade 3-4 neutropenia occurred in 85% of patients treated with SARCLISA, pomalidomide, and dexamethasone (Isa-Pd). Febrile neutropenia occurred in 12% of patients and neutropenic infections, defined as infection with concurrent grade ≥3 neutropenia, occurred in 25% of patients treated with Isa-Pd. The most frequent neutropenic infections included those of upper respiratory tract (10%), lower respiratory tract (9%), and urinary tract (3%).
Monitor complete blood cell counts periodically during treatment. Consider the use of antibiotics and antiviral prophylaxis during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay SARCLISA dose until neutrophil count recovery to at least 1.0 x 109/L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended.
Second Primary Malignancies
Second primary malignancies were reported in 3.9% of patients in the SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) arm and in 0.7% of patients in the pomalidomide and dexamethasone (Pd) arm, and consisted of skin squamous cell carcinoma (2.6% of patients in the Isa-Pd arm and in 0.7% of patients in the Pd arm), breast angiosarcoma (0.7% of patients in the Isa-Pd arm), and myelodysplastic syndrome (0.7% of patients in the Isa-Pd arm). With the exception of the patient with myelodysplastic syndrome, patients were able to continue SARCLISA treatment. Monitor patients for the development of second primary malignancies.
Laboratory Test Interference
Interference with Serological Testing (Indirect Antiglobulin Test)
SARCLISA binds to CD38 on red blood cells (RBCs) and may result in a false positive indirect antiglobulin test (indirect Coombs test). In ICARIA-multiple myeloma (MM), the indirect antiglobulin test was positive during SARCLISA treatment in 67.7% of the tested patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment. Before the first SARCLISA infusion, conduct blood type and screen tests on SARCLISA-treated patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with SARCLISA has already started, inform the blood bank that the patient is receiving SARCLISA and SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests
SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the accuracy of the determination of complete response in some patients with IgG kappa myeloma protein.
Embryo-Fetal Toxicity
Based on the mechanism of action, SARCLISA can cause fetal harm when administered to a pregnant woman. SARCLISA may cause fetal immune cell depletion and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use an effective method of contraception during treatment with SARCLISA and for at least 5 months after the last dose. The combination of SARCLISA with pomalidomide is contraindicated in pregnant women because pomalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide prescribing information on use during pregnancy.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) were neutropenia (laboratory abnormality, 96% Isa-Pd vs 92% Pd), infusion-related reactions (38% Isa-Pd vs 0% Pd), pneumonia (31% Isa-Pd vs 23% Pd), upper respiratory tract infection (57% Isa-Pd vs 42% Pd), and diarrhea (26% with Isa-Pd vs 19% Pd). Serious adverse reactions occurred in 62% of patients receiving SARCLISA. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients.
USE IN SPECIAL POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with Pd, advise lactating women not to breastfeed during treatment with SARCLISA.
Please see full Prescribing Information.
