Margetuximab-cmkb – Uses, Dosage, Side Effects, Interaction Margetuximab is an Fc-engineered human/mouse chimeric IgG1κ anti-HER2 monoclonal antibody indicated for patients with HER2-positive metastatic breast cancer. The HER2 oncoprotein, the product of the human ERBB2/mouse neu genes, is a member of the HER family of receptor tyrosine kinases that includes the epidermal growth factor receptor (EGFR). Of the various subtypes of breast cancer, HER2-positive breast cancer is characterized by ERBB2 overexpression, a higher grade, a more aggressive phenotype, and a worse prognosis compared to HER2-negative cancer.[rx] The introduction of trastuzumab improved patient outcomes in HER2-positive breast cancer, but notably depended substantially on polymorphisms in the FcγRIIIA/CD16A receptor, whereby low-affinity 158F CD16A variants are associated with shorter progression-free survival and worse patient outcomes.[rx] Margetuximab (formerly MGAH22) is an Fc-engineered human/mouse chimeric anti-HER2 IgG1κ monoclonal antibody derived from the same mouse 4D5 clone that trastuzumab is derived from and is produced in Chinese Hamster Ovary (CHO) culture.[rx] Margetuximab binds to the same epitope on the HER2 extracellular domain and induces the same effects as trastuzumab. However, due to its modified Fc region, margetuximab binds with higher affinity to both CD16A variants and exhibits weaker binding to the inhibitory CD32B Fc receptor, resulting in more efficient antibody-dependent cell-mediated cytotoxicity (ADCC) and increased efficacy compared to trastuzumab. Margextuximab was granted FDA approval on December 16, 2020, and is currently marketed under the trademark MARGENZA™ by MacroGenics, Inc.[rx] Mechanism of action The HER family of transmembrane receptor tyrosine kinases (RTKs) includes the epidermal growth factor receptor (EGFR/HER1), HER2, HER3, and HER4 proteins; HER family members are generally involved in cell proliferation, angiogenesis, cell motility and invasiveness, and resistance to apoptosis.[rx] HER2 is an oncoprotein whose overexpression is observed in breast, gastric, and other cancers.[rx,rx] HER2 undergoes both ligand-independent homodimerization and ligand-dependent heterodimerization with other HER family members, followed by RTK phosphorylation and induction of downstream oncogenic signaling pathways. EGFR/HER2 dimerization promotes EGFR recycling and prolonged signalling while HER2/HER3 dimerization potently stimulates the downstream PI3K/AKT pathway; HER2 homodimerization directly activates the RAS/MAPK pathway and indirectly activates the PI3K/AKT pathway.[rx] The prototypical anti-HER2 therapy is trastuzumab, a monoclonal antibody (mAb) that binds the HER2 extracellular domain. Trastuzumab works through several mechanisms: trastuzumab binding induces receptor internalization and c-CBL-mediated HER2 degradation; effector cell binding to the Fc region of trastuzumab through CD16A results in antibody-mediated cell-dependent cytotoxicity (ADCC); finally, trastuzumab binding dampens HER2 activation, phosphorylation, and subsequent downstream oncogenic signalling.[rx] Despite demonstrated clinical efficacy, trastuzumab efficacy is dependent on polymorphisms in CD16A. Effector cells such as natural killer (NK) cells and macrophages bind to mAbs through Fc receptors such as CD16A (FcγRIIIA), CD32A (FcγRIIA), and the inhibitory CD32B (FcγRIIB). CD16A has both high affinity (with valine at position 158; 158V) and low affinity (158F) variants; patients heterozygous or homozygous for the 158F variant have poorer responses to trastuzumab. Margetuximab is derived from the same mouse 4D5 clone as trastuzumab, but with a modified (MGFc0264) Fc region encoding five amino acid substitutions (L235V, F243L, R292P, Y300L, and P396L) to alter Fc receptor binding. Comparatively, margetuximab exhibits increased binding to both the high affinity (KD of 89 nM vs 415 nM) and low affinity (KD of 161 nM vs 1059 nM) CD16A receptors and decreased binding to the inhibitory CD32B receptor (KD of 437 nM vs 52 nM). This, in turn, increases ADCC and anti-tumour effect, especially in cells expressing lower levels of HER2 and in patients with the lower affinity 158F CD16A variant.[rx,rx] Margetuximab is a chimeric IgG1κ monoclonal antibody (mAb) directed against the extracellular domain of the human epidermal growth factor receptor 2 (HER2) cell-surface protein. Also, margetuximab has an engineered Fc region that alters its affinity for the CD16A and CD32B effector cell receptors resulting in increased antibody-dependent cell-mediated cytotoxicity (ADCC). To date, the exposure-response and time course pharmacodynamic relationships of margetuximab remain incompletely characterized. Although generally well-tolerated, margetuximab carries a risk of infusion-related reactions, including symptoms such as fever, fatigue, nausea, vomiting, headache, tachycardia, hypotension, and cutaneous manifestations such as a rash or urticaria; infusion reactions may require alterations to the infusion or, in serious reactions, discontinuation.[rx] Indications Margetuximab is an anti-HER2 monoclonal antibody indicated, in combination with chemotherapy, for the treatment of metastatic HER2-positive breast cancer in adult patients who have received two or more prior anti-HER2 regimens with at least one prior regimen for metastatic disease.[rx] Metastatic Breast Cancer With HER2 Positive Margetuximab is indicated, in combination with chemotherapy, for the treatment of adults with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. In combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Use in Cancer Margetuximab-cmkb is approved to be used with chemotherapy to treat: Breast cancer is HER2 positive (HER2+) and has metastasized (spread to other parts of the body). It is used in adults who have received two or more anti-HER2 treatments, including at least one for metastatic disease. Margetuximab-cmkb is also being studied in the treatment of other types of cancer. Contraindications Pregnancy Lactation Severe Kidney disease Severe Hepatic disease Anemia, Low Wbc Count Electrolyte Imbalance Dosage Strengths: 25 mg/mL Breast Cancer 15 mg/kg IV every 3 weeks Infuse the initial dose over 120 minutes and subsequent doses over 30 minutes. This drug may be administered immediately after the completion of chemotherapy. Continue treatment until the disease progresses or unacceptable toxicity. All therapeutic proteins, including this drug, have the potential to produce an immune response. Dose Adjustments LEFT VENTRICULAR EJECTION FRACTION (LVEF): Withhold dosing for at least 4 weeks for any of the following: If 16% or greater absolute decrease in LVEF from pretreatment values. LVEF below institutional limits of normal or 50% if no limits are available. If 10% or greater absolute decrease in LVEF from pretreatment values The dosing may be resumed if, within 8 weeks, LVEF returns to normal limits, and a total reduction from baseline is 15% or less. Permanently discontinue if LVEF decline persists for greater than 8 weeks or if dosing is interrupted on greater than 3 occasions for LVEF decline. INFUSION-RELATED REACTIONS (IRRs): For mild or moderate IRRs, decrease the rate of infusion. For dyspnea or clinically significant hypotension, interrupt the infusion. For patients with severe or life-threatening IRRs, permanently discontinue treatment. Administration advice: Administer as an IV infusion after dilution. Infuse initial dose over 120 minutes and subsequent doses over 30 minutes. This drug may be administered immediately after the completion of chemotherapy. Do not administer as an IV push or bolus. Do not mix this drug with other drugs. Do not co-administer other drugs through the same infusion line. If a patient misses a dose, administer the scheduled dose as soon as possible, and then adjust the administration schedule to maintain a 3-week interval between doses. Reconstitution/preparation techniques: The manufacturer product information should be consulted Cardiovascular: Left ventricular dysfunction by echocardiogram or MUGA scan. Immunologic: Monitor or sign and symptoms for infusion-related reactions. Pregnancy: Monitor females who received this drug for oligohydramnios during pregnancy or within 4 months prior to conception. Patient advice: Advise pregnant women and females of reproductive potential that exposure to this drug during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and 4 months after the last dose. Advise female patients to contact their healthcare provider with a known or suspected pregnancy. Advise patients to report immediately any new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness, or loss of consciousness. Side Effects The Most Common headache fatigue nausea diarrhea vomiting constipation loss of appetite stomach pain hair loss pain in hands or feet joint or muscle pain rash with blisters on hands and feet More common Back pain chest pain or tightness chills cough decreased urine output difficulty in moving dilated neck veins fever flushing headache irregular breathing irregular heartbeat muscle aches, cramps, pain, or stiffness nausea and vomiting pain in the joints redness, swelling, pain of the skin scaling of the skin on the hands and feet swelling of the face, fingers, feet, or lower legs swollen joints tingling of the hands and feet trouble breathing ulceration of the skin unusual tiredness or weakness weakness weight gain Rare Arm or leg pain burning, numbness, tingling, or painful sensations constipation decreased appetite diarrhea hair loss, thinning of hair stomach pain unsteadiness or awkwardness weakness in the arms, hands, legs, or feet Drug Interaction DRUG INTERACTION Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Margetuximab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Margetuximab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Margetuximab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Margetuximab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Margetuximab. Amivantamab The risk or severity of adverse effects can be increased when Margetuximab is combined with Amivantamab. Anifrolumab The risk or severity of adverse effects can be increased when Anifrolumab is combined with Margetuximab. Ansuvimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Ansuvimab. Anthrax imm The risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Margetuximab. Antilymphocyte i The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Margetuximab. Antithymocyte imm The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Margetuximab. Articaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Articaine. Asfotase alfa The risk or severity of adverse effects can be increased when Asfotase alfa is combined with Margetuximab. Atezolizumab The risk or severity of adverse effects can be increased when Atezolizumab is combined with Margetuximab. Atoltivimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Atoltivimab. Avelumab The risk or severity of adverse effects can be increased when Avelumab is combined with Margetuximab. Bamlanivimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Bamlanivimab. Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Margetuximab. Belantamab maf The risk or severity of adverse effects can be increased when Margetuximab is combined with Belantamab mafodotin. Belimumab The risk or severity of adverse effects can be increased when Belimumab is combined with Margetuximab. Benralizumab The risk or severity of adverse effects can be increased when Benralizumab is combined with Margetuximab. Benzocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Benzyl alcohol. Besilesomab The risk or severity of adverse effects can be increased when Besilesomab is combined with Margetuximab. Bevacizumab The risk or severity of adverse effects can be increased when Bevacizumab is combined with Margetuximab. Bezlotoxumab The risk or severity of adverse effects can be increased when Bezlotoxumab is combined with Margetuximab. Bimekizumab The risk or severity of adverse effects can be increased when Bimekizumab is combined with Margetuximab. Blinatumomab The risk or severity of adverse effects can be increased when Blinatumomab is combined with Margetuximab. Brentuximab The risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Margetuximab. Brodalumab The risk or severity of adverse effects can be increased when Brodalumab is combined with Margetuximab. Brolucizumab The risk or severity of adverse effects can be increased when Brolucizumab is combined with Margetuximab. Bupivacaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Bupivacaine. Burosumab The risk or severity of adverse effects can be increased when Burosumab is combined with Margetuximab. Butacaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Butacaine. Butamben The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Butamben. Canakinumab The risk or severity of adverse effects can be increased when Canakinumab is combined with Margetuximab. Caplacizumab The risk or severity of adverse effects can be increased when Caplacizumab is combined with Margetuximab. Capromab pendetide The risk or severity of adverse effects can be increased when Capromab pendetide is combined with Margetuximab. Capsaicin The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Capsaicin. Casirivimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Casirivimab. Catumaxomab The risk or severity of adverse effects can be increased when Catumaxomab is combined with Margetuximab. Cemiplimab The risk or severity of adverse effects can be increased when Cemiplimab is combined with Margetuximab. Certolizumab pegol The risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Margetuximab. Cetuximab The risk or severity of adverse effects can be increased when Cetuximab is combined with Margetuximab. Chloroprocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Chloroprocaine. Cilgavimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Cilgavimab. Cinchocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Cinchocaine. Cocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Cocaine. Conj estrogens Conjugated estrogens may increase the thrombogenic activities of Margetuximab. Daratumumab The risk or severity of adverse effects can be increased when Daratumumab is combined with Margetuximab. Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Margetuximab. Daunorubicin The risk or severity of cardiotoxicity can be increased when Margetuximab is combined with Daunorubicin. Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Margetuximab. Dienestrol Dienestrol may increase the thrombogenic activities of Margetuximab. Diethylstilbestrol Diethylstilbestrol may increase the thrombogenic activities of Margetuximab. Digoxin Immune The risk or severity of adverse effects can be increased when Digoxin Immune Fab (Ovine) is combined with Margetuximab. Dinutuximab The risk or severity of adverse effects can be increased when Dinutuximab is combined with Margetuximab. Diphenhydramine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Diphenhydramine. Dostarlimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Dostarlimab. Doxorubicin The risk or severity of cardiotoxicity can be increased when Margetuximab is combined with Doxorubicin. Dulaglutide The risk or severity of adverse effects can be increased when Dulaglutide is combined with Margetuximab. Dupilumab The risk or severity of adverse effects can be increased when Dupilumab is combined with Margetuximab. Durvalumab The risk or severity of adverse effects can be increased when Durvalumab is combined with Margetuximab. Dyclonine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Dyclonine. Ebola Zaire vaccine The therapeutic efficacy of Ebola Zaire vaccine (live, attenuated) can be decreased when used in combination with Margetuximab. Eculizumab The risk or severity of adverse effects can be increased when Eculizumab is combined with Margetuximab. Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Margetuximab. Eflapegrastim The risk or severity of adverse effects can be increased when Margetuximab is combined with Eflapegrastim. Eftrenonacog alfa The risk or severity of adverse effects can be increased when Eftrenonacog alfa is combined with Margetuximab. Elotuzumab The risk or severity of adverse effects can be increased when Elotuzumab is combined with Margetuximab. Emapalumab The risk or severity of adverse effects can be increased when Emapalumab is combined with Margetuximab. Emicizumab The risk or severity of adverse effects can be increased when Emicizumab is combined with Margetuximab. Epirubicin The risk or severity of cardiotoxicity can be increased when Margetuximab is combined with Epirubicin. Eptinezumab The risk or severity of adverse effects can be increased when Eptinezumab is combined with Margetuximab. Erenumab The risk or severity of adverse effects can be increased when Erenumab is combined with Margetuximab. Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Margetuximab. Esterified estrogens Esterified estrogens may increase the thrombogenic activities of Margetuximab. Estetrol Estetrol may increase the thrombogenic activities of Margetuximab. Estradiol Estradiol may increase the thrombogenic activities of Margetuximab. Estradiol acetate Estradiol acetate may increase the thrombogenic activities of Margetuximab. Estradiol benzoate Estradiol benzoate may increase the thrombogenic activities of Margetuximab. Estradiol cypionate Estradiol cypionate may increase the thrombogenic activities of Margetuximab. Estradiol valerate Estradiol valerate may increase the thrombogenic activities of Margetuximab. Estriol Estriol may increase the thrombogenic activities of Margetuximab. Estrone Estrone may increase the thrombogenic activities of Margetuximab. Estrone sulfate Estrone sulfate may increase the thrombogenic activities of Margetuximab. Ethinylestradiol Ethinylestradiol may increase the thrombogenic activities of Margetuximab. Ethyl chloride The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Ethyl chloride. Etidocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Etidocaine. Evolocumab The risk or severity of adverse effects can be increased when Evolocumab is combined with Margetuximab. Fanolesomab The risk or severity of adverse effects can be increased when Fanolesomab is combined with Margetuximab. Fremanezumab The risk or severity of adverse effects can be increased when Fremanezumab is combined with Margetuximab. Galcanezumab The risk or severity of adverse effects can be increased when Galcanezumab is combined with Margetuximab. Gemtuzumab The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Margetuximab. Golimumab The risk or severity of adverse effects can be increased when Golimumab is combined with Margetuximab. Guselkumab The risk or severity of adverse effects can be increased when Guselkumab is combined with Margetuximab. Hepatitis B globulin The risk or severity of adverse effects can be increased when Hepatitis B immune globulin is combined with Margetuximab. H cytom globulin The risk or severity of adverse effects can be increased when Human cytomegalovirus immune globulin is combined with Margetuximab. Human imm G The risk or severity of adverse effects can be increased when Human immunoglobulin G is combined with Margetuximab. Human Rho(D) im The risk or severity of adverse effects can be increased when Human Rho(D) immune globulin is combined with Margetuximab. Ibalizumab The risk or severity of adverse effects can be increased when Ibalizumab is combined with Margetuximab. Ibritumomab tiu The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Margetuximab. Idarubicin The risk or severity of cardiotoxicity can be increased when Margetuximab is combined with Idarubicin. Idarucizumab The risk or severity of adverse effects can be increased when Idarucizumab is combined with Margetuximab. Imdevimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Imdevimab. Inebilizumab The risk or severity of adverse effects can be increased when Inebilizumab is combined with Margetuximab. Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Margetuximab. Inotuzumab o The risk or severity of adverse effects can be increased when Inotuzumab ozogamicin is combined with Margetuximab. Ipilimumab The risk or severity of adverse effects can be increased when Ipilimumab is combined with Margetuximab. Isatuximab The risk or severity of adverse effects can be increased when Isatuximab is combined with Margetuximab. Ixekizumab The risk or severity of adverse effects can be increased when Ixekizumab is combined with Margetuximab. Lanadelumab The risk or severity of adverse effects can be increased when Lanadelumab is combined with Margetuximab. Lecanemab The risk or severity of adverse effects can be increased when Lecanemab is combined with Margetuximab. Levobupivacaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Levobupivacaine. Lidocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Lidocaine. Loncastuximab The risk or severity of adverse effects can be increased when Margetuximab is combined with Loncastuximab tesirine. Maftivimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Maftivimab. Meloxicam The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Meloxicam. Mepivacaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Mepivacaine. Mepolizumab The risk or severity of adverse effects can be increased when Mepolizumab is combined with Margetuximab. Mestranol Mestranol may increase the thrombogenic activities of Margetuximab. Methoxy poly The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Margetuximab. Mirvetuximab The risk or severity of adverse effects can be increased when Mirvetuximab Soravtansine is combined with Margetuximab. Mogamulizumab The risk or severity of adverse effects can be increased when Mogamulizumab is combined with Margetuximab. Mosunetuzumab The risk or severity of adverse effects can be increased when Margetuximab is combined with Mosunetuzumab. Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Margetuximab. Natalizumab The risk or severity of adverse effects can be increased when Natalizumab is combined with Margetuximab. Necitumumab The risk or severity of adverse effects can be increased when Necitumumab is combined with Margetuximab. Nivolumab The risk or severity of adverse effects can be increased when Nivolumab is combined with Margetuximab. Obiltoxaximab The risk or severity of adverse effects can be increased when Obiltoxaximab is combined with Margetuximab. Obinutuzumab The risk or severity of adverse effects can be increased when Obinutuzumab is combined with Margetuximab. Ocrelizumab The risk or severity of adverse effects can be increased when Ocrelizumab is combined with Margetuximab. Odesivimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Odesivimab. Ofatumumab The risk or severity of adverse effects can be increased when Ofatumumab is combined with Margetuximab. Olaratumab The risk or severity of adverse effects can be increased when Olaratumab is combined with Margetuximab. Omalizumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Margetuximab. Oxetacaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Oxetacaine. Oxybuprocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Oxybuprocaine. Palivizumab The risk or severity of adverse effects can be increased when Palivizumab is combined with Margetuximab. Panitumumab The risk or severity of adverse effects can be increased when Panitumumab is combined with Margetuximab. Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Margetuximab. Pembrolizumab The risk or severity of adverse effects can be increased when Pembrolizumab is combined with Margetuximab. Pertuzumab The risk or severity of adverse effects can be increased when Pertuzumab is combined with Margetuximab. Phenol The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Phenol. Plicamycin The risk or severity of cardiotoxicity can be increased when Margetuximab is combined with Plicamycin. Polatuzumab ve The risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Margetuximab. Polyestradiol ph Polyestradiol phosphate may increase the thrombogenic activities of Margetuximab. Pramocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Pramocaine. Prilocaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Prilocaine. Procaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Procaine. Proparacaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Proparacaine. Propoxycaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Propoxycaine. Quinestrol Quinestrol may increase the thrombogenic activities of Margetuximab. Ramucirumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Margetuximab. Ranibizumab The risk or severity of adverse effects can be increased when Ranibizumab is combined with Margetuximab. Ravulizumab The risk or severity of adverse effects can be increased when Ravulizumab is combined with Margetuximab. Raxibacumab The risk or severity of adverse effects can be increased when Raxibacumab is combined with Margetuximab. Reslizumab The risk or severity of adverse effects can be increased when Reslizumab is combined with Margetuximab. Risankizumab The risk or severity of adverse effects can be increased when Risankizumab is combined with Margetuximab. Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Margetuximab. Romosozumab The risk or severity of adverse effects can be increased when Romosozumab is combined with Margetuximab. Ropivacaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Ropivacaine. Sacituzumab g The risk or severity of adverse effects can be increased when Sacituzumab govitecan is combined with Margetuximab. Sarilumab The risk or severity of adverse effects can be increased when Sarilumab is combined with Margetuximab. Secukinumab The risk or severity of adverse effects can be increased when Secukinumab is combined with Margetuximab. Siltuximab The risk or severity of adverse effects can be increased when Siltuximab is combined with Margetuximab. Sotrovimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Sotrovimab. Spesolimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Spesolimab. Sulesomab The risk or severity of adverse effects can be increased when Sulesomab is combined with Margetuximab. Sutimlimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Sutimlimab. Sy Estrogens, A Synthetic Conjugated Estrogens, A may increase the thrombogenic activities of Margetuximab. Estrogens, B Synthetic Conjugated Estrogens, B may increase the thrombogenic activities of Margetuximab. Tafasitamab The risk or severity of adverse effects can be increased when Margetuximab is combined with Tafasitamab. Teplizumab The risk or severity of adverse effects can be increased when Teplizumab is combined with Margetuximab. Tetanus immun The risk or severity of adverse effects can be increased when Tetanus immune globulin, human is combined with Margetuximab. Tetracaine The risk or severity of methemoglobinemia can be increased when Margetuximab is combined with Tetracaine. Tezepelumab The risk or severity of adverse effects can be increased when Margetuximab is combined with Tezepelumab. Tibolone Tibolone may increase the thrombogenic activities of Margetuximab. Tildrakizumab The risk or severity of adverse effects can be increased when Tildrakizumab is combined with Margetuximab. Tisotumab vedotin The risk or severity of adverse effects can be increased when Margetuximab is combined with Tisotumab vedotin. Tixagevimab The risk or severity of adverse effects can be increased when Margetuximab is combined with Tixagevimab. Tocilizumab The risk or severity of adverse effects can be increased when Tocilizumab is combined with Margetuximab. Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Margetuximab. Tralokinumab The risk or severity of adverse effects can be increased when Tralokinumab is combined with Margetuximab. Trastuzumab The risk or severity of adverse effects can be increased when Trastuzumab is combined with Margetuximab. Trastuzumab der The risk or severity of adverse effects can be increased when Trastuzumab deruxtecan is combined with Margetuximab. Trastuzumab The risk or severity of adverse effects can be increased when Trastuzumab emtansine is combined with Margetuximab. Tremelimumab The risk or severity of adverse effects can be increased when Tremelimumab is combined with Margetuximab. Ublituximab The risk or severity of adverse effects can be increased when Ublituximab is combined with Margetuximab. Ustekinumab The risk or severity of adverse effects can be increased when Ustekinumab is combined with Margetuximab. Valrubicin The risk or severity of cardiotoxicity can be increased when Margetuximab is combined with Valrubicin. Vedolizumab The risk or severity of adverse effects can be increased when Vedolizumab is combined with Margetuximab. Pregnancy and Lactation US FDA pregnancy category: Not assigned Pregnancy Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of MARGENZA in pregnant women to inform the drug-associated risk. In postmarketing reports, the use of a HER2- directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In an animal reproduction study, intravenous administration of margetuximab-cmkb to pregnant cynomolgus monkeys once every 3 weeks, starting at gestational day (GD) 20 until delivery, resulted in oligohydramnios and delayed infant kidney development. Animal exposures were ≥ 3 times the human exposures at the recommended dose, based on Cmax. Advise patients of potential risks to a fetus. There are clinical considerations if MARGENZA is used during pregnancy or within 4 months prior to conception. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 – 4% and 15 – 20%, respectively. Lactation There is no information regarding the presence of MARGENZA in human milk, its effects on the breastfed child, or its effects on milk production. Published data suggest human IgG is present in human milk but does not enter neonatal or infant circulation in substantial amounts. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for MARGENZA treatment and any potential adverse effects on the breastfed child from MARGENZA or from the underlying maternal condition. This consideration should also take into account the MARGENZA washout period of 4 months. Why is this medication prescribed? Margetuximab-cmkb is used along with chemotherapy to treat a certain type of breast cancer (HER-2 positive) that has spread to other parts of the body after treatment with at least two other chemotherapy medications. Margetuximab-cmkb is in a class of medications called monoclonal antibodies. It works by stopping the growth of cancer cells. How should this medicine be used? Margetuximab-cmkb comes as a solution to be injected into a vein by a doctor or nurse in a hospital. It is usually given over 120 minutes for the first dose and then over 30 minutes once every 3 weeks (21 days) for the following doses. The length of your treatment will depend on the condition that you have and how well your body responds to treatment. Margetuximab-cmkb may cause serious reactions during the infusion of the medication. A doctor or nurse will monitor you carefully while you are receiving the medication. Tell your doctor or nurse if you experience any of the following during your infusion: fever, chills, joint pain, cough, dizziness, fatigue, nausea, vomiting, headache, sweating, racing heartbeat, hives, rash, itching, or shortness of breath. Call your doctor immediately or get immediate emergency medical attention if you experience any of these symptoms after you leave your doctor’s office or medical facility. Your doctor may slow down your infusion or temporarily or permanently stop your treatment. This depends on how well the medication works for you and the side effects you experience. Be sure to tell your doctor how you are feeling during your treatment with margetuximab-cmkb injection. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient. This medication may be prescribed for other uses; ask your doctor or pharmacist for more information. What special precautions should I follow? Before receiving margetuximab-cmkb injection, tell your doctor and pharmacist if you are allergic to margetuximab-cmkb, any other medications, or any of the ingredients in margetuximab-cmkb injection. Ask your pharmacist for a list of the ingredients. tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or any other medical condition. tell your doctor if you are breastfeeding. You should not breastfeed during your treatment with margetuximab-cmkb and for 4 months after your final dose. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761150s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761150Orig1s000MultidisciplineR.pdf https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-margetuximab-metastatic-her2-positive-breast-cancer https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/761150Orig1s000ltr.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761150Orig1s000RiskR.pdf https://www.cancer.gov/about-cancer/treatment/drugs/margetuximab-cmkb https://pubchem.ncbi.nlm.nih.gov/substance/252166886 https://go.drugbank.com/drugs/DB14967 https://en.wikipedia.org/wiki/Margetuximab https://www.drugs.com/mtm/margetuximab.htm https://medlineplus.gov/druginfo/meds/a621004.html https://www.mayoclinic.org/drugs-supplements/margetuximab-cmkb-intravenous-route/side-effects/drg-20506401 References