Version May 2024
Hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), has been reported in association with the use of gemtuzumab ozogamicin as a single agent, and as part of a combination chemotherapy regimen. Monitor frequently for signs and symptoms of VOD after treatment with gemtuzumab ozogamicin.
Note: Premedicate with acetaminophen 650 mg orally and diphenhydramine 50 mg orally or IV 1 hour prior to gemtuzumab ozogamicin infusion, and methylprednisolone 1 mg/kg (or equivalent) orally or IV within 30 minutes prior to infusion. Additional acetaminophen and diphenhydramine doses may be administered every 4 hours if needed. Repeat methylprednisolone (or equivalent) dose for any sign of infusion-related reaction (eg, fever, chills, hypotension, dyspnea) during or within 4 hours of the infusion. Institute appropriate measures to prevent tumor lysis syndrome.
Cytoreduction is recommended prior to gemtuzumab ozogamicin administration if hyperleukocytosis (leukocyte count >30,000/mm3) is present.
Acute myeloid leukemia, CD33-positive, newly diagnosed de novo: IV:
Combination therapy: Note: A treatment course consists of 1 induction cycle and 2 consolidation cycles (in combination with chemotherapy).
Induction: 3 mg/m2 (maximum: 4.5 mg/dose) on days 1, 4, and 7 (in combination with daunorubicin and cytarabine). If a second induction cycle is required, do NOT administer gemtuzumab ozogamicin during that second induction cycle.
Consolidation (2 cycles): 3 mg/m2 (maximum: 4.5 mg/dose) on day 1 (in combination with daunorubicin and cytarabine).
Single-agent regimen: Note: A treatment course consists of 1 induction cycle and up to 8 cycles of continuation therapy.
Induction: 6 mg/m2 on day 1 (no maximum dose) followed by 3 mg/m2 (no maximum dose) on day 8 (as monotherapy).
Continuation: 2 mg/m2 (no maximum dose) on day 1 every 4 weeks (as monotherapy) for up to 8 continuation cycles.
Off-label dose: Favorable cytogenetics: Adults <60 years of age: 3 mg/m2 on day 1 of course 1 (in combination with induction chemotherapy) and on day 1 of course 3 (in combination with chemotherapy) (Ref).
Acute myeloid leukemia, CD33-positive, relapsed/refractory: IV: 3 mg/m2 (maximum: 4.5 mg/dose) on days 1, 4, and 7 (as monotherapy); treatment consists of a single course of therapy.
Acute promyelocytic leukemia (off-label use): IV:
Single-agent therapy (relapsed disease): 6 mg/m2 on days 1 and 15; for patients testing PCR negative after 2 doses, a third dose was administered (Ref).
Combination therapy (high-risk patients with newly diagnosed disease) (Ref):
Induction: 9 mg/m2 as a single dose on day 1 (in combination with arsenic trioxide and tretinoin).
Post remission therapy (if arsenic trioxide or tretinoin discontinued due to toxicity): 9 mg/m2 once every 4 to 5 weeks until 28 weeks after complete remission.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, CrCl 30 to 89 mL/minute had no clinically significant effects on the pharmacokinetics.
CrCl 15 to 29 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Preexisting impairment:
Mild impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, mild hepatic impairment had no clinically significant effects on the pharmacokinetics.
Moderate (total bilirubin >1.5 to 3 times ULN) and severe (total bilirubin >3 times ULN) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment: Total bilirubin >2 times ULN or AST and/or ALT >2.5 times ULN: Delay gemtuzumab ozogamicin until recovery of total bilirubin to ≤2 times ULN and AST and ALT to ≤2.5 times ULN prior to each dose. Omit scheduled dose if delayed more than 2 days between sequential infusions.
Veno-occlusive disease (VOD): Discontinue gemtuzumab ozogamicin.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref). Note: Some indications have maximum recommended doses (refer to "Dosing: Adult").
Hematologic toxicity (when administering gemtuzumab ozogamicin in combination with chemotherapy):
Persistent thrombocytopenia: If platelet count does not recover to ≥100,000/mm3 within 14 days following the anticipated start date of the consolidation cycle (14 days after hematologic recovery following previous cycle), discontinue gemtuzumab ozogamicin (do not administer gemtuzumab ozogamicin during the consolidation cycles).
Persistent neutropenia: If neutrophil count does not recover to >500/mm3 within 14 days following the anticipated start date of the consolidation cycle (14 days after hematologic recovery following previous cycle), discontinue gemtuzumab ozogamicin (do not administer gemtuzumab ozogamicin during the consolidation cycles).
Nonhematologic toxicity (when administering gemtuzumab ozogamicin either as monotherapy or in combination with chemotherapy):
Infusion-related reactions: Interrupt the infusion and initiate appropriate medical and supportive care management; administer acetaminophen, diphenhydramine, and/or methylprednisolone, if needed. Provide supportive care measures as needed. Upon symptom resolution, consider resuming the infusion at no more than half the rate at which the reaction occurred; repeat in the event of symptom recurrence. Permanently discontinue gemtuzumab ozogamicin for severe or life-threatening infusion reactions.
Severe bleeding or hemorrhage: May require treatment delay or permanent discontinuation.
Veno-occlusive disease, also known as sinusoidal obstruction syndrome: Discontinue gemtuzumab ozogamicin.
Other severe or life-threatening toxicities: Delay gemtuzumab ozogamicin treatment until recovery to a severity of no more than mild; omit scheduled dose if delayed more than 2 days between sequential infusions.
Refer to adult dosing.
(For additional information see "Gemtuzumab ozogamicin: Pediatric drug information")
Note: Premedicate with oral acetaminophen 15 mg/kg (maximum dose: 650 mg/dose) and oral or IV diphenhydramine 1 mg/kg (maximum dose: 50 mg/dose) 1 hour prior to infusion and oral or IV methylprednisolone 1 mg/kg 30 minutes prior to infusion. Additional acetaminophen and diphenhydramine doses may be administered every 4 hours if needed. Repeat methylprednisolone (or equivalent corticosteroid) dose for any sign of infusion-related reaction (eg, fever, chills, hypotension, dyspnea) during or within 4 hours of the infusion. Dosing presented as mg/kg and mg/m2; use precaution. Antiemetics may be recommended to prevent nausea and vomiting; in pediatrics, doses of 3 to 9 mg/m2 are associated with a moderate emetic potential (Ref).
Cytoreduction is recommended prior to gemtuzumab ozogamicin administration if hyperleukocytosis (leukocyte count >30,000/mm3) is present; in pediatric protocols, conventional chemotherapy is typically administered several days (3 to 7) before gemtuzumab dose to achieve hematologic targets.
Acute myeloid leukemia, CD33-positive, newly diagnosed de novo :
Infants, Children, and Adolescents:
Induction: Note: Use in combination with standard chemotherapy; in AAML0531, gemtuzumab was administered on day 6 and used in combination therapy with cytarabine, daunorubicin, and etoposide; no gemtuzumab administered during second induction cycle (Ref).
BSA <0.6 m2: IV: 0.1 mg/kg/dose once.
BSA ≥0.6 m2: IV: 3 mg/m2/dose once.
Intensification course 2: Note: Use in combination with standard chemotherapy; in AAML0531, gemtuzuamb was administered on day 7 and used in combination therapy with cytarabine and mitoxantrone (Ref); assess risk versus benefit prior to administration.
BSA <0.6 m2: IV: 0.1 mg/kg/dose once.
BSA ≥0.6 m2: IV: 3 mg/m2/dose once.
Acute myeloid leukemia, CD33-positive, refractory/relapse:
Manufacturer labeling: Children ≥2 years and Adolescents: IV: 3 mg/m2/dose, administer as a single course of monotherapy on days 1, 4, and 7; maximum dose: 4.5 mg/dose per the manufacturer and based on adult data; however, pediatric protocols do not cap dosing.
Alternate dosing: Limited data available:
Monotherapy (Ref):
Children <3 years: IV: 0.2 mg/kg/dose on days 1 and 15.
Children ≥3 years and Adolescents: IV: 6 mg/m2/dose on days 1 and 15.
Combination therapy (Ref):
Capizzi II regimen: Used in combination with cytarabine and l-asparaginase:
Children <3 years: IV: 0.07 mg/kg/dose on day 3.
Children ≥3 years and Adolescents: IV: 2 mg/m2/dose on day 3.
MA regimen: Used in combination with mitoxantrone and cytarabine.
Children <3 years: IV: 0.1 mg/kg/dose on day 7.
Children ≥3 years and Adolescents: IV: 3 mg/m2/dose on day 7.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Nonhematologic toxicity (when administering gemtuzumab ozogamicin either as monotherapy or in combination with chemotherapy):
Infants, Children, and Adolescents:
Infusion-related reactions: See "Administration: Pediatric."
Severe bleeding or hemorrhage: May require treatment delay or permanent discontinuation.
Other severe or life-threatening toxicities: Delay gemtuzumab ozogamicin treatment until recovery to a severity of no more than mild; omit scheduled dose if delayed more than 2 days between sequential infusions.
Hematologic toxicity (when administering gemtuzumab ozogamicin in combination with chemotherapy):
Infants, Children, and Adolescents:
Persistent thrombocytopenia: Prior to each cycle, delay therapy until platelet count ≥75,000/mm3; if platelet count does not recover to ≥75,000/mm3, discontinue gemtuzumab in subsequent induction or intensification cycles.
Persistent neutropenia: Prior to each cycle, delay therapy until neutrophil count ≥1,000/mm3; if neutrophil count does not recover to ≥1,000/mm3, discontinue gemtuzumab in subsequent induction or intensification cycles.
Infants, Children, and Adolescents:
CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, data has shown that creatinine clearance in this range has no clinically significant effect on the pharmacokinetic profile.
CrCl 15 to 29 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Infants, Children, and Adolescents:
Baseline hepatic impairment:
Mild impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, mild hepatic impairment had no clinically significant effects on the pharmacokinetics.
Moderate (total bilirubin >1.5 to 3 times ULN) and severe (total bilirubin >3 times ULN) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment :
For total bilirubin >2 times ULN or AST and/or ALT >2.5 times ULN: Delay gemtuzumab ozogamicin until recovery of total bilirubin to ≤2 times ULN and AST and ALT to ≤2.5 times ULN prior to each dose. Omit scheduled dose if delayed more than 2 days between sequential infusions.
Veno-occlusive disease (VOD): Discontinue gemtuzumab ozogamicin.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Cardiotoxicity (28%)
Dermatologic: Skin rash (16%)
Endocrine & metabolic: Endocrine disease (metabolic: 16%)
Gastrointestinal: Constipation (21%), nausea and vomiting (21%), stomatitis (21%; grade 3: 4%)
Hematologic & oncologic: Febrile neutropenia (18%; grades ≥3: 18%), hemorrhage (23% to 25%; grades ≥3: 7% to 13%)
Hepatic: Hepatotoxicity (51%), increased serum alanine aminotransferase (16%), increased serum aspartate aminotransferase (40%)
Infection: Infection (42% to 44%), sepsis (grade 3: 32%)
Nervous system: Fatigue (46%), headache (19%)
Miscellaneous: Fever (79%)
1% to 10%:
Cardiovascular: Tachycardia (grade 3: 2%)
Gastrointestinal: Diarrhea (grade 3: 2%)
Hepatic: Hyperbilirubinemia (7%)
Nervous system: Pain (grade 3: 4%)
Renal: Nephrotoxicity (6%)
Respiratory: Pneumonia (grade 3: 7%), pulmonary edema (grade 3: 2%)
Frequency not defined:
Hepatic: Hepatic sinusoidal obstruction syndrome
Hypersensitivity: Severe infusion related reactions
Postmarketing:
Gastrointestinal: Neutropenic enterocolitis
Genitourinary: Hemorrhagic cystitis
Respiratory: Interstitial pneumonitis, pneumonia due to Pneumocystis jirovecii, pulmonary infection (fungal infection and bacterial infection, including Stenotrophomonas)
Hypersensitivity to gemtuzumab ozogamicin or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: Gemtuzumab ozogamicin is myelosuppressive, and prolonged thrombocytopenia (>42 days post dose) has been reported. Monitor blood counts prior to each dose (and frequently after therapy completion) until resolution of cytopenias. Provide supportive care per standard practice as clinically indicated.
• Hemorrhage: Life-threatening or fatal hemorrhage due to prolonged thrombocytopenia may occur with gemtuzumab ozogamicin therapy. Over 90% of patients in a clinical study experienced thrombocytopenia, with 20% experiencing grade 3 or 4 toxicity. Fatal bleeding events included cerebral, intracranial, and subdural hematomas. Monitor platelet counts prior to each dose and until resolution of cytopenias; monitor for signs/symptoms of bleeding and provide supportive care as clinically indicated. In addition to supportive care, severe bleeding, hemorrhage, or persistent thrombocytopenia may require treatment delay or permanent discontinuation.
• Hepatotoxicity: [US Boxed Warning]: Hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), has been reported in association with the use of gemtuzumab ozogamicin as a single agent and as part of a combination chemotherapy regimen. Monitor frequently for signs and symptoms of VOD after treatment with gemtuzumab ozogamicin. In a study in adults, the median time to VOD onset was 9 days (range: 2 to 298 days); some events occurred within 28 days of any dose, and 1 case occurred more than 28 days after the last dose. The risk for VOD may be higher in adults who receive higher gemtuzumab ozogamicin doses (as monotherapy), in patients with moderate to severe baseline hepatic impairment, in patients receiving gemtuzumab ozogamicin after hematopoietic stem cell transplant (HSCT), and in patients who receive HSCT after treatment with gemtuzumab ozogamicin. Although no relationship was found between the incidence of VOD and the time of HSCT relative to higher gemtuzumab ozogamicin doses, one clinical study recommended an interval of 2 months between the last gemtuzumab ozogamicin dose and transplant. In pediatric patients, VOD was observed with higher doses of gemtuzumab (Parigger 2016) and in patients undergoing HSCT, VOD presented within 30 days post-HSCT in most cases, which is similar to observations in adult patients; a decreased risk of VOD was observed with an interval >3 months between last gemtuzumab dose and transplant (Arceci 2005; Wadleigh 2003). Signs/symptoms of VOD include rapid weight gain, ascites, hepatomegaly (may be painful), and bilirubin/transaminase elevations. Monitor ALT, AST, total bilirubin, and alkaline phosphatase prior to each dose; more frequent monitoring of liver function tests and clinical symptoms is recommended in patients who develop abnormal liver function tests during therapy. Patients proceeding to HSCT after gemtuzumab ozogamicin therapy should also be monitored closely and frequently for liver function abnormalities. Hepatotoxicity may require dose interruption or therapy discontinuation.
• Hypersensitivity/infusion reaction: Severe hypersensitivity reactions (including anaphylaxis) and other infusion-related reactions may occur within 24 hours of infusion; may be life-threatening or fatal. Infusion-related symptoms may include fever, chills, hypotension, tachycardia, hypoxia, and/or respiratory failure. Premedicate prior to each gemtuzumab ozogamicin dose with acetaminophen, diphenhydramine, and methylprednisolone; monitor vital signs frequently throughout infusion. Immediately interrupt infusion if infusion-related reactions develop (particularly dyspnea, bronchospasm, or hypotension). Monitor during and for at least 1 hour post-infusion or until signs/symptoms resolve completely. Discontinue permanently for anaphylaxis, including severe respiratory symptoms or clinically significant hypotension.
• QT interval prolongation: Prolongation of the QT interval has been reported in patients treated with other calicheamicin-containing medications. Obtain ECGs and monitor electrolytes prior to therapy initiation and as clinically needed when administering gemtuzumab ozogamicin to patients with a history of (or predisposition for) QTc prolongation, who are taking medications known to prolong the QT interval, and in those with electrolyte disturbances.
• Tumor lysis syndrome: Tumor lysis syndrome (including renal failure) may occur as a consequence of leukemia treatment, adequate hydration and prophylactic antihyperuricemic medication must be instituted prior to use.
Disease-related concerns:
• Acute myeloid leukemia with high-risk cytogenetics: In a subgroup analysis, standard combination chemotherapy in combination with gemtuzumab ozogamicin did not improve event-free survival in patients with high-risk cytogenetics. Consider risk versus benefit of continuing treatment with gemtuzumab ozogamicin in combination with chemotherapy in these patients.
• Hyperleukocytosis: Cytoreduction is recommended prior to gemtuzumab ozogamicin administration if hyperleukocytosis (leukocyte count ≥30,000/mm3) is present.
Special populations:
• Older adult: When gemtuzumab ozogamicin was used as a single agent, patients ≥65 years of age with relapsed or refractory acute myeloid leukemia experienced a higher rate of fever and severe infections.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Mylotarg: 4.5 mg (1 ea) [contains dextran 40]
No
Solution (reconstituted) (Mylotarg Intravenous)
4.5 mg (per each): $11,700.37
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Mylotarg: 4.5 mg (1 ea) [contains dextran 40]
In Canada, gemtuzumab is available through a special access program (access information is available from Health Canada).
IV: Infuse over 2 hours through a 0.2-micron polyethersulfone in-line filter and infusion set made of PVC with DEHP, PVC non-DEHP, polyethylene, or polyurethane. Protect IV bag from light during infusion using a light-blocking cover (infusion line does not need to be protected from light). Do not administer as IV push or bolus.
Premedicate with acetaminophen, diphenhydramine, and methylprednisolone prior to each infusion (see Dosing). Monitor for infusion reactions during and for at least 1 hour after the end of infusion. If infusion reaction occurs, interrupt infusion and initiate appropriate management. Upon symptom resolution, consider resuming the infusion at no more than half the rate at which the reaction occurred; repeat in the event of symptom recurrence (discontinue for severe or life-threatening infusion reaction).
Do not mix or administer with other medications.
Note: Antiemetics may be recommended to prevent nausea and vomiting; in pediatrics, doses of 3 to 9 mg/m2 are associated with a moderate emetic potential (Ref). Stable for 6 hours at room temperature; if refrigerated, consider time for room temperature equilibration and the infusion duration. Premedicate with oral acetaminophen (15 mg/kg; maximum dose: 650 mg/dose) and oral or IV diphenhydramine (1 mg/kg; maximum dose: 50 mg/dose) administered 1 hour prior to infusion and oral or IV methylprednisolone (1 mg/kg) administered 30 minutes prior to infusion. Additional acetaminophen and diphenhydramine doses may be administered every 4 hours if needed.
Parenteral:
IV: After premedication, infuse over 2 hours through a 0.2-micron polyethersulfone (PES) in-line filter and infusion set made of PVC with DEHP, PVC non-DEHP, polyethylene, or polyurethane. Protect IV infusion container (eg, bag, syringe) from light during infusion using a light-blocking cover (infusion line does not need to be protected from light). Do not administer as IV push or bolus. Monitor for infusion reactions during and for at least 1 hour after the end of infusion. Do not mix or administer with other medications.
Infusion-related reactions: Interrupt the infusion and initiate appropriate medical and supportive care management; administer acetaminophen, diphenhydramine, and/or methylprednisolone, if needed. Upon symptom resolution, consider resuming the infusion at no more than half the rate at which the reaction occurred; repeat infusion interruption in the event of symptom recurrence. Permanently discontinue gemtuzumab ozogamicin for severe or life-threatening infusion reactions.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Acute myeloid leukemia, CD33-positive, newly diagnosed de novo: Treatment of newly diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients ≥1 month of age.
Acute myeloid leukemia, CD33-positive, relapsed/refractory: Treatment of relapsed or refractory CD33-positive AML in adults and pediatric patients ≥2 years of age.
Acute promyelocytic leukemia
Gemtuzumab ozogamicin may be confused with gemcitabine, inotuzumab ozogamicin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment and for at least 6 months after the last gemtuzumab ozogamicin dose. Males with female partners of reproductive potential should use effective contraception during therapy and for at least 3 months after the last gemtuzumab ozogamicin dose.
Based on the mechanism of action and data animal reproduction studies, in utero exposure to gemtuzumab ozogamicin may cause fetal harm.
It is not known if gemtuzumab ozogamicin is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 1 month after the last gemtuzumab ozogamicin dose.
Monitor liver function tests (ALT, AST, total bilirubin, and alkaline phosphatase) prior to each dose, and more frequently if clinically indicated, particularly if veno-occlusive disease (VOD) is suspected and/or in HSCT patients; blood counts frequently (before each dose and at least 3 times per week through recovery from treatment-related toxicities); serum chemistries at least 3 times per week through recovery from treatment-related toxicities; electrolytes. Verify pregnancy status in women of reproductive potential prior to therapy initiation. Obtain ECG prior to therapy initiation and as clinically needed when administering to patients with a history of (or predisposition for) QTc prolongation, who are taking medications known to prolong the QT interval, and in those with electrolyte disturbances.
The American Society of Clinical Oncology hepatitis B virus screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Monitor during and for at least 1 hour after the end of infusion for infusion-related reactions. Monitor for signs and symptoms of VOD (rapid weight gain, hepatomegaly, ascites), signs/symptoms of bleeding or hemorrhage, and tumor lysis syndrome.
Gemtuzumab ozogamicin is a humanized CD-33 directed monoclonal antibody-drug conjugate, which is composed of the IgG4 kappa antibody gemtuzumab linked to a cytotoxic calicheamicin derivative. CD33 is expressed on leukemic cells in over 80% of patients with AML (Castaigne 2012). Gemtuzumab ozogamicin binds to the CD33 antigen, resulting in internalization of the antibody-antigen complex. Following internalization, the calicheamicin derivative is released inside the myeloid cell. The calicheamicin derivative binds to DNA resulting in double strand breaks, inducing cell cycle arrest and apoptosis.
Distribution: Antibody portion: ~21.4 L
Protein binding: Calicheamicin: ~97% to human plasma proteins
Metabolism: Calicheamicin is extensively metabolized, primarily through nonenzymatic reduction of the disulfide moiety
Half-life elimination: Based on a 9 mg/m2 dose: Antibody portion: 62 hours (after first dose); 90 hours (after second dose)
Excretion: Clearance: Based on a 9 mg/m2 dose: Antibody portion: 0.35 L/hour (after first dose); 0.15 L/hour (after second dose)
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