Gemtuzumab Ozogamicin

Pronunciation

(gem TOO zoo mab oh zog a MY sin)

U.S. Brand Names

Mylotarg®

Generic Available

Canadian Brand Names

Mylotarg®

Use

Treatment of acute myeloid leukemia (CD33 positive) in first relapse in patients who are

60 years of age and who are not considered candidates for cytotoxic chemotherapy.

Pregnancy Risk Factor

Pregnancy Implications

May cause fetal harm when administered to a pregnant woman. Women of childbearing potential should avoid becoming pregnant while receiving treatment. If used in pregnancy, or if patient becomes pregnant during treatment, the patient should be apprised of potential hazard to the fetus.

Lactation

Excretion in breast milk unknown/not recommended

Contraindications

Hypersensitivity to gemtuzumab ozogamicin, calicheamicin derivatives, or any component of the formulation; patients with anti-CD33 antibody; pregnancy

Warnings/Precautions

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Gemtuzumab has been associated with severe veno-occlusive disease or hepatotoxicity. Risk may be increased by combination chemotherapy, previous hepatic disease, or hematopoietic stem cell transplant.

Infusion-related events are common, generally reported to occur with the first dose at the end of the 2-hour intravenous infusion. These symptoms usually resolved after 2-4 hours with a supportive therapy of acetaminophen, diphenhydramine, and intravenous fluids. Fewer infusion-related events were observed after the second dose. Infusion-related reactions may be severe (including anaphylaxis, pulmonary edema, or ARDS). Symptomatic intrinsic lung disease or high peripheral blast counts may increase the risk of severe reactions. Consider discontinuation in patients who develop severe infusion-related reactions.

Severe myelosuppression occurs in all patients at recommended dosages. Use caution in patients with renal impairment (no clinical experience) and hepatic impairment (no clinical experience in patients with bilirubin >2 mg/dL). Tumor lysis syndrome may occur as a consequence of leukemia treatment, adequate hydration and prophylactic allopurinol must be instituted prior to use. Other methods to lower WBC <30,000 cells/mm³ may be considered (hydroxyurea or leukapheresis) to minimize the risk of tumor lysis syndrome, and/or severe infusion reactions. Postinfusion reactions, which may include fever, chills, hypotension, or dyspnea, may occur during the first 24 hours after administration. Safety and efficacy have not been established in pediatric patients or in patients with poor performance status and organ dysfunction have not been established.

Adverse Reactions

Percentages established in adults >60 years of age. Note: A postinfusion symptom complex (fever, chills, less commonly hypertension, and/or dyspnea) may occur within 24 hours of administration.

>10%:

Cardiovascular: Peripheral edema (21%), hypertension (16%), hypotension (20%)

Central nervous system: Chills (66%), fever (82%), headache (37%), pain (25%), dizziness (11%), insomnia (18%)

Dermatologic: Rash (23%), petechiae (21%), ecchymosis (15%), cutaneous herpes simplex (21%)

Endocrine & metabolic: Hypokalemia (30%)

Gastrointestinal: Nausea (68%), vomiting (58%), diarrhea (38%), anorexia (31%), abdominal pain (29%), constipation (28%), stomatitis/mucositis (25%), abdominal distention (11%), dyspepsia (11%)

Hematologic: Neutropenia (98%; median recovery 40.5 days), thrombocytopenia (99%; median recovery 39 days); anemia (52%), bleeding (15%), lymphopenia

Hepatic: Hyperbilirubinemia (29%), LDH increased (18%), transaminases increased (9% to 18%)

Local: Local reaction (25%)

Neuromuscular & skeletal: Weakness (45%), back pain (18%)

Respiratory: Dyspnea (26%), epistaxis (29%; severe 3%), cough (19%), pharyngitis (14%)

Miscellaneous: Infection (30%), sepsis (24%), neutropenic fever (20%)

1% to 10%:

Cardiovascular: Tachycardia (10%)

Central nervous system: Depression (10%), cerebral hemorrhage (2%), intracranial hemorrhage (2%)

Dermatologic: Pruritus (6%)

Endocrine & metabolic: Hypomagnesemia (4%), hyperglycemia (10%)

Genitourinary: Hematuria (10%; severe 1%), vaginal hemorrhage (7%)

Hematologic: Hemorrhage (8%), disseminated intravascular coagulation (DIC) (2%)

Hepatic: PT increased, veno-occlusive disease (range: 1% to 20% in relapsed patients; higher frequency in patients with prior history of subsequent hematopoietic stem cell transplant)

Neuromuscular & skeletal: Arthralgia (10%)

Respiratory: Rhinitis (10%), hypoxia (6%), pneumonia (10%)

<1% (Limited to important or life-threatening symptoms): Hepatic failure, jaundice, hepatosplenomegaly

Postmarketing and/or case reports: Acute respiratory distress syndrome, anaphylaxis, gastrointestinal hemorrhage, hypersensitivity reactions, noncardiogenic pulmonary edema, renal failure (secondary to tumor lysis syndrome)

Overdosage/Toxicology

Symptoms are unknown. General supportive measures should be instituted. Gemtuzumab ozogamicin is not dialyzable.

Drug Interactions

No formal drug interaction studies have been conducted.

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (due to GI irritation).

Stability

Storage: Light sensitive; protect from light. Store vials under refrigeration 2°C to 8°C (36°F to 46°F). Reconstituted vials may be stored under refrigeration for up to 8 hours.

Reconstitution: Prepare in biologic safety hood with the fluorescent light turned off . Allow to warm to room temperature prior to reconstitution. Reconstitute vial with 5 mL sterile water for injection, USP. Final concentration in vial is 1 mg/mL. Dilute desired dose in 100 mL of 0.9% sodium chloride injection. The resulting I.V. bag should be placed in a UV protectant bag and infused immediately.

Compatibility: No information (infuse via separate line)

Compatibility

No information; infuse via separate line

Mechanism of Action

Antibody to CD33 antigen, which is expressed on leukemic blasts in >80% of patients with acute myeloid leukemia (AML), as well as normal myeloid cells. Binding results 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 and cell death. Pluripotent stem cells and nonhematopoietic cells are not affected.

Pharmacodynamics/Kinetics

Half-life elimination: Calicheamicin: Total: Initial: 45 hours, Repeat dose: 60 hours; Unconjugated: 100 hours (no change noted in repeat dosing)

Dosage

I.V.: Adults

60 years: 9 mg/m² , infused over 2 hours. A full treatment course is a total of two doses administered with 14 days between doses. Full hematologic recovery is not necessary for administration of the second dose. There has been only limited experience with repeat courses of gemtuzumab ozogamicin.

Note: The patient should receive diphenhydramine 50 mg orally and acetaminophen 650-1000 mg orally 1 hour prior to administration of each dose. Acetaminophen dosage should be repeated as needed every 4 hours for two additional doses. Pretreatment with methylprednisolone may ameliorate infusion-related symptoms.

Dosage adjustment in renal impairment: No recommendation (not studied)

Dosage adjustment in hepatic impairment: No recommendation (not studied)

Administration

Administer as infusion only, over at least 2 hours. Do not administer I.V. push (bolus). Infuse through a separate line equipped with a low protein-binding 1.2 micron terminal filter. May be infused peripherally or through a central line. Premedication with acetaminophen and diphenhydramine should be administered prior to each infusion.

Monitoring Parameters

Monitor vital signs during the infusion and for 4 hours following the infusion. Monitor for signs/symptoms of postinfusion reaction. Monitor electrolytes, LFTs, CBC with differential, and platelet counts frequently. Monitor for signs and symptoms of hepatitis reaction (weight gain, right upper quadrant abdominal pain, hepatomegaly, ascites).

Test Interactions

None known

Patient Education

This medication can only be administered intravenously. During infusion you will be closely monitored. You will need frequent laboratory tests during course of therapy. Do not use alcohol, aspirin-containing medications, or any prescription or OTC medications without consulting your prescriber. It is important to maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake, and nutrition (small, frequent meals will help). You will be highly susceptible to infection (avoid crowds and exposure to infection). You may experience nausea or vomiting (small, frequent meals, good mouth care, sucking lozenges or chewing gum may help); contact prescriber if nausea and vomiting persists. Frequent mouth care with a soft toothbrush or soft swabs and avoidance of spicy or salty foods may reduce mouth sores. Report immediately, fever, chills; unusual bleeding or bruising; signs of infection (eg, sore throat, cough, white plaques in mouth or perianal area, burning on urination); respiratory difficulties; chest pain or palpitations; yellowing of the eyes or skin; swelling of extremities; rapid weight gain; right upper quadrant pain; or other persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Stomatitis and mucositis.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Dizziness, insomnia, and depression are common

Mental Health: Effects on Psychiatric Treatment

Hypotension is common; caution with low potency antipsychotics and TCAs; nausea and vomiting are common, use caution with the SSRIs. Neutropenia is common, use caution with carbamazepine and clozapine.

Dosage Forms

Injection, powder for reconstitution: 5 mg

International Brand Names

Mylotarg™ (CA); Mylotarg® (CO, PR, SG)

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