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|Gemtuzumab Ozogamicin

Gemtuzumab Ozogamicin

Trade Names:
Mylotarg
- Powder for injection, lyophilized 5 mg (protein equivalent) per vial

Mechanism of Action

Pharmacology

Chemotherapy agent composed of a recombinant humanized immunoglobulin G ₄ kappa antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin, isolated from fermentation of a bacterium. The antibody portion of gemtuzumab ozogamicin binds specifically to the CD33 antigen, which is expressed on the surface of leukemic blasts in patients with acute myeloid leukemia (AML). This ultimately results in DNA double-strand breaks and cell death.

Pharmacokinetics

Absorption

AUC doubles after second dose.

Metabolism

Many metabolites found in liver microsomes, cytosol, and HL-60 promyelocytic leukemia cells.

Elimination

First dose t _{1/ 2} is about 40 hr (total), 140 hr (unconjugated). Second dose t _{1/ 2} is about 60 hr (total).

Indications and Usage

CD33-positive AML in first relapse in patients at least 60 yr of age who are not candidates for other antineoplastics.

Contraindications

Standard considerations.

Dosage and Administration

IV 9 mg/m ² /dose for a total of 2 doses, given on days 0 and 14. The second dose may be given in the absence of full hematologic recovery.

General Advice

• Protect reconstituted and diluted solutions from sunlight and unshielded fluorescent light. Turn off the light in the biologic safety hood during preparation; ambient room lights may be left on.
• Allow vial to warm to room temperature before reconstitution.
• Reconstitute vial aseptically with 5 mL of sterile water for injection and swirl gently. The final gemtuzumab ozogamicin concentration will be 1 mg/mL.
• Withdraw appropriate dose from vial and dilute in 100 mL sodium chloride 0.9%. Visually inspect the solution for particulates and discoloration.
• Administer by IV infusion over 2 hr. Do not administer as an IV push or bolus.
• Administer through a separate IV line with a low protein-binding 1.2 micron terminal filter.

Storage/Stability

Total max time allowed for storage of reconstituted and diluted solution and completion of infusion is 20 hr, consisting of reconstitution at 2 hr or less at room temperature or refrigeration, dilution at 16 hr or less at room temperature, and administration over a 2-hr infusion.

Store unopened vials in refrigerator (36° to 46°F). Protect from light.

Drug Interactions

Coadministration of drugs with similar pharmacologic effects may cause additive adverse reactions, including toxicity.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (20%); hypertension (16%); hemorrhage (11%); tachycardia (10%); venoocclusive disease (5%).

CNS

Headache (37%); dizziness, insomnia (12%); depression (9%); anxiety (8%).

Dermatologic

Cutaneous herpes simplex (21%); rash (18%); pruritus (6%).

EENT

Epistaxis (28%); pharyngitis (12%); rhinitis (8%).

GI

Nausea (68%); vomiting (58%); diarrhea (32%); anorexia, oral mucositis, stomatitis (25%); constipation (23%); dyspepsia (10%); gum hemorrhage (9%).

Genitourinary

Vaginal hemorrhage (4%); metrorrhagia (3%).

Hematologic-Lymphatic

Thrombocytopenia (treatment phase: 99% experienced grade 3 or 4; treatment emergent: 49% experienced grade 3 or 4); neutropenia (treatment phase: 98% experienced grade 3 or 4); anemia (treatment phase: 52% experienced grade 3 or 4; treatment emergent: 14% experienced grade 3 or 4); leukopenia (47%); petechiae (19%); neutropenic fever (17%); ecchymosis (10%).

Hepatic

Hyperbilirubinemia (29%); abnormal LFTs (24%); elevated AST (18%); elevated ALT (9%).

Metabolic-Nutritional

Hypokalemia (26%); increased LDH (16%); peripheral edema (14%); bilirubinemia (12%); hyperglycemia, hypocalcemia (10%); hypophosphatemia, increased alkaline phosphatase (8%); hypomagnesemia (6%).

Musculoskeletal

Back pain (14%); myalgia (6%).

Respiratory

Dyspnea (26%); increased cough (17%); pneumonia (13%); pulmonary physical findings (9%).

Miscellaneous

Fever (82%); chills (66%); asthenia (36%); abdominal pain (32%); infection (treatment phase: 30% experienced grade 3 or 4; treatment emergent: 9%); sepsis (26%); local reaction (22%); pain (18%); neutropenic fever (17%); bleeding events (treatment phase: 13% experienced grade 3 or 4); hypoxia (5%).

Precautions

Pregnancy

Category D .

Lactation

Undetermined. Because many drugs, including immunoglobulins, are excreted in breast milk, and because of the potential for serious adverse reactions in breast-feeding infants from gemtuzumab ozogamicin, decide whether to discontinue breast-feeding or the drug, taking into account the importance of the drug to the mother.

Children

Safety and efficacy not studied.

Renal Function

Not studied in adult patients with renal function impairment. Use with caution.

Hepatic Function

Not studied in patients with a bilirubin more than 2 mg/dL. Use with caution. Exercise caution when administering in patients with hepatic function impairment.

Infusion reactions

The infusion may be slowed or continued at the same rate if the patient experiences a reaction. Interrupt the infusion for dyspnea or profound hypotension. Symptoms may be treated with diphenhydramine (eg, Benadryl ), acetaminophen (eg, Tylenol ), bronchodilators, or IV fluids. Monitor the patient until symptoms resolve completely. Patients who react to the initial infusion may receive a second dose. The infusion duration may be increased at the health care provider"s discretion.

Pretreatment regimens

Reduce incidence of infusion reactions with premedication. Give acetaminophen 650 to 1,000 mg (oral or rectal) and diphenhydramine 50 mg (oral or IV) 60 min before administering gemtuzumab ozogamicin.

Tumor lysis syndrome

May be a consequence of leukemia treatment. Take appropriate measures (eg, allopurinol, hydration) to prevent hyperuricemia.

Overdosage

Symptoms

No cases of overdose have been reported. Signs of overdose are unknown.

Patient Information

• Explain name, dose, action, and potential adverse reactions of drug.
• Obtain patient history, including drug history and any known allergies.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver that additional medications will be given before administration to reduce adverse reactions of gemtuzumab.
• Advise patient, family, or caregiver to immediately report any of the following symptoms to health care provider: rash; difficulty breathing; fever, chills, or other signs of infection; sores in mouth; unusual bleeding or bruising.
• Advise patient, family, or caregiver to report any of the following symptoms to health care provider: persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness.
• Caution patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Advise women to avoid becoming pregnant while being treated.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
• Advise patient that frequent follow-up visits and laboratory tests will be required to monitor therapy and to keep appointments.