gemtuzumab ozogamicin

gem-TU-zoo-mab o-zo-ga-MY-sin

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, antitumor antibiotics

High Alert

Treatment of newly diagnosed CD33 positive acute myeloid leukemia.
Treatment of relapsed or refractory CD33 positive acute myeloid leukemia.

The antibody portion (gemtuzumab) attaches to the CD33 antigen on the surface of acute myeloid leukemic cells. Binding produces a complex that is internalized by the leukemic cells. Once internalized the antitumor antibiotic portion of the drug (ozogamicin, also know as calicheamicin) is released and binds to DNA resulting in breaks in double strand DNA and cell death.

Therapeutic effects:

Induction of remission.

Absorption: IV administration results in complete bioavailability.

Distribution: Binds to CD33 receptor sites, is then internalized by leukemic cells, releasing ozogamicin.

Metabolism/Excretion: Ozogamicin is probably metabolized by the liver.

Half-Life: 62 hr (↑ with second dose).

ROUTE	ONSET	PEAK	DURATION
IV	rapid	following infusion	2 wk

Contraindicated in:

Hypersensitivity;
OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Moderate-severe hepatic impairment, patients treated after hematopoietic stem cell transplantation (HSCT), and patients undergoing HSCT after treatment (↑ risk of veno-occlusive liver disease);
QT interval prolongation at baseline, taking QT-interval prolonging medications, or electrolyte disturbances (↑ risk of QT interval prolongation);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Children <1 mo (safety and efficacy not established).

CV: QT INTERVAL PROLONGATION, tachycardia

Derm: rash

F and E: hypokalemia, hyponatremia, hypophosphatemia

GI: constipation, mucositis, nausea, vomiting, ↑bilirubin, diarrhea, HEPATOTOXICITY(INCLUDING VENO-OCCLUSIVE LIVER DISEASE)

GU: ↓fertility

Hemat: anemia, BLEEDING, neutropenia, thrombocytopenia

Neuro: headache

Resp: pulmonary edema

Misc: chills, fever, ANAPHYLAXIS, INFECTION, INFUSION REACTIONS, tumor lysis syndrome

Drug-drug:

None reported to date.

Newly Diagnosed CD33–Positive AML (in combination with chemotherapy)

IV (Adults ): Induction cycle 1: 3 mg/m²(up to one 4.5–mg vial) on Days 1, 4, and 7 (in combination with daunorubicin and cytarabine). Consolidation cycles: 3 mg/m² (up to one 4.5–mg vial) on Day 1 (in combination with daunorubicin and cytarabine).
IV (Children ≥1 mo and body surface area [BSA] ≥0.6 m²): Induction cycle 1: 3 mg/m²once (in combination with standard chemotherapy). Intensification course 2: 3 mg/m²once (in combination with standard chemotherapy).
IV (Children ≥1 mo and BSA <0.6 m²): Induction cycle 1: 0.1 mg/kg once (in combination with standard chemotherapy). Intensification course 2: 0.1 mg/kg once (in combination with standard chemotherapy).

Newly Diagnosed CD33–Positive AML (as monotherapy)

IV (Adults ): Induction cycle: 6 mg/m²on Day 1 and 3 mg/m²on Day 8. Continuation therapy: 2 mg/m² on Day 1 every 4 wk.

Relapsed or Refractory CD33–Positive AML (as monotherapy)

IV (Adults and Children ≥2 yr): 3 mg/m²(up to one 4.5-mg vial) on Days 1, 4, and 7.

Lyophilized powder for injection: 4.5 mg/vial

Monitor for signs and symptoms of infusion reaction (fever, chills, hypotension, dyspnea) during and for at least 4 hr after infusion. If infusion reactions occur, hold infusion and institute appropriate medical management. Administer acetaminophen, diphenhydramine and/or methylprednisolone, if needed. Provide supportive care measures as needed. For mild, moderate or severe infusion-related reactions, once symptoms resolve, consider resuming infusion at no more than half the rate at which the reaction occurred. Repeat if symptoms recur. If severe infusion reaction occurs, permanently discontinue therapy.
Monitor for signs and symptoms of bleeding (nose bleed, blood in urine or emesis, black, tarry stools) during therapy. Manage severe bleeding, hemorrhage or persistent thrombocytopenia using dose delay or permanent discontinuation therapy and provide supportive care.
Monitor for development of tumor lysis syndrome. May require hydration and allopurinol to prevent hyperuricemia.

Lab Test Considerations:

Verify a negative pregnancy test before starting therapy.
- Monitor hematologic status (electrolytes, hepatic function, CBC, platelet counts) at least 3 times/wk during therapy. Severe myelosuppression (anemia, thrombocytopenia) will occur in all patients given the recommended dose of gemtuzumab. Full recovery from hematologic toxicities is not required before second infusion.
- For persistent thrombocytopenia: In adults, if platelet count does not recover to ≥100 x 10³ cells/mm³ within 14 days following planned start date of consolidation cycle (14 days after hematologic recovery following previous cycle), discontinue therapy (do not administer gemtuzumab ozogamicin in consolidation cycles). In pediatrics, patients should have a platelet count of 75 x 10³cells/mm³ before next cycle (induction or intensification).
- Persistent neutropenia: In adults, if neutrophil count does not recover to >0.5 x 10³ cells/mm³ within 14 days following the planned start date of consolidation cycle (14 days after hematologic recovery following previous cycle), discontinue therapy (do not administer gemtuzumab ozogamicin in the consolidation cycles). In pediatrics, patients should have a neutrophil count of 1 x 10³ cells/mm³ before next cycle (induction or intensification).
- Assess ALT, AST, total bilirubin, and alkaline phosphatase prior to each dose of gemtuzumab ozogamicin. After treatment, monitor frequently for signs and symptoms of hepatotoxicity and veno-occlusive liver disease (VOD) (↑ ALT, AST, total bilirubin, hepatomegaly [may be painful], rapid weight gain, ascites). Monitoring only total bilirubin may not identify all patients at risk of VOD. If total bilirubin >2 × ULN, or AST and/or ALT >2.5 × ULN, hold therapy until recovery of total bilirubin to ≤2 × ULN and AST and ALT to ≤2.5 × ULN before each dose. Omit scheduled dose if delayed more than 2 days between sequential infusions. For patients who develop abnormal liver tests, monitor liver tests and clinical signs and symptoms of hepatotoxicity frequently. For patients who proceed to hematopoietic stem cell transplantation (HSCT), monitor liver tests frequently during post-HSCT period. Manage signs or symptoms of hepatic toxicity by dose interruption or discontinuation of therapy. If VOD occurs, discontinue therapy.
- Assess CBC prior to each dose and monitor CBC frequently after treatment until resolution of cytopenias.

High Alert: Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations, and infusion pump settings. Gemtuzumab should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. May be administered in a outpatient setting. Do not administer by intravenous push or bolus.
Protect medication from direct and indirect light and unshielded fluorescent lights during preparation and administration. Must be prepared under a biologic safety hood with the fluorescent light off.
Premedicate adults with diphenhydramine 50 mg PO or IV, and acetaminophen 650 mg PO and pediatric patients 1 month or older with diphenhydramine 1 mg/kg (50 mg max) and acetaminophen 15 mg/kg (650 mg max) 1 hr prior to administration; may be repeated every 4 hr as needed. Administer 1 mg/kg methylprednisolone PO or IV or equivalent for adults and 1 mg/kg 30 min before infusion; repeat for any sign of infusion reaction during or within 4 hr after infusion.
For patients with hyperleukocytosis (leukocyte count greater than or equal to 30 x 10³ cells/mm³), cytoreduction is recommended prior to administration.

IV Administration:

Intermittent Infusion: Prior to reconstitution, allow drug to come to room temperature for about 5 min. Reconstitution: Reconstitute each vial with 5 mL of sterile water for injection for a concentration of 1 mg/mL. Gently swirl each vial to aid dissolution. Solution may contain small white to off-white, opaque to translucent, and amorphous to fiber-like particles; do not administer solutions that are discolored or contain particulate matter. Solution is stable for up to 1 hr if refrigerated.Diluent: To dilute for administration, withdraw desired volume from each vial and protect from light. For doses 3.9 mg, add reconstituted solution to a syringe with 0.9% NaCl for administration via syringe. For doses 3.9 mg, dilute in a syringe or IV bag of 0.9% NaCl. Gently invert to mix; do not shake. Concentration: 0.075 mg/mL to 0.234 mg/mL. Infuse diluted solution immediately. Solution is stable for up to 6 hr at room temperature, which includes 2 hr infusion time and 1 hr to allow solution to equilibrate to room temperature, or up to 12 hr if refrigerated; do not freeze.
Rate: Infuse over 2 hr via a separate IV line with a low protein-binding 0.2-micron polyethersulfone (PES) filter. Protect IV bag from light using a light-blocking cover during infusion; infusion line does not need to be protected from light.
Y-Site Compatibility:
- allopurinol
- amifostine
- ampicillin
- ampicillin/sulbactam
- argatroban
- carboplatin
- cefuroxime
- chloramphenicol
- clindamycin
- cytarabine
- dacarbazine
- daunorubicin hydrochloride
- diphenhydramine
- dopamine
- ertapenem
- foscarnet
- fosphenytoin
- gemcitabine
- glycopyrrolate
- heparin
- hydromorphone
- ifosfamide
- imipenem/cilastatin
- irinotecan
- levofloxacin
- linezolid
- magnesium sulfate
- mannitol
- melphalan
- meropenem
- methotrexate
- metronidazole
- moxifloxacin
- nafcillin
- nitroglycerin
- nitroprusside
- oxaliplatin
- pentamidine
- potassium chloride
- propranolol
- sodium bicarbonate
- sufentanil
- theophylline
- topotecan
- trimethoprim/sulfamethoxazole
- vecuronium
- verapamil
Y-Site Incompatibility:
- acyclovir
- amikacin
- aminophylline
- amiodarone
- amphotericin B deoxycholate
- amphotericin B lipid complex
- amphotericin B liposome
- anidulafungin
- arsenic trioxide
- atracurium
- azithromycin
- aztreonam
- bumetanide
- buprenorphine
- butorphanol
- calcium chloride
- calcium gluconate
- caspofungin
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- chlorpromazine
- ciprofloxacin
- cisatracurium
- cyclophosphamide
- cyclosporine
- dantrolene
- daptomycin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- diazepam
- digoxin
- diltiazem
- dobutamine
- doxorubicin hydrochloride
- doxycycline
- droperidol
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- eptifibatide
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- fluconazole
- fludarabine
- furosemide
- ganciclovir
- gentamicin
- granisetron
- haloperidol
- hydralazine
- hydrocortisone
- hydroxyzine
- idarubicin
- insulin, regular
- isoproterenol
- ketorolac
- leucovorin calcium
- lidocaine
- lorazepam
- meperidine
- mesna
- methohexital
- methylprednisolone
- metoclopramide
- metoprolol
- midazolam
- milrinone
- mitoxantrone
- morphine
- mycophenolate
- nalbuphine
- naloxone
- nicardipine
- norepinephrine
- ondansetron
- paclitaxel
- palonosetron
- pamidronate
- pantoprazole
- pentobarbital
- phenobarbital
- phentolamine
- phenytoin
- piperacillin/tazobactam
- potassium acetate
- potassium phosphate
- procainamide
- prochlorperazine
- promethazine
- remifentanil
- rocuronium
- sodium acetate
- sodium phosphate
- succinylcholine
- tacrolimus
- thiopental
- thiotepa
- tobramycin
- vancomycin
- vasopressin
- vinblastine
- vincristine
- voriconazole
- zidovudine
- zoledronic acid
Do not mix with, or administer as an infusion with, other medicinal products.

Explain purpose of medication to patient.
Advise patient to notify health care professional immediately if signs and symptoms of liver toxicity (rapid weight gain, right upper quadrant pain and tenderness, hepatomegaly, ascites), bleeding, or infusion reactions occur.
Instruct patient to notify healthcare professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult healthcare professional before taking other Rx, OTC, or herbal products.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 6 mos after last dose and to avoid breastfeeding during and for at least 1 mo after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for at least 3 mos after last dose. Inform patient may impair female and male fertility.

Remission in patients with leukemia.

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Indications ⬆ ⬇

Action ⬆ ⬇

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Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆