Zenocutuzumab
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: EMBRYO-FETAL TOXICITY Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1 , 8.3) ]. WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1 , 8.3) ].
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
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Recommended Dosage The recommended dosage of BIZENGRI is 750 mg as an intravenous (IV) infusion every 2 weeks until disease progression or unacceptable toxicity [see Dosage and Administration ]. Administer premedications before each BIZENGRI infusion as recommended to reduce the risk of infusion-related reactions [see Dosage and Administration ] .
Recommended Premedications Prior to each infusion of BIZENGRI, administer premedications to reduce the risk of infusion-related reactions (IRRs) [see Warnings and Precautions ] (see Table 1 ) . [See table below.]
Preparation Dilute and prepare BIZENGRI for intravenous infusion before administration. For the initial infusion, prepare BIZENGRI as close to administration time as possible to allow for the possibility of extended infusion time in the event of an infusion-related reaction. Check that the BIZENGRI solution is clear to slightly opalescent, colorless to slightly yellow.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if discoloration or visible particles are present. Withdraw and then discard 37.5 mL 0.9% Sodium Chloride Injection from the 250 mL infusion bag. Only use infusion bags made of polyvinylchloride (PVC), polyolefin or polyolefin/polyamide coextruded plastic.
Withdraw a total of 37.5 mL of BIZENGRI from 2 vials and add it to the infusion bag. The final volume in the infusion bag should be 250 mL. Discard any unused portion left in the vial. Gently invert the bag to mix the solution. Do not shake. If not used immediately, store the diluted solution refrigerated at 2°C to 8°C (36°F to 46°F) and protect from light after preparation unless the infusion is initiated within 2 hours of preparation.
Administration If the infusion time exceeds the recommended storage time, the infusion bag must be discarded and a new infusion bag prepared to continue the infusion. Diluted BIZENGRI solution must by administered within: 6 hours from end of preparation of infusion solution stored at room temperature [15°C to 25°C (59°F to 77°F)] 28 hours from end of preparation of infusion solution stored refrigerated [2°C to 8°C (36°F to 46°F)] If the diluted BIZENGRI solution has been refrigerated, allow it to reach room temperature (approximately 30 minutes) prior to administration.
Administer diluted BIZENGRI solution [see Dosage and Administration ] by intravenous infusion using an infusion set made of either PVC, polyethylene (PE), polyurethane (PUR) or polybutadiene (PB) with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.2 micrometer). Do not infuse BIZENGRI concomitantly in the same IV line with other agents.
Administer BIZENGRI infusion via a peripheral or central line. Monitor patients closely for signs and symptoms of infusion-related reactions during BIZENGRI infusion and monitor patients for at least 1 hour following completion of the first BIZENGRI infusion and as clinically indicated [see Warnings and Precautions ]. Administer intravenous infusion over 4 hours.
| Medication | Dose | Route of Administration |
|---|---|---|
| CorticosteroidOptional after initial BIZENGRI infusion | Dexamethasone (10 mg) | Oral or intravenous |
| Antipyretic | Acetaminophen (1,000 mg) | Oral or intravenous |
| H1 Antihistamine | Dexchlorpheniramine (5 mg) or other anti-H1 equivalent | Intravenous or oral |
| Adverse Reaction | Severity | Dose Modifications and Management |
|---|---|---|
| Infusion-related reactions (IRRs)/Hypersensitivity/Anaphylactic Reactions [see Warnings and Precautions (5.1)] | ≤ Grade 3 IRR | Interrupt BIZENGRI infusion if IRR is suspected and monitor patient until reaction symptoms resolve.Provide symptomatic treatment as needed.Resume the infusion at 50% of the infusion rate at which the reaction occurred. The infusion rate may be escalated if there are no additional symptoms.Corticosteroid premedication can be used as necessary for subsequent BIZENGRI infusions [see Recommended Premedications (2.4)]. |
| Grade 4 IRR or any grade hypersensitivity/anaphylactic reaction | Permanently discontinue BIZENGRI. | |
| Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2)] | Grade 1 | Interrupt BIZENGRI until recovery.Consider prompt initiation of corticosteroids when the diagnosis is suspected.Resume treatment after resolution. |
| ≥ Grade 2 | Permanently discontinue BIZENGRI.Promptly treat with corticosteroids. | |
| Left Ventricular Dysfunction [see Warnings and Precautions (5.3)] | LVEF is 45-49% and absolute decrease from baseline ≥10% or LVEF less than 45% | Interrupt BIZENGRI.Repeat LVEF assessment within 3 weeks.If LVEF is less than 45% or LVEF has not recovered to within 10% from baseline, permanently discontinue BIZENGRI.If LVEF is 50% or greater or LVEF is 45-49% and recovered to within 10% of baseline, resume BIZENGRI and monitor LVEF every 12 weeks while on treatment and as clinically indicated. |
| Symptomatic congestive heart failure (CHF) | Permanently discontinue BIZENGRI. | |
| Other Clinically Relevant Adverse Reactions [see Adverse Reactions (6.1)] | Grade 3 or 4 | Withhold BIZENGRI until recovery to ≤ Grade 1 or baseline.Provide symptomatic treatment as needed.Resume treatment after resolution of symptoms. |
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for zenocutuzumab. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of BIZENGRI in pregnant women to inform a drug-associated risk. Animal studies have demonstrated that HER2 and/or HER3 deficiency results in embryo-fetal malformation, including effects on cardiac, vascular and neuronal development, and embryolethality (see Data ) . Human IgG1 is known to cross the placenta; therefore, BIZENGRI has the potential to be transmitted from the mother to the developing fetus. Advise patients of the potential risk to a fetus.
There are clinical considerations if BIZENGRI is used in pregnant women, or if a patient becomes pregnant within 2 months after the last dose of BIZENGRI ( see Clinical Considerations ) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received BIZENGRI during pregnancy or within 2 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care.
Data Human Data There are no available data on the use of BIZENGRI in pregnant women. In literature reports in pregnant women receiving a HER2-directed antibody, cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported. These case reports described oligohydramnios in pregnant women who received HER2-directed antibody alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after use of a HER2-directed antibody was stopped. Animal Data There were no animal reproductive or developmental toxicity studies conducted with zenocutuzumab-zbco.
A literature-based assessment of the effects on reproduction demonstrated that HER2 and HER3 are critically important in embryo-fetal development. HER2 knockout mice or mice expressing catalytically inactive HER2 die at mid-gestation due to cardiac dysfunction. HER2 knockout mice have also shown abnormal sympathetic nervous system development. In HER3-deficient mice, embryolethality occurred on embryonic day 13.5 due to cardiac and vascular defects, as well as abnormalities in other organs (neural crest, pancreas, stomach, and adrenal). In addition, HER3 is shown to be involved in mammary gland…
Breastfeeding (LactMed)
No information is available on the use of zenocutuzumab during breastfeeding. Because zenocutuzumab is a large protein molecule with a molecular weight of about 146,000 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal. Because no information is available on the use of zenocutuzumab during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. The manufacturer recommends that breastfeeding be discontinued during therapy and for 2 months after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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