Bizengri (zenocutuzumab-zbco)

The recommended dosage modifications of zenocutuzumab-zbco for adverse reactions are provided in Table 1. No dose reduction is recommended.

Table 1: Recommended Zenocutuzumab-zbco Dosage Modifications and Management for Adverse Reactions

Adverse Reaction Severity Dose Modifications and Management Infusion-related <=Grade 3 IRR Interrupt reactions zenocutuzumab-zbco (IRRs)/Hypersensitivity/ infusion if IRR is Anaphylactic Reactions 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 b e escalated if there are no additional symptoms. Corticosteroid premedication can be used as necessary for subsequent zenocutuzumab-zbco infusions. Infusion-related Grade 4 IRR or any grade Permanently discontinue reactions hypersensitivity/anaphyl zenocutuzumab-zbco. (IRRs)/Hypersensitivity/ actic reaction Anaphylactic Reactions Interstitial Lung Grade 1 Interrupt Disease zenocutuzumab-zbco until (ILD)/Pneumonitis recovery. Consider prompt initiation of corticosteroids when the diagnosis is suspected. Resume treatment after resolution. Interstitial Lung >=Grade 2 Permanently discontinue Disease zenocutuzumab-zbco. (ILD)/Pneumonitis Promptly treat with corticosteroids. Left Ventricular Left ventricular Interrupt Dysfunction ejection fraction (LVEF) zenocutuzumab-zbco. is 45-49% and absolute Repeat LVEF assessment decrease from baseline within 3 weeks. If LVEF >=10% or LVEF <45% is <45% or LVEF has not recovered to within 10% from baseline, permanently discontinue zenocutuzumab-zbco. If LVEF is >=50% or LVEF is 45-49% and recovered to within 10% of baselin e, resume zenocutuzumab-zbco and monitor LVEF every 12 weeks while on treatment and as clinically indicated. Left Ventricular Symptomatic congestive Permanently discontinue Dysfunction heart failure (CHF) zenocutuzumab-zbco. Other Clinically Grade 3 or 4 Withold Relevant Adverse zenocutuzumab-zbco until Reactions recovery to <=Grade 1 or baseline. Provide symptomatic treatment as needed. Resume treatment after resolution of symptoms.

Zenocutuzumab-zbco is administered via IV infusion only. The drug is supplied as a 20 mg/mL injection concentrate that must be further diluted prior to administration.

Store zenocutuzumab-zbco vials in a refrigerator at 2-8degreesC in original carton to protect from light. Do not freeze or shake.

For the initial infusion, prepare zenocutuzumab-zbco as close to administration time as possible to allow for an extended infusion time in the event of an IRR.

Check that zenocutuzumab-zbco solution is clear to slightly opalescent, colorless to slightly yellow. Do not use if discoloration or visible particles are present.

If not used immediately, store the diluted solution refrigerated at 2-8degreesC and protect from light after preparation unless the infusion is initiated within 2 hours of preparation.

Administer premedications prior to zenocutuzumab-zbco (see Premedication and Prophylaxis under Dosage and Administration).

Administer diluted zenocutuzumab-zbco solution using an infusion set made of either polyvinylchloride (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).

Administer zenocutuzumab-zbco infusion via a peripheral or central line.

If the diluted zenocutuzumab-zbco solution has been refrigerated, allow it to reach room temperature for approximately 30 minutes prior to administration.

Do not infuse zenocutuzumab-zbco concomitantly in the same IV line with other agents.

No dosing information is available for this tab.

No drug-drug interaction studies were performed. Zenocutuzumab-zbco showed small transient elevations of cytokines in patients, which are not expected to modulate activity of cytochrome P450 (CYP450). No interactions with concomitant medications are expected.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Biologic Therapies/Anifrolumab

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use of anifrolumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1)

CLINICAL EFFECTS: Concurrent use of anifrolumab with other biologic therapies may increase the risk of serious infections.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The concurrent use of anifrolumab with other biologic therapies is not recommended.(1)

DISCUSSION: The combination of anifrolumab with other biologic therapies has not been studied and is not recommended.(1)

Igg Antibodies And Derivatives/Efgartigimod-Alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

Igg Antibodies And Derivatives/Nipocalimab-Aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Biologic Therapies/Belimumab

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Concurrent use of belimumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1)

CLINICAL EFFECTS: Concurrent use of belimumab with other biologic therapies may increase the risk of serious infections.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The concurrent use of belimumab with other biologic therapies should be approached with caution.(1)

DISCUSSION: In a randomized, double-blind, placebo-controlled trial, more patients who received belimumab and rituximab experienced serious adverse events, serious infections, and post-injection systemic reactions (22.2%, 9%, and 13.2%, respectively) than patients who received belimumab with placebo (13.9%, 2.8%, 9.7%) or standard therapy (19.7%, 5.3%, 5.3%).(1) The combination of belimumab with other biologic therapies has not been studied and should be used cautiously.(1)

Igg Antibodies And Derivatives/Rozanolixizumab-Noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

*None.

There are no contraindication contraindications for this drug.

• Chronic heart failure
• Interstitial lung disease
• Pregnancy

There are no moderate contraindications for this drug.

The most common adverse reactions (>=10%) in patients were diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions (IRRs), dyspnea, rash, constipation, vomiting, abdominal pain, and edema.

The most common Grade 3 or 4 laboratory abnormalities (>=2%) were increased GGT, decreased hemoglobin, decreased sodium, decreased platelets, increased AST, increased ALT, increased alkaline phosphatase, decreased magnesium, decreased phosphate, increased aPTT, and increased bilirubin.

More Frequent

• Abnormal hepatic function tests
• Back pain
• Bleeding hemorrhoids
• Dyspnea
• Edema
• Gamma-glutamyl transferase raised
• Hypokalemia
• Hypomagnesemia
• Hypophosphatemia
• Increased aspartate transaminase
• Injection site sequelae
• Leukopenia
• Myelodysplastic syndrome
• Obstructive hyperbilirubinemia
• Tachycardia

Less Frequent

• Acute kidney injury
• Acute respiratory failure
• Agitation
• Ascites
• Bradycardia
• Cardiac arrhythmia
• Carotid artery stenosis
• Cellulitis
• Cholecystitis
• Dehydration
• Dizziness
• Dysphagia
• Gastrointestinal obstruction
• Heart failure
• Hemorrhage
• Hyperbilirubinemia
• Hyponatremia
• Ileus
• Increased alkaline phosphatase
• Infection
• Interstitial pneumonitis
• Left ventricular failure
• Liver abscess
• Lymphadenopathy
• Neutropenic disorder
• Pericardial effusion
• Pneumonia
• Prolonged activated partial thromboplastin time
• Pulmonary hypertension
• Sepsis
• Thrombocytopenic disorder
• Upper respiratory infection
• Urinary tract infection
• Viral infection

More Frequent

• Abdominal distension
• Acute abdominal pain
• Anemia
• Anorexia
• Constipation
• Diarrhea
• Dry skin
• Fatigue
• Fever
• Hypoalbuminemia
• Increased alanine transaminase
• Musculoskeletal pain
• Nausea
• Skin rash
• Symptoms of anxiety
• Vomiting

Less Frequent

• Stomatitis

No enhanced messaging available.

The safety and effectiveness of zenocutuzumab-zbco have not been established in pediatric patients.

Based on its mechanism of action, zenocutuzumab-zbco can cause fetal harm when administered to a pregnant woman. There are no available data on the use of zenocutuzumab-zbco 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.

Human IgG1 is known to cross the placenta; therefore, zenocutuzumab-zbco has the potential to be transmitted from the mother to the developing fetus. Advise patients of the potential risk to a fetus.

Monitor women who received zenocutuzumab-zbco 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.

There are no data on the presence of zenocutuzumab-zbco in human milk, the effects on the breastfed child, or the effects on milk production. Maternal IgG1 is known to be present in human milk. The effects of local GI exposure and limited systemic exposure in the breastfed child to zenocutuzumab-zbco are unknown. Consider the developmental and health benefits of breast feeding along with the mother's clinical need for zenocutuzumab-zbco treatment and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Of the 175 patients with NRG1 gene fusion positive tumors in the eNRGy study treated with zenocutuzumab-zbco at a dosage of 750 mg every 2 weeks, 75 patients (43%) were 65 years of age or older and 26 patients (15%) were 75 years of age and older. No clinically important differences in safety or efficacy were observed between patients who were >=65 years of age and younger patients.