Emrelis (telisotuzumab vedotin-tllv)

Modifications of the dosage of telisotuzumab vedotin-tllv may be needed based on adverse effects. If dosage reduction is required, the dosage of telisotuzumab vedotin-tllv should be reduced as described in Table 2.

Telisotuzumab vedotin-tllv should be permanently discontinued in patients that are unable to tolerate the 1 mg/kg dosage.

Table 2: Recommended Dosage Reduction Level for Telisotuzumab Vedotin-tllv Toxicity

Dose Reduction Recommended Dosage First dose reduction 1.6 mg/kg every 2 weeks Second dose reduction 1.3 mg/kg every 2 weeks Third dose reduction 1 mg/kg every 2 weeks Requirement for further reduction Permanently discontinue

Table 3 indicates the recommended dosage modification (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) for adverse effects according to severity.

Table 3: Recommended Dosage Modifications and Management for Telisotuzumab Vedotin-tllv Toxicity

Adverse Effect Severity Dosage Modification and Treatment Recommendations Peripheral Neuropathy Grade 2 or 3 Withhold drug until recovery to Grade <=1 Resume drug at the next lower dosage level Grade 4 Permanently discontinue drug Interstitial lung Grade 1 Withhold drug and disease consider corticosteroids (ILD)/Pneumonitis as soon as ILD/pneumonitis suspected Resume drug upon radiographic resolution Grade >=2 Permanently discontinue drug Keratitis Grade 2 Withhold drug Refer patient to eye care professional for ophthalmic examination and treatment (e.g., lubricating and/or steroidal eye drops) Resume drug at same dose at discretion of clinician Grade 3 or 4 Refer patient to eye care professional for ophthalmic examination and treatment (e.g., lubricating and/or steroidal eye drops) Permanently discontinue drug Infusion-related Grade 1-3 Interrupt infusion and Reactions administer supportive treatment Resume infusion at a 50% rate reduction; increase infusion rate as tolerated for subsequent doses Administer premedication prior to all future doses Grade 4 Administer supportive treatment Permanently discontinue drug Peripheral Edema Grade >=2 For first occurrence, withhold drug until recovery to Grade <=1, then resume drug at the same dose level For subsequent occurrence, withhold drug until recovery to Grade <=1, then resume drug at the next lower dose level Other Adverse Effects Grade 3 For first occurrence, withhold drug until recovery to Grade <=1, then resume drug at the same dose level For subsequent occurrence, withhold drug until recovery to Grade <=1, then resume drug at the next lower dose level Grade 4 Permanently discontinue drug

Telisotuzumab vedotin-tllv is administered by IV infusion through a dedicated IV line with a 0.20- or 0.22-mcm in-line filter made of either polyether sulfone, polyvinylidene fluoride, or polyamide. Telisotuzumab vedotin-tllv is commercially available as a lyophilized powder that requires reconstitution and further dilution prior to IV administration.

Telisotuzumab vedotin-tllv should not be mixed or administered with other drugs through the same IV line.

Store telisotuzumab vedotin-tllv vials refrigerated at 2-8degreesC in the original carton protected from light. Do not freeze or shake telisotuzumab vedotin-tllv vials.

No dosing information is available for this tab.

Telisotuzumab vedotin-tllv metabolism has not been evaluated. The small molecule, monomethyl auristatin E (MMAE), is a substrate of cytochrome P-450 (CYP) 3A4/5 and P-glycoprotein (P-gp) and is an inhibitor of CYP3A4/5.

No clinical studies have evaluated the potential for drug-drug interactions with telisotuzumab vedotin-tllv.

There are no contraindication interactions for this drug.

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

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)

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

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.

• Lactation

• Pregnancy

• Peripheral neuropathy

The most common adverse effects of telisotuzumab vedotin-tllv (>=20% of patients) are peripheral neuropathy, fatigue, decreased appetite, and peripheral edema.

The most common Grade 3 or 4 laboratory abnormalities (>=2%) are decreased lymphocytes, increased glucose, increased ALT, increased gamma-glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium.

Less Frequent

• Interstitial pneumonitis
• Pleural effusions
• Pneumonia

More Frequent

• Abnormal hepatic function tests
• Anemia
• Anorexia
• Blurred vision
• Constipation
• Fatigue
• Hyperglycemia
• Hypoalbuminemia
• Hypocalcemia
• Hypokalemia
• Hypomagnesemia
• Hyponatremia
• Hypophosphatemia
• Keratitis
• Leukopenia
• Lymphopenia
• Nausea
• Neutropenic disorder
• Peripheral edema
• Peripheral neuropathy
• Thrombocytopenic disorder
• Vomiting

No enhanced messaging available.

Safety and effectiveness of telisotuzumab vedotin-tllv have not been established in pediatric patients.

There are no available human data on telisotuzumab vedotin-tllv use in pregnant women to inform a drug-associated risk. Based on the mechanism of action and findings in animals, telisotuzumab vedotin-tllv can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, administration of the small molecule component of telisotuzumab vedotin-tllv, MMAE, to pregnant rats during organogenesis resulted in embryo-fetal mortality and structural abnormalities at exposures similar to the clinical exposure at the recommended dose. Advise patients of the potential risks to a fetus.

There are no data on the presence of telisotuzumab vedotin-tllv or MMAE in human milk, the effects on the breast-fed child, or the effects on milk production. Because of the potential for serious adverse effects in a breast-fed child, advise lactating women not to breast-feed during treatment with telisotuzumab vedotin-tllv and for 1 month after the last dose.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Of the 168 patients with previously treated epidermal growth factor receptor wild-type non-squamous NSCLC with c-Met protein overexpression treated with telisotuzumab vedotin-tllv, 50% were >=65 years of age and 12% were >=75 years of age. No overall differences in safety or effectiveness were observed between older and younger patients.