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Hepatic Impairment Avoid use of EMRELIS in patients with moderate or severe hepatic impairment (total bilirubin >1.5 x ULN and any AST). Patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions. EMRELIS has not been studied in patients with moderate or severe hepatic impairment.

No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin >ULN and ≤1.5 x ULN and any AST) [see Clinical Pharmacology ] .

2 DOSAGE AND ADMINISTRATION For intravenous infusion only. The recommended dosage of EMRELIS is 1.9 mg/kg administered intravenously every 2 weeks until disease progression or unacceptable toxicity. Reconstitute and further dilute EMRELIS prior to intravenous infusion. 2.1 Patient Selection Select patients for treatment with EMRELIS based on the presence of high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining] in patients with non-squamous NSCLC [see Indications and Usage and Clinical Studies] .

Information on FDA-approved tests for the detection of high c-Met protein overexpression is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosage of EMRELIS is 1.9 mg/kg (up to a maximum of 190 mg for patients greater than or equal to 100 kg) administered as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. 2.3 Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are provided in Table 1. [See table below.] The recommended dosage modifications of EMRELIS for adverse reactions are provided in Table 2. [See table below.] 2. 4 Recommended Premedications for Patients Who Experience Infusion-Related Reactions Table 3 contains the recommended premedications for patients who experience infusion-related reactions to EMRELIS, for subsequent infusions. [See table below.] H2 Antihistamine Famotidine 20 mg Intravenously or orally Administer 30-60 minutes prior to each infusion Antipyretic Acetaminophen 650 to 1,000 mg Intravenously or orally Administer 30-60 minutes prior to each infusion Glucocorticoid Methylprednisolone 125 mg or equivalent Intravenously Administer 30-60 minutes prior to each infusion 2. 5 Preparation and Administration EMRELIS contains a hazardous component.

Follow applicable special handling and disposal procedures in accordance with local requirements. 1 Reconstitute and further dilute EMRELIS prior to intravenous infusion. Reconstitution of Lyophilized EMRELIS Before reconstitution, allow the vial to reach room temperature after removal of the vial from storage condition.

The reconstituted solution has a concentration of 20 mg/mL EMRELIS. [See table below.] Swirl the vial gently until completely dissolved. Do not shake. Inspect the reconstituted solution for particulate matter and discoloration. The solution should appear clear to slightly opalescent and colorless to slightly yellow. Discard the vial if the reconstituted solution is discolored, is cloudy, or contains visible particulates.

Use reconstituted EMRELIS immediately. If not used immediately, store the reconstituted EMRELIS vials in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours from the time of reconstitution. Do not freeze. Each vial of EMRELIS is intended for one-time use only. Discard any unused drug remaining in the vial. Dilution in Infusion Bag Calculate the required dose volume (mL) of reconstituted EMRELIS solution based on the prescribed dose.

Withdraw the calculated dose volume (mL) of reconstituted solution from the EMRELIS vial using a sterile syringe. Discard any unused portion remaining in the vial(s). Inject the calculated amount of reconstituted solution into 0.9% Sodium Chloride Injection infusion bag so that the final EMRELIS concentration is between 1 mg/mL and 10 mg/mL.

Use only 0.9% Sodium Chloride Injection. Gently invert the infusion bag to thoroughly mix the solution. Do not shake. After preparing the dose for infusion, visually inspect the bag content for particulates and discard if present. If not used immediately, the diluted solution can be stored in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours and an additional 4 hours at room temperature at 9°C to 30°C (48°F to 86°F) until the end of administration.

Do not freeze. Method of Administration If the prepared infusion solution was stored refrigerated at 2°C to 8°C (36°F to 46°F), allow the solution to reach room temperature prior to administration. Administer by intravenous infusion over 30 minutes using a dedicated infusion line with a 0.20 or 0.22 micron in-line filter made of polyether sulfone (PES), polyvinylidene fluoride (PVDF), or Polyamide (PA).