Hepzato Kit

Hepzato Kit is an FDA-registered drug product whose active ingredient is MELPHALAN HYDROCHLORIDE INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION. It is labelled by Delcath Systems, Inc. taken by intra-arterial and marketed as a human prescription drug product. Identifiers on file: NDC 75833-601, application NDA201848, label effective 20260609. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing MELPHALAN HYDROCHLORIDE INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION are most often described in connection with: extrahepatic disease, indicated liver-directed, adult patients, uveal melanoma, unresectable hepatic, metastases affecting, bone lymph, nodes subcutaneous. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE HEPZATO for injection, as a component of the HEPZATO KIT, is indicated as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation. HEPZATO is an alkylating drug indicated as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.( 1 )

2 DOSAGE AND ADMINISTRATION HEPZATO, a component of the HEPZATO KIT, is administered by intra-arterial infusion into the hepatic artery (see instructions for use [IFU]). The recommended dose is 3 mg/kg based on ideal body weight (see Table 1 ), with a maximum absolute dose of 220 mg during a single HEPZATO treatment. ( 2.2 ). The drug is infused over 30 minutes followed by a 30-minute washout period (see IFU). Treatments should be administered every six (6) to eight (8) weeks but can be delayed until recovery from toxicities and as per clinical judgement. ( 2.3 ) 2.1 Important Pre-Treatment and Administration Information HEPZATO is a component of the HEPZATO KIT Hepatic Delivery System [HDS]. Refer to the HEPZATO KIT Hepatic Delivery System Instructions for Use (IFU) for additional instructions including pre-infusion evaluation, hydration, premedication, anticoagulation, and supportive care. Caution: The double balloon catheter component of the HDS contains natural rubber latex which may cause allergic reactions [see Contraindications ( 4 ) ]. Healthcare providers must complete the required HEPZATO KIT REMS training prior to administration of the HEPZATO KIT [see Warnings and Precautions ( 5.2 )]. Discontinue oral anticoagulation and drugs affecting platelet function prior to the procedure [see Warnings and Precautions ( 5.1 )]. Discontinue ACE-inhibitors, calcium channel blockers, or alpha-1-adrenergic blockers prior to the procedure [see Warnings and Precautions ( 5.1 )]. Conduct baseline hematologic testing. Administer intra-hepatic HEPZATO with the HEPZATO KIT only to patients with the following [see Warnings and Precautions ( 5.3 )]. Hemoglobin ≥ 10 g/dL Platelets ≥ 100,000/microliter Neutrophils > 2000/microliter 2.2 Recommended Dosage Administer HEPZATO via the HEPZATO KIT Hepatic Delivery System only to patients weighing 35 kg or greater due to potential size limitations with respect to percutaneous catheterization. HEPZATO, a component of the HEPZATO KIT, is administered by infusion into the hepatic artery (see IFU) every 6 to 8 weeks for up to 6 total infusions. The recommended HEPZATO dose is 3 mg/kg based on ideal body weight (IBW), as calculated per Table 1 below, with a maximum of 220 mg during a single treatment. Table 1: Calculation of IBW for HEPZATO Dosing Height Ideal Body Weight Men ≥ 152 cm 52 kg + (0.75 kg/cm of height greater than 152 cm) < 152 cm 52 kg – (0.75 kg/cm of height less than 152 cm) Women ≥ 152 cm 49 kg + (0.67 kg/cm of height greater than 152 cm) < 152 cm 49 kg – (0.67 kg/cm of height less than 152 cm) 2.3 Dosage Modifications for Adverse Reactions A dosage reduction to 2 mg/kg is recommended for subsequent treatments for the following reasons: Grade 4 neutropenia of > 5 days duration despite growth factor support or associated with neutropenic fever; Grade 4 thrombocytopenia of > 5 days duration or associated with a hemorrhage that required a transfusion; HEPZATO administered with the HEPZATO KIT should be discontinued if patients have life threatening or HEPZATO-related persistent toxicity that has not resolved to Grade 2 or less by 8 weeks following treatment. 2.4 Preparation and Administration Refer to the HEPZATO KIT Hepatic Delivery System IFU for further details and instructions. Reconstitute and dilute melphalan immediately prior to beginning intra-arterial infusion. Reconstituted and diluted solutions of HEPZATO are unstable. No more than 60 minutes should elapse from reconstitution and completion of the intra-hepatic infusion of the diluted HEPZATO solution. A citrate derivative of melphalan has been detected in reconstituted HEPZATO in 30 minutes, and nearly 1% of labeled strength of melphalan hydrolyzes every 10 minutes when reconstituted HEPZATO is further diluted in 0.9% Sodium Chloride. A precipitate forms if the reconstituted solution is stored at 5°C. Do not refrigerate HEPZATO once reconstituted. HEPZATO is a hazardous drug 1 . Follow applicable special handling and disposal procedures. Reconstitution and Dilution Instructions: Rapidly (in 5 seconds or less) inject 10 mL of the supplied sterile diluent [ see Dosage Forms and Strengths (3.0) ] into the HEPZATO 50 mg vial using a sterile needle (20-gauge or larger) and syringe. The resulting solution will contain melphalan 5 mg/mL Immediately shake the vial vigorously until a clear solution is obtained. No more than five (5) seconds should elapse between the discharge of the syringe and the commencement of shaking. Immediately further dilute the required dose with the provided 0.9% sodium chloride injection, United States Pharmacopeia (USP), to a concentration not greater than 0.45 mg/mL, as follows HEPZATO doses up to 110 mg: Dilute in 250 mL of 0.9% sodium chloride injection HEPZATO doses 111 mg to 220 mg: Divide the total dose equally into 2 and dilute each in 250 mL of 0.9% sodium chloride injection (for example, if the total dose is 200 mg, dilute 100 mg in each 250 mL 0.9% sodium chloride injection) Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulates and discolorations are noted, the product should not be used. Administer diluted HEPZATO intra-arterially as described in the IFU. Complete the infusion within 30 minutes, followed by a 30-minute washout period. Refer to the IFU for additional administration procedures.

4 CONTRAINDICATIONS HEPZATO and the HEPZATO KIT are contraindicated in patients with: Active intracranial metastases or brain lesions with a propensity to bleed Liver failure, portal hypertension, or known varices at risk for bleeding Surgery or medical treatment of the liver in the previous 4 weeks Uncorrectable coagulopathy Inability to safely undergo general anesthesia, including active cardiac conditions including, but not limited to, unstable coronary syndromes (unstable or severe angina or myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease History of allergies or known hypersensitivity to melphalan History of allergies or known hypersensitivity to a component or material utilized within the HEPZATO KIT including History of allergy to natural rubber latex History of allergy or hypersensitivity to heparin or presence of heparin-induced thrombocytopenia (HIT) History of severe allergic reaction to iodinated contrast not controlled by premedication with antihistamines and steroids Active intracranial metastases or brain lesions with a propensity to bleed Liver failure, portal hypertension, or known varices at risk for bleeding Surgery or medical treatment of the liver in the previous 4 weeks Active cardiac conditions including, but not limited to, unstable coronary syndromes (unstable or severe angina or myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease History of allergies or known hypersensitivity to melphalan or a component or material utilized within the HEPZATO KIT including natural rubber latex, heparin, and severe hypersensitivity to iodinated contrast not controlled by antihistamines and steroids ( 4 )

6 ADVERSE REACTIONS Below are adverse reactions associated with HEPZATO KIT. Additional adverse reactions related to the procedure and/or medical device are described in further detail in the HEPZATO KIT IFU. The following clinically significant adverse reactions are described elsewhere in the labeling: Peri-procedural complications [see Warnings and Precautions ( 5.1 )] Myelosuppression [see Warnings and Precautions ( 5.3 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.5 )] Secondary Malignancies [see Warnings and Precautions ( 5.6 )] Most common (≥20%) adverse reactions or laboratory abnormalities are thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased aspartate aminotransferase, increased alkaline phosphatase, and dyspnea. To report SUSPECTED ADVERSE REACTIONS, contact Delcath at 1-833-632-0458 and www.Delcath.com or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug-device combination cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse drug reactions (ADRs) described in this section were identified from the FOCUS trial. FOCUS was a multicenter trial that evaluated HEPZATO (melphalan) administered via the HEPZATO KIT in patients with unresectable hepatic metastases from uveal melanoma. In the FOCUS trial, a total of 95 patients were enrolled into the HEPZATO KIT arm, of which 91 patients received treatment with HEPZATO. Serious adverse reactions occurred in 45% of patients who received HEPZATO. Serious adverse reactions occurring in ≥ 2% of patients were thrombocytopenia (10%), neutropenia (8%), febrile neutropenia (7%), platelet count decreased (6%), leukopenia (4.2%), cardiac arrest (3.2%), neutrophil count decreased (2.1%), hypoxia (2.1%), pleural effusion (2.1%), pulmonary edema (2.1%), and deep vein thrombosis (2.1%). Fatal adverse reactions occurred in 3 (3.2%) patients who were treated with HEPZATO; these included cardiac arrest, acute hepatic failure and bacterial peritonitis. HEPZATO was permanently discontinued due to adverse reactions in 18% of patients with neutropenia being the most common adverse reaction (3.2%) requiring permanent discontinuation. Dose reductions due to an adverse reaction occurred in 14% of patients who received HEPZATO. Adverse reactions which required dose reductions occurring in ≥ 2% of patients were platelet count decreased (6%), neutropenia (4.2%), anemia (2.1%), and thrombocytopenia (2.1%). Adverse reactions that required dosage interruption in ≥ 2% of patients who received HEPZATO were platelet count decreased (6%), neutropenia (5%), thrombocytopenia (3.2%), anemia (3.2%) and febrile neutropenia (2.1%). The most common (≥20%) adverse reactions or laboratory abnormalities reported in patients treated with HEPZATO were thrombocytopenia (65%), fatigue (65%), anemia (63%), nausea (57%), musculoskeletal pain (46%), leukopenia (46%), abdominal pain (39%), neutropenia (35%), vomiting (35%), increased alanine aminotransferase (32%), prolonged activated partial thromboplastin time (28%), increased aspartate aminotransferase (28%), increased blood alkaline phosphatase (27%), and dyspnea (23%). Table 2 and Table 3 summarize adverse reactions and laboratory abnormalities, respectively, that occurred in FOCUS. Table 2 All Adverse Reactions Observed at a Frequency of >10% in Patients Treated with HEPZATO 1 Represents a composite of multiple, related preferred terms All Adverse Reactions N=95 All Grades (%) Grades 3 or 4 (%) Gastrointestinal disorders Nausea 57 0 Abdominal Pain 1 39 1 Vomiting 1 35 0 Diarrhea 1 17 1 General disorders Fatigue 1 65 0 Pyrexia 1 16 0 Musculoskeletal And Connective Tissue Disorders Musculoskeletal Pain 1 46 1 Groin Pain 11 0 Respiratory disorders Dyspnea 1 23 2 Cough 1 15 0 Nervous system disorders Headache 1 19 0 Lethargy 12 0 Dizziness 1 11 0 Injury and procedural complications Contusion 17 0 Metabolism and nutrition disorders Decreased appetite 16 0 Vascular disorders Hemorrhage 1 15 1 Hypotension 1 13 3 Table 3: Laboratory Abnormalities Observed at a Frequency of >10% in Patients Treated with HEPZATO a Represents a composite of multiple, related preferred terms Laboratory Abnormality All Laboratory Abnormalities N=95 All Grades (%) Grades 3 or 4 (%) Platelets decreased a 65 55 Hemoglobin decreased a 63 33 Leukocytes decreased a 46 34 Neutrophils decreased a 35 30 Alanine aminotransferase increased 32 3 International normalized ratio increased 31 8 Activated partial thromboplastin time prolonged 28 8 Aspartate aminotransferase increased 28 4 Blood alkaline phosphatase increased 27 2 Calcium decreased 13 3 Troponin I increased 13 2 Blood bilirubin increased 11 3

What is Hepzato Kit used for?
1 INDICATIONS AND USAGE HEPZATO for injection, as a component of the HEPZATO KIT, is indicated as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation. …

Who makes Hepzato Kit?
Delcath Systems, Inc. is the labeler of record for Hepzato Kit.

What form does Hepzato Kit come in?
administered by intra-arterial. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Hepzato Kit prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has Hepzato Kit been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.