Hepzato Kit
Melphalan hydrochloride injection, powder, lyophilized, for solution · Kit · Intra-arterial
Uses
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 )
Dosage and administration
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.
Dosage forms and strengths
(melphalan) is supplied in the HEPZATO KIT that contains the following: Melphalan for injection: 5 single dose, clear glass vials for injection, containing 50 mg white to pale yellow lyophilized powder, intended for reconstitution with the supplied diluents For injection: HEPZATO includes 50 mg freeze-dried (lyophilized) melphalan powder per vial in five (5) single dose vials, intended for reconstitution with the supplied diluents. ( 3 )
Contraindications
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 )
Warnings and precautions
Hypersensitivity reactions, including anaphylaxis, have occurred in patients who received an intravenous (IV) formulation of melphalan. Immediately terminate hepatic arterial melphalan infusion for hypersensitivity reactions and administer supportive care. ( 5.4 ) Gastrointestinal disturbances such as nausea and vomiting, abdominal pain and diarrhea are common. ( 5.5 ) Carcinogenic/Mutagenic effects: Secondary malignancies, including acute nonlymphocytic leukemia, myeloproliferative syndrome, and carcinoma, have been reported in patients with cancer treated with alkylating drugs (including melphalan). Melphalan has been shown to cause chromatid or chromosome damage in humans. ( 5.6 ) Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) Infertility: Melphalan-based chemotherapy regimens have been reported to cause suppression of ovarian function in premenopausal women and testicular suppression in men. ( 5.8 ) 5.1 Peri-Procedural Complications Hemorrhage, hepatocellular injury, and thromboembolic events have been observed when HEPZATO has been administered via hepatic intra-arterial administration. Administration of HEPZATO requires general anesthesia and extracorporeal bypass of circulation which may cause life threatening or fatal adverse effects. Ensure the patient is euvolemic but do not overhydrate the patient. Monitor for these peri-procedural complications during the procedure and for at least 72 hours following the procedure. To mitigate the risk of thromboembolic events, administer anticoagulation as described in the IFU during the procedure. Due to the risk of bleeding, do not use in patients with uncorrectable coagulopathies and delay treatment with the HEPZATO KIT for at least 4 weeks after surgery or other medical procedure involving the liver. Platelets and clotting factors may be removed during the HEPZATO KIT procedure. Monitor platelets and coagulation parameters as described in the IFU. If life-threatening bleeding occurs during the procedure, reverse anticoagulation as described in the IFU and correct coagulopathy as appropriate. Discontinue anticoagulation with warfarin or other oral anticoagulants prior to the procedure; resume when hemostasis has been restored after the procedure, provided no bleeding complications have been observed. Refer to the Prescribing Information of the anticoagulant agent for bridging recommendations for anti-coagulation prior to surgical procedures. Discontinue drugs affecting platelet function such as aspirin, non-steroidal anti-inflammatory drugs, or other anti-platelet drugs one week before the procedure. Patients with abnormal hepatic vascular (especially arterial supply) or biliary (especially re-implantation of bile duct) anatomy or gastric acid hypersecretion syndromes may be at increased risk of peri-procedural complications or other severe adverse reactions. Screen patients for a history of prior surgeries involving the bile duct to assess whether the patient is an appropriate candidate for HEPZATO KIT and monitor patients for adverse reactions following HEPZATO KIT administration. Procedure-related reductions in blood pressure including severe hypotension can occur during the HEPZATO KIT procedure. Closely monitor blood pressure during the procedure. Patients may require fluid support and vasopressors. To reduce the risk of severe hypotension, assess hypothalamic-pituitary-adrenal axis function, and temporarily discontinue ACE-inhibitors, calcium channel blockers, or alpha-1-adrenergic blockers for at least 5 half-lives prior to treatment with the HEPZATO-KIT. If necessary, use other short-acting antihypertensive drugs to manage blood pressure during the peri-procedure period. 5.2 HEPZATO KIT REMS PROGRAM The HEPZATO KIT is only available through a restricted program under a REMS, because of the risk of severe peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events defined in the REMS. The HEPZATO KIT should only be used by trained healthcare providers [see Warnings and Precautions ( 5.1 )]. Important requirements of the HEPZATO KIT REMS include: Healthcare settings that dispense and administer HEPZATO KIT must be enrolled, certified, and comply with the REMS requirements. Certified healthcare facilities must ensure that healthcare providers who perform the Percutaneous Hepatic Perfusion (PHP) procedure are trained on the use of HEPZATO KIT and must only dispense HEPZATO when authorized to do so by the REMS. Certified healthcare facilities must ensure that patients are assessed for severe peri-procedural complications during the procedure and for at least 72 hours following the procedure. Further information is available at www.HEPZATOKITREMS.com or contact Delcath Systems at 1-833-632-0457. 5.3 Myelosuppression Hematologic adverse reactions, including thrombocytopenia, anemia, and neutropenia have been reported in patients treated with HEPZATO. The risk of hematologic adverse reactions may be increased in patients who have received prior chemotherapy, bone irradiation, or who have compromised bone marrow function. In the 95 patients who received HEPZATO in the FOCUS trial, 68% had Grade 3 or 4 myelosuppression. A total of 55%, 33%, and 30% experienced Grade 3 or 4 thrombocytopenia, anemia, and neutropenia, respectively. Median time to thrombocyte nadir was 13 days (range: 3-33) after treatment with median recovery in 20 days (range: 4-29) after treatment. Median time to hemoglobin nadir was 10 days (range: 3-21) after treatment with median recovery in 13 days (range: 4-28) after treatment. Median time to neutrophil nadir was 11 days (range: 3-36) after treatment with median recovery in 17 days (range: 9-36) after treatment. Monitor patients for severe infections, bleeding, and symptomatic anemia.
Side effects
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
Use in specific populations
8 USE IN SPECIFIC POPULATIONS HEPZATO should not be used in patients < 35 kg. ( 2.2 ) Lactation: Advise not to breastfeed ( 8.2 ) 8.1 Pregnancy Risk Summary Based on animal studies and its mechanism of action, melphalan can cause fetal harm when administered to a pregnant woman, including teratogenicity and/or embryo-fetal lethality [see Clinical Pharmacology ( 12.1 ) ]. Melphalan is a genotoxic drug and can cause chromatid or chromosome damage in humans [see Nonclinical Toxicology ( 13.1 ) ]. In animal studies, melphalan was embryolethal and teratogenic in rats at doses below the recommended clinical doses [see Data ]. Advise a pregnant woman of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the United States general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data Adequate animal studies have not been conducted with IV melphalan. Melphalan was embryolethal and teratogenic in rats following oral administration of 6 to 18 mg/m 2 /day for ten (10) days (0.05 to 0.16 times the recommended clinical dose of 3 mg/kg or 111 mg/m 2 /day) and intraperitoneal administration of 18 mg/m 2 (0.16 times the highest recommended clinical dose). Malformations resulting from melphalan administration included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, and hepatocele (exomphaly). 8.2 Lactation Risk Summary It is not known whether melphalan is present in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing children from melphalan, breastfeeding is not recommended during treatment with melphalan and for one week after the last dose. 8.3 Females and Males of Reproductive Potential Melphalan can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating HEPZATO [see Use in Specific Populations ( 8.1 )] . Contraception Females Advise females of reproductive potential to use effective contraception during treatment with HEPZATO and for 6 months after the last dose. Males HEPZATO administration may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Advise males with female partners of reproductive potential to use effective contraception during treatment with HEPZATO and for 3 months after the last dose [see Nonclinical Toxicology ( 13.1 ) ]. Infertility Females Melphalan causes suppression of ovarian function in premenopausal women, resulting in amenorrhea in a significant number of patients. Males Reversible and irreversible testicular suppression has been reported in male patients after administration of melphalan. 8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of HEPZATO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In the FOCUS trial, 30 of the 91 patients (33%) were 65 years and older.
Pregnancy
8.1 Pregnancy Risk Summary Based on animal studies and its mechanism of action, melphalan can cause fetal harm when administered to a pregnant woman, including teratogenicity and/or embryo-fetal lethality [see Clinical Pharmacology ( 12.1 ) ]. Melphalan is a genotoxic drug and can cause chromatid or chromosome damage in humans [see Nonclinical Toxicology ( 13.1 ) ]. In animal studies, melphalan was embryolethal and teratogenic in rats at doses below the recommended clinical doses [see Data ]. Advise a pregnant woman of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the United States general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data Adequate animal studies have not been conducted with IV melphalan. Melphalan was embryolethal and teratogenic in rats following oral administration of 6 to 18 mg/m 2 /day for ten (10) days (0.05 to 0.16 times the recommended clinical dose of 3 mg/kg or 111 mg/m 2 /day) and intraperitoneal administration of 18 mg/m 2 (0.16 times the highest recommended clinical dose). Malformations resulting from melphalan administration included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, and hepatocele (exomphaly).
Pediatric use
8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Clinical studies of HEPZATO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In the FOCUS trial, 30 of the 91 patients (33%) were 65 years and older.
Description
Melphalan, is a bifunctional alkylating drug that is active against selected human neoplastic diseases. Melphalan is available as melphalan hydrochloride salt. The chemical name of melphalan hydrochloride is 4-[bis(2-chloroethyl)amino]-L-phenylalanine hydrochloride. The molecular formula is C 13 H 18 Cl 2 N 2 O 2 .HCl and the molecular weight is 341.67. Melphalan is practically insoluble in water and has a pKa1 of ~2.5. HEPZATO, for injection, is supplied as a sterile, nonpyrogenic, freeze-dried white to pale yellow freeze-dried cake/ powder. Each single dose vial contains melphalan 50 mg, equivalent to 56 mg of melphalan hydrochloride and 20 mg povidone. HEPZATO (melphalan) is reconstituted using the sterile diluent provided. Each vial of sterile diluent contains sodium citrate 0.2 g, propylene glycol 6.0 mL, ethanol (96%) 0.52 mL, and water for injection to a total of 10 mL. HEPZATO (melphalan) for use with the hepatic delivery system is administered intra-arterially. Figure
Mechanism of action
12.1 Mechanism of Action Melphalan is an alkylating drug of the bischloroethylamine type. As a result, its cytotoxicity appears to be related to the extent of its interstrand cross-linking with DNA, probably by binding at the N7 position of guanine. It is active against both resting and rapidly dividing tumor cells.
How supplied
How Supplied The HEPZATO KIT includes the HEPZATO 5 x 5 Drug Pack and the Hepatic Delivery System (HDS). Each 5 x 5 HEPZATO KIT Drug Pack includes HEPZATO (melphalan) and diluents for reconstitution and dilution: Each vial of HEPZATO contains 50 mg melphalan for injection supplied as a sterile, nonpyrogenic, freeze-dried cake/powder in a carton containing 5 single-dose, glass vials (NDC 75833-800-01). Each vial of sterile diluent contains sodium citrate 0.2 g, propylene glycol 6.0 mL, ethanol (96%) 0.52 mL, and water for injection to a total of 10 mL in a carton containing 5 single-dose, glass vials for reconstitution (NDC 75833-700-01). Each of two 250 mL plastic containers of 0.9% sodium chloride injection USP (NDC 0264-7800-20). HEPZATO (melphalan) for injection must only be administered with the HDS device supplied with the HEPZATO KIT and components specified by Delcath Systems, Inc, in the IFU [see Dosage and Administration ( 3 )]. Storage and Handling HEPZATO for injection and its associated diluents including 0.9% sodium chloride must be stored at controlled room temperature 20°C to 25°C (68°F to 77°F). Temperature excursions are permitted between 15°C- 30°C (59°F-86°F) [see USP Controlled Room Temperature]. The Hepatic Delivery System components may be stored at room temperature. Melphalan is a hazardous drug. Follow applicable special handling and disposal procedures. 1 HEPZATO is light sensitive. Retain in original carton until use. HEPZATO (melphalan) for injection Manufactured for: Delcath Systems, Inc. Queensbury, NY 12804 by Mylan Institutional LLC Made in Italy HEPZATO KIT (melphalan for Injection/Hepatic Delivery System) Packaged and Distributed by: Delcath Systems, Inc. Queensbury, NY 12804
Storage
Storage and Handling HEPZATO for injection and its associated diluents including 0.9% sodium chloride must be stored at controlled room temperature 20°C to 25°C (68°F to 77°F). Temperature excursions are permitted between 15°C- 30°C (59°F-86°F) [see USP Controlled Room Temperature]. The Hepatic Delivery System components may be stored at room temperature. Melphalan is a hazardous drug. Follow applicable special handling and disposal procedures. 1 HEPZATO is light sensitive. Retain in original carton until use. HEPZATO (melphalan) for injection Manufactured for: Delcath Systems, Inc. Queensbury, NY 12804 by Mylan Institutional LLC Made in Italy HEPZATO KIT (melphalan for Injection/Hepatic Delivery System) Packaged and Distributed by: Delcath Systems, Inc. Queensbury, NY 12804
Patient information
17 Patient Counseling Information Advise patients or their caregivers of the following risks of the HEPZATO KIT: Peri-Procedural Complications Advise patients of the severe procedural risks associated with administration of melphalan using the HEPZATO KIT including hemorrhage, hepatic injury, and thromboembolic events. Advise patients that they will be monitored in a hospital setting following each treatment. Advise patients taking anti-coagulant and anti-hypertensive medications that these may need to be discontinued prior to treatment with HEPZATO KIT [see Warnings and Precautions ( 5.1 )]. Myelosuppression Advise patients to immediately contact their healthcare provider for a fever, bruising, or bleeding. Advise patients of the need for monitoring of blood counts [see Warnings and Precautions ( 5.3 )]. Hypersensitivity Inform patients of the signs and symptoms of hypersensitivity. Advise patients to immediately report symptoms of hypersensitivity [see Warnings and Precautions ( 5.4 )]. Latex Allergy The double balloon catheter component of the HEPZATO KIT Hepatic Delivery System contains natural rubber latex which may cause allergic reactions in latex-sensitive individuals [see Contraindications ( 4 )]. Gastrointestinal Advise patients to report symptoms of nausea, vomiting and diarrhea, so that appropriate antiemetic and/or antidiarrheal medications can be administered [see Warnings and Precautions ( 5.5 )]. Secondary Malignancies Advise patients that treatment with HEPZATO has the potential long-term risk of secondary malignancy [see Warnings and Precautions ( 5.6 )]. Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus [see Warnings and Precautions ( 5.7 ) and Use in Specific Populations ( 8.1 )]. Advise females of reproductive potential to use effective contraception during treatment with HEPZATO and for 6 months after the last dose. Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking HEPZATO [see Warnings and Precautions ( 5.7 ) and Use in Specific Populations ( 8.1 , 8.3 )]. Advise males with female partners of reproductive potential to use effective contraception during treatment with HEPZATO and for 3 months after the last dose [see Use in Specific Populations ( 8.3 )]. Lactation Advise women not to breastfeed during treatment with HEPZATO and for one week after the last dose [see Warnings and Precautions ( 5.7 ) and Use in Specific Populations ( 8.2 )] Infertility Inform both females and males of reproductive potential about the risk of infertility [see Warnings and Precautions ( 5.8 ) and Use in Specific Populations ( 8.3 )]. HEPZATO (melphalan) for Injection Manufactured for: Delcath Systems, Inc. Queensbury, NY 12804 by Mylan Institutional LLC Made in Italy HEPZATO KIT (melphalan for Injection/Hepatic Delivery System) Packaged and Distributed by: Delcath Systems, Inc. Queensbury, NY 12804 © Copyright, 2023 Delcath Systems, Inc. All rights reserved. 120070.A
Label text from the FDA structured product label by Delcath Systems, Inc. (revised Jun 9, 2026). Long sections are shortened; the complete label is on DailyMed.
Hepzato Kit NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 75833-601 | Kit | Delcath Systems, Inc. | NDA |
Frequently asked questions
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.…
What are the side effects of Hepzato Kit?
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… See the full label for the complete list.
Who makes Hepzato Kit?
Hepzato Kit is listed by 1 labeler in the FDA NDC directory, including Delcath Systems, Inc..