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Hepzato Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Kit—1 (HDS + drug pack [vials × 5 + diluents × 5] + sodium chloride 0.9% inj × 2)
Manufacturer
Generic Availability
NO
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.
Hepzato Indications
Indications
Liver-directed treatment for adults with uveal melanoma with unresectable hepatic metastases affecting <50% of 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 Dosage and Administration
Adult
<35kg: not recommended. For use via Hepzato Kit Hepatic Delivery System (HDS): see full labeling. Premedicate with a PPI day prior to and morning of procedure; administer anti-emetics in subsequent cycles if required. Give by intra-hepatic infusion within 30mins (followed by 30-min washout period) every 6–8wks for up to 6 total infusions. Dose based on ideal body wt. ≥35kg: 3mg/kg; max 220mg per treatment. Reduce to 2mg/kg if Grade 4 neutropenia lasting >5 days despite growth factor support or associated with neutropenic fever; or Grade 4 thrombocytopenia lasting >5 days associated with hemorrhage that required a transfusion.
Children
Not established.
Hepzato Contraindications
Contraindications
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 liver in the past 4 weeks. Uncorrectable coagulopathy. Inability to safely undergo general anesthesia, including active cardiac conditions (eg, unstable or severe angina, MI), worsening or new-onset CHF, significant arrhythmias, or severe valvular disease. Allergies or hypersensitivity to latex, heparin or presence of heparin-induced thrombocytopenia (HIT), or iodinated contrast not controlled by premedication (antihistamines, steroids).
Hepzato Boxed Warnings
Boxed Warning
Severe peri-procedural complications. Myelosuppression.
Hepzato Warnings/Precautions
Warnings/Precautions
Ensure euvolemia. Monitor for peri-procedural complications (eg, hemorrhage, hepatocellular injury, thromboembolic events) during and for ≥72hrs after procedure. Delay treatment for ≥4wks after surgery or medical procedure involving liver. Monitor platelets and coagulation parameters; reverse anticoagulation if life-threatening bleeding occurs. Abnormal hepatic vascular or biliary anatomy. Gastric acid hypersecretion syndromes. Screen for history of prior surgeries involving bile duct. Severe hypotension; monitor BP during procedure. Assess HPA axis function. Prior irradiation or chemotherapy. Bone marrow suppression. Monitor for severe infections, bleeding, symptomatic anemia. Conduct baseline hematologic testing. Administer therapy only if platelets >100000/µL, hemoglobin ≥10g/dL, and neutrophils >2,000/µL. Discontinue immediately if hypersensitivity reactions occur. Secondary malignancies. Risk for leukemogenesis. Infertility. Embryo-fetal toxicity. Advise to use effective contraception during and for 6 months (females of reproductive potential) or for 3 months (males w. female partners of reproductive potential) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after the last dose).
REMS
Hepzato Pharmacokinetics
Absorption
Geometric mean of systemic melphalan maximum concentration (Cmax): 2.4 (%CV 3.0) mcg/mL; AUC0-last: 1.8 (%CV 1.1) mcg*hr/mL.
Median (range) time to Cmax (Tmax): 0.57 (0.05–1.18) hours after Hepzato administration.
Distribution
Plasma protein bound: ~78%.
Elimination
Renal. Half-life: 1.07 hours.
Hepzato Interactions
Interactions
Discontinue oral anticoagulants, drugs affecting platelet function for 1 week prior to procedure (eg, aspirin, NSAIDs); and ACE inhibitors, CCBs, or alpha-1 adrenergic blockers for ≥5 half-lives prior to procedure.
Hepzato Adverse Reactions
Adverse Reactions
Thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased ALT/AST/ALP, prolonged aPTT, dyspnea; peri-procedural complications, hypersensitivity reactions, cardiac arrest, hypoxia, pleural effusion.
Hepzato Clinical Trials
See Literature
Hepzato Note
Notes
This product is only available through the Hepzato Kit REMS program. For more information call (833) 632-0457.
Hepzato Patient Counseling
See Literature
