• Hepzato:

  Hepzato is part of the Hepzato Kit Hepatic Delivery System [HDS], which is only available through the Hepzato Kit Hepatic Delivery System REMS. Health care professionals must complete required Hepzato Kit REMS training before administering Hepzato Kit, and health care facilities must be certified to offer the program. Oral anticoagulation, drugs affecting platelet function, ACE inhibitors, calcium channel blockers, and alpha-1-adrenergic blockers must be discontinued before the procedure.

• Assess for latex allergies. The double balloon catheter component of the HDS contains natural rubber latex, which may cause allergic reactions.
• If Grade 4 neutropenia of >5 days duration despite growth factor support or associated with neutropenic fever OR Grade 4 thrombocytopenia of >5 days duration or associated with a hemorrhage that required a transfusion occurs, a dose reduction to 2 mg/kg is recommended for subsequent treatments. Discontinue Hepzato if patients have life-threatening or Hepzato-related persistent toxicity that has not resolved to Grade ≤ 2 by 8 wk following treatment.

• Rapidly (in ≤5 seconds) inject 10 mL of the supplied sterile diluent into the Hepzato 50 mg vial using a sterile needle (≥20-gauge) and syringe. Resulting solution will contain melphalan 5 mg/mL. Immediately shake vial vigorously until a clear solution is obtained. No >5 seconds should elapse between discharge of the syringe and shaking. Immediately further dilute the required dose with the provided 0.9% NaCl, to a concentration <0.45 mg/mL. For Hepzato doses <110 mg: dilute in 250 mL of 0.9% NaCl. For Hepzato doses 111 mg–220 mg: divide total dose equally into 2 and dilute each in 250 mL of 0.9% NaCl. Solution is clear; do not administer solutions that are discolored or contain particulate matter. Administer diluted Hepzato intra-arterially with the Hepzato kit hepatic delivery system. Complete infusion within 30 min, followed by a 30-min washout period. Reconstituted and diluted solutions of Hepzato are unstable. No more than 60 min should elapse from reconstitution and completion of the intra-hepatic infusion of the diluted Hepzato solution. Do not refrigerate Hepzato once reconstituted.

• Administration of Hepzato requires general anesthesia and extracorporeal bypass of circulation. Ensure patient is euvolemic, but do not overhydrate. Monitor for hemorrhage, hepatocellular injury, and thromboembolic events during the procedure and for at least 72 hr following the procedure. Closely monitor blood pressure during procedure; patients may require fluid support and vasopressors.

IV Administration:

• Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated container.
  • If solution contacts skin or mucosa, immediately wash skin or mucosa with soap and water.
• Intermittent Infusion: Reconstitution: Reconstitute with 10 mL of diluent supplied.Concentration: 5 mg/mL. Shake vigorously until solution is clear. Diluent: Dilute dose immediately with 0.9% NaCl.Concentration: Not to exceed 0.45 mg/mL. Administer within 60 min of reconstitution. Store at room temperature and protect from light; do not refrigerate reconstituted solution.
• Rate: Administer over 15–30 min. Keep time between reconstitution/dilution and administration to a minimum; reconstituted and diluted solutions are unstable.
• Rate: Infuse over 30 min via injection port or central venous catheter; may cause local tissue damage if extravasation occurs. Do not administer IV push into a peripheral vein. Administer Evomela by injecting slowly into a fast-running IV infusion via a central venous access line.