Hepzato Dosage

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

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.

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.

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 drug1. Follow applicable special handling and disposal procedures.

Reconstitution and Dilution Instructions:

1. 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
2. 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.
3. 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)
4. 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.
5. 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.