Drug Detail:Pepaxto ( melphalan flufenamide)
Generic Name: melphalan flufenamide hydrochloride 20mg in 50mL
Dosage Form: injection, powder, lyophilized, for solution
Drug Class: Alkylating agents
Recommended Dosage
The recommended dosage of PEPAXTO is 40 mg administered intravenously over 30 minutes on Day 1 of each 28-day cycle until disease progression or until unacceptable toxicity. Administer dexamethasone 40 mg orally or intravenously on Days 1, 8, 15 and 22 of each cycle. For patients 75 years of age or older, reduce the dose of dexamethasone to 20 mg. Refer to the prescribing information for dexamethasone for additional dosing information [see Clinical Studies (14)].
Recommended Premedication and Concomitant Medications
Consider providing a serotonin-3 (5-HT3) receptor antagonist or other antiemetics prior to and during the treatment with PEPAXTO.
Dosage Modifications for Adverse Reactions
Withold PEPAXTO if the neutrophil count is less than 1 × 109/L or the platelet count is less than 50 × 109/L.
The recommended dose reductions and dosage modifications for adverse reactions for PEPAXTO are presented in Table 1 and Table 2, respectively.
| Dose Reduction | Dosage* |
|---|---|
|
|
| First | 30 mg |
| Second | 20 mg |
| Subsequent | Permanently discontinue PEPAXTO in patients who are unable to tolerate 20 mg. |
| Adverse Reaction | Severity | Dosage Modification |
|---|---|---|
| Myelosuppression [see Warnings and Precautions (5.1, 5.2)] |
Platelet count less than 50 × 109/L on an intended PEPAXTO dosing day |
|
| Absolute neutrophil count less than 1 × 109/L on an intended PEPAXTO dosing day |
|
|
| Grade 4 hematological adverse reaction on an intended PEPAXTO dosing day in 2 consecutive cycles |
|
|
| Non-Hematologic Adverse Reaction [see Adverse Reactions (6.1)] | Grade 2 |
|
| Grade 3 or 4 |
|
Preparation and Administration
PEPAXTO is a hazardous drug. Follow applicable special handling and disposal procedures.1
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if visibly opaque particles, discoloration or foreign particles are observed.
Reconstitute and dilute PEPAXTO prior to infusion.
Additional agents required for preparation:
- 5% Dextrose Injection, USP (room temperature)
- 250 mL bag of cold (2°C to 8°C / 36°F to 46°F) 0.9% Sodium Chloride Injection, USP (refrigerate for at least 4 hours)
Preparation Steps:
Read the complete instructions prior to starting preparation.
Steps 3 to 5 must be completed within 30 minutes.
| Reconstitution and dilution steps |
| Step 1 Determine the dose, the total volume of reconstituted PEPAXTO solution required, and the number of PEPAXTO vials needed. More than one vial may be needed for a full dose. Place PEPAXTO vial(s) at room temperature for at least 30 minutes. |
| Step 2 Shake the vial(s) vigorously or vortex to disintegrate the lyophilized PEPAXTO powder cake into a loose powder. |
| Step 3 to 5 must be completed within 30 minutes |
| Step 3 Aseptically reconstitute each vial with 40 mL of 5% Dextrose Injection, USP to obtain a final concentration of 0.5 mg/mL. Ensure the 5% Dextrose Injection, USP is room temperature (20°C to 25°C / 68°F to 77°F). Shake the vial(s) vigorously until solution is clear. Let the vial(s) stand to allow air bubbles to dissipate to confirm a clear solution. |
| Step 4 Withdraw 80 mL from a refrigerated (2°C to 8°C / 36°F to 46°F) 250 mL infusion bag of 0.9% Sodium Chloride Injection, USP. Discard the withdrawn 80 mL. |
| Step 5 Withdraw the required volume of reconstituted solution from the PEPAXTO vial(s) and transfer into an intravenous bag containing 0.9% Sodium Chloride Injection, USP to obtain a final concentration of 0.1 mg/mL to 0.16 mg/mL. Discard any unused portion left in the vial(s). Gently invert the bag to mix the solution. Do not shake. Check that the PEPAXTO solution is clear and colorless to pale yellow. Do not use if solution discoloration or particles are observed. |
Storage timelines:
PEPAXTO degrades in solution, especially at room temperature, and the storage timelines for diluted solution should not be exceeded:
| For immediate administration: |
| Infusion of the diluted PEPAXTO solution must begin within 60 minutes of start of reconstitution (step 3). |
| For delayed administration: |
| If not used for immediate administration, the diluted PEPAXTO solution should be placed in a refrigerator (2°C to 8°C / 36°F to 46°F) within 30 minutes after initial reconstitution (step 3) and store for up to 6 hours. |
Administration:
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if visibly opaque particles, discoloration or foreign particles are observed.
| Administration steps |
| Step 6 Administer PEPAXTO as a 30-minute intravenous infusion via a central venous access device, for example mediport, PICC or tunneled central venous catheter. If the infusion bag has been stored in a refrigerator, allow to reach to room temperature (20°C to 25°C / 68°F to 77°F). Start infusion within 30 minutes of removing the diluted PEPAXTO solution from the refrigerator. |
| Step 7 Administer PEPAXTO as an intravenous infusion via a central catheter over 30 minutes. |
| Step 8 Upon completion of PEPAXTO infusion, flush the central catheter per individual institutional guidelines. |
