Pepaxto

About Melphalan flufenamide

• Pepaxto, contains the active ingredient melphalan flufenamide. It is an antineoplastic that belongs to the class of drugs known as alkylating agents.
• Melphalan flufenamide received FDA approval on February 26, 2021.
• It provides a new treatment avenue for patients with advanced multiple myeloma who have limited options. Indicated for relapsed or refractory multiple myeloma in adults who’ve undergone at least four prior lines of therapy. 
• Using Pepaxto as a conditioning regimen for transplant outside of controlled clinical trials is neither indicated nor recommended.
• Pepaxto, operates as a peptide-conjugated alkylating drug, targeting aminopeptidases overexpressed in multiple myeloma cells. 
• This action leads to the rapid release of alkylating agents into tumor cells, causing irreversible DNA damage and apoptosis of cancer cells. By leveraging aminopeptidases prevalent in multiple myeloma cells, Pepaxto induces the release of cytotoxic agents.
• Administered intravenously with dexamethasone, it induces irreversible DNA damage, prompting cancer cell apoptosis, specifically in those resistant to other treatments.

Strength: 

• Each single-dose vial contains 20 mg of Melphalan flufenamide as a lyophilized powder for reconstitution and dilution.

Recommended Dosage:

Consider antiemetics before and during Pepaxto injection. Inspect drug products visually for abnormalities prior to administration. Reconstitute Pepaxto by shaking vial(s) with 40 mL of 5% Dextrose Injection, USP. Withdraw 80 mL from a refrigerated 250 mL infusion bag of 0.9% Sodium Chloride Injection, USP. Discard 80 mL, and transfer reconstituted solution to achieve a concentration of 0.1-0.16 mg/mL. 

For immediate use, infuse within 60 minutes of reconstitution; refrigerate for delayed use and administer within 6 hours. Administer Pepaxto as a 30-minute IV infusion via a central venous access device, and flush the catheter post-infusion. Adhere strictly to storage timelines and visually inspect products to prevent adverse events.

• The recommended dosage of Pepaxto is 40 mg given intravenously over 30 minutes on Day 1 of every 28-day cycle, continuing until disease progression or unacceptable toxicity occurs. 
• Dexamethasone should be administered orally or intravenously at a dose of 40 mg on Days 1, 8, 15, and 22 of each cycle. For patients aged 75 years or older, the dose of dexamethasone should be reduced to 20 mg.

Important:

Prior to initiating treatment, it is essential to engage in a comprehensive discussion with your healthcare provider regarding any current medications, medical conditions, pregnancy status, or intentions for breastfeeding. This dialogue allows your doctor to evaluate potential drug interactions and customize a treatment regimen that aligns with your specific requirements, emphasizing your safety and health. For personalized information and guidance, it is recommended to seek further clarification and advice from your doctor.

Warnings & Precautions

• Pepaxto injection is contraindicated in patients with a documented history of severe hypersensitivity reactions to melphalan flufenamide or melphalan. 
• Thrombocytopenia, neutropenia, and anemia should be monitored regularly during treatment, with potential dose adjustments to manage these hematologic abnormalities. 
• Vigilance for signs of infection is crucial, and prompt treatment initiation is necessary if infection occurs. 
• The use of Pepaxto at dosages exceeding recommendations may increase the risk of mortality, and long-term surveillance is advised to detect secondary malignancies. 
• Patients of reproductive potential should be informed about the potential embryo-fetal toxicity and advised to use effective contraception during the therapy.

Common Pepaxto Side Effects:

• Fatigue
• Nausea
• Diarrhea
• Pyrexia (fever)
• Respiratory tract infection
• Decreased leukocytes
• Decreased platelets
• Decreased lymphocytes
• Decreased neutrophils
• Decreased hemoglobin
• Increased creatinine levels

Use in Specific Population

• Pepaxto poses a risk of fetal harm due to its mechanism of action, and its genotoxic nature underscores the need for caution in pregnant women.
• Due to insufficient data on melphalan flufenamide in breast milk, breastfeeding is not recommended during Pepaxto treatment and for one week after the last dose due to potential adverse effects on infants.
• Both men and women of reproductive age should undergo pregnancy testing before starting Pepaxto. Females should use contraception during treatment and for six months after the last dose, while males should use contraception for three months post-treatment due to potential genotoxicity.
• Pepaxto can affect fertility in both men and women and hasn’t been extensively studied in pediatric or older patients. No dose adjustment is needed for renal function with creatinine clearance between 45 and 89 mL/min, but its use in patients with renal impairment below 45 mL/min hasn’t been studied.

Storage and Handling

• Store Pepaxto at 2°C to 8°C (36°F to 46°F)
• Keep the medicine protected from moisture.
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.