Melphalan Flufenamide: Uses, Side Effects, Dosage - Drugvu

ℹ️ Compiled from public regulatory records · Last regulator revision: November 21, 2025🚩 Report this page

Melphalan Flufenamide

Nitrogen Mustard Analogues

Sold as Pepaxti

EU EMAGB MHRA

Drug class: Nitrogen Mustard Analogues
Availability: See label
Markets covered: 2
Products on record: 3

Overview

Melphalan Flufenamide is an active pharmaceutical ingredient in the Nitrogen Mustard Analogues group (L01AA). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.

Regulatory status by market

Market	Regulator	Products	Last revision
EU European Union	EMA	1	January 13, 2025
GB United Kingdom	MHRA	2	November 21, 2025

EUEuropean Union· EMA

1 product

Uses

EUOfficial regulatory label· revised January 13, 2025[1]

Pepaxti is indicated, in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy.
4).

How to take

GBUnited Kingdom· MHRA

2 products

2 products on record with this regulator. Detailed label text (uses, dosage, side effects) is being ingested — the original document is linked under Sources [2].

Drug interactions

Known interactions involving Melphalan Flufenamide. Select one for details. This list is informational and not a complete interaction checker.

Cytarabine Dacarbazine Ifosfamide Vinblastine Daunorubicin Gatifloxacin Trovafloxacin Zinc Chloride Zinc Gluconate Zinc Sulfate

Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.

Sources & citations

[1]European Medicines Agency · EMEA/H/C/005681 · revised January 13, 2025
[2]MHRA (UK) · PLGB461170001 · revised November 21, 2025

Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.

Treatment with Pepaxti must be initiated and supervised by physicians experienced in the treatment of multiple myeloma. Posology The recommended starting dose of Pepaxti is 40 mg on Day 1 of each 28-day treatment cycle. For patients with a body weight of 60 kg or less the recommended starting dose is 30 mg on Day 1 of each 28-day cycle.
1). The recommended dose of dexamethasone is 40 mg orally on Days 1, 8, 15 and 22 of each 28-day treatment cycle. For patients 75 years of age and older the recommended dose of dexamethasone is 20 mg. 1 and the corresponding Summary of Product Characteristics.
Dose modification for adverse reactions Pepaxti must be withheld if the neutrophil count is less than 1 × 109/L or the platelet count is less than 50 × 109/L. The recommended dose reduction and dosage modifications for adverse reactions of Pepaxti are presented in Table 1 and Table 2, respectively.
3 Table 1: Recommended dose reduction for adverse reactions of Pepaxti Dose reduction Dose* in patients with body weight greater than 60 kg Dose* in patients with body weight of 60 kg or less 40 mg 30 mg First 30 mg 20 mg Second 20 mg 15 mg Third 15 mg Permanently discontinue Pepaxti in patients who are unable to tolerate 15 mg Subsequent Permanently discontinue Pepaxti in patients who are unable to tolerate 15 mg - *Administered intravenously on Day 1 of each 28-day cycle.
4) Platelet count less than 50 × 109/L on an intended Pepaxti dosing day • Withhold Pepaxti and monitor platelet count weekly until platelet count is 50 × 109/L or greater. • Resume Pepaxti at 1 dose level lower. Absolute neutrophil count less than 1 × 109/L on an intended Pepaxti dosing day • Withhold Pepaxti and monitor neutrophil count weekly until neutrophil count is 1 × 109/L or greater.
• Resume Pepaxti at 1 dose level lower. 8) Grade 2 • Consider withholding Pepaxti until resolved to at least Grade 1 or baseline. • Consider resuming Pepaxti at 1 dose level lower. Grade 3 or 4 • Withhold Pepaxti until resolved to at least Grade 1 or baseline.
• Consider resuming Pepaxti at 1 dose level lower. 8). 4). Special populations Elderly No dose adjustment is recommended for elderly patients. 73 m2. 73 m2. 2). 2). There are insufficient data in patients with moderate or severe hepatic impairment to support a dose recommendation.
4 Paediatric population The safety and efficacy of Pepaxti in children below 18 years of age have not been established. No data are available. Method of administration Pepaxti is for intravenous use. Pepaxti should be administered as a 30-minute infusion via a peripheral venous route or a central venous access device, such as a peripherally inserted central catheter (PICC) or a tunnelled central venous catheter.
If administered peripherally, it is recommended to alternate veins for infusion. In case of extravasation, the administration should be interrupted immediately and a central venous line should be used. Pepaxti must be reconstituted and diluted by a healthcare professional prior to administration.
Infusion of the diluted solution must begin within 60 minutes of start of initial reconstitution or be placed in a refrigerator within 30 minutes from start of initial reconstitution. 6.

Side effects & warnings

EUOfficial regulatory label· Adverse reactions· revised January 13, 2025[1]

8. When the melphalan flufenamide metabolite melphalan is used in combination with lenalidomide and prednisone, and to a lesser extent in combination with thalidomide and prednisone, it has been linked to an increased risk of solid SPMs for elderly patients with newly diagnosed multiple myeloma.
Melphalan flufenamide is not indicated in combination with lenalidomide or thalidomide. Patients should be monitored closely before and during treatment for occurrence of SPM. 1). This is based on results from study OP-103 (OCEAN), a randomised phase 3 trial in patients with relapsed or refratory multiple myeloma following 2 to 4 lines of prior therapy and refractory to lenalidomide and the last line of therapy.
1; n=101), respectively. 0; n=145) on melphalan flufenamide/dexamethasone vs. 5; n=148) in the pomalidomide/dexamethasone arm. Myeloablative conditioning treatment The efficacy and safety of Pepaxti at doses required for myeloablation have not been studied in humans.
Pepaxti should not be used for conditioning treatment prior to stem cell transplantation. Renal impairment Since patients with renal impairment may have marked bone marrow suppression, these patients should be closely monitored. 2). Attenuated live vaccines A risk of severe illness that may lead to fatal outcome has been described with the metabolite melphalan in patients receiving attenuated live vaccines.
This risk is increased in patients who are already immunosuppressed by their underlying disease. An inactivated or mRNA based vaccine should be used when such a vaccine exists. 5 Interaction with other medicinal products and other forms of interaction No interaction studies have been performed with melphalan flufenamide.
2). 6 Fertility, pregnancy and lactation Women of childbearing potential/Contraception in males and females As with all cytotoxic treatments, male and female patients who use melphalan flufenamide should use effective and reliable contraceptive methods until six months after cessation of treatment.
Pregnancy There are no data from the use of melphalan flufenamide in pregnant women. 3). Due to the genotoxic properties and structural similarity of melphalan flufenamide with known teratogenic compounds, it is possible that melphalan flufenamide can induce congenital malformations in offspring of treated patients.
Melphalan flufenamide should not be used during pregnancy unless the clinical condition of the woman requires treatment with melphalan flufenamide. Breast-feeding It is unknown whether melphalan flufenamide or its metabolites are excreted in human milk.
3). Fertility Melphalan flufenamide, as other agents with alkylating properties, is expected to suppress ovary function in premenopausal women, resulting in amenorrhea in a large number of patients. 3). Cryopreservation of semen before treatment is advised.
7 Effects on ability to drive and use machines Pepaxti has moderate influence on the ability to drive and use machines. It is possible that certain adverse reactions of melphalan flufenamide, such as dizziness and nausea, may affect this ability.
8 Undesirable effects Summary of the safety profile The safety of Pepaxti in combination with dexamethasone has been evaluated in 491 patients with multiple myeloma, including 147 patients with triple-class refractory disease who have received at least three prior lines of therapies.
The most frequent adverse reactions are thrombocytopenia (83%), neutropenia (72%), anaemia (66%), nausea (21%), diarrhoea (19%) and pyrexia (19%). The most frequent serious adverse reactions are pneumonia (11%), thrombocytopenia (5%) and respiratory tract infection (4%).
Tabulated list of adverse reactions Table 3 summarises adverse reactions that were reported in patients receiving Pepaxti. The data reflect exposure of Pepaxti in 13 patients as single agent and in 478 patients in combination with dexamethasone.
Adverse reactions are described using MedDRA terms. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000) and not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 3:
Adverse reactions reported in patients with multiple myeloma treated with Pepaxti in clinical studies System OrganClass Adverse reactions Frequency overall Frequency Grade 3/4 Infections and infestations Septic shock Uncommon Uncommon Sepsis1 Common Common Pneumonia2 Very common Common Respiratory tract Infection3 Very common Common Neoplasms […]

EUOfficial regulatory label· Warnings and precautions· revised January 13, 2025[1]

Melphalan flufenamide can cause local tissue damage. 2). Thrombocytopenia Pepaxti may cause thrombocytopenia. 8). As thrombocytopenia may increase the risk for serious bleeding events, patients should be advised to contact a physician if signs or symptoms of bleeding and bruising occur.
Platelet counts should be monitored at baseline, during treatment, and as clinically indicated. Patients should be monitored more frequently during the first two months of treatment. Pepaxti should not be administered if the platelet count is less than 50 × 109/L.
Treatment should be withheld until platelet count is 50 × 109/L or greater (without recent transfusions) and resume treatment at one dose level lower. 2). Treating thrombocytopenia with transfusions and/or other treatments should be considered as clinically indicated.
Neutropenia Pepaxti may cause neutropenia. 8). As neutropenia may increase the risk for infections, patients should be advised to contact a physician if signs or symptoms of infection occur. Neutrophil count should be monitored at baseline, during treatment, and as clinically indicated.
Patients should be monitored more frequently during the first two months of treatment. Pepaxti should not be administered if absolute neutrophil count is less than 1 × 109/L. Treatment should be withheld until absolute neutrophil count is 1 × 109/L or greater and resume treatment at one dose level lower.
2). 2). 8). Red blood cell counts should be monitored at baseline, during treatment, and as clinically indicated. Patients should be monitored more frequently during the first two months of treatment. Treating anaemia with transfusions and/or erythropoietin should be considered as clinically indicated.
8). Patients should be closely monitored for signs of infection. Treating infections with antimicrobials should be considered as clinically indicated. 8). 2). 8). Patients with known risk factors for thromboembolism, including prior thrombosis, should be closely monitored.
A decision to take prophylactic measures should be made after a careful assessment of the individual patient’s underlying risk factors, including the occurrence of thrombocytopenia. In high-risk patients, anti-thrombotic prophylaxis can be considered.

This is not medical advice. Consult a qualified healthcare professional.