{{Short description|An article about the chemotherapy drug Melphalan flufenamide}}
* Melphalan flufenamide (PEPAXTO) is an alkylating drug indicated in combination with [[dexamethasone]], for the treatment of adult patients with relapsed or [[refractory]] [[multiple myeloma]].
==Overview==
[[File:Melphalan_flufenamide.svg|thumb|right|Chemical structure of Melphalan flufenamide]]
'''Melphalan flufenamide''', also known as '''melflufen''', is a peptide-conjugated alkylating agent used in the treatment of multiple myeloma. It is a prodrug of [[melphalan]], designed to enhance the delivery of the active drug to cancer cells by exploiting the increased expression of aminopeptidases in these cells.
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==Mechanism of Action==
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Melphalan flufenamide is a lipophilic dipeptide that is rapidly taken up by cells. Once inside the cell, it is cleaved by aminopeptidases to release melphalan, which then exerts its cytotoxic effects by forming cross-links with DNA. This cross-linking inhibits DNA replication and transcription, ultimately leading to cell death.
Melphalan flufenamide is primarily used in the treatment of [[multiple myeloma]], a type of blood cancer that affects plasma cells. It is often used in patients who have received prior therapies and have relapsed or refractory disease. The drug is administered intravenously and is typically used in combination with other agents such as [[dexamethasone]].
* This medicine used in combination with the medicine [[dexamethasone]] to treat adults with [[multiple myeloma]] who did not respond to or stopped responding to at least four prior medicines including at least one [[proteasome inhibitor]], one immunomodulatory agent and one CD38-directed antibody.
==Side Effects==
* PEPAXTO is not for use to prepare for transplant.
The side effects of melphalan flufenamide are similar to those of other alkylating agents. Common adverse effects include myelosuppression, which can lead to [[neutropenia]], [[thrombocytopenia]], and [[anemia]]. Other side effects may include nausea, fatigue, and infections due to immunosuppression.
== '''How does this medicine work?''' ==
==Pharmacokinetics==
Melphalan flufenamide is rapidly distributed in the body after intravenous administration. The prodrug is designed to enhance the delivery of melphalan to tumor cells, thereby increasing its efficacy while potentially reducing systemic toxicity. The drug is metabolized by aminopeptidases and other enzymes, and its metabolites are excreted primarily in the urine.
* A peptide-drug conjugate composed of a peptide conjugated, via an aminopeptidase-targeting linkage, to the alkylating agent melphalan, with potential [[antineoplastic]] and [[Anti-angiogenic peptide|anti-angiogenic]] activities.
==Development and Approval==
* Upon administration, the '''highly lipophilic melphalan flufenamide penetrates cell membranes and enters cells'''.
Melphalan flufenamide was developed to improve the therapeutic index of melphalan by increasing its selectivity for cancer cells. It has undergone clinical trials to evaluate its safety and efficacy in patients with multiple myeloma. The drug has been approved for use in several countries for patients with relapsed or refractory multiple myeloma.
* In aminopeptidase-positive tumor cells,''' melphalan flufenamide is hydrolyzed by peptidases to release the hydrophilic alkylating agent melphalan'''.
* This '''results in the specific release and accumulation of melphalan in aminopeptidase-positive tumor cells'''.
* Melphalan alkylates DNA at the N7 position of guanine residues and induces DNA intra- and inter-strand cross-linkages.
* This results in the '''inhibition of DNA and RNA synthesis and the induction of apoptosis, thereby inhibiting tumor cell proliferation'''.
* Peptidases are overexpressed by certain cancer cells.
* The administration of melphalan flufenamide allows for enhanced efficacy and reduced toxicity compared to melphalan.
== '''Who Should Not Use this medicine ?''' ==
==Related pages==
* [[Melphalan]]
* [[Multiple myeloma]]
* [[Chemotherapy]]
* [[Alkylating agent]]
This medicine cannot be used in patients with:
[[Category:Chemotherapy]]
* a history of serious [[hypersensitivity]] reaction to melphalan flufenamide or melphalan.
[[Category:Antineoplastic drugs]]
'''Limitations of Use:''' PEPAXTO is not indicated and is not recommended for use as a conditioning regimen for transplant outside of controlled clinical trials.
== '''Is this medicine FDA approved?''' ==
* It was approved for use in the United States in 2021.
== '''How should this medicine be used?''' ==
'''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.
* Consider providing a serotonin-3 (5-HT3) receptor antagonist or other antiemetics prior to and during the treatment with PEPAXTO.
'''Administration'''
* PEPAXTO is given to you by your healthcare provider into your vein through intravenous (IV) infusion over 30 minutes.
* PEPAXTO is usually given 1 time every 28 days.
* Your healthcare provider will decide how many treatments you need.
* Your healthcare provider will do blood tests before and during your treatment with PEPAXTO to check for side effects.
* Your healthcare provider may prescribe medicines to help prevent nausea before your infusion and during treatment with PEPAXTO.
== '''What are the dosage forms and brand names of this medicine?''' ==
This medicine is available in fallowing doasage form:
* '''As injection:''' 20 mg melphalan flufenamide as a lyophilized powder in single-dose vial for reconstitution and dilution.
This medicine is available in fallowing brand namesː
*'''PEPAXTO'''
=='''What side effects can this medication cause?'''==
The most common side effects of this medicine include:
PEPAXTO may cause serious side effects, including:
* Low blood cell counts
* Infections
* Secondary cancers
==''' What special precautions should I follow?''' ==
* [[Thrombocytopenia]] may occur. Monitor platelet counts at baseline, during treatment, and as clinically indicated. Dose delay or dose reduction may be required to allow recovery of platelets.
* This medicine may cause [[Neutropenia]] Monitor neutrophil counts at baseline, during treatment and as clinically indicated. Monitor patients with neutropenia for signs of infection. Dose delay or dose reduction may be required to allow recovery of neutrophils.
* Monitor red blood cell counts at baseline, during treatment, and as clinically indicated.
* Monitor for signs/symptoms of infection and treat promptly.
* Dosages exceeding the recommended dose for PEPAXTO may be associated with mortality.
* Monitor patients long-term for the development of secondary malignancies.
* This medicine Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception.
== '''What to do in case of emergency/overdose?''' ==
* Dosages exceeding the recommended dose for PEPAXTO may be associated with mortality.
== '''Can this medicine be used in pregnancy?''' ==
* PEPAXTO can cause fetal harm when administered to a pregnant woman.
* There are no available data on PEPAXTO use in pregnant women to evaluate for a drug-associated risk.
=='''Can this medicine be used in children?'''==
* The safety and effectiveness of PEPAXTO have not been established in pediatric patients.
== '''What are the active and inactive ingredients in this medicine?''' ==
'''Active ingredient:''' melphalan flufenamide
'''Inactive ingredient:''' sucrose
== '''Who manufactures and distributes this medicine?''' ==
* Manufactured for Oncopeptides AB (publ)
* Marketed and distributed by Oncopeptides Inc.
== '''What should I know about storage and disposal of this medication?''' ==
'''Storage'''
* Store refrigerated at 2°C to 8°C (36°F to 46°F) and protect from light.
* Retain in original carton until use.
'''Handling and Disposal'''
* PEPAXTO is a hazardous drug.
* Follow special handling and disposal procedures.
* All materials that have been utilized for dilution and administration, including any reconstituted solution made over 30 minutes prior, should be disposed of according to standard procedures for hazardous drugs.
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{{DEFAULTSORT:Melphalan Flufenamide}}
[[Category:Alkylating agents]]
[[Category:Cancer treatments]]
[[Category:Dipeptides]]
[[Category:Orphan drugs]]
[[Category:Prodrugs]]
[[Category:Prodrugs]]
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{{antineoplastic-agents-stub}}
Revision as of 05:42, 16 February 2025
An article about the chemotherapy drug Melphalan flufenamide
Melphalan flufenamide, also known as melflufen, is a peptide-conjugated alkylating agent used in the treatment of multiple myeloma. It is a prodrug of melphalan, designed to enhance the delivery of the active drug to cancer cells by exploiting the increased expression of aminopeptidases in these cells.
Mechanism of Action
Melphalan flufenamide is a lipophilic dipeptide that is rapidly taken up by cells. Once inside the cell, it is cleaved by aminopeptidases to release melphalan, which then exerts its cytotoxic effects by forming cross-links with DNA. This cross-linking inhibits DNA replication and transcription, ultimately leading to cell death.
Clinical Use
Melphalan flufenamide is primarily used in the treatment of multiple myeloma, a type of blood cancer that affects plasma cells. It is often used in patients who have received prior therapies and have relapsed or refractory disease. The drug is administered intravenously and is typically used in combination with other agents such as dexamethasone.
Side Effects
The side effects of melphalan flufenamide are similar to those of other alkylating agents. Common adverse effects include myelosuppression, which can lead to neutropenia, thrombocytopenia, and anemia. Other side effects may include nausea, fatigue, and infections due to immunosuppression.
Pharmacokinetics
Melphalan flufenamide is rapidly distributed in the body after intravenous administration. The prodrug is designed to enhance the delivery of melphalan to tumor cells, thereby increasing its efficacy while potentially reducing systemic toxicity. The drug is metabolized by aminopeptidases and other enzymes, and its metabolites are excreted primarily in the urine.
Development and Approval
Melphalan flufenamide was developed to improve the therapeutic index of melphalan by increasing its selectivity for cancer cells. It has undergone clinical trials to evaluate its safety and efficacy in patients with multiple myeloma. The drug has been approved for use in several countries for patients with relapsed or refractory multiple myeloma.
