melphalan flufenamide

Action and Spectrum

Actions and Spectrum 

melphalan flufenamide is an alkylating drug that prevents cancer cells from proliferating and developing by interconnecting DNA strands. melphalan flufenamide attempts to boost the uptake and retention of melphalan within cancer cells, potentially improving its therapeutic efficacy. 

Regarding the range of activity, multiple myeloma, a type of cancer that affects plasma cells in the bone marrow, has been the primary target of research on melphalan flufenamide. 

Drug Interaction

Adverse Reaction

Frequency defined  

 >10% 

Gastrointestinal: Constipation (15%), diarrhea (27%), nausea (32%), decreased appetite (14%), vomiting (13%) 

Cardiovascular: Peripheral edema (14%) 

Respiratory: Cough (17%), pneumonia (13%), respiratory tract infection (24%), dyspnea (11%) 

Endocrine & metabolic: Hypokalemia (14%) 

Infection: Infection (58%) 

Miscellaneous: Fever (24%) 

Nervous system: Dizziness (11%), headache (13%), fatigue (55%), insomnia (11%) 

Hematologic & oncologic: Anemia (84%), neutropenia (95%), thrombocytopenia (99%), lymphocytopenia (97%), hemorrhage (28%), leukopenia (99%) 

Neuromuscular & skeletal: Back pain (12%), ostealgia (13%), limb pain (13%) 

Renal: Increased serum creatinine (68%) 

1-10% 

Neuromuscular & skeletal: Arthralgia (10%) 

Infection: Sepsis (4%) 

Hypersensitivity: Hypersensitivity reaction (7%) 

Endocrine & metabolic: Hypocalcemia (10%) 

Hematologic & oncologic: Febrile neutropenia (6%) 

Respiratory: Dyspnea on exertion (10%) 

Frequency not defined 

Respiratory: Respiratory failure 

Hematologic & oncologic: Second primary malignant neoplasm 

Black Box Warning

Black Box Warning 

There was no specific black box warning associated with melphalan flufenamide drug. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• melphalan flufenamide or any of its components should not be used by people with known history of allergic or hypersensitive to them. 

Caution: 

• Because there is a chance that drug metabolism and elimination may be modified in patients with substantial renal impairment, dose modifications or close monitoring may be necessary. 
• Due to possible alterations in medication metabolism and clearance, patients with substantial hepatic impairment may need dosage modifications or close monitoring. 
• Blood cell counts may fall as a result of bone marrow suppression brought on by melphalan flufenamide. Patients with pre-existing blood problems should use caution. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion into human milk is unknown  

Pregnancy Categories:         

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.  

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women. 

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 

Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology  

melphalan flufenamide is made specifically to target cancer cells. Through peptide transporter systems, the peptide carrier enhances the drug’s uptake into cancer cells. melphalan flufenamide undergoes enzymatic cleavage once it has entered the cancer cells, releasing the active form of melphalan.  

The alkylating compound melphalan produces covalent DNA adducts, which cross-link DNA strands and prevent DNA replication and transcription. The demise of cancer cells is the ultimate effect of this interference with DNA function. 

Pharmacodynamics 

The normal structure and operation of DNA are hampered by the creation of DNA cross-links. DNA strands are kept from separating during the replication and transcription processes by cross-links. This interference prevents the creation of fresh DNA strands and RNA molecules, impairing crucial cellular functions and ultimately causing cell death. 

melphalan flufenamide mostly affects cells that are actively dividing, especially those that are in the S-phase of the cell cycle, which is when DNA replication takes place. During different stages of the cell cycle, it can potentially cause cytotoxic effects in the cells. 

Pharmacokinetics 

Absorption   

melphalan flufenamide is infused slowly intravenously when being administered. It achieves quick and thorough systemic absorption when administered intravenously. 

Distribution 

melphalan flufenamide distributes into the bodily tissues and has a moderate volume of distribution. It is present in breast milk and can penetrate the placenta and blood-brain barrier. 

Metabolism 

melphalan flufenamide is metabolized primarily in the liver through a process called hepatic biotransformation. Nonenzymatic hydrolysis is a key metabolic step that produces mono- and dihydroxy derivatives. Compared to the parent drug, these metabolites have decreased cytotoxic effect. 

Elimination and excretion 

melphalan flufenamide and its metabolites are mostly eliminated from the body through the kidneys after metabolism. It is primarily excreted through renal clearance, with a minor amount also passing through feces. 

Adminstartion

Administration 

melphalan flufenamide was administered as an intravenous (IV) infusion.

Patient Information Leaflet

Patient information leaflet 

Generic Name: melphalan flufenamide 

Why do we use melphalan flufenamide? 

Multiple myeloma, a form of cancer that affects plasma cells in the bone marrow, has been studied as a potential treatment for the investigational drug melphalan flufenamide.