enfortumab vedotin

Action and Spectrum

Actions and Spectrum: 

Actions: 

The actions of enfortumab vedotin include: 

• Selective targeting: The antibody component of enfortumab vedotin recognizes and binds specifically to Nectin-4, a protein overexpressed on the surface of urothelial cancer cells. This targeting allows for selective delivery of the cytotoxic payload to cancer cells while sparing normal healthy cells. 
• Internalization and payload release: After binding to Nectin-4, enfortumab vedotin is internalized into the cancer cell through receptor-mediated endocytosis. Once inside the cell, the drug is processed, and the cytotoxic payload (MMAE) is released. 
• Microtubule disruption: The released MMAE inhibits microtubule assembly, which is essential for cell division and maintenance of cell structure. By disrupting the microtubule network, enfortumab vedotin induces cell cycle arrest and triggers apoptotic cell death in the cancer cells. 

Spectrum: 

enfortumab vedotin’s activity primarily focuses on locally advanced or metastatic urothelial cancer that has progressed after platinum-containing chemotherapy. It is not indicated for treating other types of cancer or earlier stages of urothelial cancer. The drug has shown promising clinical results in patients who have experienced disease progression despite prior treatment, providing a new treatment option for those in need.

Drug Interaction

Adverse Reaction

Adverse drug reactions:    

Frequency defined 

>10%  

Peripheral neuropathy (50-58%) 

Fatigue (48-56%) 

Rash (52-66%) 

Nausea (30-45%) 

Dysgeusia (26-42%) 

Alopecia (47-53%) 

Decreased appetite (40-52%) 

Anemia (20-38%) 

Pruritus (26-35%) 

Diarrhea (35-42%) 

Dry eye (30-40%) 

Musculoskeletal pain (25%) 

Pyrexia (22%) 

Weight decreased (16-35%) 

Constipation (28%) 

Dry skin (17-26%) 

Abdominal pain (20%) 

Vomiting (14%) 

AST increased (12%) 

Vomiting (13-18%) 

Urinary tract infection (17%) 

Hemorrhage (16-17%) 

1-10%    

ALT increased (9-10%) 

Hemoglobin decreased (4-10%) 

Hyperglycemia (10%) 

Urate increased (7-9%) 

Pneumonitis (3-4%) 

Phosphate decreased (7-10%) 

Sodium decreased (7-8%) 

Hyperglycemia (9%) 

Lipase increased (8-9%) 

Decreased appetite (2-6%) 

Infusion site extravasation (0.7-1%) 

Diarrhea (6-8%) 

Peripheral neuropathy (4-8%) 

Urinary tract infection (6%) 

<1% 

Dry eye (0.7%) 

Black Box Warning

Black Box Warning: 

The overdose may cause severe skin infections. Monitor the patient for skin reactions. 

Permanently discontinue the medication if Stevens-Johnson syndrome or toxic epidermal necrolysis occurs. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications: 

• Hypersensitivity: enfortumab vedotin should not be used in patients who are hypersensitive to the drug or its components. 
• Severe renal impairment: enfortumab vedotin has not been studied in patients with severe renal impairment; hence use cautiously. 

Cautions: 

Caution should be maintained in the patients with the below conditions: 

• Hyperglycemia 
• Ocular disorders 
• Peripheral nephropathy 
• Hepatic impairment 
• Drug interactions 
• Pregnancy 
• Lactation 

Pregnancy / Lactation

Pregnancy  

The animal study reports show enfortumab is unsuitable for the ingrowing fetus; hence is not advised to be administered during pregnancy. 

Breastfeeding warnings:    

The excretion of a drug into the breastmilk is unknown 

Due to the potential adverse drug reactions reported, the drug is not recommended in lactating females during treatment. 

Pregnancy Categories:      

• Category A: Satisfactory and well-controlled studies show no risk to the fetus.  
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women      
• Category C: No adequate evidence for a result in humans must take care of potential risks in pregnant women      
• Category D: There is adequate data available 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 risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. Apart from this medication, pregnant women can prefer better alternatives. 
• Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology: 

enfortumab vedotin targets a protein called Nectin-4 that overexpresses urothelial cancer cells. The drug contains an anti-Nectin-4 monoclonal antibody that binds to Nectin-4 on cancer cells. The antibody is linked to a cytotoxic payload known as monomethyl auristatin E (MMAE). 

Upon binding to Nectin-4, enfortumab vedotin is internalized into the cancer cell through receptor-mediated endocytosis. Within the cancer cell, the linker connecting the antibody and MMAE is cleaved, releasing MMAE into the cytoplasm of the cancer cell. 

MMAE is a microtubule-disrupting agent that inhibits microtubule assembly. Microtubules are essential for cell division and maintaining cell structure. By disrupting the microtubule network, enfortumab vedotin induces cell cycle arrest and triggers apoptotic cell death in the cancer cells. 

Pharmacodynamics: 

enfortumab vedotin targets a protein called Nectin-4, which is overexpressed on the surface of specific cancer cells, particularly urothelial cancer cells. The drug contains an anti-Nectin-4 monoclonal antibody that binds to Nectin-4 on cancer cells. The antibody is linked to a cytotoxic payload known as monomethyl auristatin E (MMAE). 

Upon binding to Nectin-4, enfortumab vedotin is internalized into the cancer cell through receptor-mediated endocytosis. Within the cancer cell, the linker connecting the antibody and MMAE is cleaved, releasing MMAE into the cytoplasm of the cancer cell. 

MMAE is a microtubule-disrupting agent that inhibits microtubule assembly. Microtubules are essential for cell division and maintaining cell structure. By disrupting the microtubule network, enfortumab vedotin induces cell cycle arrest and triggers apoptotic cell death in the cancer cells. 

Pharmacokinetics:  

Absorption 

enfortumab vedotin is administered intravenously, resulting in rapid and complete systemic exposure to the drug. The bioavailability of enfortumab vedotin following intravenous administration is 100%.  

Distribution 

enfortumab vedotin distributes throughout the body to tumor tissues expressing the target protein Nectin-4. The volume of distribution of enfortumab vedotin at steady state is approximately 3.47 L. 

Metabolism  

enfortumab vedotin undergoes proteolytic degradation in the body, primarily mediated by enzymes such as cathepsin B and lysosomal proteases. The specific metabolic pathways and enzymes involved in the degradation of enfortumab vedotin have yet to be fully characterized.  

Elimination and excretion 

The elimination half-life of enfortumab vedotin is approximately 4 to 6 days. The drug is primarily eliminated through proteolytic degradation, with a small portion excreted unchanged in the feces. Renal excretion is not a significant route of elimination for enfortumab vedotin. 

Adminstartion

Administration: 

enfortumab vedotin is supplied as a lyophilized powder in single-dose vials. Before administration, the powder must be reconstituted and diluted. Follow the manufacturer’s instructions and the prescribing information for the specific reconstitution and dilution process. 

Dilute the reconstituted solution further with 0.9% Sodium Chloride.  The solution formed should be clear to slightly opalescent and free from visible particles. Inspect the solution visually before administration, and do not use it if it appears cloudy or contains particulate matter. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: enfortumab vedotin 

Pronounced: en-FORT-ue-mab-ve-DOE-tin 

Why do we use enfortumab vedotin? 

enfortumab vedotin (Padcev) is used to treat adult patients with metastatic urothelial cancer who have already received platinum-containing chemotherapy and a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

enfortumab vedotin is specifically indicated for patients who may have received platinum-containing chemotherapy before, such as cisplatin or carboplatin, a standard treatment for advanced or metastatic urothelial cancer.