IntravenousLocally advanced urothelial cancer, Metastatic urothelial cancerAdult: As single agent in patients who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy: 1.25 mg/kg (Max: 125 mg for patients ≥100 kg) via IV infusion over 30 minutes given on Days 1, 8, and 15 of a 28-day cycle. Continue until disease progression or unacceptable toxicity. In combination with pembrolizumab in patients who are ineligible for cisplatin-containing chemotherapy: 1.25 mg/kg (Max: 125 mg for patients ≥100 kg) via IV infusion over 30 minutes given on Days 1 and 8 of a 21-day cycle. Continue until disease progression or unacceptable toxicity. Dose reduction, dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).
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Moderate to severe (>1.5 times the ULN and any AST level): Contraindicated.
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Powder for solution for infusion: Calculate the appropriate dose to determine the correct number and strength of vials needed. Reconstitute vials labelled as 20 mg or 30 mg with 2.3 mL or 3.3 mL of sterile water for inj, respectively, by directing the stream along the inside walls of the vial to prepare a concentration of 10 mg/mL. Slowly swirl the vial to dissolve the contents and allow the reconstituted vial to settle for at least 1 minute until the bubbles are gone. Withdraw the appropriate dose volume from the vial, then dilute with NaCl 0.9% solution, dextrose 5% in water, or lactated Ringer's solution to make a final concentration of 0.3 mg/mL to 4 mg/mL. Mix by gentle inversion. Do not shake.
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Moderate to severe hepatic impairment. Pregnancy and lactation.
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Patient with pre-existing hyperglycaemia, diabetes and high BMI (≥30 kg/m2). Avoid extravasation.
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Significant: Peripheral neuropathy, particularly peripheral sensory and motor neuropathy; ocular effects (e.g. blurred vision, keratitis, conjunctivitis, keratopathy, limbal stem cell deficiency, dry eye syndrome), dermatologic effects (e.g. maculopapular rash, pruritus); skin and soft tissue injury (particularly if extravasation occurs).
Blood and lymphatic system disorders: Anaemia, neutropenia, febrile neutropenia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, abdominal pain, stomatitis, dysgeusia.
General disorders and administration site conditions: Fatigue, fever, gait disturbances.
Immune system disorders: Antibody development.
Investigations: Increased AST, ALT, and serum K; increased serum creatinine and uric acid; decreased Hb and serum Na levels; decreased weight.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Musculoskeletal pain, muscular weakness.
Nervous system disorders: Paraesthesia, hypoaesthesia.
Skin and subcutaneous tissue disorders: Alopecia, dry skin, erythematous or vesicular rash, bullous dermatitis, blister, eczema, skin exfoliation, palmar-plantar erythrodysaesthesia syndrome, drug eruption.
Vascular disorders: Haemorrhage.
Potentially Fatal: Interstitial lung disease (ILD) or pneumonitis; severe cutaneous adverse reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome); hyperglycaemia, diabetic ketoacidosis.
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Women of childbearing potential must use proven birth control methods during therapy and for at least 12 months after stopping the treatment. Men with female partners of childbearing potential should use proven birth control methods during treatment and for up to 9 months after treatment discontinuation.
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Confirm pregnancy status within 7 days before therapy initiation in women of childbearing potential. Monitor CBC with differential, LFTs, and blood glucose. For ocular effects that do not resolve, consider ophthalmologic evaluation. Hepatitis B virus screening with HBsAg, hepatitis B core antibody, total Ig or IgG, and antibody to HBsAg is recommended before or at the beginning of systemic chemotherapy. Closely monitor the infusion site. Assess for signs and symptoms of pneumonitis or ILD, new or worsening peripheral neuropathy, ocular effects, and skin reactions.
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May increase the exposure of unconjugated monomethyl auristatin E (MMAE) metabolite with strong CYP3A4 inhibitors (e.g. itraconazole, clarithromycin, ritonavir, nelfinavir, telaprevir, nefazodone) and ketoconazole (a combined P-gp and strong CYP3A4 inhibitor). May decrease the exposure of unconjugated MMAE metabolite with strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital).
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May decrease the exposure of unconjugated MMAE metabolite with St. John's wort.
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Description:
Mechanism of Action: Enfortumab vedotin is an antibody-drug conjugate (ADC) that targets nectin-4, an adhesion protein located on cell surfaces of urothelial cancer cells. It contains a fully human IgG1 kappa anti-nectin-4 antibody conjugated to a microtubule-disrupting agent, monomethyl auristatin E (MMAE), via a protease cleavable linker. ADC binds to nectin-4-expressing cells, followed by internalisation of ADC-nectin-4 complex within the cell, and the release of MMAE via proteolytic cleavage. The release of MMAE disrupts the microtubule network within the cell, subsequently resulting in the induction of cell cycle arrest and apoptosis.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: At the end of infusion (ADC); approx 2 days following the dose (unconjugated MMAE).
Distribution: Plasma protein binding: 68-82% (unconjugated MMAE).
Metabolism: Undergoes catabolism to form small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites. Unconjugated MMAE is released by ADC via proteolytic cleavage and metabolised mainly via oxidation by CYP3A4.
Excretion: Unconjugated MMAE: Via faeces (17%) and urine (6%) as unchanged drug. Elimination half-life: 2.6 days (unconjugated MMAE); 3.6 days (ADC).
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Intact vial: Store between 2-8°C. Do not freeze. Protect from direct sunlight. Reconstituted solution: Store between 2-8°C for up to 24 hours. Diluted solution for infusion: Store between 2-8°C for up to 8 hours. Do note freeze reconstituted and diluted solutions. Storage and stability recommendations may vary among countries and individual products (refer to specific product guidelines). This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
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L01FX13 - enfortumab vedotin ; Belongs to the class of other monoclonal antibodies and antibody drug conjugates. Used in the treatment of cancer.
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Anon. Enfortumab Vedotin-ejfv. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/05/2024. Buckingham R (ed). Enfortumab Vedotin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/05/2024. Enfortumab Vedotin. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 02/05/2024. Joint Formulary Committee. Enfortumab Vedotin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/05/2024. Padcev 20 mg and 30 mg (Astellas Pharma [Thailand] Co., Ltd.). MIMS Thailand. http://www.mims.com/thailand. Accessed 02/05/2024. Padcev 20 mg Powder for Concentrate for Solution for Infusion (Astellas Pharma Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2024. Padcev EJFV Injection, Powder, Lyophilized, for Solution (Seagen Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/05/2024.
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