Enfortumab vedotin, an anti-nectin-4 antibody conjugated with the microtubule inhibitor monomethyl auristatin E (MMAE), is an antineoplastic agent.1, 3, 4
Enfortumab vedotin-ejfv is used for the treatment of locally advanced or metastatic urothelial carcinoma in patients who have previously received platinum-containing therapy and an anti-programmed-death receptor-1 (anti-PD-1) or anti-programmed-death ligand-1 (anti-PD-L1) antibody.1 Platinum-containing therapy may have been used in the neoadjuvant or adjuvant setting or for locally advanced or metastatic disease.1 The accelerated approval of enfortumab vedotin for this indication is based on objective response rate.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory studies.1
The current indication for enfortumab vedotin-ejfv is based on the results for a cohort of 125 patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-containing therapy and an anti-PD-1 or anti-PD-L1 antibody in a multicenter, noncomparative phase 2 study (EV-201).1, 2 Patients who received prior platinum-containing therapy were enrolled in the study if platinum-containing therapy was used for locally advanced or metastatic disease or if disease progression or recurrence occurred within 12 months of completion of platinum-containing therapy in the neoadjuvant and/or adjuvant setting.2
In this study, 125 patients received enfortumab vedotin-ejfv at the recommended dosage (1.25 mg/kg [up to a maximum dose of 125 mg] IV on days 1, 8, and 15 of each 28-day cycle).2 Treatment was continued until unacceptable toxicity or disease progression occurred or the patient withdrew from the study.2 The primary measure of efficacy was objective response rate (as evaluated by blinded independent central review) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1); an additional outcome measure was duration of response.1, 2 In this study, the median age of patients was 69 years (range: 40-84 years); 70% were male, 85% were Caucasian, 90% had visceral metastases, and 40% had liver metastases.1, 2 Approximately 67% of patients had histologic evidence of transitional cell carcinoma (TCC) only, and 33% had TCC with other histologic variants.1 All patients enrolled in the study had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.1, 2 Patients enrolled in the study had received a median of 3 prior systemic therapies; 66, 26, or 8% of patients had received prior cisplatin-, carboplatin-, or cisplatin- and carboplatin-based therapy, respectively, and 46, 42, or 13% of patients had received prior anti-PD-1, anti-PD-L1, or anti-PD-1 and anti-PD-L1 therapy, respectively.1 All tumor biopsy samples from 120 patients who had adequate tissue for testing had detectable nectin-4 expression.1, 2 This study excluded patients with active brain metastases, ongoing grade 2 or greater sensory or motor neuropathy, or uncontrolled diabetes mellitus (defined as glycosylated hemoglobin [hemoglobin A1c; HbA1c] concentration of 8% or higher or HbA1c concentration of 7% or higher with symptoms of diabetes).1
At a median follow-up of 10.2 months, the objective response rate was 44%; complete response was achieved in 12% of patients.1, 2 The median duration of response was 7.6 months.1, 2
Enfortumab vedotin-ejfv is available only from specialty distributors.6 The manufacturer should be contacted for additional information.6
Procedures for proper handling and disposal of antineoplastic agents should be followed.1
Enfortumab vedotin-ejfv is administered by IV infusion over 30 minutes.1 The drug should not be administered by rapid IV injection, such as IV push or bolus.1 Enfortumab vedotin-ejfv should not be mixed with or administered simultaneously through the same IV line with other drugs.1
Unopened vials of enfortumab vedotin-ejfv injection should be stored at 2-8°C and retained in the original carton; the vials should not be frozen or shaken.1
Prior to administration, enfortumab vedotin-ejfv lyophilized powder for injection must be reconstituted and diluted using proper aseptic technique.1 The powder is reconstituted by adding 2.3 mL of sterile water for injection to a vial labeled as containing 20 mg of the drug or adding 3.3 mL of sterile water for injection to a vial labeled as containing 30 mg of the drug to provide a solution containing 10 mg/mL.1 The diluent should be directed toward the wall of the vial and not directly at the enfortumab vedotin-ejfv powder.1 The vial should be gently swirled until complete dissolution of the powder occurs, and then allowed to stand for at least 1 minute to allow dissipation of bubbles; the resulting solution should not be shaken.1
Reconstituted solutions of enfortumab vedotin-ejfv should be inspected visually for particulate matter and discoloration prior to dilution.1 The reconstituted solution should be clear to slightly opalescent, colorless to light yellow, and free of visible particulates; the reconstituted solution should be discarded if the solution is discolored or contains particulates.1 Reconstituted solutions of the drug should be diluted immediately since the powder for injection contains no preservative.1 If reconstituted solutions are not diluted immediately, the solution may be stored for up to 4 hours at 2-8°C.1 The reconstituted solution should not be frozen or exposed to direct sunlight.1
For preparation of the final diluted enfortumab vedotin-ejfv solution for infusion, the required amount of reconstituted enfortumab vedotin-ejfv solution should be added into an infusion bag containing a sufficient volume of 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection to produce a final solution with an enfortumab vedotin-ejfv concentration of 0.3-4 mg/mL.1 The final diluted enfortumab vedotin-ejfv solution for infusion should be mixed by gentle inversion.1 The diluted solution should not be shaken.1 Prior to use, the diluted solution for infusion should be inspected visually for particulate matter and discoloration.1 Diluted solutions of enfortumab vedotin may be administered immediately or stored for up to 8 hours at 2-8°C.1 Diluted solutions of the drug should not be frozen or exposed to direct sunlight.1
Any unused portions in the vials or infusion bag should be discarded since enfortumab vedotin-ejfv powder for injection contains no preservative.1
For the treatment of previously treated locally advanced or metastatic urothelial carcinoma, the recommended adult dosage of enfortumab vedotin-ejfv is 1.25 mg/kg (up to a maximum dose of 125 mg) administered as a 30-minute IV infusion on days 1, 8, and 15 of each 28-day cycle.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Toxicity
If adverse reactions occur during enfortumab vedotin therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.1 If dosage reduction is required, the dosage of enfortumab vedotin should be reduced as described in Table 1.1
Dosage Reduction Level | Dosage Reduction after Recovery from Toxicity (Initial Dose = 1.25 mg/kg [maximum dose 125 mg]) |
|---|---|
First | Resume at 1 mg/kg (up to a maximum dose of 100 mg) |
Second | Resume at 0.75 mg/kg (up to a maximum dose of 75 mg) |
Third | Resume at 0.5 mg/kg (up to a maximum dose of 50 mg) |
The following Recommended Dosage Modification for Enfortumab Vedotin Toxicity table indicates the recommended dosage modification (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) for adverse effects according to severity.1
Adverse Reaction and Severity | Dosage Modification |
|---|---|
Hyperglycemia | |
Blood glucose concentration >250 mg/dL | Withhold therapy; when blood glucose concentration improves to ≤250 mg/dL, resume at same dosage |
Peripheral Neuropathy | |
Grade 2 | First occurrence: Withhold therapy; when peripheral neuropathy improves to grade 1 or less, resume at same dosage |
Subsequent occurrence: Withhold therapy; when peripheral neuropathy improves to grade 1 or less, resume at next lower dosage (see Table 1) | |
Grade 3 or greater | Permanently discontinue therapy |
Dermatologic Reactions | |
Grade 3 | First occurrence: Withhold therapy; when toxicity improves to grade 1 or less, resume at same dosage or at next lower dosage (see Table 1) |
Subsequent occurrence: Permanently discontinue therapy | |
Grade 4 | Permanently discontinue therapy |
Hematologic Toxicity | |
Grade 2 thrombocytopenia | Withhold therapy; when toxicity improves to grade 1 or less, resume at same dosage or at next lower dosage (see Table 1) |
Grade 3 hematologic toxicity | Withhold therapy; when toxicity improves to grade 1 or less, resume at same dosage or at next lower dosage (see Table 1) |
Grade 4 hematologic toxicity | Withhold therapy; when toxicity improves to grade 1 or less, resume at next lower dosage (see Table 1) or discontinue therapy |
Other Nonhematologic Toxicity | |
Grade 3 | Withhold therapy; when toxicity improves to grade 1 or less, resume at same or at next lower dosage (see Table 1) |
Grade 4 | Permanently discontinue therapy |
Dosage adjustment is not necessary in patients with mild hepatic impairment (Child-Pugh class A).1
Use of enfortumab vedotin in patients with moderate or severe hepatic impairment (Child-Pugh class B or C) should be avoided.1 (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
Dosage adjustment is not necessary in patients with mild, moderate, or severe renal impairment (creatinine clearance 90 mL/minute or less).1 (See Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
The manufacturer states that there are no known contraindications to the use of enfortumab vedotin.1
Hyperglycemia and diabetic ketoacidosis, sometimes fatal, have been reported in enfortumab vedotin-treated patients with or without preexisting diabetes mellitus.1 In the principal efficacy study, grade 3 or 4 hyperglycemia occurred in 8% of patients treated with enfortumab vedotin-ejfv.1 Patients with higher body mass index (BMI) and those with higher baseline glycosylated hemoglobin (hemoglobin A1c; HbA1c) concentration appear to be at greater risk for grade 3 or 4 hyperglycemia.1 Patients with baseline HbA1c concentration of 8% or higher or HbA1c concentration of 7% or higher with symptoms of diabetes were excluded from the principal efficacy study.1
Blood glucose concentrations should be closely monitored in patients with diabetes mellitus or hyperglycemia and in those with risk factors for such disease.1 Temporary interruption of therapy may be necessary if hyperglycemia occurs.1 (See Dosage Modification for Toxicity under Dosage and Administration: Dosage.)
Peripheral neuropathy, mainly sensory neuropathy, has been reported in enfortumab vedotin-treated patients with or without preexisting peripheral neuropathy.1 In clinical trials, peripheral neuropathy occurred in 49% of patients receiving enfortumab vedotin-ejfv and was grade 3 in 2% of patients.1 In the principal efficacy study, the median time to onset of grade 2 or greater peripheral neuropathy was 3.8 months (range: 0.6-9.2 months).1 Enfortumab vedotin-ejfv was discontinued because of peripheral neuropathy in 6% of patients; complete or partial resolution of peripheral neuropathy occurred in 19 or 26%, respectively, of patients.1 Patients with ongoing grade 2 or greater sensory or motor neuropathy were excluded from the principal efficacy study.1
Patients receiving enfortumab vedotin should be monitored for new or worsening peripheral neuropathy.1 Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of enfortumab vedotin may be necessary if peripheral neuropathy occurs.1 (See Dosage Modification for Toxicity under Dosage and Administration: Dosage.)
Ocular disorders have been reported in patients receiving enfortumab vedotin.1 In clinical trials, ocular disorders were reported in 46% of patients receiving enfortumab vedotin-ejfv.1 Most of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency, and other events associated with dry eye.1 Symptoms of dry eye or blurred vision occurred in 36 or 14%, respectively, of patients receiving enfortumab vedotin-ejfv.1 The median time to onset of symptomatic ocular disorder was 1.9 months (range: 0.3-6.2 months).1
Patients receiving enfortumab vedotin should be monitored for ocular disorders.1 Dry eye prophylaxis with artificial tear substitutes should be considered.1 If ocular symptoms occur or do not resolve, an ophthalmologic evaluation should be considered; topical ophthalmic corticosteroid therapy should be considered as clinically indicated.1 Temporary interruption of therapy or dose reduction of enfortumab vedotin may be necessary if symptomatic ocular disorders occur.1 (See Dosage Modification for Toxicity under Dosage and Administration: Dosage.)
Cutaneous reactions have been reported in patients receiving enfortumab vedotin-ejfv.1 In clinical trials, cutaneous reactions occurred in 54% of patients and were grade 3 or 4 in 10% of patients receiving enfortumab vedotin-ejfv.1 Pruritus or maculopapular rash was reported in 30 or 26%, respectively, of patients.1 Grade 3 or 4 cutaneous reactions included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia.1 In the principal efficacy study, the median time to onset of severe cutaneous reactions was 0.8 months (range: 0.2-5.3 months).1 Complete or partial resolution of rash occurred in 65 or 22%, respectively, of patients.1
Patients receiving enfortumab vedotin should be monitored for dermatologic reactions.1 Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of enfortumab vedotin may be necessary if dermatologic reactions occur.1 (See Dosage Modification for Toxicity under Dosage and Administration: Dosage.) Appropriate treatment (e.g., topical corticosteroid, antihistamine) should be considered as clinically indicated.1
Skin and soft tissue reactions secondary to extravasation have been observed following administration of enfortumab vedotin-ejfv; delayed reactions have been reported.1 In clinical trials, skin and soft tissue reactions occurred in 1.3% of patients receiving enfortumab vedotin-ejfv.1 Erythema, swelling, increased temperature, and pain worsened up to 2-7 days after extravasation and resolved within 1-4 weeks of peaking.1 Secondary cellulitis, bullae, or exfoliation occurred in 1% of patients.1
Adequate venous access should be ensured prior to infusion of enfortumab vedotin and the infusion site should be closely monitored for signs of extravasation during administration.1 If extravasation occurs, the infusion should be discontinued immediately.1
Fetal/Neonatal Morbidity and Mortality
Enfortumab vedotin may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings.1 There are no data regarding use of enfortumab vedotin in pregnant women.1 In pregnant rats receiving enfortumab vedotin during the period of organogenesis, embryofetal toxicity (e.g., abortion), teratogenicity (e.g., structural malformations, skeletal abnormalities), and maternal toxicity were observed at exposure levels similar to human exposure at the recommended dosage.1
Pregnancy should be avoided during enfortumab vedotin therapy.1 The manufacturer states that a pregnancy test should be performed prior to initiation of enfortumab vedotin therapy in women of reproductive potential and that such women should be advised to use effective contraceptive methods while receiving the drug and for 2 months after the last dose.1 In addition, men who are partners of such women should use effective contraceptive methods while receiving enfortumab vedotin and for 4 months after the last dose.1
If enfortumab vedotin is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential fetal hazard.1
There is a potential for immunogenicity with enfortumab vedotin therapy.1 Development of anti-enfortumab vedotin antibodies was detected in 5 of 365 patients receiving enfortumab vedotin-ejfv.1 Among the 5 patients who tested positive for antibody formation during treatment, 4 patients had transiently positive test results and 1 patient had persistently positive test results.1 No effects of antibody formation on pharmacokinetics, efficacy, or safety of the antibody-drug conjugate were observed.1
Based on findings from animal studies, enfortumab vedotin may impair male fertility.1 Decreased testes and epididymis weight, seminiferous tubule degeneration, spermatid/spermatocyte depletion in testes and cell debris, sperm granuloma, hypospermatogenesis, and abnormal spermatids in the epididymis were observed in rats receiving enfortumab vedotin-ejfv at exposure levels similar to human exposure at the recommended dosage.1 Findings in the testes and epididymis did not reverse by the end of the recovery period.1
Enfortumab vedotin may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)
It is not known whether enfortumab vedotin is distributed into human milk.1 The effects of the drug on nursing infants or on milk production also are unknown.1 Because of the potential for serious adverse reactions to enfortumab vedotin in nursing infants, women should be advised to discontinue nursing during enfortumab vedotin therapy and for at least 3 weeks after the last dose.1
Safety and efficacy of enfortumab vedotin have not been established in pediatric patients.1
In clinical trials, 60% of patients receiving enfortumab vedotin-ejfv were 65 years of age or older, while 26% were 75 years of age or older.1 No overall differences in safety and efficacy were observed between geriatric patients and younger adults.1
Population pharmacokinetic analysis suggests that the area under the concentration-time curve (AUC) of the microtubule-disrupting component (monomethyl auristatin E [MMAE]) of the drug was increased by 48% in patients with mild hepatic impairment (bilirubin concentration not exceeding the upper limit of normal [ULN] with AST concentration exceeding the ULN, or bilirubin concentration exceeding the ULN, but no more than 1.5 times the ULN, with AST not exceeding the ULN) compared with individuals with normal hepatic function.1 The effect of moderate or severe hepatic impairment (ALT or AST exceeding 2.5 times the ULN or total bilirubin concentration exceeding 1.5 times the ULN) or liver transplantation on the pharmacokinetics of the antibody-drug conjugate or MMAE has not been established.1
In patients receiving an MMAE-containing antibody-drug conjugate similar in structure to enfortumab vedotin, grade 3 or 4 adverse reactions and deaths occurred more frequently in patients with moderate or severe hepatic impairment (Child-Pugh class B or C) compared with patients with normal hepatic function.1
Population pharmacokinetic analysis suggests that the AUC of the antibody-drug conjugate and MMAE are not substantially altered in patients with mild, moderate, or severe renal impairment (creatinine clearance of 90 mL/minute or less) compared with individuals with normal renal function.1, 5 The effect of end-stage renal disease, and dialysis on the pharmacokinetics of the antibody-drug conjugate or MMAE has not been established.1
Adverse effects reported in 20% or more of patients receiving enfortumab vedotin-ejfv include fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, dysgeusia, diarrhea, dry eye, pruritus, and dry skin.1 Grade 3 or 4 laboratory abnormalities reported in 5% or more of patients receiving enfortumab vedotin-ejfv include anemia, lymphopenia, hypophosphatemia, elevated concentrations of lipase, hyperglycemia, hyponatremia, hyperuricemia, and neutropenia.1
No formal drug interaction studies have been performed with enfortumab vedotin; however, pharmacokinetic interactions with monomethyl auristatin E (MMAE), the microtubule-disrupting component of the antibody-drug conjugate, have been studied with an MMAE-containing antibody-drug conjugate similar in structure to enfortumab vedotin.1, 5
MMAE is a substrate of P-glycoprotein (P-gp), but not an inhibitor of P-gp in vitro.1
Drugs Affecting Hepatic Microsomal Enzymes
Concomitant use of enfortumab vedotin with potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A4 may result in increased systemic exposure of MMAE and increased risk of enfortumab vedotin toxicity.1 When the potent CYP3A4 inhibitor ketoconazole was administered concomitantly with an MMAE-containing antibody-drug conjugate similar in structure to enfortumab vedotin, peak plasma concentration and area under the concentration-time curve (AUC) of MMAE increased by 25 and 34%, respectively, and exposure of the antibody-drug conjugate was unchanged.1 Similar pharmacokinetic interactions are expected if enfortumab vedotin is used concomitantly with potent CYP3A4 inhibitors.1
If enfortumab vedotin is used concomitantly with potent CYP3A4 inhibitors, no dosage adjustment is necessary;5 however, patients should be closely monitored for signs of enfortumab vedotin toxicity.1
Concomitant use of enfortumab vedotin with potent CYP3A4 inducers may result in decreased systemic exposure of MMAE.1 When the potent CYP3A4 inducer rifampin was administered concomitantly with an MMAE-containing antibody-drug conjugate similar in structure to enfortumab vedotin, peak plasma concentration and AUC of MMAE decreased by 44 and 46%, respectively, and exposure of the antibody-drug conjugate was unchanged.1 Similar pharmacokinetic interactions are expected if enfortumab vedotin is used concomitantly with potent CYPA3A4 inducers.1
Because potent CYP3A4 inducers do not affect the metabolism of intracellular MMAE, no dosage adjustment is necessary if enfortumab vedotin is used concomitantly with potent CYP3A4 inducers.5
Drugs Metabolized by Hepatic Microsomal Enzymes
Enfortumab vedotin is not expected to alter the systemic exposure of drugs that are metabolized by CYP3A4.1 When an MMAE-containing antibody-drug conjugate similar in structure to enfortumab vedotin was administered concomitantly with the sensitive CYP3A4 substrate midazolam, systemic exposure of midazolam was unchanged.1
Enfortumab vedotin, an anti-nectin-4 antibody-drug conjugate, is an antineoplastic agent.1, 3, 4 The anti-nectin-4 antibody, a fully human IgG1 kappa monoclonal antibody, is conjugated with the microtubule inhibitor monomethyl auristatin E (MMAE) via a protease-cleavable maleimidocaproyl valine-citrulline linker.1, 3, 4 Approximately 4 molecules of MMAE are attached to each antibody molecule.1, 3 The antibody portion of enfortumab vedotin binds specifically to nectin-4 (also known as poliovirus receptor-related protein 4; PVRL4), a transmembrane adhesion protein located on the surface of cells that is highly expressed in several solid tumors, including breast cancer, urothelial carcinoma, gastric cancer, and lung carcinomas.1, 2, 3, 4 Nectin-4 also has limited expression in normal tissue (e.g., skin keratinocytes, transitional epithelium of bladder, salivary and sweat glands).2, 3, 4 Following binding of the antibody portion of enfortumab vedotin to nectin-4, the resultant complex is internalized by the cell.1 MMAE is released via proteolytic cleavage of the maleimidocaproyl valine-citrulline linker and disrupts the intracellular microtubule network, resulting in cell cycle arrest and apoptosis.1
Peak plasma concentrations of the antibody-drug conjugate are observed near the end of IV infusion, and peak plasma concentrations of MMAE are observed approximately 2 days after IV infusion.1 Minimal accumulation of enfortumab vedotin and MMAE occurs following repeated administration.1 Steady-state concentrations of the antibody-drug conjugate and MMAE are achieved after one treatment cycle (i.e., 3 doses).1 In vitro, MMAE is 68-82% bound to plasma proteins.1 The antibody-drug conjugate is expected to undergo catabolism to small peptides, amino acids, free MMAE, and free MMAE-related catabolites.1 MMAE is primarily metabolized by the cytochrome P-450 (CYP) 3A4 isoenzyme.1 Elimination of enfortumab vedotin has not been characterized; however, following administration of an MMAE-containing antibody-drug conjugate similar in structure to enfortumab vedotin, 17 or 6% of the total administered dose of MMAE is excreted over a 1-week period in feces or urine, respectively, mainly as unchanged drug.1 A similar excretion profile is expected following IV administration of enfortumab vedotin.1 The elimination half-lives of the antibody-drug conjugate and MMAE are 3.4 and 2.4 days, respectively.1 Elimination of MMAE appears to be limited by the rate of release from the antibody-drug conjugate.1
The pharmacokinetics of the antibody-drug conjugate do not appear to be affected substantially by age (24-87 years), sex, and race or ethnicity.1
Importance of advising patients to read the manufacturer's patient information.1
Risk of hyperglycemia.1 Importance of informing clinician immediately if symptoms of hyperglycemia (e.g, frequent urination, increased thirst, blurred vision) occur.1
Risk of peripheral neuropathy.1 Importance of informing clinician if symptoms of peripheral neuropathy (e.g., tingling or numbness of the hands or feet, muscle weakness) occur.1
Risk of adverse ocular effects.1 Importance of informing clinician immediately if adverse ocular effects (e.g., blurry vision, dry eye) occur.1 Advise patients to use artificial tear substitutes to prevent or manage symptoms of dry eye.1
Risk of rash and severe cutaneous reactions.1 Importance of informing clinician if signs or symptoms of progressive or intolerable cutaneous reactions occur.1
Risk of extravasation.1 Importance of informing clinician immediately if signs or symptoms of an infusion-related reaction (e.g., redness, swelling, itching, discomfort at the infusion site) occur.1
Risk of fetal harm.1 Necessity of advising women of reproductive potential to use effective contraception during therapy and for at least 2 months after the last dose.1 Necessity of advising men who are partners of such women to use effective contraception during therapy and for 4 months after the last dose.1 Importance of women informing their clinicians if they become pregnant during therapy or think they may be pregnant.1 Advise pregnant women of potential risk to the fetus.1
Importance of advising women to avoid breast-feeding while receiving the drug and for 3 weeks after the last dose.1
Risk of impaired male fertility.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., diabetes mellitus, hyperglycemia, peripheral neuropathy).1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Distribution of enfortumab vedotin-ejfv is restricted.6 (See Restricted Distribution under Dosage and Administration: General.)
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV infusion only | 20 mg | Seattle Genetics | |
30 mg | Padcev® | Seattle Genetics |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions October 19, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Seattle Genetics, Inc. Padcev® (enfortumab vedotin-ejfv) for injection prescribing information. Bothell, WA; 2019 Dec.
2. Rosenberg JE, O'Donnell PH, Balar AV, et al. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2019;37(29):2592-2600. [PubMed 31356140]
3. Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res. 2016;76(10):3003-3013. [PubMed 31356140]
4. Vlachostergios PJ, Jakubowski CD, Niaz MJ, et al. Antibody-Drug Conjugates in Bladder Cancer. Bladder Cancer. 2018;4(3):247-259. [PubMed 30112436]
5. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761137Orig1s000: Multi-discipline review. From FDA website. [Web]
6. Astellas Pharma US, Inc. PADCEV Network Specialty Distributors. From Astellas Pharma Support Solutions website. Accessed Jun 2, 2020. [Web]