enfortumab vedotin (Rx)

Brand and Other Names:Padcev, enfortumab vedotin-ejfv
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 20mg single-dose vial
  • 30mg single-dose vial

Urothelial Carcinoma

Indicated for locally advanced or metastatic urothelial cancer in adults previously treated with a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy OR

In adults who are ineligible for cisplatin-containing chemotherapy and previously received ≥1 prior lines of therapy

1.25 mg/kg (up to 125 mg) IV on Days 1, 8, and 15 of a 28-day cycle

Weight ≥100kg: Not to exceed 125 mg/dose

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dose reduction schedule

  • First dose reduction: 1 mg/kg up to 100 mg
  • Second dose reduction: 0.75 mg/kg up to 75 mg
  • Third dose reduction: 0.5 mg/kg up to 50 mg

Skin reactions

  • Suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN): Immediately withhold, consult a specialist to confirm diagnosis; if not SJS/TEN see Grade 3 skin reactions
  • Confirmed SJS or TEN; Grade 4 or recurrent Grade 3: Permanently discontinue
  • Grade 3 (severe) skin reactions: Withhold until Grade ≤1, then resume at same dose level or consider dose reduction by 1 dose level

Hyperglycemia

  • Blood glucose (BG) >250 mg/dL: Withhold until BG improves to ≤250 mg/dL, then resume at same dose level

Pneumonitis

  • Grade 2: Withhold until Grade ≤1 for persistent or recurrent Grade 2 pneumonitis, consider dose reduction by 1 dose level
  • Grade ≥3: Permanently discontinue

Peripheral neuropathy

  • Grade 2: Withhold until Grade ≤1, then resume at same dose level (if first occurrence)
  • If recurs, withhold until Grade ≤1, then reduce dose by 1 dose level
  • Grade ≥3: Permanently discontinue

Other nonhematologic toxicity

  • Grade 3: Withhold until Grade ≤1, then resume at same dose level or consider dose reduction by 1 dose level
  • Grade 4: Permanently discontinue

Hematologic toxicity

  • Grade 3, or Grade 2 thrombocytopenia: Withhold until Grade ≤1, then resume at the same dose level or consider reduction by 1 dose level
  • Grade 4: Withhold until Grade ≤1, then reduce dose by 1 dose level or discontinue treatment

Renal impairment

  • Mild, moderate, or severe (CrCl ≤90 mL/min): No dose adjustment required

Hepatic impairment

  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate (Child-Pugh B): Avoid use; only studied in limited number of patients with moderate impairment
  • Severe (Child-Pugh C): Avoid use; not studied

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiation

Safety and efficacy not established

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Interactions

Interaction Checker

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      Serious - Use Alternative

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            Contraindicated (0)

              Serious - Use Alternative (4)

              • abametapir

                abametapir increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

              • fexinidazole

                fexinidazole will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

              • grapefruit

                grapefruit increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • tucatinib

                tucatinib will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              Monitor Closely (34)

              • apalutamide

                apalutamide will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • atazanavir

                atazanavir increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • belzutifan

                belzutifan will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

              • carbamazepine

                carbamazepine will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • chloramphenicol

                chloramphenicol increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • clarithromycin

                clarithromycin increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • cobicistat

                cobicistat increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • conivaptan

                conivaptan increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • darunavir

                darunavir increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • enzalutamide

                enzalutamide will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • idelalisib

                idelalisib increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • indinavir

                indinavir increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • isavuconazonium sulfate

                enfortumab vedotin and isavuconazonium sulfate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor.

              • isoniazid

                isoniazid increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • itraconazole

                itraconazole increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • ketoconazole

                ketoconazole increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • lopinavir

                lopinavir increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • mifepristone

                mifepristone increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • mitotane

                mitotane will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nefazodone

                nefazodone increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • nelfinavir

                nelfinavir will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • phenobarbital

                phenobarbital will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • phenytoin

                phenytoin will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • posaconazole

                posaconazole increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • primidone

                primidone will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • rifampin

                rifampin will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ritonavir

                ritonavir increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • rucaparib

                rucaparib will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

              • saquinavir

                saquinavir increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • stiripentol

                stiripentol increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • tazemetostat

                tazemetostat will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tipranavir

                tipranavir increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              • voriconazole

                voriconazole increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              Minor (1)

              • ribociclib

                ribociclib will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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              Adverse Effects

              >10%

              All grades

              • Rash (52-66%)
              • Peripheral neuropathy (50-58%)
              • Fatigue (48-56%)
              • Alopecia (47-53%)
              • Decreased appetite (40-52%)
              • Nausea (30-45%)
              • Dysgeusia (26-42%)
              • Diarrhea (35-42%)
              • Dry eye (30-40%)
              • Anemia (20-38%)
              • Pruritus (26-35%)
              • Weight decreased (16-35%)
              • Constipation (28%)
              • Dry skin (17-26%)
              • Musculoskeletal pain (25%)
              • Pyrexia (22%)
              • Abdominal pain (20%)
              • Vomiting (13-18%)
              • Urinary tract infection (17%)
              • Hemorrhage (16-17%)
              • Vomiting (14%)
              • AST increased (12%)

              Grade 2-4

              • Lymphocytes decreased (32-43%)
              • Phosphate decreased (25-39%)
              • Hemoglobin decreased (28-34%)
              • Glucose increased (non-fasting) (23-36%)
              • Neutrophils decreased (14-27%)
              • Creatinine increased (18-23%)
              • Potassium decreased (8-19%)
              • Lipase increased (13-18%)

              Grade 3-4

              • Rash (13-17%)
              • Lymphocytes decreased (10-15%)
              • Glucose increased (non-fasting) (8-13%)
              • Neutrophils decreased (5-12%)
              • Fatigue (6-11%)
              • Anemia (6-11%)

              1-10%

              All grades

              • Hyperglycemia (10%)
              • ALT increased (9-10%)
              • Pneumonitis (3-4%)
              • Infusion site extravasation (0.7-1%)

              Grade 2-4

              • Urate decreased (7-9%)
              • Sodium decreased (7-8%)

              Grade 3-4

              • Phosphate decreased (7-10%)
              • Hemoglobin decreased (4-10%)
              • Hyperglycemia (9%)
              • Lipase increased (8-9%)
              • Urate increased (7-9%)
              • Sodium decreased (7-8%)
              • Diarrhea (6-8%)
              • Peripheral neuropathy (4-8%)
              • Urinary tract infection (6%)
              • Decreased appetite (2-6%)
              • Potassium decreased (1-6%)
              • Nausea (1-3%)
              • Hemorrhage (3%)
              • Creatinine increased (2-3%)
              • Pruritus (2-3%)
              • Vomiting (2%)
              • Musculoskeletal pain (2%)
              • Pyrexia (2%)
              • Nausea (1%)
              • Constipation (1%)
              • Abdominal pain (1%)
              • Dry skin (1%)
              • Weight decreased (0.3-1%)

              <1%

              Grade 3-4

              • Dry eye (0.7%)

              Postmarketing Reports

              Skin and subcutaneous tissue disorders: Epidermal necrosis, SJS, TEN

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              Warnings

              Black Box Warnings

              Serious skin reactions

              • Severe and fatal cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), predominately occurred during the first cycle of treatment, but may occur later
              • Closely monitor for skin reactions
              • Immediately withhold and consider referral for specialized care for suspected SJS or TEN or severe skin reactions
              • Permanently discontinue in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions

              Contraindications

              None

              Cautions

              Hyperglycemia and diabetic ketoacidosis occurred in patients with or without pre-existing diabetes mellitus; incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and with higher baseline A1C; Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia; if blood glucose is elevated (>250 mg/dL), withhold therapy

              Peripheral neuropathy, including sensory and motor neuropathy, occurred; monitor for symptoms of new or worsening peripheral neuropathy and consider dose interruption or reduction when peripheral neuropathy occurs; permanently discontinue therapy in patients who develop Grade >3 peripheral neuropathy

              Can cause fetal harm, based on the mechanism of action and findings in animals

              Ocular disorders

              • Majority of events involved the cornea, including keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy, and other conditions associated with eyes; monitor for symptoms; consider dose interruption or reduction if symptomatic
              • Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve
              • Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam

              Pneumonitis

              • Severe, life-threatening, or fatal pneumonitis occurred; median time to onset of pneumonitis was 2.9 months; monitor for signs and symptoms indicative of pneumonitis (eg, hypoxia, cough, dyspnea, interstitial infiltrates on radiologic exams)
              • Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations;
              • Withhold therapy for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction; permanently discontinue therapy in all patients with Grade 3 or 4 pneumonitis

              Skin reactions

              • Severe cutaneous adverse reactions, including fatal cases of SJS or TEN reported
              • SJS and TEN has occurred predominantly during first cycle of treatment but may occur later
              • Other skin reactions (eg, maculopapular rash, pruritis, symmetrical drug-related intertriginous and flexural exanthema, dermatitis bullous, dermatitis exfoliative, and palmoplantar erythrodysesthesia) reported
              • Withhold therapy and refer for specialized care for suspected SJS, TEN, or for severe (Grade 3) skin reactions
              • Permanently discontinue drug in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions
              • Closely monitor during treatment for skin reactions
              • Consider topical corticosteroids and antihistamines, as needed

              Infusion site extravasation

              • Skin and soft tissue reactions secondary to extravasation have observed after administration
              • Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak
              • Ensure adequate venous access before starting therapy and monitor for possible extravasation during administration
              • If extravasation occurs, stop infusion, and monitor for adverse reactions

              Drug interaction overview

              • Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage
              • MMAE is a substrate of P-glycoprotein (P-gp) and CYP3A4
              • Dual P-gp and strong CYP3A4 inhibitors
                • Closely monitor for signs of toxicities of enfortumab
                • Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase free MMAE exposure and increase the incidence or severity of toxicities of enfortumab
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              Pregnancy & Lactation

              Pregnancy

              Based on the mechanism of action and findings in animals, can cause fetal harm

              There are no available human data regarding use in pregnancy

              Advise patients of potential risk and verify pregnancy status in females of reproductive potential before initiating

              Animal studies

              • Administration to pregnant rats during organogenesis caused maternal toxicity, embryo-fetal lethality, structural malformations, and skeletal anomalies at maternal exposures approximately similar to the exposures at the recommended human dose of 1.25 mg/kg

              Contraception

              • Females of reproductive potential: Use effective contraception during treatment and for 2 months after last dose
              • Males with female partners of reproductive potential: Use effective contraception during treatment and for 4 months after last dose

              Infertility

              • Based on findings from animal studies, may impair male fertility

              Lactation

              Data are not available regarding the presence of enfortumab vedotin in human milk, effects on the breastfed child, or effects on milk production

              Advise lactating women not to breastfeed during treatment and for at least 3 weeks after last dose

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Enfortumab vedotin is an antibody-drug conjugate (ADC) composed of an anti-nectin-4 monoclonal antibody attached to the cell-killing agent, monomethylauristatin E (MMAE)

              Nectin-4 is a cell adhesion molecule that is expressed on many solid tumors; once the antibody attaches to nectin-4, the complex is internalized in the lysosome, which releases MMAE

              Absorption

              Steady-state concentrations of ADC and MMAE were reached after 1 treatment cycle

              Peak plasma concentration

              • ADC: 28 mcg/mL
              • Unconjugated MMAE: 5.5 ng/mL

              AUC (0-28 days)

              • ADC: 110 mcg⋅d/mL
              • Unconjugated MMAE: 85 ng⋅d/mL

              Pre-dose concentration on Day 28

              • ADC: 0.31 mcg/mL
              • Unconjugated MMAE: 0.81 ng/mL

              Distribution

              Vd (steady-state): 12.8 L

              Protein bound: 68-82%

              Metabolism

              Enfortumab vedotin-ejfv catabolism not studied in humans

              However, it is expected to undergo catabolism to small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites

              Enfortumab vedotin-ejfv releases MMAE via proteolytic cleavage, and MMAE is primarily metabolized by CYP3A4

              Elimination

              Half-life

              • ADC: 3.4 days
              • Unconjugated MMAE: 2.4 days

              Clearance

              • ADC: 0.1 L/hr
              • Unconjugated MMAE: 2.7 L/hr

              Excretion

              • Feces: 17% of the total MMAE
              • Urine: 6% in urine
              • Primarily as unchanged drug
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              Administration

              IV Incompatibilities

              Do not mix with or administer as an infusion with other medicinal products

              IV Compatibilities

              Dextrose 5%, 0.9% NaCl, or lactated ringer

              IV Preparation

              Reconstitution

              • Reconstitute each vial with 2.3 mL (20-mg vial) or 3.3 mL (30-mg vial) of sterile water for injection (SWFI), resulting in 10 mg/mL
              • If possible, direct stream of SWFI along walls of vial and not directly onto lyophilized powder
              • Slowly swirl each vial until contents are completely dissolved
              • Allow reconstituted vial(s) to settle for at least 1 min until the bubbles are gone
              • Do not shake vial; do not expose to direct sunlight
              • Visually inspect for particulate matter and discoloration befire administration, whenever solution and container permit
              • Reconstituted solution should be clear to slightly opalescent, colorless to light yellow, and free of visible particles
              • Add reconstituted solution to the infusion bag immediately
              • Discard unused vials with reconstituted solution beyond the recommended storage time

              Dilution

              • Calculate dosage volume (mL) and withdraw dose from vial(s)
              • Patients weighing >100 kg: dose should be calculated for 100 kg
              • Dilute reconstituted solution to allow enough diluent to achieve a final concentration of 0.3-4 mg/mL
              • Gently invert bag to mix solution; do not shake
              • Do not expose to direct sunlight
              • Visually inspect the infusion bag for any particulate matter or discoloration before use; reconstituted solution should be clear to slightly opalescent, colorless to light yellow, and free of visible particles
              • Do not use the infusion bag if particulate matter or discoloration is observed
              • Discard any unused portion left in the single-dose vial

              IV Administration

              Infuse over 30 min

              Do not administer as an IV push or bolus

              Storage

              Do not freeze; do not shake

              Unused vials: Refrigerate at 2-8ºC (36-46ºF) in the original carton

              Reconstituted vials

              • Does not contain a preservative
              • If not used immediately, refrigerate for up to 4 hr at 2-8ºC (36-46ºF)

              Diluted solutions

              • If not administered immediately, refrigerate for up to 8 hr at 2-8ºC (36-46ºF)

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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
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              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.