Locally advanced or metastatic urothelial cancer in patients who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.
Locally advanced or metastatic urothelial cancer in patients who are not eligible for cisplatin-containing chemotherapy and have previously received ≥1 line of therapy.
Acts as an antibody-drug conjugate (ADC) composed of a humanized IgG1 monoclonal antibody directed against Nectin-4 (an adhesion protein located on cell surface), a cleavable linker, and monomethyl auristatin E (MMAE) (an agent that disrupts microtubles and subsequently causes apoptosis).
Reduced progression of locally advanced or metastatic urothelial cancer.
Absorption: IV administration results in complete bioavailability.
Distribution: Minimally distributed to extravascular tissues.
Metabolism and Excretion: Monoclonal antibody component is degraded into smaller peptides via catabolism. MMAE is primarily metabolized in the liver via CYP3A4 isoenzyme. 17% of MMAE excreted in feces, and 6% excreted in urine, primarily as unchanged drug.
Half-life: ADC– 3.4 days; MMAE– 2.4 days.
TIME/ACTION PROFILE (plasma concentrations)
|IV||unknown||ADC: end of infusion; MMAE: 2 days||unknown|
- Moderate or severe hepatic impairment
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- Patients with or at risk for diabetes mellitus (↑ risk of hyperglycemia)
- Rep: Women of reproductive potential and men with female partners of reproductive potential
- Pedi: Safety and effectiveness not established in children.
Adverse Reactions/Side Effects
Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, alopecia, dry skin, palmar-plantar erythrodysesthesia, pruritus, rash, cellulitis
EENT: blurred vision, dry eye, keratitis
Endo: DIABETIC KETOACIDOSIS, HYPERGLYCEMIA, hyperuricemia
F and E: hypokalemia, hypophosphatemia, hyponatremia
GI: diarrhea, ↑ lipase, nausea, vomiting
GU: ↑ serum creatinine, acute kidney injury, ↓ fertility (males), urinary tract infection
Hemat: anemia, leukopenia, lymphocytopenia, neutropenia
Metabolic: ↓ appetite
Neuro: dysgeusia, peripheral neuropathy
Misc: fatigue, herpes zoster infection
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Strong CYP3A4 inhibitors, including ketoconazole, may ↑ levels and risk of toxicity of MMAE; monitor closely.
IV (Adults ≥100 kg): 125 mg on Days 1, 8, and 15 of a 28–day cycle; continue until disease progression or unacceptable toxicity.
IV (Adults <100 kg): 1.25 mg/kg on Days 1, 8, and 15 of a 28–day cycle; continue until disease progression or unacceptable toxicity.
Lyophilized powder for injection: 20 mg/vial, 30 mg/vial
- Monitor for symptoms of new or worsening peripheral neuropathy (burning, numbness, tingling in hands or feet; muscle weakness) during therapy. If Grade 2 neuropathy occurs, hold medication until Grade ≤1, then resume therapy at same dose (if first occurrence). For a recurrence, withhold until Grade ≤1 then, resume therapy reduced by one dose level. If Grade 3 neuropathy occurs, permanently discontinue enfortumab vedotin.
Monitor for signs and symptoms of skin reactions (maculopapular rash, pruritus) during therapy. Consider topical corticosteroids and antihistamines as clinically indicated. For suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), or Grade 3 (severe) skin reactions, hold medication until ≤Grade 1, then resume therapy at same or reduced dose. If confirmed SJS or TEN, Grade 4 or recurrent Grade 3 skin reactions occur, permanently discontinue therapy.
- Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. May use ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider interrupting therapy or reducing dose for symptomatic ocular disorders.
- Monitor for extravasation during therapy. Delayed reaction symptoms (erythema, swelling, increased temperature, pain) may occur. If extravasation occurs, stop infusion and monitor for adverse reactions.
Lab Test Considerations:
Verify negative pregnancy test before starting therapy.
- Monitor blood glucose closely in patients with or at risk for hyperglycemia or diabetes mellitus. If blood glucose >250 mg/dL, hold medication until blood glucose <250 mg/dL, then resume therapy at same dose.
- May cause ↓ hemoglobin, lymphocytes, neutrophils and leukocytes.
- Deficient knowledge, related to medication regimen (Patient/Family/Teaching)
- High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.
- Dose Reduction Schedule: Starting dose: 1.25 mg/kg up to 125 mg. First dose reduction: 1.0 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.
- Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers.
- Intermittent Infusion: Reconstitution: Reconstitute 20 mg vial with 2.3 mL and 30 mg vial with 3.3 mL of Sterile Water for Injection. Direct stream to walls of vial, not to powder. Swirl vial to dissolve contents. Allow vial to settle for at least 1 min until bubbles are gone; Do not shake or expose to direct sunlight. Solution is clear to slightly opalescent, colorless to light yellow; do not administer solutions that are cloudy, discolored, or contain particulate matter. Dilution: 0.9% NaCl or LR. Concentration: 0.3–4 mg/mL.Mix diluted solution by gently inverting; do not shake or expose to direct sunlight. Solution is stable for up to 8 hrs if refrigerated; do not freeze.
- Rate: Infuse over 30 min; do not give IV push.
- Y-Site Incompatibility: Do not mix or administer as an infusion with other medications.
- Explain purpose of medication to patient.
Advise patient to notify health care professional if signs and symptoms of hyperglycemia (frequent urination, increased thirst, blurred vision, confusion, drowsiness, loss of appetite, fruity breath smell, nausea, vomiting, stomach pain, difficulty controlling blood sugar; peripheral neuropathy; ocular disorders (visual changes); skin reactions; or infusion site reactions occur.
- Discuss with patient the possibility of hair loss. Explore methods of coping.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 2 mo after last dose and males with female partners of reproductive potential to use effective contraception for 4 mo after last dose. Advise patient to avoid breastfeeding during and for at least 3 wks after last dose. Advise patient to notify health care professional immediately if pregnancy is suspected. May impair male fertility.
Reduced progression of locally advanced or metastatic urothelial cancer.