enfortumab vedotin

High Alert

Locally advanced or metastatic urothelial cancer in patients who are not eligible for cisplatin-containing chemotherapy (in combination with pembrolizumab).
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.
Locally advanced or metastatic urothelial cancer in patients who are not eligible for cisplatin-containing chemotherapy and have previously received ≥1 line of therapy.

Action ⬆ ⬇

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).

Therapeutic effects:

Reduced progression of locally advanced or metastatic urothelial cancer.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to extravascular tissues.

Metabolism/Excretion: Monoclonal antibody component is degraded into smaller peptides via catabolism. MMAE is primarily metabolized in the liver via the CYP3A4 isoenzyme. 17% of MMAE excreted in feces; 6% excreted in urine, primarily as unchanged drug.

Half-Life: ADC: 3.4 days; MMAE: 2.4 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	ADC: end of infusion; MMAE: 2 days	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Moderate or severe hepatic impairment;
OB: Pregnancy;
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.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia, dry skin, palmar-plantar erythrodysesthesia, pruritus, rash, cellulitis, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: blurred vision, dry eye, keratitis

Endo: hyperglycemia, DIABETIC KETOACIDOSIS

F and E: hypokalemia, hypophosphatemia, hyponatremia

GI: ↓appetite, ↑lipase, diarrhea, nausea, vomiting

GU: ↑serum creatinine, ↓fertility (men), acute kidney injury, urinary tract infection

Hemat: anemia, leukopenia, lymphocytopenia, neutropenia

Local: extravasation

Metab: hyperuricemia

Neuro: dysgeusia, fatigue, peripheral neuropathy

Resp: pneumonitis/interstitial lung disease, dyspnea

Misc: herpes zoster infection

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including ketoconazole, may ↑ levels and risk of toxicity of MMAE; monitor closely.

Route/Dosage ⬆ ⬇

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.

Availability ⬆ ⬇

Lyophilized powder for injection: 20 mg/vial; 30 mg/vial

Assessment ⬆ ⬇

Monitor for symptoms of new or worsening peripheral neuropathy (burning, numbness, or 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 1st occurrence). For a recurrence, withhold until Grade ≤1; then resume therapy 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 persistent or recurrent Grade 2 skin reactions, consider holding dose until Grade ≤1; then resume treatment at the same dose level or ↓ dose by one dose level. If Grade 3 skin reactions occur, hold dose until Grade ≤1; then resume treatment at same dose level or ↓ dose by one dose level. If SJS or TEN is suspected, immediately hold dose; consult a specialist to confirm diagnosis. If not SJS/TEN, see Grade 2–4 skin reactions. If confirmed SJS or TEN and Grade 4 or recurrent Grade 3 skin reactions occur, permanently discontinue enfortumab vedotin.
Monitor 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 ↓ dose for symptomatic ocular disorders.

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 ↓ hemoglobin, lymphocytes, neutrophils, and leukocytes.

Implementation ⬆ ⬇

IV Administration:

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.
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.
Dose Reduction Schedule: 1st dose reduction: 1 mg/kg (up to 100 mg). 2nd dose reduction: 0.75 mg/kg (up to 75 mg). 3rd dose reduction: 0.5 mg/kg (up to 50 mg).
Enfortumab vedotin is an irritant. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Advise patient to notify health care provider if signs and symptoms of hyperglycemia (frequent urination, ↑ 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.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during and for 2 mo after last dose and men with female partners of reproductive potential to use effective contraception for 4 mo after last dose. Advise patient to avoid breastfeeding during and for >3 wk after last dose. Advise patient to notify health care provider immediately if pregnancy is suspected. May reversibly impair female fertility and may impair male fertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇