Enfortumab Vedotin

Enfortumab Vedotin is a prescription medication used for the treatment of Urothelial Carcinoma.

• Enfortumab Vedotin is available under the following different brand names: Padcev, enfortumab Vedotin-ejfv. 

Common side effects of Enfortumab Vedotin include:

• numbness or tingling
• muscle weakness
• tiredness
• nausea
• loss of appetite
• diarrhea
• rash
• dry skin
• hair loss 
• changes in the sense of taste

Serious side effects of Enfortumab Vedotin include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• increased thirst
• dry mouth
• fruity breath odor
• increased urination
• confusion
• drowsiness
• nausea
• vomiting
• stomach pain
• loss of appetite
• numbness, tingling, or burning pain in the hands or feet.
• pain, redness, and peeling skin on the feet
• severe skin rash with itching, scaling, or blisters
• severely dry eyes
• vision problems
• redness, itching, swelling, or discomfort where the medicine was injected.

Rare side effects of Enfortumab Vedotin include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injection, lyophilized powder for reconstitution

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

Urothelial Carcinoma

Adult dosage

Combination with pembrolizumab

• 1.25 mg/kg IV on Days 1, 8, and 15 of a 28-day cycle
• Weight 100kg or more: Not to exceed 125 mg/dose.
• Administer approximately 30 minutes before pembrolizumab when given on the same day.
• Continue until disease progression, unacceptable toxicity, or up to 24 months.

Single-agent therapy

• 1.25 mg/kg (up to 125 mg) IV on Days 1, 8, and 15 of a 28-day cycle
• Weight 100kg or more: Not to exceed 125 mg/dose.
• Continue until disease progression or unacceptable toxicity.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Enfortumab Vedotin has severe interactions with no other drugs.
• Enfortumab Vedotin has serious interactions with the following drugs:
  • abametapir
  • fexinidazole
  • grapefruit 
• Enfortumab Vedotin has moderate interactions with at least 37 other drugs.
• Enfortumab Vedotin has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib
  • ribociclib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Enfortumab Vedotin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Enfortumab Vedotin?”

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; fatal events of hyperglycemia and diabetic ketoacidosis reported when administered as a single agent; closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia; if blood glucose is elevated (more than 250 mg/dL), withhold therapy
• Patients 65 years of age or older receiving this drug as a single agent experienced a higher incidence of serious and fatal adverse reactions than younger patients; no significant difference observed in the pharmacokinetics of this drug between patients 65 years and older and younger patients.
• Can cause fetal harm, based on the mechanism of action and findings in animals
• Neuropathy
  • 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 above 3 peripheral neuropathy
• Combination with pembrolizumab
  • The incidence of peripheral neuropathy occurred at a higher rate when this medication was given in combination with pembrolizumab
  • When given in combination with pembrolizumab, 65% of patients treated with combination therapy had peripheral neuropathy of any grade, 45% had Grade 2 neuropathy, and 3.3% had Grade 3 neuropathy
  • The median time to onset of Grade greater than or equal to 2 peripheral neuropathy was 6 months (range: 0.3 to 25 months)
• Ocular disorders
  • Majority of events involved the cornea, including keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, keratopathy, and other conditions associated with eyes when used as a single agent
  • 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
• Combination with pembrolizumab
  • Incidence of pneumonitis/ILD, including severe events, occurred at a higher rate when this drug was given in combination with pembrolizumab
  • When given in combination with pembrolizumab, 9% of the 121 patients treated with combination therapy had pneumonitis/ILD of any grade and 3.3% had Grade 3
  • A fatal event of pneumonitis occurred in one patient (0.8%); the median time to onset of pneumonitis/ILD was 6 months (range: 0.6 to 26 months)
• Skin reactions
  • Severe cutaneous adverse reactions, including fatal cases of SJS or TEN reported
  • SJS and TEN has occurred predominantly during the 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
  • Closely monitor throughout treatment for skin reactions
  • For persistent or recurrent grade 2 skin reactions, consider withholding therapy until grade ≤1
  • Consider topical corticosteroids and antihistamines, as clinically indicated
  • Refer to dosage modifications for when to withhold therapy, reduce dose, or permanently discontinue
• Combination with pembrolizumab
  • When this drug was given in combination with pembrolizumab, the incidence of skin reactions, including severe events, occurred at a higher rate
  • The majority of skin reactions that occurred with combination therapy included maculo-papular rash, macular rash, and papular rash; the median time to onset of severe skin reactions was 2.6 months (range: 0.3 to 16 months)
  • Skin reactions led to discontinuation of therapy in 6% of patients
• Infusion site extravasation
  • Skin and soft tissue reactions secondary to extravasation have been 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 the 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

Pregnancy and Lactation

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