Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 20mg single-dose vial
- 30mg single-dose vial
Urothelial Carcinoma
Combination with pembrolizumab
- Indicated for locally advanced or metastatic urothelial carcinoma in adults who are ineligible for cisplatin-containing chemotherapy
- 1.25 mg/kg IV on Days 1 and 8 of a 28-day cycle
- Weight ≥100kg: Not to exceed 125 mg/dose
- Administer ~30 minutes before pembrolizumab when given on the same day
- Continue until disease progression or unacceptable toxicity
- Refer to prescribing information for dosing information of pembrolizumab
Single-agent therapy
- 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 and 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
- Persistent or recurrent Grade 2: Consider withholding until Grade ≤1, then resume at same dose level or reduce dose by 1 level
- Grade 3: Withhold until Grade ≤1, then resume at same dose level or consider dose reduction by 1 level
- 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
-
Permanently discontinue
- Confirmed SJS or TEN
- Recurrent Grade 3
- Grade 4
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (3)
- 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.
Monitor Closely (37)
- 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.
clarithromycin will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs 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.
cobicistat will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs 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.
- 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.
itraconazole will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs 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.
ketoconazole will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs of toxicities. - lenacapavir
lenacapavir will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- levoketoconazole
levoketoconazole 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.
levoketoconazole will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs 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.
- nirmatrelvir
nirmatrelvir will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs 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.
posaconazole will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs 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.
ritonavir will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs 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.
- tucatinib
tucatinib will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs 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.
voriconazole will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs of toxicities.
Minor (5)
- acetazolamide
acetazolamide will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ribociclib
ribociclib will increase the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
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
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; 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 (>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 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 >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 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 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
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.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
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)
Images
Formulary
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.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
