enfortumab vedotin

Trade Name:

Padcev®

Appearance:

colourless to light yellow liquid, mixed into larger bags of fluids

Monograph Name:

enfortumab vedotin

Monograph Body:

Drug Monograph

A - Drug Name

enfortumab vedotin

COMMON TRADE NAME(S): Padcev®

B - Mechanism of Action and Pharmacokinetics

Enfortumab vedotin is an antibody drug conjugate (ADC) targeting Nectin-4, an adhesion protein located on the surface of most urothelial cancer cells. It contains a fully human IgG1-kappa antibody attached to the microtubule-disrupting agent (MMAE) by a protease-cleavable linker. After binding to Nectin-4-expressing cells, the ADC-Nectin-4 complex is internalized, and the MMAE is released via proteolytic cleavage. MMAE disrupts the microtubule network in cells, inducing cell cycle arrest and apoptosis.

Distribution

PPB	68 to 82% (MMAE); MMAE is unlikely to displace or to be displaced by highly protein-bound drugs.

Metabolism

Expected to undergo catabolism to small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites. A small fraction of released MMAE from ADC is metabolized.

Main enzymes involved

CYP3A4 (MMAE)

Elimination

MMAE elimination appears to be limited by its rate of release from the ADC; approximately 24% of MMAE is recovered unchanged in feces and urine after a single dose of another ADC.

Half-life

3.6 days (ADC); 2.6 days (MMAE)

C - Indications and Status

Health Canada Approvals:

Urothelial cancer

Refer to the product monograph for a full list and details of approved indications

D - Adverse Effects

Emetogenic Potential:

Low

Extravasation Potential: Irritant

The following table lists adverse effects that occurred in > 10% of patients with previously treated unresectable locally advanced or metastatic urothelial cancer, in a randomized Phase III study. It also includes severe or life-threatening adverse effects from other sources and post-marketing.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Tachycardia (<10%)	E
Dermatological	Alopecia (47%)	E
	Rash (54%) (including hand-foot syndrome) (14% severe)	E D
	Stevens-Johnson syndrome (rare)	E D
	Toxic epidermal necrolysis (rare)	E D
Gastrointestinal	Abdominal pain (20%)	E
	Anorexia, weight loss (41%)	E
	Constipation (28%)	E
	Diarrhea (35%)	E
	Nausea, vomiting (30%) (1% severe)	E
General	Fatigue (50%)	E
Hematological	Myelosuppression ± infection, bleeding (11%)	E
Hepatobiliary	↑ LFTs (12%)	E
Injection site	Infusion site extravasation (1%) (may be severe)	I E
Metabolic / Endocrine	Hyperglycemia (11%) (7% severe)	E
Musculoskeletal	Musculoskeletal pain (25%)	E
Nervous System	Dysgeusia (26%)	E D
	Insomnia (11%)	E
	Peripheral neuropathy (50%) (5% severe)	E D
Ophthalmic	Dry eye (24%) (1% severe; including keratitis or keratopathy)	E D
Respiratory	Pneumonitis (3%)	E D

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The most common side effects for enfortumab vedotin include rash, fatigue, peripheral neuropathy, alopecia, anorexia, weight loss, diarrhea, nausea, vomiting, constipation, dysgeusia and musculoskeletal pain.

Severe skin reactions, including epidermal necrosis, SJS, TEN, symmetrical drug-related intertriginous and flexural exanthema, with fatal outcome have been reported with enfortumab vedotin during clinical trials and post-marketing. Adverse reactions mainly occur during the first cycle of treatment, but may occur in subsequent cycles.

Extravasation has been observed following enfortumab vedotin administration. Reactions may be delayed; symptoms may continue to worsen for 2-7 days after extravasation and resolve within 1-4 weeks of the worst symptoms. Ensure good venous access prior to starting treatment. If extravasation occurs during administration, stop the infusion and monitor for adverse reactions.

Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, have been reported in patients with and without pre-existing diabetes mellitus treated with enfortumab vedotin. Hyperglycemia occurred more frequently in patients with pre-existing hyperglycemia or a high BMI (≥30 kg/m²). The incidence of Grade 3 or 4 hyperglycemia increased consistently in patients with higher BMI or higher baseline HbA1C. Patients with baseline hemoglobin A1C ≥ 8% were excluded from clinical trials.

Peripheral neuropathy, mostly sensory, has been reported in patients with and without pre-existing peripheral neuropathy. The median time to onset was approximately 5 months for Grade ≥ 2.

Severe or life-threatening pneumonitis have been reported with enfortumab vedotin. During clinical trials, the median time to onset was approximately 3 months; two patients experienced fatal events.

Ocular events, mostly corneal disorders or dry eyes, have occurred in clinical trials. The median time to onset was approximately 2 months. Consider prophylaxis for dry eyes with artificial tears. An ophthalmologic referral should be considered if symptoms do not resolve or worsen.

Higher incidences of skin reactions, peripheral neuropathy, and pneumonitis occurred when enfortumab vedotin was given in combination with pembrolizumab, compared to enfortumab vedotin as a single agent.

E - Dosing

Refer to protocol by which patient is being treated.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Premedication (Prophylaxis for Infusion Reactions):

Routine premedication is not recommended. No premedication was given for the first dose of enfortumab vedotin during clinical trials.
Patients who experience an infusion reaction may be premedicated for subsequent infusions. Premedication may include acetaminophen, an antihistamine (e.g., diphenhydramine hydrochloride), and a corticosteroid given 30–60 minutes prior to each infusion. (Powles 2021)

Adults:

Monotherapy:

Intravenous: 1.25 mg/kg* days 1, 8, and 15 q28days

Subsequent doses should NOT be administered less than 1 week apart.

*Dose is capped at a weight of 100 kg.

Combination therapy:

Various dosing and schedules are used depending on the indication. Refer to the product monograph or related regimen monographs for details.

Dosage with Toxicity:

Dose Level	Enfortumab Vedotin Dose (mg/kg)*
0	1.25
-1	1
-2	0.75
-3	0.5
-4	Discontinue

*For patients ≤ 100 kg. If weight is > 100 kg, dose should be based on 100 kg.

Toxicity	Grade/Severity	Action
Skin Reactions	Grade 1 or 2	Consider topical corticosteroids and antihistamines as needed.
	Grade 3, worsening reactions, or suspected SJS or TEN	Hold*. Consider dermatological referral. Resume at same dose or consider 1 dose level ↓.
	Grade 4, recurrent Grade 3, or confirmed SJS or TEN	Discontinue.
Hyperglycemia	Blood glucose > 13.9 mmol/L	Hold*. Resume at same dose.
Pneumonitis	Grade 2	Hold*. Resume at the same dose or consider 1 dose level ↓.
Pneumonitis	Grade 3 or 4	Discontinue.
Peripheral Neuropathy	Grade 2	Hold*. 1st occurrence: resume at same dose. Recurrence: resume at 1 dose level ↓.
Peripheral Neuropathy	Grade 3 or 4	Discontinue.
Ocular Toxicity	Any	Consider holding or reducing dose. Consider ophthalmology referral if symptoms do not resolve or worsen.
Other Non-hematologic Toxicity	Grade 3	Hold*. Resume at same dose or consider 1 dose level ↓.
Other Non-hematologic Toxicity	Grade 4	Discontinue.
Hematologic Toxicity	Grade 2 thrombocytopenia	Hold*. Resume at same dose or consider 1 dose level ↓.
	Grade 3	Hold*. Resume at same dose or consider 1 dose level ↓.
	Grade 4	Hold*. Resume at 1 dose level ↓ or discontinue.

*Do not restart treatment until blood glucose resolved to < 13.9 mmol/L, and other toxicities < Grade 1.

Dosage with Hepatic Impairment:

MMAE exposure is likely increased in patients with moderate or severe hepatic impairment.

Hepatic Impairment	Enfortumab Vedotin Dose
Child-Pugh A	No adjustment required.
Child-Pugh B	Not studied; avoid use.
Child-Pugh C	Not studied; avoid use.

Dosage with Renal Impairment:

No dosage adjustment is required with renal impairment. The effect of end stage renal disease with or without dialysis on the pharmacokinetics of ADC or unconjugated MMAE is unknown.

Dosage in the elderly:

No dose adjustment is required in patients ≥ 65 years of age. No overall differences in efficacy were observed between patients ≥ 65 years and those < 65 years. Patients ≥ 65 years were more likely to experience serious adverse events or treatment discontinuation.

Dosage based on gender:

No clinically significant differences on the pharmacokinetics of enfortumab vedotin were observed based on gender.

Dosage based on ethnicity:

No clinically significant differences on the pharmacokinetics of enfortumab vedotin were observed based on ethnicity.

Children:

Safety and effectiveness have not been evaluated in children < 18 years of age.

F - Administration Guidelines

Reconstitute each vial with Sterile Water for Injection. Swirl gently; do not shake the solution.
Dilute in D5W, NS, or Ringer's lactate. Invert infusion bag gently to mix.
Final concentration should be 0.3 mg/mL to 4 mg/mL.
Administer as an IV infusion over 30 minutes. Do NOT administer as an IV push or bolus.
If given with pembrolizumab on the same day, administer enfortumab vedotin first, with an interval of 30 minutes between infusions (for at least Cycle 1, Day 1). If well tolerated, subsequent intervals between infusions may be reduced to 15 minutes.
Do NOT administer other drugs through the same IV line.
If extravasation occurs during administration, stop the infusion and monitor for adverse reactions (e.g., skin and soft tissue injury).
Do not expose the vials or diluted drug to direct sunlight.
Store unopened vials in a refrigerator at 2-8^oC. Do not freeze.

G - Special Precautions

Contraindications:

Patients who have a hypersensitivity to this drug or any of its components

Other Warnings/Precautions:

Do NOT start enfortumab vedotin in patients with pre-existing grade ≥ 2 neuropathy, ongoing clinically significant toxicity from previous treatment, active CNS metastases, uncontrolled diabetes, active keratitis or corneal ulcerations.

Other Drug Properties:

Carcinogenicity: Unknown

Pregnancy and Lactation:

Embryotoxicity: Yes
Fetotoxicity: Yes
Mutagenicity: No
Genotoxicity: Yes

Enfortumab vedotin is not recommended for use in pregnancy.
- Adequate contraception should be used by patients who can become pregnant and their partners during treatment, and for at least 6 months after the last dose.
- Adequate contraception should be used by patients who produce sperm and their partners during treatment, and for at least 4 months after the last dose.
Excretion into breast milk: Unknown

Breastfeeding is not recommended during treatment and for at least 6 months after the last dose.
Fertility effects: Probable

Testicular toxicity was observed in animals.

H - Interactions

No drug interaction studies have been conducted.

In vitro, MMAE is a substrate of P-gp and does not inhibit P-gp.

In vitro, MMAE inhibits CYP3A4/5 but not other CYP450 enzymes, and does not induce major CYP450 enzymes. MMAE is predicted not to alter the exposure of CYP3A4 substrates (e.g., midazolam).

AGENT	EFFECT	MECHANISM	MANAGEMENT
Combined strong P-gp and CYP3A4 inhibitors (i.e. ketoconazole)	↑ MMAE exposure by 38%, no changed in ADC exposure (with ketoconazole)	↓ metabolism of MMAE	No enfortumab vedotin dose adjustment required. Monitor for adverse reactions closely.
Strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, posaconazole, ritonavir, voriconazole)	↑ MMAE exposure (theoretical)	↓ metabolism of MMAE	Monitor for adverse reactions closely.
Strong CYP3A4 inducers (i.e. rifampin)	↓ MMAE exposure by 53%, no change in ADC exposure (with rifampin)	↑ metabolism of MMAE	Caution; monitor for enfortumab vedotin ↓ therapeutic response.

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
CBC	Baseline, before each dose, and as clinically indicated
Liver function tests	Baseline, before each dose, and as clinically indicated
Blood glucose	Baseline and as clinically indicated (more frequently in patients with or at risk for diabetes mellitus or hyperglycemia)
Clinical toxicity assessment for infection, bleeding, extravasation, peripheral neuropathy, GI, ocular, respiratory and skin effects	At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Supplementary Public Funding

New Drug Funding Program (NDFP Website )

Enfortumab Vedotin - Previously Treated Advanced or Metastatic Urothelial Cancer

K - References

ASCO Guidelines: Emetic Risk of Single Intravenous Antineoplastic Agents in Adults. American Society of Clinical Oncology 2020.

Butler, J. et al. Extravasation injury from chemotherapy and other non-antineoplastic vesicants. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed on June 13, 2022.

CADTH reimbursement recommendation: Enfortumab vedotin (unresectable, locally advanced or metastatic urothelial cancer). January 2022.

Enfortumab vedotin and Rifampin. Lexicomp: Interactions. UpToDate, Inc. 2022. Accessed on June 20, 2022.

National Library of Medicine (U.S.). (2018, June - 2020, July). An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin vs Chemotherapy in Subjects with Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301). Identifier NCT03474107. https://https://clinicaltrials.gov/ct2/show/NCT03474107.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Antiemesis. Version 2.2022, March 23, 2022.

Powles T. et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021;384:1125-35.

Prescribing Information: Padcev® (enfortumab vedotin-ejfv). Seagen Inc, Inc. May 2022.

Product Monograph: Padcev® (enfortumab vedotin). Seagen Canada Inc. August 20, 2024.

Summary of Product Characteristics. Padcev® (enfortumab vedotin). Astellas Pharma Ltd. December 5, 2022.

January 2025 Updated Adverse effects, Dosing, and Administration sections

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Info Sheet Name:

enfortumab vedotin (patient)

Info Sheet Introduction:

For treating a certain type of bladder cancer

Info Sheet Date: Friday, March 1, 2024 Info Sheet body:

Medication Information Sheet

enfortumab vedotin (en-FORT-ue-mab-ve-DOE-tin)

This document provides general information about your medication. It does not replace the advice of your health care professional. Always discuss your therapy with your health care professional and refer to the package insert for more details.

Other Name: Padcev®

Appearance:

colourless to light yellow liquid, mixed into larger bags of fluids

What is this medication for?

For treating a certain type of bladder cancer

What should I do before I have this medication?

Tell your health care team if you have or had significant medical condition(s), especially if you have / had:

liver or eye problems,
diabetes or high blood sugar,
numbness or tingling in your hands or feet, or
any allergies.

Remember to:

Tell your health care team about all of the other medications you are taking.
Keep taking other medications that have been prescribed for you, unless you have been told not to by your health care team.

You will have a blood test to check for hepatitis B before starting treatment. See the Hepatitis B and Cancer Medications pamphlet for more information.

How will this medication affect sex, pregnancy and breastfeeding?

Talk to your health care team about:

How this medication may affect your sexual health.
How this medication may affect your ability to have a baby, if this applies to you.

This medication may harm an unborn baby. Tell your health care team if you or your partner are pregnant, become pregnant during treatment, or are breastfeeding.

If there is any chance you may become pregnant, you and your partner together must use 2 effective forms of birth control at the same time until at least 6 months after your last dose. Talk to your health care team about which birth control options are best for you.
If you are a patient that can get somebody pregnant, you and your partner together must use 2 effective forms of birth control at the same time until at least 4 months after your last dose. Talk to your health care team about which birth control options are best for you.
Do not breastfeed while on this medication and for at least 6 months after your last dose.

How is this medication given?

This drug is given through an IV (injected into a vein). Talk to your health care team about your treatment schedule.
If you missed your treatment appointment, talk to your health care team to find out what to do.

To Prevent or Treat Nausea and Vomiting

You may be given medications to prevent or stop nausea (feeling like throwing up) and vomiting (throwing up) before they start. These are called anti-nausea medications.

Medications to prevent nausea and vomiting before they start include ondansetron (Zofran®), granisetron (Kytril®), or others.

If you already have nausea and/or vomiting, some anti-nausea medication can stop them from getting worse. You may be given these medications to have at home in case you start to feel nausea or if you vomit.

Medications to stop nausea and vomiting include prochlorperazine (Stemetil®), metoclopramide (Maxeran®), or others.

What else do I need to know while on this medication?

Will this medication interact with other medications or natural health products?

This medication can interact with other medications, vitamins, foods and natural health products. Interactions can make the treatment not work as well or cause severe side effects.
Tell your health care team about all of your:
- prescription and over-the-counter (non-prescription) medications and all other drugs, such as cannabis/marijuana (medical or recreational)
- natural health products such as vitamins, herbal teas, homeopathic medicines, and other supplements
Check with your health care team before starting or stopping any of them.

What should I do if I feel unwell, have pain, a headache or a fever?

Always check your temperature to see if you have a fever before taking any medications for fever or pain (such as acetaminophen (Tylenol®) or ibuprofen (Advil®)).
- Fever can be a sign of infection that may need treatment right away.
- If you take these medications before you check for fever, they may lower your temperature and you may not know you have an infection.

How to check for fever:

Keep a digital (electronic) thermometer at home and take your temperature if you feel hot or unwell (for example, chills, headache, mild pain).

You have a fever if your temperature taken in your mouth (oral temperature) is:
- 38.3°C (100.9°F) or higher at any time
  
  OR
- 38.0°C (100.4°F) or higher for at least one hour.

If you do have a fever:

Try to contact your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away.
Ask your health care team for the Fever pamphlet for more information.

If you do not have a fever but have mild symptoms such as headache or mild pain:

Ask your health care team about the right medication for you. Acetaminophen (Tylenol®) is a safe choice for most people.
Talk to your health care team before you start taking Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or ASA (Aspirin®), as they may increase your chance of bleeding or interact with your cancer treatment.
Talk to your health care team if you already take low dose aspirin for a medical condition (such as a heart problem). It may still be safe to take.

What to DO while on this medication:

DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures.
DO tell your health care team if you have any new pain, numbness or tingling of your hands or feet. This is especially important if you are having trouble doing tasks (like doing up buttons, writing, walking) or if you have severe pain or numbness.
DO test your blood sugar regularly if you are taking any medications for diabetes. This treatment may cause changes in your blood sugar levels.

What NOT to DO while on this medication:

DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.

What are the side effects of this medication?

The following table lists side effects that you may have when getting enfortumab vedotin. The table is set up to list the most common side effects first and the least common last. It is unlikely that you will have all of the side effects listed and you may have some that are not listed.

Read over the side effect table so that you know what to look for and when to get help. Refer to this table if you experience any side effects while on enfortumab vedotin.

Very Common Side Effects (50 or more out of 100 people)
Side effects and what to do	When to contact health care team
Rash; dry, itchy skin (May be severe) What to look for? You may have cracked, rough, flaking or peeling areas of the skin. Your skin may look red and feel warm, like a sunburn. Your skin may itch, burn, sting or feel very tender when touched. What to do? To prevent and treat dry skin: Use fragrance-free skin moisturizer. Protect your skin from the sun and the cold. Use sunscreen with UVA and UVB protection and a SPF of at least 30. Avoid perfumed products and lotions that contain alcohol. Drink 6 to 8 cups of non-alcoholic, non-caffeinated liquids each day, unless your health care team has told you to drink more or less. Rash may be severe in some rare cases and cause your skin to blister or peel. If this happens, get emergency medical help right away.	Talk to your health care team if it does not improve or if it is severe.
Fatigue What to look for? Feeling of tiredness or low energy that lasts a long time and does not go away with rest or sleep. What to do? Be active. Aim to get 30 minutes of moderate exercise (you are able to talk comfortably while exercising) on most days. Check with your health care team before starting any new exercise. Pace yourself, do not rush. Put off less important activities. Rest when you need to. Ask family or friends to help you with things like housework, shopping, and child or pet care. Eat well and drink at least 6 to 8 glasses of water or other liquids every day (unless your health care team has told you to drink more or less). Avoid driving or using machinery if you are feeling tired. Ask your health care team for the Fatigue pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
Neuropathy (Tingling, numb toes or fingers) (May be severe) What to look for? Numbness or tingling of your fingers and toes may happen after starting your treatment. It can also happen to other parts of your body. Sometimes it can be painful and feel like a burning sensation, which may be severe. What to do? Talk to your health care team if you have symptoms of neuropathy. Numbness and tingling may slowly get better after your treatment ends. In rare cases, it may continue long after treatment ends. If you continue to have bothersome symptoms, talk to your health care team for advice.	Talk to your health care team, especially if you have trouble doing tasks like doing up buttons, writing, moving, or if you have severe pain or numbness.

Common Side Effects (25 to 49 out of 100 people)
Side effects and what to do	When to contact health care team
Hair thinning or loss What to look for? Your hair may become thin or fall out during or after treatment. In most cases, your hair will grow back after treatment. The texture or colour may change. In very rare cases, hair loss may be permanent. What to do? Use a gentle soft brush. Do not use hair sprays, bleaches, dyes and perms.	Talk to your health care team if this bothers you.
Low appetite What to look for? Loss of interest in food or not feeling hungry. Weight loss. What to do? Try to eat your favourite foods. Eat small meals throughout the day. You may need to take meal supplements to help keep your weight up. Talk to your health care team if you have no appetite. Ask your health care team for the Loss of Appetite pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
Diarrhea What to look for? Loose, watery, unformed stool (poo) that may happen days to weeks after you get your treatment. What to do? If you have diarrhea: Take anti-diarrhea medication if your health care team prescribed it or told you to take it. Do not eat foods or drinks with artificial sweetener (like chewing gum or ‘diet’ drinks), coffee and alcohol, until your diarrhea has stopped. Eat many small meals and snacks instead of 2 or 3 large meals. Drink at least 6 to 8 cups of liquids each day, unless your health care team has told you to drink more or less. Talk to your health care team if you can’t drink 6 to 8 cups of liquids each day when you have diarrhea. You may need to drink special liquids with salt and sugar, called Oral Rehydration Therapy. Talk to your health care team if your diarrhea does not improve after 24 hours of taking diarrhea medication or if you have diarrhea more than 7 times in one day. Ask your health care team for the Diarrhea pamphlet for more information.	Talk to your health care team if no improvement after 24 hours of taking diarrhea medication or if severe (more than 7 times in one day).
Nausea and vomiting (Generally mild) What to look for? Nausea is feeling like you need to throw up. You may also feel light-headed. You may feel nausea within hours to days after your treatment. What to do? To help prevent nausea: It is easier to prevent nausea than to treat it once it happens. If you were given anti-nausea medication(s), take them as prescribed, even if you do not feel like throwing up. Drink clear liquids and have small meals. Get fresh air and rest. Do not eat spicy, fried foods or foods with a strong smell. Limit caffeine (like coffee, tea) and avoid alcohol. If you have nausea or vomiting: Take your rescue (as-needed) anti-nausea medication(s) as prescribed. Ask your health care team for the Nausea & Vomiting pamphlet for more information. Talk to your health care team if: nausea lasts more than 48 hours vomiting lasts more than 24 hours or if it is severe	Talk to your healthcare team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if it is severe.
Constipation What to look for? Having bowel movements (going poo) less often than normal. Small hard stools (poo) that look like pellets. The need to push hard and strain to have any stool (poo) come out. Stomach ache or cramps. A bloated belly, feeling of fullness, or discomfort. Leaking of watery stools (poo). Lots of gas or burping. Nausea or vomiting. What to do? To help prevent constipation: Try to eat more fiber rich foods like fruits with skin, leafy greens and whole grains. Drink at least 6 to 8 cups of liquids each day unless your health care team has told you to drink more or less. Be Active. Exercise can help to keep you regular. If you take opioid pain medication, ask your health care team if eating more fibre is right for you. To help treat constipation: If you have not had a bowel movement in 2 to 3 days you may need to take a laxative (medication to help you poo) to help you have regular bowel movements. Ask your health care team what to do. Ask your health care team for the Constipation Pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
Taste changes What to look for? Food and drinks may taste different than usual. What to do? Eat foods that are easy to chew, such as scrambled eggs, pasta, soups, cooked vegetables. Taste foods at different temperatures, since the flavour may change. Try different forms of foods, like fresh, frozen or canned. Experiment with non-spicy foods, spices and seasonings.	Talk to your health care team if it does not improve or if it is severe.
Mild joint, muscle pain or cramps What to look for? New pain in your muscles or joints, muscle cramps, or feeling achy. What to do? Take pain medication (acetaminophen or opioids such as codeine, morphine, hydromorphone, oxycodone) as prescribed. Read the above section: "What should I do if I feel unwell, have pain, a headache or a fever?" before taking acetaminophen (Tylenol®), ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or Aspirin. These medications may hide an infection that needs treatment or they may increase your risk of bleeding. Rest often and try light exercise (such as walking) as it may help. Ask your health care team for the Pain pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.

Less Common Side Effects (10 to 24 out of 100 people)
Side effects and what to do	When to contact health care team
Dry eyes; eye problems (May be severe) What to look for? Your eyes may feel dry, irritated, or painful. They may look red and have a lot of tears. They may feel sensitive to light and your vision may be blurry. What to do? Avoid wearing contact lenses. Wear sunglasses with UV protection. Use protective eyewear (goggles or helmet with face mask) when playing sports, mowing the lawn or doing anything that may get particles or fumes in your eyes. You may try artificial tears (eye drops) or ointment.	Talk to your health care team as soon as possible.
Liver problems Your health care team may check your liver function with a blood test. Liver changes do not usually cause any symptoms. What to look for? Rarely, you may develop yellowish skin or eyes, unusually dark pee or pain on the right side of your belly. What to do? If you have any symptoms of liver problems, get emergency medical help right away.	Get emergency medical help right away.
Low neutrophils (white blood cells) in the blood (neutropenia) (May be severe) When neutrophils are low, you are at risk of getting an infection more easily. Ask your health care team for the Neutropenia (Low white blood cell count) pamphlet for more information. What to look for? If you feel hot or unwell (for example if you have chills or a new cough), you must check your temperature to see if you have a fever. Do not take medications that treat a fever before you take your temperature (for example, Tylenol® (acetaminophen), or Advil® (ibuprofen)). Do not eat or drink anything hot or cold right before taking your temperature. You have a fever if your temperature taken in your mouth (oral temperature) is: 38.3°C (100.9°F) or higher at any time OR 38.0°C (100.4°F) or higher for at least one hour. What to do? If your health care team has told you that you have low neutrophils: Wash your hands often to prevent infection. Check with your health care team before getting any vaccines, surgeries, medical procedures or visiting your dentist. Keep a digital thermometer at home so you can easily check for a fever. If you have a fever: If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you must get emergency medical help right away.	If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you MUST get emergency medical help right away.
Low platelets in the blood When your platelets are low, you are at risk for bleeding and bruising. Ask your health care team for the Low Platelet Count pamphlet for more information. What to look for? Watch for signs of bleeding: bleeding from your gums unusual or heavy nosebleeds bruising easily or more than normal black coloured stools (poo) or blood in your stools (poo) coughing up red or brown coloured mucus dizziness, constant headache or changes in your vision heavy vaginal bleeding red or pink coloured urine (pee) What to do? If your health care team has told you that you have low platelets: Tell your pharmacist that your platelet count may be low before taking any prescriptions or over-the-counter medication. Check with your healthcare team before you go to the dentist. Take care of your mouth and use a soft toothbrush. Try to prevent cuts and bruises. Ask your health care team what activities are safe for you. Your treatment may have to be delayed if you have low platelets. Your health care team may recommend a blood transfusion. If you have signs of bleeding: If you have a small bleed, clean the area with soap and water or a saline (saltwater) rinse. Apply pressure for at least 10 minutes. If you have bleeding that does not stop or is severe (very heavy), you must get emergency medical help right away.	Talk to your health care team if you have any signs of bleeding. If you have bleeding that doesn’t stop or is severe (very heavy), you MUST get emergency help right away.
High blood sugar (May be severe) What to look for? You may feel thirsty. You may pee more often than usual. You may feel tired or sleepy. What to do? Your health care team may do a blood test to check your blood sugar level. You may be told to change your diet or given medication to lower your blood sugar. If you have diabetes, check your blood sugar regularly. Your health care team may ask you to check it more often than usual.	Talk your health care team as soon as possible.
Trouble Sleeping Your medications may cause trouble sleeping. It may get better once your body gets used to the medication or when your treatment ends. What to look for? You may find it hard to fall asleep or stay asleep. How well you sleep may change over your treatment. For example, you may have several nights of poor sleep followed by a night of better sleep. You may wake up too early or not feel well-rested after a night's sleep. You may feel tired or sleepy during the day. What to do? Talk to your health care team if it does not improve or if it is severe.	Talk to your health care team if it does not improve or if it is severe.

Other rare, but serious side effects are possible.
If you experience ANY of the following, speak to your cancer health care provider or get emergency medical help right away:

an irregular or fast heartbeat
cough, breathing problems, or cough up blood
pain, redness, swelling or tenderness where your medication was given
tingling or swelling of the skin on the palms of your hands and the bottoms of your feet

Who do I contact if I have questions or need help?

My cancer health care provider is: ______________________________________________

During the day I should contact:________________________________________________

Evenings, weekends and holidays:______________________________________________

Other Notes:

____________________________________________________________________________

March 2024 Updated “How will this medication affect sex, pregnancy and breastfeeding?“ section

For more links on how to manage your symptoms go to www.cancercareontario.ca/symptoms.

The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

Info Sheet (English):

enfortumab vedotin patient.pdf Info Sheet (French):

enfortumab vdotin pour le patient.pdf Monograph:

enfortumab vedotin.pdf Funding Program: New Drug Funding Program Funding Instance:

Enfortumab Vedotin - Previously Treated Advanced or Metastatic Urothelial Cancer

Phonetic Spelling:

en-FORT-ue-mab-ve-DOE-tin

Eligibility Form:

Enfortumab Vedotin - Previously Treated Advanced or Metastatic Urothelial Cancer Cancer Type: Genitourinary Bladder / Urothelial Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Monday, January 13, 2025 Universal Date: 2025-01-13 00:00:00 AddThis: Title URL: enfortumabvedotin Drug Display Status: Active Revision Summary:
Drug Monograph: Updated Adverse effects, Dosing, and Administration sections