enzalutamide

Trade Name:

Xtandi®

Appearance:

white capsule

Monograph Name:

enzalutamide

Monograph Body:

Drug Monograph

A - Drug Name

enzalutamide

COMMON TRADE NAME(S): Xtandi®

B - Mechanism of Action and Pharmacokinetics

Enzalutamide is an androgen receptor inhibitor, which has no known agonistic properties. Enzalutamide competitively inhibits the binding of androgen to the receptor, inhibiting nuclear translocation of androgen receptors and their interaction with DNA.

Absorption

Bioavailability

At least 84.2%

Effects with food

Food had no significant effect on enzalutamide exposure, although a C_max of 30% higher was observed when this drug was given in fasting state.

Time to reach steady state

28 days; accumulates approximately 8.3x relative to a single dose.

Peak plasma levels

~ 1 hr (range: 0.52 h to 3.02 h)

Distribution

Extensive extravascular distribution.

Cross blood brain barrier?

Yes, both enzalutamide and the active metabolite

PPB

Enzalutamide: 97-98%; metabolites: 95%

No protein binding displacement between enzalutamide and other highly bound drugs in vitro.

Metabolism

Extensively metabolized by CYP2C8 and a lesser extent by CYP3A4/5.

Active metabolites

Yes

Inactive metabolites

Yes

Elimination

Cleared via renal excretion of hepatic metabolites.

Urine

71% (primarily as inactive metabolites)

Feces

14% (0.4% unchanged)

Half-life

5.8 days (enzalutamide); 8-9 days (active metabolite)

C - Indications and Status

Health Canada Approvals:

Non-metastatic castration-sensitive prostate cancer (nmCSPC)
Metastatic castration-sensitive prostate cancer (mCSPC)
Non-metastatic castration-resistant prostate cancer (nmCRPC)
Metastatic castration-resistant prostate cancer (mCRPC)

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

D - Adverse Effects

Emetogenic Potential:

Not applicable

Extravasation Potential: Not applicable

The following adverse effects were reported in ≥ 2% of patients with nmCRPC in the phase III trial comparing enzalutamide to placebo, where incidence was at least 2% or more compared to placebo. It also includes severe, life-threatening and post-marketing adverse effects from other sources.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arterial thromboembolism (rare)	E D
	Hypertension (12%) (may be severe)	E
	Other - Ischemic heart disease (4% , may be severe)	E D
	QT interval prolonged (rare)	E
Dermatological	Rash (4%) (including dry skin)	E
Gastrointestinal	Anorexia, weight loss (10%)	E
	Constipation (9%)	E
	Diarrhea (22%)	E
	Nausea (11%)	E
	Other - Gastrointestinal bleed (<2%)	E
General	Edema (15%)	E
	Fatigue (40%) (4% severe)	E
Hematological	Myelosuppression ± infection (1%) (severe)	E
Hypersensitivity	Hypersensitivity (rare)	E
Musculoskeletal	Fracture (5%)	E D
	Musculoskeletal pain (26%)	E
	Other - fall (11%)	E D
Neoplastic	Secondary malignancy (rare)	L
Nervous System	Anxiety (6%)	E
	Cognitive disturbance (5%)	E
	Dizziness (12%)	E
	Hallucinations (<2%)	E
	Headache (9%)	E
	Insomnia (9%)	E
	Other - Hypoesthesia (4%)	E
	Paresthesia (7%)	E
	Posterior reversible encephalopathy syndrome (PRES) (rare)	E
	Seizure (1%)	E
Reproductive and breast disorders	Androgen deprivation symptoms (13%)	E
Urinary	Urinary symptoms (7%)	E

* "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 enzalutamide include fatigue, musculoskeletal pain, diarrhea, edema, androgen deprivation symptoms, dizziness, hypertension, fall, nausea, anorexia and weight loss.

Enzalutamide is associated with an increased risk of seizure, especially at doses above 160mg. The lowering of the seizure threshold may be due to enzalutamide and its active metabolite crossing the blood brain barrier and inhibiting GABA-gated chloride channel activity.

Enzalutamide was associated with increases in systolic and diastolic blood pressure and an increased risk of hypertension or worsening of pre-existing hypertension in studies.

Posterior reversible encephalopathy syndrome (PRES) has been reported rarely, with and without associated hypertension.

Increases in non-pathological fractures and falls were observed as compared to placebo. Fall-related injuries included contusion, excoriation, head injury, joint injury, laceration, periorbital hematoma, and skeletal injury. Concomitant neurological symptoms or pre-syncope were rarely reported with the falls.

Hypersensitivity reactions, including facial, tongue, lip or pharyngeal edema have been observed with enzalutamide.

E - Dosing

Refer to protocol by which patient is being treated.

Patients with nmCRPC, mCRPC, or mCSPC, who have not had orchiectomy, should receive/remain on GnRH agonists during enzalutamide treatment.

Patients with nmCSPC with biochemical recurrence at high risk of metastasis (high-risk BCR) may be treated with or without a GnRH agonist.

Patients were allowed, but not required, to take glucocorticoids in several phase III CRPC clinical trials (Beer 2014, Hussain 2018, Scher 2012).

Prior to starting enzalutamide treatment:

Patients with cardiac history should be assessed for active cardiac disease.
Management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia should be optimized.
Patients should be assessed for the risk of fracture and fall and managed according to guidelines with consideration given to the use of bone-targeted agents.

Adults:

Oral: 160 mg Daily

For nmCSPC with high-risk BCR, refer to the product monograph for details on intermittent treatment.

Dosage with Toxicity:

Dose Level	Enzalutamide Dose (mg/day)
0	160
-1	120
-2	80
-3	Discontinue

Toxicity	Grade	Action
Hypersensitivity reactions	Any	Hold and promptly seek medical care.
Hypersensitivity reactions	≥ grade 3	Discontinue.
PRES	Any	Discontinue.
Seizure	Any	Discontinue.
Ischemic heart disease	≥ grade 3	Discontinue.
Treatment emergent hypertension	Any	Monitor blood pressure and treat appropriately.
All other toxicities	Intolerable or ≥ grade 3	Hold until ≤ grade 2. Resume at the same dose OR ↓ dose level, if warranted. Consider discontinuing if grade 4.

Dosage with Hepatic Impairment:

Hepatic Impairment	Enzalutamide Dose (mg/day)
Mild or moderate (Child-Pugh Class A or B)	No adjustment required
Severe (Child-Pugh C)	Increased drug half-life was observed; clinical significance unknown. No dosage adjustment required.

Dosage with Renal Impairment:

Creatinine Clearance (mL/min)	Enzalutamide Dose (mg/day)
≥ 30	No adjustment required
< 30	Has not been studied. Exercise caution.

Dosage in the elderly:

No dose adjustment required. No overall differences in safety or efficacy were found in patients ≥ 65 years compared to younger patients; however, an increased frequency of dose interruption/reduction and discontinuation was observed.

Dosage based on ethnicity:

Based on a pharmacokinetic study in Japanese patients, no clinically relevant differences in exposure were found between Japanese and Caucasians.

Children:

Safety and efficacy have not been established.

F - Administration Guidelines

Swallow capsules whole with a glass of water, with or without food.
Do not chew, dissolve, or open the capsules.
Take the dose at around the same time each day.
If a dose is missed for the day, give it as soon as it is remembered on the same day. If it is forgotten for the whole day, skip this dose and give the next usual dose. Do not double the dose to make up for the missed one.

Store at room temperature (15 to 30°C).

G - Special Precautions

Contraindications:

Patients who have a hypersensitivity to this drug or any of its components
Patients who are or may become pregnant, or who are lactating

Other Warnings/Precautions:

Exercise caution in these patient populations:
- nmCRPC at low risk of developing metastatic disease: Enzalutamide has not been studied in this population and the benefit and risk profile in these patients is unknown.
- nmCSPC with high-risk BCR: Enzalutamide was studied in combination with leuprolide during clinical trials. Other GnRH agonists may have potential differences in patterns of testosterone recovery, PSA expression, duration of treatment suspension and compliance to treatment.
- Significant cardiovascular disease. Patients with significant cardiovascular disease (i.e. recent MI, unstable angina, LVEF < 45%, bradycardia or uncontrolled hypertension) were excluded from clinical trials.
- History of QT prolongation, risk factors for Torsades de Pointes, or on medications known for QT prolongation.
- History of seizures or have risk factors for seizures (e.g. brain injury with loss of consciousness, recent TIA, CVA, brain metastases). These patients were excluded from clinical trials. Avoid dosing above 160mg as this was observed to have a greater risk of seizures.
- Enzalutamide may cause neuropsychiatric events such as cognitive or memory impairment, seizures, hallucinations, etc. Patients should take caution and avoid tasks in which mental impairment or loss of consciousness may harm themselves or others.
- Severe hepatic impairment (Child-Pugh C) at baseline. These patients were excluded from clinical trials.
Patients with hereditary fructose intolerance should not take enzalutamide as it contains sorbitol.

Other Drug Properties:

Carcinogenicity: No

Pregnancy and Lactation:

Genotoxicity: Yes

(metabolite, only at cytotoxic concentrations)
Embryotoxicity: Yes
Fetotoxicity: Yes

Enzalutamide is contraindicated in pregnancy. Adequate contraception (one of which must include condoms) should be used by patients and their patients and their partners during treatment and for 3 months after the last dose.
Excretion into breast milk: Yes

Breastfeeding is contraindicated.
Fertility effects: Yes

H - Interactions

Enzalutamide is a substrate of CYP2C8 and to a lesser extent, CYP3A4. It is an inducer and inhibitor of several CYP isoenzymes and susceptible to many drug interactions. Since the half-life of enzalutamide is 5.8 days, the effects on enzymes may persist for ≥1 month after stopping the drug.

CYP3A4 inhibitors may increase enzalutamide exposure, but no dosage adjustment is recommended.

Enzalutamide is an inhibitor of CYP2C8 and an inducer/inhibitor of CYP2B6, but no dosage adjustment is required.

AGENT	EFFECT	MECHANISM	MANAGEMENT
CYP2C8 inhibitors (i.e. gemfibrozil, montelukast)	↑ enzalutamide exposure (up to 2.2x) and/or toxicity	↓ metabolism of enzalutamide	Avoid; if concomitant use with strong CYP2C8 inhibitor cannot be avoided, reduce enzalutamide dose to 80mg daily.
CYP3A4 and CYP2C8 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc)	↓ enzalutamide concentration and/or efficacy (rifampin ↓ enzalutamide AUC 37% with no effect on Cmax)	↑ metabolism of enzalutamide	No dosage adjustment required. Avoid concomitant use with strong CYP3A4 inducers.
CYP3A4 substrates (i.e. midazolam, cyclosporine, pimozide, tacrolimus, triazolo-benzodiazepines, dihydropyridine calcium-channel blockers, certain HMG-CoA reductase inhibitors)	↓ substrate exposure and/or efficacy (up to 86% ↓)	enzalutamide is a strong CYP3A4 inducer	Avoid substrates with narrow therapeutic range; consider dose adjustment of substrate if concomitant use cannot be avoided.
CYP 2C9 substrates (i.e. warfarin, meloxicam, fluvastatin)	↓ substrate exposure and/or efficacy (up to 56% ↓), or ↑ substrate exposure	enzalutamide is a moderate CYP2C9 inducer, also has potential to inhibit CYP2C9	Avoid substrates with narrow therapeutic range; monitor INR closely (e.g. with warfarin); consider dose adjustment of substrate if concomitant use cannot be avoided.
CYP2C19 substrates (i.e. omeprazole)	↓ substrate exposure and/or efficacy (up to 70% ↓), or ↑ substrate exposure	enzalutamide is a moderate CYP2C19 inducer, also has potential to inhibit CYP2C19	Avoid substrates with narrow therapeutic range; consider dose adjustment of substrate if concomitant use cannot be avoided.
UGT1A1 substrates (i.e. irinotecan), CYP2B6 or UGT1A4 substrates	↓ substrate exposure and/or efficacy	enzalutamide can induce these enzymes or transporters	Avoid substrates with narrow therapeutic range; consider dose adjustment of substrate if concomitant use cannot be avoided.
P-glycoprotein substrates (i.e. verapamil, digoxin, morphine, ondansetron)	↑ P-gp substrate exposure/toxicity (↑ single dose digoxin exposure by 33%, after at least 55 days of enzalutamide 160 mg); ↓ in substrate concentration at higher enzalutamide concentrations	Inhibition or possible induction of P-gp	Caution with substrates with a narrow therapeutic range; dose adjustment of substrate may be required.
MRP2 substrates (i.e. topotecan, cisplatin)	↑ substrate exposure and/or toxicity	enzalutamide can inhibit MRP2	Caution with substrates with a narrow therapeutic range; dose adjustment of substrate may be required.
Substrates of OATP1B1/3 (i.e. statins), OAT3 (i.e. furosemide, methotrexate), and OCT1 (i.e. metformin)	↑ substrate exposure and/or toxicity	enzalutamide may inhibit these enzymes	Caution
Drugs that may prolong QT (i.e. amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron, etc)	↑ risk of QT prolongation	Additive	Caution

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.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
Blood pressure	Baseline and as clinically indicated
ECG and electrolytes	Baseline and as clinically indicated, in patients at risk of QT prolongation
Disease progression radiographically in addition to serum PSA	As clinically indicated, in patients with nmCRPC or nmCSPC with high-risk BCR
INR monitoring for patients on warfarin	Baseline and as clinically indicated
Clinical toxicity assessment for ischemic heart disease, androgen withdrawal, gastrointestinal effects, hypersensitivity, fatigue, seizures and other neuropsychiatric effects, musculoskeletal effects including falls/fractures and edema	At each visit

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

J - Supplementary Public Funding

Exceptional Access Program (EAP Website)

enzalutamide - For the treatment of metastatic castrate-resistant prostate cancer (mCRPC), with specific clinical criteria
enzalutamide - For the treatment of high risk non-metastatic castration-resistant prostate cancer (nmCRPC), with specific clinical criteria
enzalutamide - For the treatment metastatic castration sensitive prostate cancer (mCSPC), with specific clinical criteria

K - References

Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol 2019 Nov 10;37(32):2974-2986.

Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014 Jul 31;371(5):424-33.

Hussain M, et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474.

Prescribing Information: Xtandi® (enzalutamide). Astellas Pharma US Inc., December 2019.

Product Monograph: Xtandi® (enzalutamide). Astellas Pharma Canada Inc., January 5, 2024.

Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367(13):1187-97.

June 2024 Updated Adverse Effects, Dosing, Special Precautions, and Monitoring 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:

enzalutamide (patient)

Info Sheet Introduction:

• For treating prostate cancer

Info Sheet Date: Monday, April 8, 2024 Info Sheet body:

Medication Information Sheet

enzalutamide (EN-za-LOO-ta-mide)

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: Xtandi®

Appearance:

white capsule

What is this medication for?

For treating prostate 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:
- seizures or at risk of having seizures,
- liver, kidney or heart problems (including irregular heartbeat),
- high blood pressure,
- a history of fainting spells,
- thin bones or are at risk of falls and bone breaks,
- low salt levels in the blood or
- any allergies
Enzalutamide contains a small amount of sorbitol. If you cannot have fructose, talk to your health care team.

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.

How will this medication affect sex, pregnancy and breastfeeding?

Talk to your health care team about:

How this medication may affect your sexual health.
Symptoms such as hot flashes.
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 or become pregnant during treatment.

If there is any chance of pregnancy happening, you and your partner together must use 2 effective forms of birth control (one of which must include condoms) at the same time until 3 months after your last dose. Talk to your health care team about which birth control options are best for you.

How is this medication given?

This medication is usually taken once a day by mouth. Talk to your health care team about how and when to take your medication.
Swallow capsules whole with a glass of water, with or without food.
Do not chew, dissolve, or open the capsules.
If a dose is missed for the day, take it as soon as it is remembered on the same day. If it is forgotten for the whole day, skip this dose and take the next usual dose. Do not double the dose to make up for the missed one.
If you vomit (throw up) after taking your medication, talk to your health care team about what to do.
If you take too much of your medication by accident, or if you think a child or a pet may have swallowed your medication, you must call the Ontario Poison Control Center right away at: 1-800-268-9017.

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.
If you are taking a blood thinner (such as warfarin), your health care team may need extra blood tests and may change your dose.

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 talk to your health care team about your risk of getting other cancers after this treatment.
DO wear shoes that have nonslip soles and some ankle support. Also try to stand up slowly after sitting or lying down to lower your chance of falling down.

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.
DO NOT drive, operate machinery or do any tasks that need you to be alert if you feel tired, drowsy or dizzy.

How should I safely store this medication?

Keep this medication in the original packaging at room temperature in a dry place, away from heat and light. Keep out of sight and reach of children and pets.
Do not throw out any unused medications at home. Bring them to your pharmacy to be thrown away safely.

How to safely touch oral anti-cancer medications

If you are a patient:

Wash your hands before and after touching your oral anti-cancer medication.
Swallow each pill whole. Do not crush or chew your pills.

If you are a caregiver:

Wash your hands before and after touching the oral anti-cancer medication.

If you are pregnant or breastfeeding or there is a chance there is a chance you may become pregnant:

Wear nitrile or latex gloves when touching tablets, capsules or liquids.
Wash your hands before putting on your gloves and after taking them off, even if your skin did not touch the oral anti-cancer medication.
Throw out your gloves after each use. Do not re-use gloves.

What to do if oral anti-cancer medication gets on your skin or in your eyes

If medication gets on your skin:

Wash your skin with a lot of soap and water.
If your skin gets red or irritated, talk to your health care team.

If medication gets in your eyes:

Rinse your eyes with running water right away. Keep water flowing over your open eyes for at least 15 minutes.

What are the side effects of this medication?

The following table lists side effects that you may have when getting enzalutamide. 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 enzalutamide.

Common Side Effects (25 to 49 out of 100 people)
Side effects and what to do	When to contact health care team
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.
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. 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
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).
Changes to your hormone levels Your treatment causes changes in the levels of testosterone in your body. This can affect your mood, energy levels or physical appearance, among other things. You may have many of these symptoms or none at all. Your symptoms may also change at different times in your treatment. What to look for? Hot flashes: A hot flash feels like a sudden warmth in your upper body and face. It can happen quickly and with no warning. Your face may get flushed (turn red) and you may sweat more Hot flashes can cause you to have trouble sleeping Other symptoms of having low testosterone levels: Problems with erectile dysfunction (getting or keeping erections) or less desire to have sex Breast swelling or tenderness Low energy Mood changes, depression Thinning of the bones and higher risk of fracture High cholesterol and effects on your heart What to do? To help prevent hot flashes : Avoid triggers such as spicy food, alcohol and caffeine (tea, coffee, and soft drinks), Exercise regularly. Ask your health care team what exercises are appropriate for you before you start any new exercise. Quitting smoking may also help. If you have hot flashes : To keep cool, dress in light, cotton clothing or in layers that you can easily remove. Use a fan Drink plenty of water or other liquids (at least 6 to 8 cups) unless your health care team has told you to drink more or less. Lay a towel on top of your bed sheet before you sleep so you can change it easily if you sweat at night. Hot flashes may improve over time. Talk to your health care team if this or any symptoms of low testosterone are bothersome for you.	Talk to your health care team if it does not improve or if it is severe.
Mild swelling What to look for? You may have mild swelling or puffiness in your arms and/or legs. Rarely, this may be severe. What to do? To help prevent swelling: Eat a low-salt diet. If you have swelling: Wear loose-fitting clothing. For swollen legs or feet, keep your feet up when sitting.	Talk to your health care team if it does not improve or if it is severe.
High blood pressure (May be severe) What to look for? There are usually no signs of high blood pressure. Rarely, you may have headaches, shortness of breath or nosebleeds. What to do? Check your blood pressure regularly. Your doctor may prescribe medication to treat high blood pressure. If you have a severe headache get emergency help right away as it may be a sign your blood pressure is too high.	Talk to your health care team if it does not improve or if it is severe.
Dizziness What to look for? You may feel light-headed and like you might faint (pass out). What to do? Lay down right away so you do not fall. Slowly get up and start moving once you feel better. Do not drive a motor vehicle or use machinery if you feel dizzy.	Talk to your health care team if it does not improve or if it is severe.
Nausea or 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.
Low appetite or weight loss What to look for? Loss of interest in food or not feeling hungry. Unusual 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.

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

signs of an allergic reaction such as flushing, itchiness, rash, swollen lips, face or tongue, wheezing, chest or throat tightness
feeling anxious or confused, having trouble remembering things, seeing and/or hearing things that are not there
passing out or seizures
irregular heartbeat, chest pain, shortness of breath, or swelling in your legs, ankles and belly
severe headache, trouble speaking or changes in your vision
severe or unusual bone pain
sudden, severe pain in your belly or stomach area
blood in your stools (poo) or black stools (poo), or vomiting (throwing up) blood
unusual bleeding or bruising
signs of infection of the blood such as fever or very low body temperature, chills, less urine (pee) than usual, low blood pressure

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:

____________________________________________________________________________

April 2024 Updated rare side effects

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):

enzalutamide patient.pdf Info Sheet (French):

enzalutamide pour le patient.pdf Monograph:

enzalutamide.pdf Funding Program: Exceptional Access Program Funding Instance:

enzalutamide - For the treatment of metastatic castrate-resistant prostate cancer (mCRPC), with specific clinical criteria
enzalutamide - For the treatment of high risk non-metastatic castration-resistant prostate cancer (nmCRPC), with specific clinical criteria
enzalutamide - For the treatment metastatic castration sensitive prostate cancer (mCSPC), with specific clinical criteria

Phonetic Spelling:

EN-za-LOO-ta-mide

Cancer Type: Genitourinary Prostate Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Thursday, June 13, 2024 Universal Date: 2024-06-13 00:00:00 AddThis: Title URL: enzalutamide Drug Display Status: Active Revision Summary:
Drug Monograph: Updated Adverse Effects, Dosing, Special Precautions, and Monitoring sections