apalutamide

Trade Name:

Erleada®

Appearance:

tablet

Monograph Name:

apalutamide

Monograph Body:

Drug Monograph

A - Drug Name

apalutamide

COMMON TRADE NAME(S): Erleada®

B - Mechanism of Action and Pharmacokinetics

Apalutamide is a nonsteroidal androgen receptor (AR) inhibitor that binds directly to the AR ligand-binding domain to inhibit nuclear translocation, DNA binding, and AR-mediated transcription. In mouse xenograft models of prostate cancer, apalutamide administration caused decreased tumour cell proliferation and increased apoptosis leading to decreased tumour volume.

Absorption

Bioavailability

100%. Apalutamide is completely absorbed after oral administration. Median t_max is 2 hours.

Effects with food

Food administration has no significant effect on apalutamide exposure, however the median time to reach t_max was delayed approximately 1-2 hours with food.

Administration of apalutamide 60 mg tablets as a dispersed mixture in applesauce resulted in comparable exposures and shorter t_max (shorter by 1 hour) compared to administration as whole tablets. Dissolution of apalutamide 240 mg tablets was comparable with or without food.

Time to reach steady state

4 weeks; accumulates approximately 5x relative to a single dose.

Distribution

Cross blood brain barrier?

Apalutamide and N-desmethyl apalutamide (active metabolite) have been observed to cross the blood brain barrier in animal studies.

PPB

96% Apalutamide; 95% N-desmethyl apalutamide

Metabolism

Apalutamide is primarily metabolized by CYP2C8 and CYP3A4.

Active metabolites

Yes. 44% N-desmethyl apalutamide

Inactive metabolites

Yes

Elimination

Urine

65%; 1% as apalutamide and 3% as N-desmethyl apalutamide

Feces

24%; 2% as apalutamide and 2% as N-desmethyl apalutamide

Half-life

~ 3 days

C - Indications and Status

Health Canada Approvals:

Prostate cancer

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

D - Adverse Effects

Emetogenic Potential:

Not applicable

The following adverse effects were reported in ≥ 10% of patients with non-metastatic castration resistant prostate cancer (nmCRPC) in the phase III trial comparing apalutamide with androgen deprivation therapy (ADT) to placebo with ADT, where incidence was at least 2% or more compared to placebo. Severe adverse effects from other studies or post-marketing may also be included.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arterial thromboembolism (4%)	E
	Cardiotoxicity (2%)	E
	Hypertension (25%) (14% severe)	E
	QT interval prolonged (rare)	E
Dermatological	Rash, pruritus (25%) (5% severe)	D
	Stevens-Johnson syndrome (rare)	E
	Toxic epidermal necrolysis (rare)	E
Gastrointestinal	Anorexia, weight loss (16%)	E
	Diarrhea (20%)	E
	Nausea (18%)	E
General	Edema (11%)	E
	Fall (16%)	E D
	Fatigue (39%)	E
Hematological	Anemia (<1%) (severe)	E D
	Myelosuppression (2%) (severe)	E
Hypersensitivity	DRESS syndrome (%)	E
Metabolic / Endocrine	↑ Cholesterol (6%) (or triglycerides)	E
	Hyperglycemia (2%) (severe; non-fasting)	E
	Hypothyroidism (8%)	E D
	↑ K (2%) (severe)	E
Musculoskeletal	Arthralgia (16%)	E
	Fracture (12%)	D
Nervous System	Seizure (<1%)	E
	Syncope (2%)	E
Reproductive and breast disorders	Androgen deprivation symptoms (14%)	E
Respiratory	Interstitial lung disease (<1%)	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 apalutamide include fatigue, hypertension, rash, pruritus, diarrhea, nausea, anorexia, weight loss, arthralgia, fall, androgen deprivation symptoms and fracture.

Rash (usually macular or maculopapular) onset typically occurred at a median of 83 days with resolution within a median of 78 days in most patients. Rash was commonly managed with oral antihistamines and topical corticosteroids, though some patients required systemic corticosteroids. Rash recurred in approximately half of patients who were re-challenged with apalutamide.

Grade 1 or 2 hypothyroidism has been reported with apalutamide. Thyroid replacement therapy should be initiated or adjusted as clinically indicated as apalutamide may induce UDP-glucuronosyl transferase (UGT).

Fall and fractures, which were not associated with loss of consciousness or seizure, have been observed in patients receiving apalutamide. The median time to onset of fracture was approximately 10 months (range: 20 to 953 days). 40-50% of patients experienced a fall within 7 days before the fracture event. Most of the severe fractures occurred in the weight bearing bones.

Seizures were observed in patients receiving apalutamide, with a reported onset of 159 to 650 days after treatment initiation and may be related to off target effects on GABAA gated channels. It is unknown whether anti-epileptic medications will prevent apalutamide-associated seizures.

E - Dosing

Refer to protocol by which patient is being treated.

Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy.

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.

Patients with a cardiac or stroke history should be assessed before starting treatment. Manage patients optimally for risk factors such as hypertension, diabetes, or dyslipidemia.

Adults:

Oral: 240 mg (4 x 60mg tablets) Daily

Dosage with Toxicity:

Dose Level	Apalutamide Dose (mg/day)
0	240
-1	180
-2	120
-3	Discontinue

Toxicity	Action
Intolerable or ≥ Grade 3	Hold until recovery to ≤ grade 1 or baseline, resume at the same dose or at ↓ 1-2 dose level(s), if indicated. Recurrence ≥ grade 3: Hold until recovery to ≤ grade 1 or baseline, then ↓ 1 dose level.
Seizure	Discontinue.
Stevens-Johnson syndrome, Toxic epidermal necrolysis, or DRESS	Discontinue.
Interstitial lung disease	Hold and investigate. Discontinue if confirmed.

Dosage with Hepatic Impairment:

Hepatic Impairment at baseline	Action
Mild or moderate (Child-Pugh A or B)	No adjustment required
Severe (Child-Pugh C)	No data

Dosage with Renal Impairment:

Renal Impairment	Action
Mild to moderate (CrCL ≥ 30 mL/min)	No adjustment required
Severe or ESRD (CrCL ≤ 29 mL/min)	No data

Dosage in the elderly:

No dose adjustment is necessary for elderly patients. Patients ≥ 75 years treated with apalutamide experienced higher incidence of grade 3 or 4 adverse events and lower tolerance. Monitor elderly patients more closely for toxicity and adjust dose when needed.

Dosage based on ethnicity:

No dose adjustments are necessary. There is no clinically relevant difference in exposure between White (Caucasian or Hispanic or Latino), Black (of African heritage or African American), Asian (non-Japanese), or Japanese patients. In clinical studies, the incidence of rash was more than 2-fold higher in the Japanese population compared with the entire study population.

Children:

Safety and effectiveness of apalutamide in pediatric patients have not been evaluated.

F - Administration Guidelines

Tablets should be swallowed whole with a glass of water.
Tablets can be taken with or without food.
Take the dose at around the same time each day.
A missed dose should be taken as soon as possible on the same day with a return to the normal schedule on the following day. The patient should not take extra tablets to make up the missed dose.
For patients who have difficulty swallowing 60 mg tablets, the dose may be mixed in applesauce. Refer to product monograph for the most up-to-date instructions.
- Mix whole 60 mg tablets in 120 mL of applesauce by stirring. Do not crush the tablets.
- Wait 15 minutes, then stir the applesauce.
- Wait another 15 minutes, then stir the applesauce until the tablets are well mixed with no chunks remaining.
- Using a spoon, swallow the mixture right away.
- Rinse the mixture container with 60 mL of water and drink this immediately.
- Repeat the rinsing with another 60 mL of water, then drink this to ensure the entire dose is taken.
- The mixture should be taken within 1 hour of preparation.
For patients who have difficulty swallowing 240 mg tablets, the dose may be dispersed in non-fizzy water, then mixed with non-fizzy beverages or soft foods. Refer to product monograph for the most up-to-date instructions.
- Place whole 240 mg tablet in a cup. Do not crush or split the tablet.
- Add about 10 mL of non-fizzy water. Wait 2 minutes for the tablet to disperse, then stir the mixture.
- Add 30 mL of the following non-fizzy beverages or soft foods: orange juice, green tea, applesauce, or drinkable yogurt), then stir the mixture.
- The mixture should be swallowed immediately.
- Rinse the cup with enough water, then drink it immediately, to make sure the whole dose is taken.
For nasogastric (NG) tube administration (8 French or greater), the 240 mg tablet may be dispersed in 10 mL of non-carbonated water (in at least a 20 mL syringe). Wait 10 minutes and shake vigorously to disperse the tablet; then administer immediately through the NG tube. Flush the NG tube with non-carbonated water until no dispersed tablet is remaining in the syringe or the NG tube.

Store tablets at 15°C to 30°C, in the original package to protect from light and moisture.
If tablets are provided in a bottle, do not remove the silica gel desiccant from the bottle.

G - Special Precautions

Contraindications:

Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

Other Warnings/Precautions:

Exercise caution in patients with:
- Cardiac disorders. Patients with clinically significant cardiovascular disease in the past 6 months including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events or clinically significant ventricular arrhythmias were excluded from clinically trials.
- Seizures. Patients with a history of seizures or predisposing factors for seizures were excluded from clinical studies; patients on medications known to lower seizure threshold were prohibited while receiving apalutamide.
- QT prolongation, risk factors for Torsade de pointes or on medications known to prolong QTc.
- nmCRPC at low risk of developing metastases. Apalutamide has not been studied in these patients and the benefit and risk profile is unknown.

Other Drug Properties:

Carcinogenicity: Unknown

Pregnancy and Lactation:

Abortifacient effects: Probable
Genotoxicity: No
Embryotoxicity: Likely
Pregnancy:
- Apalutamide is contraindicated in patients who are or may become pregnant. It may cause harm to a developing fetus or lead to loss of pregnancy. Adequate contraception should be used by patients and their partners who can become pregnant during treatment, and for at least 3 months after the last dose.
- Patients who produce sperm should use a condom and not donate sperm during treatment, and for 3 months after the last dose.
Breastfeeding:
- Apalutamide is only indicated in patients with prostate cancer. There are no data on the presence of apalutamide or its metabolites in human milk.
Fertility effects: Probable

Documented in animal studies.

H - Interactions

In vitro studies showed that apalutamide and N-desmethyl apalutamide are moderate to strong CYP2B6 inducers, and moderate inhibitors of CYP2B6.
Apalutamide did not cause clinically significant changes in exposure to the CYP2C8 substrate.
Based on in vitro data, inhibition of organic cation transporter 2 (OCT2), organic anion transporter 3 (OAT3) and multidrug and toxin extrusions (MATEs) by apalutamide and its N-desmethyl apalutamide cannot be excluded.
GABA inhibition is an off-target activity of both apalutamide and N-desmethyl apalutamide. This interaction is considered the mechanism for the seizures/convulsions observed in general toxicology studies at high doses in animals.
Acid lowering agents (e.g., proton pump inhibitor, H2-receptor antagonist, antacid) are not expected to affect the solubility and bioavailability of apalutamide.

AGENT	EFFECT	MECHANISM	MANAGEMENT
CYP 2C8 strong inhibitors (i.e. gemfibrozil)	↑ apalutamide concentration	↓ metabolism of apalutamide	Caution; consider dose adjustment for apalutamide based on tolerability.
CYP 3A4 strong inhibitors (i.e. itraconazole, clarithromycin, ritonavir, nelfinavir, etc.)	↑ apalutamide concentration	↓ metabolism of apalutamide	Caution; consider dose adjustment for apalutamide based on tolerability.
CYP 3A4 strong inducers (i.e. phenytoin, rifampin, carbamazepine, phenobarbital, St. John’s Wort, etc.)	↓ apalutamide concentration	↑ metabolism of apalutamide	Caution, no adjustment needed.
CYP3A4 substrates (e.g. cyclosporine, pimozide, tacrolimus, triazolo-benzodiazepines, dihydropyridine calcium-channel blockers, certain HMG-CoA reductase inhibitors)	↓ substrate concentration and/or efficacy	↑ metabolism of substrate (apalutamide is a strong inducer of CYP 3A4)	Avoid or substitute if possible. Evaluate for loss of efficacy if medication is continued.
CYP 2C19 substrates (e.g. omeprazole)	↓ substrate concentration and/or efficacy	↑ metabolism of substrate (apalutamide is a strong inducer of CYP 2C19)	Avoid or substitute if possible. Evaluate for loss of efficacy if medication is continued.
CYP 2C9 substrates (e.g. warfarin, meloxicam, fluvastatin)	↓ substrate concentration and/or efficacy	↑ metabolism of substrate (apalutamide is a weak inducer of CYP 2C9)	Avoid or substitute if possible. Evaluate for loss of efficacy (e.g. INR) if medication is continued.
P-glycoprotein substrates (i.e. verapamil, digoxin, fexofenadine)	↓ substrate concentration and/or efficacy	↑ metabolism of substrate (apalutamide is a weak inducer of Pgp)	Caution; evaluate for loss of efficacy if medication is continued.
BCRP substrates (i.e. topotecan)	↓ substrate concentration and/or efficacy	↑ metabolism of substrate (apalutamide is a weak inducer of BCRP)	Caution; evaluate for loss of efficacy if medication is continued.
OATP1B1 substrates (i.e. rosuvastatin)	↓ substrate concentration and/or efficacy	↑ metabolism of substrate (apalutamide is a weak inducer of OATP1B1)	Caution; evaluate for loss of efficacy if medication is continued.
UGT substrates (i.e. estradiol, irinotecan, levothyroxine, thyroxine)	↓ substrate concentration and/or efficacy	↑ metabolism of substrate	Caution; evaluate for loss of efficacy if medication is continued.
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 and arrhythmias	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
TSH	Baseline and as clinically indicated
ECG	Baseline and as clinically indicated; more frequent in patients at risk of QTc increase or taking medications known to prolong QT interval
INR	If warfarin cannot be discontinued; baseline and during apalutamide treatment
PSA and radiographic disease progression	Baseline and as clinically indicated
Clinical toxicity assessment for androgen deprivation symptoms, hypertension, fatigue, infection, seizure, cardiac, stroke, gastrointestinal, respiratory or dermatologic effects, and risk of fracture and falls	At each visit

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

Suggested Clinical Monitoring

Monitor Type	Monitor Frequency
Cholesterol and triglycerides	As clinically indicated
Blood glucose	As clinically indicated

J - Supplementary Public Funding

Exceptional Access Program (EAP Website)

apalutamide - For the treatment of non-metastatic castration resistant prostate cancer (nmCRPC), based on criteria
apalutamide - For the treatment of metastatic castration sensitive prostate cancer (mCSPC), based on criteria

K - References

Prescribing Information: Erleada® (apalutamide). Janssen Ortho LLC. November 2020.

Product Monograph: Erleada® (apalutamide). Janssen Inc. August 8, 2024.

Smith MR, Saad F, Chowdhury S, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med 2018;378:1408-18.

January 2025 Updated Effects with food, Adverse Effects, Dosing, and Fertility effects 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:

apalutamide (patient)

Info Sheet Introduction:

• For treating prostate cancer

Info Sheet Date: Jeudi, avril 4, 2024 Info Sheet body:

Medication Information Sheet

apalutamide (a-pa-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: Erleada®

Appearance:

tablet

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:
- high blood pressure or high blood sugar
- high levels of fat or cholesterol in your blood
- heart disease or irregular heartbeat
- risk of falls or broken bones
- underactive thyroid (called hypothyroidism)
- seizures, brain injury, stroke, or brain tumors (non-cancerous or cancerous) 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.

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 your partner is pregnant or becomes pregnant during treatment.

If there is any chance that your partner may become pregnant, you and your partner together must use 2 effective forms of birth control at the same time until 3 months after your last dose. Tell your health care team if your partner is pregnant or becomes pregnant during treatment.

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 whole with a glass of water, with or without food. If you cannot swallow your medication whole, talk to your health care team about what to do.
Take the dose at about the same time each day.
If you miss a dose, take your normal dose as soon as possible on the same day. Go back to your regular schedule on the following day. You should not take 2 doses or extra tablets to make up the missed dose.
If you vomit (throw up) after taking your medication, talk to your health care team about what to do.
Apalutamide is usually taken with another medication known as a gonadotropin-releasing hormone (GnRH) analogue, unless you had a surgery to remove your testicles in order to lower the amount of testosterone in your body. Your healthcare professional will tell you exactly how and when to take apalutamide and the GnRH analogue.
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 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 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 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.

How should I safely store this medication?

Do not throw out any unused medications at home. Bring them to your pharmacy to be thrown away safely.

Keep this medication in the original packaging at room temperature (15°C to 30°C) in a dry place, away from heat and light. Keep out of sight and reach of children and pets.
If your apalutamide tablets are provided to you in a bottle, the bottle contains silica gel desiccant to help keep your medication dry. Do not remove desiccant from the bottle.

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 there is a chance your partner 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 apalutamide. 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 apalutamide.

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
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

Less Common Side Effects (10 to 24 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
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
Low appetite, weight loss 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
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
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
Bone pain; Bone loss or Bone fractures Your treatment may cause your bones to thin earlier than normal. Thin bones are weak and fragile. They may break easily from simple falls or movements. Your health care team may check your bone density (measure of how strong your bones are) with a bone scan. What to look for? You may have severe or unusual bone pain especially in your back, hips and wrist. What to do? To help prevent bone loss and fractures Your health care team may ask you to change your diet, or may ask you to take calcium and vitamin D supplements, or other prescription medications. Talk to your health care team before taking any supplements. Get emergency medical help if you experience severe bone pain or are unable to move as these may be signs of a bone fracture. See our Bone Health pamphlet for more information.	Talk to your health care team if it does not improve. Get emergency medical help if you have severe bone pain or are unable to move.
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

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:

Irregular heartbeat, shortness of breath, chest pain, fainting spells or swelling in your legs, ankles and belly
Trouble with seeing, speaking or using your arms or legs
Seizures
Unusual weight gain which may be accompanied with: feeling tired or having low energy, dry skin, nails or hair that breaks easily, or sensitivity to cold
Breathing problems, chest pain or cough up blood
Redness, blistering and/or peeling of large areas of the skin and/or inside of the lips, eyes, mouth, nasal passages or genitals, along with fever, chills, headache, cough, body aches or swollen glands

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/Revised "Less Common Side Effects" 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):

apalutamide patient.pdf Info Sheet (French):

apalutamide pour le patient.pdf Monograph:

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

apalutamide - For the treatment of non-metastatic castration resistant prostate cancer (nmCRPC), based on criteria
apalutamide - For the treatment of metastatic castration sensitive prostate cancer (mCSPC), based on criteria

Phonetic Spelling:

a-pa-LOO-ta-mide

Cancer Type: Genitourinary Prostate Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Vendredi, janvier 31, 2025 Universal Date: 2025-01-31 00:00:00 AddThis: Title URL: apalutamide Drug Display Status: Active Revision Summary:
Drug Monograph: Updated Effects with food, Adverse Effects, Dosing, and Fertility effects sections