bicalutamide

Trade Name:

Casodex® (multiple brands available)

Appearance:

tablet

Monograph Name:

bicalutamide

Monograph Body:

Drug Monograph

A - Drug Name

bicalutamide

COMMON TRADE NAME(S): Casodex® (multiple brands available)

B - Mechanism of Action and Pharmacokinetics

Bicalutamide is a selective, non-steroidal antiandrogen. It binds to the androgen receptors in target tissue and competitively inhibits the action of androgen, resulting in regression of prostatic tumours. Bicalutamide is a racemate and the (R)-enantiomer is primarily responsible for its anti-androgenic activity.

Absorption

Oral: Well absorbed. Food does not appear to affect the rate or extent of absorption.

Distribution

The (R)-enantiomer accumulates about 10-fold with daily administration.

Cross blood brain barrier?

Probably poor penetration

PPB

> 96 %

Metabolism

Bicalutamide undergoes stereospecific metabolism, with hepatic biotransformation via glucuronidation and oxidation. The (S)-enantiomer is very rapidly cleared relative to the (R)-enantiomer.

Active metabolites

R-enantiomer

Elimination

Metabolites are eliminated equally via renal and biliary routes.

Feces

43 % over 9 days

Urine

36 % over 9 days

Half-life

1 week

C - Indications and Status

Health Canada Approvals:

For use in combination with LHRH analogue or surgical castration in the treatment of metastatic (stage D2) prostate cancer.

D - Adverse Effects

Emetogenic Potential:

Not applicable

Extravasation Potential: Not applicable

The following adverse effects were observed in metastatic prostate cancer patients, in combination with a LHRH agonist.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arrhythmia (<5%)	D
	Arterial thromboembolism (<5%)	E D
	Cardiotoxicity (4%)	D
	Hypertension (8%)	D
	Venous thromboembolism (<5%)	E D
Dermatological	Alopecia (4%)	E
	Hirsutism (2%)	D
	Photosensitivity (rare)	E
	Rash (9%)	E
Gastrointestinal	Abdominal pain (11%)	E
	Anorexia (6%)	E
	Constipation (22%)	E
	Diarrhea (12%)	I
	Dyspepsia (7%)	E
	GI hemorrhage (<5%)	E
	GI obstruction (<5%)	E
	Nausea, vomiting (14%)	I
	Weight changes (7%)	D
General	Edema (13%)	D
	Fatigue (22%)	E
Hematological	Anemia (13%)	D
Hepatobiliary	↑ LFTs (7%) (may be severe)	D
Hypersensitivity	Hypersensitivity (1%) (angioedema, urticaria)	I
Infection	Infection (18%)	D
Metabolic / Endocrine	↑ Ca (<5%)	D
	↑ Cholesterol (<5%)	D
	Hyperglycemia (7%)	D
Musculoskeletal	Musculoskeletal pain (35%)	E
	Osteoporosis (4%) /Fractures	D
Nervous System	Anxiety (5%)	E
	Cognitive disturbance (<5%)	E
	Depression (4%)	E
	Dizziness (10%)	I E
	Headache (7%)	E
	Insomnia (7%)	I E
	Neuropathy (8%)	E
Ophthalmic	Cataract (<5%)	E D
	Conjunctivitis (<5%)	E D
Renal	Creatinine increased (<5%)	E
Reproductive and breast disorders	Androgen deprivation symptoms (53%)	D
Respiratory	Cough, dyspnea (13%)	D
	Pneumonitis (rare)	D
Urinary	Urinary symptoms (12%)	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.
Dose-limiting side effects are underlined.

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

Bicalutamide is well-tolerated in general, with expected adverse effects including hot flashes, breast tenderness and gynecomastia, which may be reduced by concomitant surgical or medical castration. Bicalutamide may also be associated with occurrence of diarrhea, nausea, vomiting and fatigue. Fluid retention may occur.

In the pivotal trial comparing bicalutamide to flutamide, an imbalance in cardiac deaths was noted (18 patients vs. 9 patients receiving flutamide). The combined use of anti-androgen plus LHRH analogue / surgical castration increases risk of cardiovascular disease and osteoporosis or the potential of QT prolongation. (especially in patients with risk factors). Assess benefit-risk ratio in these patients before starting treatment. Use bicalutamide with caution in patients with cardiac disease as well as in patients at risk for prolonged QTc.

Bone loss may occur during the hypoandrogenic state caused by long-term combined androgen blockade. Risk factors such as older patients, pre-existing osteopenia, family history of osteoporosis, chronic use of corticosteroids or anticonvulsants, or chronic alcohol/tobacco abuse should be carefully considered before starting treatment. Reduction of glucose tolerance has also been observed in patients receiving combined androgen blockade.

Severe, sometimes fatal hepatic failure and hepatic changes have been observed rarely. Hepatotoxicity generally occurs within the first 3-4 months of treatment. Interstitial lung disease (ILD), including fatal reports, has been reported rarely, especially at doses of over 50mg.

In some patients, antiandrogens may increase rather than inhibit growth of prostate cancer; patients with increasing PSA or worsening symptoms should discontinue bicalutamide and be assessed for 6-8 weeks for an antiandrogen withdrawal response.

Photosensitivity reactions have been reported rarely. If the reaction is persistent and/or severe, appropriate symptomatic treatment should be given.

E - Dosing

Refer to protocol by which patient is being treated. Bicalutamide should be started at the same time as the LHRH analogue for patients who have not had surgical castration. Bicalutamide doses of 150 mg/day should not be used as this increases mortality (phase III localized prostate trials).

Patients should be advised to avoid direct exposure to excessive sunlight and may consider the use of sunscreens.

Adults:

Oral: 50 mg daily

Dosage with Toxicity:

Toxicity	Action
Myelosuppression	No adjustment required
Pneumonitis	Hold; investigate. If confirmed, discontinue.
Cardiac failure, arterial or venous thromboembolism	Discontinue
Grade 3 or 4 LFT increases	Discontinue

Dosage with Hepatic Impairment:

No adjustment required in the presence of mild hepatic impairment. Caution should be exercised in moderate to severe hepatic impairment, as bicalutamide is extensively metabolized in the liver. Elimination is lower in subjects with severe hepatic impairment, leading to increased accumulation.

Dosage with Renal Impairment:

No adjustment required.

Dosage in the elderly:

No adjustment required.

Children:

CONTRAINDICATED in children

F - Administration Guidelines

Outpatient prescription for home administration
May be taken with or without food

G - Special Precautions

Contraindications:

in patients with hypersensitivity to the drug or any of its components
in localized prostate cancer undergoing ”watchful waiting”
in females and children

Other Warnings/Precautions:

contains lactose; use should be carefully considered in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption
results in fluid retention and should be used with caution in patients with cardiac disease as well as in patients at risk for prolonged QTc

Pregnancy and Lactation:

Genotoxicity: No
Fetotoxicity: Yes

Bicalutamide is CONTRAINDICATED in pregnancy and breastfeeding. Patients and their partners should use adequate contraception for at least 130 days after the last dose.
Fertility effects: Probable

Male fertility impairment may be reversible.

H - Interactions

No drug/drug interactions were observed with LHRH analogues.

AGENT	EFFECT	MECHANISM	MANAGEMENT
Drugs metabolized by CYP3A4	Bicalutamide (R-enantiomer) inhibits CYP3A4 (and 2C9, 2C19, 2D6 to a lesser extent)	↑ levels of drugs	Caution when using with drugs with narrow therapeutic index
warfarin	↑ PT/INR	Increased anticoagulant effect and risk of bleeding; bicalutamide displaces warfarin from protein binding	Monitor PT/INR closely; warfarin dose may require adjustment
Drugs that may prolong QT interval	Potential risk in ↑ QT interval	Additive effects when combined with LHRH analogue and anti-androgen	Caution and monitor

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
Liver function tests	baseline and regular
Electrolytes	baseline, also during treatment for patients at risk of electrolyte abnormality and QT prolongation
Blood glucose	especially in diabetic patients; baseline and regular
ECG	baseline; also during treatment for patients at risk of QT prolongation
Bone density	as clinically indicated
INR, for patients on warfarin	as clinically indicated
Clinical assessment for fluid retention, pneumonitis, androgen withdrawal effects, cardiovascular, hepatic effects and thromboembolism	at each visit

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

Suggested Clinical Monitoring

Monitor Type	Monitor Frequency
Hemoglobin	baseline and as clinically indicated

J - Supplementary Public Funding

ODB - General Benefit (

ODB Formulary

)

bicalutamide ()

K - References

Prescribing Information: Casodex® (bicalutamide). AstraZeneca US Inc., December 2008.

Product Monograph: Casodex® (bicalutamide). AstraZeneca Canada Inc., July 13, 2017.

November 2017 modified contraception, interactions 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:

bicalutamide (patient)

Info Sheet Introduction:

• Used alone or with other medications to treat prostate cancer

Info Sheet Date: Lundi, avril 8, 2024 Info Sheet body:

Medication Information Sheet

bicalutamide (bye-cal-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: Casodex®, Generic brand(s) available

Appearance:

tablet

What is this medication for?

Used alone or with other medications to treat 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), such as:
- diabetes
- liver or lung problems
- bone thinning or osteoporosis
- irregular heartbeat or heart problems
- any allergies
This drug contains a small amount of lactose. If you cannot tolerate lactose, talk to your doctor.
Patients who have cancer are at a higher risk of developing blood clots. Some cancer drug treatments may increase this risk. Discuss this with your doctor.

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?

While this may not be directly applicable to you, 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 while taking this drug. Keep using birth control for at least 130 days after your last dose unless your health care team told you differently. Talk to your health care team to figure out the best method(s) for you and/or your partner.
Let your health care team know if your partner is pregnant or becomes pregnant during your bicalutamide treatment.
This medication may affect fertility (ability to get your partner pregnant).

How is this medication given?

Take it exactly as directed by your doctor.
Swallow whole with a glass of water, with or without food.
Do not crush or chew the tablets.

If you miss a dose, skip this and take your next dose as scheduled. Do not double the dose to make up for the forgotten one.
Bicalutamide is usually taken once a day, at about the same time each day.
Drinking alcohol while taking bicalutamide may produce excessive facial flushing. Avoid drinking alcohol if this becomes bothersome.

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

This medication can interact with other medications and can result in the treatment not working as well or cause severe side effects.
Make sure your health care team knows about all your medications (prescription, over-the-counter, herbals and supplements). Check with your health care team before starting or stopping any of them.

For mild aches and pain or fever:
- If you feel unwell, take your temperature before taking any medications for pain or fever. They may hide a fever.
- You may take acetaminophen (Tylenol®) tablets. Ask your health care team about the right dose for you.
- Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or aspirin (acetylsalicylic acid, ASA), including low dose aspirin for heart conditions, may increase your chance of bleeding. Talk to your health care team before you start or stop these medications.
Drinking alcohol and smoking during your treatment may increase some side effects and make your medication less effective. Speak to your health care team about smoking and drinking alcohol while on treatment.

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.

What are the side effects of this medication?

You may not have all of the side effects below. You may have side effects that are not listed.

Side effects and what to do	When to contact doctor?
Very Common Side Effects (50 or more out of 100 people)

Hot flashes, feeling or wave of warmth

You may sweat more or have trouble sleeping because of this.

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 :

Keep cool; dress lightly or in layers that you can easily remove and drink plenty of liquids unless you have been told otherwise.

Hot flashes may improve over time. Talk to your health care team if this is bothersome for you.

Other symptoms of low testosterone levels :

Decreased sexual function or desire to have sex
Breast swelling or tenderness
Low energy
Mood changes, depression
Thinning of the bones and increased risk of fracture

Contact your health care team if these feelings bother you.

Contact your health care team if no improvement or if severe.

Side effects and what to do	When to contact doctor?
Common Side Effects (25 to 49 out of 100 people)

Headache; mild joint, muscle pain or cramps

Take your pain medication as prescribed by your doctor.
You can take acetaminophen (Tylenol®) tablets as needed for mild aches and pains. Ask your doctor or pharmacist about the right dose for you.
Talk to your doctor or pharmacist first before taking ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or aspirin. These medication may increase bleeding risk.
Rest often and try light exercise as it may help.

Contact your health care team if no improvement or if severe.

Side effects and what to do	When to contact doctor?
Less Common Side Effects (10 to 24 out of 100 people)

Constipation

To help prevent constipation :

Drink more liquids and eat well. Drink at least 6 to 8 cups of liquids each day unless you have been told otherwise.
Be Active. Exercise can help to keep you regular.
Try to eat more fiber (e.g. fruits with skin, leafy greens and whole grains). 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. Ask your health care team what to do.

See the Constipation Pamphlet for more information.

Contact your health care team if no improvement or if severe.

Fatigue (tiredness)

Be active and 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.
Eat well and stay hydrated by drinking at least 6 to 8 glasses of water or other liquids every day (unless your doctor told you to drink more or less).
Avoid driving or using machinery if you are feeling tired

See our Fatigue pamphlet for more information.

Contact your health care team if no improvement or if severe.

Infection

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, Advil® or 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 (or 100.4°F) or higher for at least one hour.

What to do?

Wash your hands often to prevent infection.
Check with your doctor 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, 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.

Nausea and vomiting

(Generally mild)

May occur in hours to days after your treatment.

If you have nausea or vomiting:

Take anti-nausea medication(s) as prescribed to you by your doctor.
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 (e.g. coffee, tea) and alcohol.
Contact your health care team if the prescribed anti-nausea medications are not helping to control your nausea and vomiting.

Also see Nausea & Vomiting pamphlet for more information.

Talk to your health care team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if severe.

Anemia (low red blood cells)

You may feel more tired or weak than normal and have pale skin.
This may occur in days to weeks after you start or receive your medication.
Rest often and eat well.
Light exercise, such as walking may help.
You may need medication or a blood transfusion.
If it is very bad, your doctor may ask you to stop the medication that is causing the low red blood cells.

Contact your health care team if no improvement or if severe.

Cough; feeling short of breath

You may have cough and feel short of breath without any signs of infection, such as a sore throat or a stuffed nose.

Rarely this may be severe with chest pain, trouble breathing or coughing up blood. If this happens get medical help right away.

Contact your health care team if no improvement or if severe.

Mild swelling in arms and legs; puffiness

To help prevent swelling :

Eat a low-salt diet.
Avoid tight fitting clothing.

If you have swelling in your legs, keep your feet up when sitting.

Contact your health care team if no improvement or if severe.

Diarrhea

May happen days to weeks after you get your treatment.

If you have diarrhea :

Take anti-diarrhea medication if your health care team prescribed 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. Talk to your health care team if you can’t drink 6-8 cups of liquids each day when you have diarrhea. You may need special liquids with salt and sugar, called Oral Rehydration Therapy.

See the Diarrhea pamphlet for more information.

Contact your health care team if no improvement or if severe.

Bladder problems

You may feel like you need to pee often, have burning or pain when peeing, have bloody pee or pee leaks and dribbles due to bladder control problems.
In some cases you may also have fever.

Contact your health care team as soon as possible (office hours).

Pains or cramps in the belly

If you have constipation or diarrhea it may be causing the pain in your belly.
If the pain is severe, gets worse or doesn’t go away, talk to your health care team about other possible causes.

Contact your health care team if no improvement or if severe.

Dizziness

You may feel light headed.
Lay down if this happens.
Get up and move slowly once you feel better.
Do not drive a motor vehicle or use machinery if you feel dizzy.

Contact your health care team if no improvement or if 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:

itchiness, rash, swollen lips, face or tongue, chest and throat tightness
severe or unusual bone pain or difficulty moving
feeling thirsty and peeing more often than usual
irregular heartbeat, fainting spells or unusual swelling in your legs, ankles and belly
chest pain, shortness of breath or coughing blood
pain in your arm or leg, swelling and hardening of the vein in your arm or leg
feeling confused, have a sudden loss of vision, trouble speaking or using your arms or legs
yellowish skin or eyes, unusually dark pee or pain on the right side of your belly
severe belly pain, vomiting blood or what looks like coffee-grounds, or passing poo with bright red blood or which looks black or tarry-coloured

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 information sheet

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):

bicalutamide patient.pdf Info Sheet (French):

bicalutamide pour le patient.pdf Monograph:

bicalutamide.pdf Funding Program: ODB - General Benefit Funding Instance:

bicalutamide

Phonetic Spelling:

bye-cal-LOO-ta-mide

Cancer Type: Genitourinary Prostate Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Mercredi, novembre 29, 2017 Universal Date: 2024-04-08 00:00:00 AddThis: Title URL: bicalutamide Drug Display Status: Active Revision Summary:
Patient Info Sheet EN: Updated/Revised information sheet
Patient Info Sheet FR: Updated/revised information sheet (Fiche d’information mise à jour/révisée)