Consumer medicine information

Bi Eligard cp

Leuprorelin acetate; Bicalutamide

BRAND INFORMATION

Brand name

Bi Eligard cp

Active ingredient

Leuprorelin acetate; Bicalutamide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Bi Eligard cp.

What is in this leaflet

This leaflet answers some common questions about Bi ELIGARD cp. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Bi ELIGARD cp against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Bi ELIGARD cp is used for

Bi ELIGARD cp combination therapy is the brand name for packs containing ELIGARD (leuprorelin acetate) 7.5 mg or 22.5 mg subcutaneous injection plus MPL-BICALUTAMIDE 50 mg tablets.

Bi ELIGARD cp is used to reduce the symptoms of advanced cancer of the prostate gland.

Bicalutamide tablets can also be used to treat disease flare associated with previous leuprorelin therapy.

Bi ELIGARD cp is a combination pack consisting of an anti-androgen (MPL-BICALUTAMIDE) medicine and a Luteinising Hormone Releasing Hormone (LHRH) agonist (ELIGARD).

Androgens such as testosterone are natural male sex hormones. In some types of prostate cancer, androgens may help the cancer cells to grow.

LHRH agonists reduce the level of testosterone in men.

Bi ELIGARD cp interferes with some of the actions of these hormones.

Bi ELIGARD cp should only be taken by men.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

Before you are given Bi ELIGARD cp

When you must not be given it

You must not be given Bi ELIGARD cp if you have an allergy to:

  • any medicine containing bicalutamide or leuprorelin
  • any of the ingredients listed at the end of this leaflet
  • any other anti-androgen medicines
  • any other LHRH agonists.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not use Bi ELIGARD cp following surgical removal of your testes, as in that case Bi ELIGARD cp does not lead to further decrease in serum testosterone levels.

You must not be given this medicine if you are pregnant or plan to become pregnant or are breastfeeding.

This medicine has not been studied in women.

If used during pregnancy, it may affect the developing baby.

This medicine must not be given to children. Safety and effectiveness has not been established in children.

Do not use Bi ELIGARD cp if you are taking cisapride or the antihistamines, terfenadine and astemizole.

You must not be given this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have nerve problems caused by bone lesions in the spine, problems passing urine or blood in your urine. These conditions may get worse for a short time after treatment is started. Your doctor may prescribe another medicine when you first receive Bi ELIGARD cp to reduce the likelihood of this occurring.

Tell your doctor if you have or have had any of the following medical conditions:

  • liver problems
  • diabetes
  • cardiovascular disease, heart problems or blood vessel conditions, including heart rhythm problems (arrhythmia), or are being treated with medicines for these conditions. The risk of you having further heart rhythm problems may increase with Bi ELIGARD cp
  • osteoporosis
  • history of epilepsy, fits or seizures
  • tumour in your pituitary gland.

Talk to your doctor about the effects Bi ELIGARD cp may have on fertility. This medicine may impair fertility in men.

If you have not told your doctor about any of the above, tell him/her before you start treatment with Bi ELIGARD cp.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Bi ELIGARD cp may interfere with some medicines used to treat heart rhythm problems, such as:

  • quinidine
  • disopyramide
  • amiodarone
  • sotalol.

Bi ELIGARD cp may increase the risk of heart rhythm problems when used with other medicines which also have the same risk, such as:

  • methadone (used for pain relief and part of drug addiction detoxification)
  • moxifloxacin (an antibiotic)
  • antipsychotics used for serious mental illness.

Some medicines may interfere with Bi ELIGARD cp and these include:

  • medicines used to prevent blood clots, especially warfarin as Bi ELIGARD cp may reduce their effectiveness which may lead to bleeding and you therefore may need more monitoring
  • midazolam
  • cyclosporin
  • medicines used to treat high cholesterol
  • calcium channel blockers
  • carbamazepine
  • antiviral medicines for HIV infection.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How Bi ELIGARD cp is given

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

How much is given

An ELIGARD injection will be injected underneath the skin every month for the 7.5 mg strength, or once every 3 months for the 22.5 mg strength.

One 50 mg tablet of MPL-BICALUTAMIDE is then taken each day for one or three months, as considered appropriate by your doctor.

How it is given

The injection should only be given to you by a doctor or nurse. It will be administered once a month or once every three months.

The content of the two syringes in the ELIGARD kit (one containing the active ingredient and the other containing the delivery system) will be mixed together, then injected underneath the skin. The site of the injection should be varied from time to time.

The tablets should be taken at about the same time each day.

Swallow your tablet whole with a full glass of water. It does not matter if you take the tablets before, with or after food.

How long it is given for

Continue treatment with your medicine for as long as your doctor tells you. This medicine helps to control your condition, but does not cure it. It is important that you continue to receive your medicine even if you feel well.

If you forget to take it

If you have missed your injection, contact your doctor or pharmacist to find out what to do.

If you miss taking a tablet, take it as soon as you remember, as long as it is 12 hours before the next dose is due. If it is less than 12 hours to the next dose, do not take the dose you have missed.

Do not take a double dose to make up for the dose that you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or pharmacist or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are being given Bi ELIGARD cp

Things you must do

If your condition worsens, tell your doctor.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being given Bi ELIGARD cp.

Tell any other doctors, dentists, and pharmacists who treat you that you are being given this medicine.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may do some blood and other tests from time to time to make sure the medicine is working.

Things you must not do

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop treatment with your medicine without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how Bi ELIGARD cp affects you. This medicine may cause fatigue, dizziness and visual disturbances in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are being given BI ELIGARD cp.

This medicine helps most people with advanced prostate cancer, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • hot flushes or sweating
  • breast tenderness or changes in breast size
  • itching or dry skin, rashes
  • increased hairiness or hair loss
  • stomach pain or indigestion
  • nausea or vomiting
  • diarrhoea or constipation
  • flatulence (wind)
  • dry mouth
  • loss of appetite or weight changes
  • depression
  • unusual tiredness or weakness
  • dizziness or light-headedness
  • changes in blood pressure
  • difficulty sleeping
  • headache
  • pelvic pain
  • painful joints
  • chills
  • tingling in fingers or toes
  • decrease in your sexual drive
  • inability to get or maintain an erection
  • trouble passing urine or experience lower back pain
  • your testicles getting smaller.

Bi ELIGARD cp may also cause a period of low fertility or infertility whilst you are taking it and for a period afterwards. However, you may not be infertile and as Bi ELIGARD cp may affect your sperm, effective contraception must be used by you and/or your partner while you are taking Bi ELIGARD cp and for at least 130 days after you have stopped taking Bi ELIGARD cp.

Tell your doctor, nurse or pharmacist immediately if you notice any of the following:

  • frequent urination
  • shortness of breath and dizziness when exercising and looking pale (anaemia)
  • excessive thirst with weight loss, and passing large amounts of urine.

The above list includes serious side effects that may require medical attention.

If any of the following happen, tell your doctor or nurse immediately or go to Accident and Emergency at your nearest hospital:

  • signs of an allergic reaction, such as shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, rash, itching or hives on the skin
  • yellowing of the skin or eyes and dark coloured urine
  • serious breathlessness, or sudden worsening of breathlessness possibly with a cough or fever
  • chest pain.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Some of these side can only be found when your doctor does tests from time to time to check your progress.

Because Bi ELIGARD cp lowers the amount of sex hormones in your body your sex drive will probably be reduced.

It is also unlikely that you can father a child while using Bi ELIGARD cp, but you must use your normal contraceptive method to make sure.

After being given Bi ELIGARD cp

Storage

Bi ELIGARD cp will be stored in the refrigerator (below 8°C) in the pharmacy.

Once Bi ELIGARD cp is dispensed to you, keep it in a place where the temperature stays below 25°C. It may be stored in this manner for a period of up to 8 weeks prior to administration.

Keep this medicine in the original pack until it is time to use it. If you take it out of the pack, it may not keep well.

Keep MPL-BICALUTAMIDE tablets in the blister foil until it is time to take them.

Do not store it or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Bi ELIGARD cp is available in three different combinations:

  • 1 x ELIGARD 7.5 mg pack + 28 (1 month) tablets MPL-BICALUTAMIDE 50 mg
  • 1 x ELIGARD 22.5 mg pack + 28 (1 month) tablets MPL-BICALUTAMIDE 50 mg
  • 1 x ELIGARD 22.5 mg pack + 84 (1 month) tablets MPL-BICALUTAMIDE 50 mg

ELIGARD is available in a single use kit, containing a cardboard frame and two removable sealed plastic trays. The tray containing syringe A contains a syringe filled with the delivery system, known as the Atrigel® Delivery System, plus a long white replacement plunger rod and a desiccant pack (to absorb moisture). The tray containing syringe B contains a syringe filled with a powder which is the active ingredient, plus a needle and a desiccant pack (to absorb moisture).

Once the contents of syringe A and syringe B have been mixed together (prior to injection), the colour of the resulting liquid will be:

  • light tan to tan for ELIGARD1 month
  • colourless to pale yellow for ELIGARD 3 month, ELIGARD.

The mixed solution may appear slightly grey due to tiny air bubbles. This is acceptable and not representative of product quality.

The tablets are packaged in a blister strip and are white to off-white, round, film-coated, biconvex tablet, engraved with 'BC 50' on one face and plain on the other.

The tablets are packed in blister foils of 28 tablets.

Ingredients

ELIGARD contains leuprorelin acetate as the active ingredient. The Atrigel® delivery system consists of a biodegradable polymer, dissolved in a solvent (N-methyl-2-pyrrolidone).Each presentation of ELIGARD contains a different mixture and volume of the polymer.

Each tablet contains 50 mg of bicalutamide as the active ingredient, plus:

  • lactose monohydrate
  • sodium starch glycollate type A
  • povidone
  • magnesium stearate
  • Opadry Complete film coating system White Y-1-7000 (PI 1475).

Bi ELIGARD cp does not contain added sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Bi ELIGARD cp is supplied in Australia by:

Mundipharma Pty Limited
ABN 87 081 322 509
10 Carrington Street
SYDNEY NSW 2000
Phone: 1800 188 009

® ELIGARD and ATRIGEL are registered trademarks of Tolmar Therapeutics, Inc. used under licence.

This leaflet was prepared in September 2022.

Bi ELIGARD cp 7.5 mg/50 mg tablets (pack of 28) AUST R 237653

Bi ELIGARD cp 22.5 mg/50 mg tablets (pack of 28) AUST R 238311

Bi ELIGARD cp 22.5 mg/50 mg tablets (pack of 84) AUST R 237652

Published by MIMS November 2022

BRAND INFORMATION

Brand name

Bi Eligard cp

Active ingredient

Leuprorelin acetate; Bicalutamide

Schedule

S4

 

1 Name of Medicine

Bicalutamide.
Leuprorelin acetate.

2 Qualitative and Quantitative Composition

Bicalutamide.

MPL-Bicalutamide tablets are white film-coated tablets containing 50 mg bicalutamide. Each tablet contains the following excipients: lactose monohydrate, sodium starch glycollate type A, povidone, magnesium stearate, hypromellose, macrogol 400 and titanium dioxide.
Excipient with known effect: lactose monohydrate.

Leuprorelin.

Eligard is a sterile polymeric matrix formulation of leuprorelin acetate for subcutaneous injection. It is designed to deliver leuprorelin acetate at a controlled rate over a therapeutic period.
Leuprorelin acetate is a synthetic nonapeptide analogue of naturally occurring gonadotropin releasing hormone (GnRH or LH-RH) that, when given continuously, inhibits pituitary gonadotropin secretion and suppresses testicular steroidogenesis. The analogue possesses greater potency than the natural hormone.
Eligard 1 month contains 10.6 mg of lyophilised leuprorelin acetate. Eligard 1 month delivers 7.5 mg of leuprorelin acetate (equivalent to approximately 7.0 mg leuprorelin free base) dissolved in 160 mg N-methyl-2-pyrrolidone and 82.5 mg polyglactin. The approximate weight of the administered formulation is 250 mg. It is designed to deliver 7.5 mg of leuprorelin acetate at a controlled rate over a 1 month therapeutic period.
Eligard 3 month contains 29.2 mg lyophilised leuprorelin acetate. Eligard 3 month delivers 22.5 mg of leuprorelin acetate (equivalent to approximately 21 mg leuprorelin free base) dissolved in 193.9 mg N-methyl-2-pyrrolidone and 158.6 mg polyglactin. The approximate weight of the administered formulation is 375 mg. It is designed to deliver 22.5 mg of leuprorelin acetate at a controlled rate over a 3 month therapeutic period.
The Atrigel Delivery System is a polymeric (non-gelatin containing) delivery system consisting of a biodegradable polyglactin. The polymer is dissolved in a biocompatible solvent, N-methyl-2-pyrrolidone. The polyglactin mixture and volume differ with each presentation of Eligard.
Eligard contains no anti-microbial agent. Eligard does not contain: lactose, sucrose, gluten, tartrazine, or any other azo dyes.

3 Pharmaceutical Form

Bi Eligard cp is a composite pack consisting of:
Eligard modified release suspension syringe, available in a single use kit (1 month and 3 month). Eligard is prefilled and supplied in two separate, sterile syringes whose contents are mixed immediately prior to administration. The two syringes are joined and the single dose product is mixed until it is homogenous. Eligard is administered subcutaneously where it forms a solid drug delivery depot; and
MPL-Bicalutamide 50 mg film coated tablets (a white to off-white, round, film-coated, biconvex tablet, engraved with 'BC 50' on one face and plain on the other).

4 Clinical Particulars

4.1 Therapeutic Indications

Bicalutamide.

Treatment of advanced prostate cancer in combination with LH-RH agonist therapy.

Leuprorelin.

Eligard is indicated for the palliative treatment of advanced prostate cancer.

4.2 Dose and Method of Administration

Bicalutamide.

Adult males including the elderly.

One tablet (50 mg) once a day.
Treatment with bicalutamide 50 mg should be started at the same time as treatment with a LH-RH agonist.

Use in adult males with renal impairment.

No dosage adjustment is necessary for patients with renal impairment.

Use in adult males with hepatic impairment.

No dosage adjustment is necessary for patients with mild hepatic impairment.
Increased accumulation may occur in patients with moderate to severe hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use). In such cases, a lower or less frequent dose may be considered.

Leuprorelin.

Important.

Allow the product to reach room temperature before using. Once mixed, Eligard must be administered within 30 minutes. Discard the constituted product if not administered within 30 minutes.
The two syringes are coupled and the product is mixed by transferring the contents from syringe to syringe immediately before administration to the patient. Refer to the enclosed leaflet titled Eligard Mixing Procedure in the Eligard carton for the full mixing instructions. The syringes are uncoupled and the needle is attached prior to injection. The product is injected subcutaneously into areas with adequate amounts of subcutaneous tissue (such as the abdomen) and that do not have excessive pigment, nodules, lesions, or hair. As with other drugs administered by subcutaneous injection, the injection site should be varied periodically.
When thoroughly mixed, the suspension will appear a light tan to tan colour (Eligard 1 month) or a colourless to pale yellow colour (Eligard 3 month). The mixed solution colour is not representative of product quality. An occasional slightly grey appearance of the mixed solution may be due to tiny air bubbles and will not affect the product quality.
Eligard should not be injected in the arm.
The recommended dose of Eligard 1 month is one injection every month.
The recommended dose of Eligard 3 month is one injection every three months.
Eligard 1 and 3 month presentations have different release characteristics and therefore, fractional, multiple and/or combinational doses are not equivalent to each other and should not be given.
Eligard contains no antimicrobial agent and is for single use in one patient only. Discard any residue.
The injection delivers leuprorelin acetate, incorporated in a polymer formulation. It is administered subcutaneously and provides continuous release of leuprorelin for one month for Eligard 1 month, three months for Eligard 3 month.

4.3 Contraindications

Bicalutamide.

Bicalutamide is contraindicated in females and children.
Known hypersensitivity to bicalutamide or any other constituents of the formulation.
Coadministration of terfenadine, astemizole or cisapride with bicalutamide is contraindicated (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Leuprorelin.

Eligard is contraindicated in patients with hypersensitivity to GnRH, GnRH agonist analogues or any of the components of Eligard. Anaphylactic reactions to synthetic GnRH or GnRH agonist analogues have been reported in the literature.
Eligard is contraindicated in women who are breastfeeding, pregnant or intending to become pregnant and in paediatric patients. Eligard was not studied in women or children. Moreover, leuprorelin acetate can cause foetal harm when administered to a pregnant woman. Major foetal abnormalities were observed in rabbits but not in rats after administration of leuprorelin acetate throughout gestation. There were increased foetal mortality and decreased foetal weights in rats and rabbits. The effects on foetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug. The possibility exists that spontaneous abortion may occur.
Eligard is contraindicated in patients who previously underwent orchiectomy (as with other GnRH agonists, Eligard does not result in further decrease of serum testosterone in case of surgical castration). Eligard is contraindicated as a sole treatment in prostate cancer patients with spinal cord compression or evidence of spinal metastases.

4.4 Special Warnings and Precautions for Use

Bicalutamide.

In patients with metastatic prostate cancer, treatment with bicalutamide monotherapy has been associated with reduced survival compared to castration. Bicalutamide should therefore not be used without concomitant LHRH agonist therapy in these patients.
Rare cases of death or hospitalisation due to severe liver injury have been observed with bicalutamide (see Section 4.8 Adverse Effects (Undesirable Effects)). Bicalutamide therapy should be discontinued if at any time a patient develops jaundice or if serum ALT rises above two times the upper limit of normal.
A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes. Consideration should therefore be given to monitoring blood glucose in patients receiving bicalutamide in combination with LHRH agonists.
Potentiation of coumarin anticoagulant effects have been reported in patients receiving concomitant bicalutamide therapy, which may result in increased Prothrombin Time (PT) and International Normalised Ratio (INR). Some cases have been associated with risk of bleeding. Close monitoring of PT/INR is advised and anticoagulant dose adjustment should be considered (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

QT/QTc interval prolongation.

Androgen deprivation therapy may prolong QT/QTc interval. Prescribers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities and in patients taking drugs known to prolong the QT interval. Electrolyte imbalances should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

Leuprorelin.

Eligard, like other LH-RH agonists, causes a transient increase in serum concentrations of testosterone during the first week of treatment. Patients may experience worsening of symptoms or onset of new signs and symptoms during the first few weeks of treatment, including bone pain, neuropathy, haematuria, or bladder outlet obstruction. Isolated cases of ureteral obstruction and/or spinal cord compression, which may contribute to paralysis with or without fatal complications, have been observed in the palliative treatment of advanced prostate cancer using LH-RH agonists.
Initiating therapy with a non-steroidal anti-androgen at the same time as leuprorelin acetate therapy has proven benefit in reducing flare reactions in 'at risk' patients (e.g. those with thecal indentation, or at risk of cord compression, and patients with bladder neck obstruction).
Additional administration of an appropriate antiandrogen should be considered beginning 3 days prior to leuprorelin therapy and continuing for the first two to three weeks of treatment. This has been reported to prevent the sequelae of an initial rise in serum testosterone.
If spinal cord compression or renal impairment develops, standard treatment of these complications should be instituted.
Long-term administration of leuprorelin will cause suppression of pituitary gonadotropins and gonadal hormone production with clinical symptoms of hypogonadism. These changes have been observed to reverse on discontinuation of therapy. However, whether the clinical symptoms of induced hypogonadism will reverse in all patients has not yet been established.

General.

Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy.
Response to Eligard should be monitored by measuring serum concentrations of testosterone and prostate-specific antigen periodically.
Results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.
Following surgical castration, Eligard does not lead to a further decrease in serum testosterone levels in male patients.
A proportion of patients will have tumors which are not sensitive to hormone manipulation. This is termed castrate-resistant prostate cancer. Signs and/or symptoms of tumor progression despite adequate testosterone suppression are diagnostic of this condition. Current treatment paradigms recommend continued GnRH therapy along with other therapeutic regimes for this circumstance.

Hyperglycemia and diabetes.

Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.

Cardiovascular diseases.

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Effect on QT/QTc interval.

Androgen deprivation therapy may prolong the QT interval. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

Changes in bone density.

Bone loss can be expected as part of natural aging and can also be anticipated during the hypo-androgenic state caused by long-term use of leuprorelin acetate. In patients with significant risk factors for decreased bone mineral content and/or bone mass such as family history of osteoporosis, chronic use of corticosteroids or anticonvulsants or chronic abuse of alcohol or tobacco, leuprorelin acetate may pose additional risk. In these patients, risk versus benefit must be weighed carefully before initiation of leuprorelin acetate therapy.

Convulsions.

Post marketing reports of convulsions have been observed in patients on leuprorelin acetate therapy with or without a history of predisposing factors. These included patients in the female and paediatric populations, patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumours, and in patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above. Convulsions are to be managed according to the current clinical practice.

Respiratory.

There have been post-marketing reports of interstitial pneumonitis associated with leuprorelin use. Treatment should be discontinued immediately if the patient develops any signs or symptoms suggestive of interstitial lung disease.

Use in hepatic impairment.

Bicalutamide.

Bicalutamide is extensively metabolised in the liver. Data suggests that its elimination may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of bicalutamide. Therefore, bicalutamide should be used with caution in patients with moderate to severe hepatic impairment.
Periodic liver function testing should be considered due to the possibility of hepatic changes. The majority of these changes occur within the first 6 months of bicalutamide therapy.

Leuprorelin.

Eligard was not studied in hepatically and renally impaired patients.

Use in renal impairment.

Leuprorelin.

Eligard was not studied in hepatically and renally impaired patients.

Use in the elderly.

Bicalutamide.

No data available.

Leuprorelin.

The majority of the patients (approximately 70%) studied in the clinical trials were age 70 and older.

Paediatric use.

Bicalutamide.

See Section 4.3 Contraindications.

Leuprorelin.

The safety and effectiveness of Eligard in paediatric patients have not been established (see Section 4.3 Contraindications).

Effects on laboratory tests.

Bicalutamide.

No data available.

Leuprorelin.

In the majority of non-orchiectomised patients, testosterone levels increased during the first week of treatment. They then decreased and by day 14 had returned to baseline levels or below. Castrate levels were reached in 2 to 4 weeks. Once achieved, castrate levels were maintained as long as the patient received their injections. Transient increases in acid phosphatase levels may occur early in the treatment period; however, by the fourth week the elevated levels usually decreased to values at or near normal. Therapy with leuprorelin results in suppression of the pituitary-gonadal system. Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after leuprorelin therapy may be affected.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Bicalutamide.

Bicalutamide is extensively metabolised (via oxidation and glucuronidation) in the liver. Bicalutamide has shown no evidence of causing enzyme induction in humans during dosing at 50 mg daily in man. In vitro studies have shown that R-bicalutamide is an inhibitor of CYP 3A4, with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity.
The clinically or potentially significant medicine interactions between bicalutamide and the following agents/medicine classes, which are theoretical or have been observed, are described below. The medicine/medicine interactions described include both interactions mediated through effects on P450 metabolism and interactions mediated through other mechanisms.
Effects of bicalutamide on other medicines.

LHRH agonists.

Although there is no evidence of any pharmacodynamic or pharmacokinetic interactions between bicalutamide 50 mg and LHRH agonists at steady state, bicalutamide 50 mg may prevent the harmful clinical consequences of flare associated with the start of LHRH agonist therapy.

Cytochrome P450.

Bicalutamide is an inhibitor of CYP 3A4 and has been shown to increase plasma levels of midazolam by up to 80%. Therefore, concomitant use of terfenadine, astemizole and cisapride is contraindicated. Caution should be exercised with other medicines metabolised by CYP 3A4, such as cyclosporin, calcium channel blockers, HIV antivirals, HMG-CoA reductase inhibitors, carbamazepine, quinidine etc.
Demonstrated interactions.

Warfarin.

In vitro studies have shown that bicalutamide can displace the coumarin anticoagulant, warfarin, from its protein binding sites. There have been reports of increased effect of warfarin and other coumarin anticoagulants when co-administered with bicalutamide. It is therefore recommended that if bicalutamide is administered in patients who are already receiving coumarin anticoagulants, PT/INR should be closely monitored and adjustments of anticoagulant dose considered (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).
Theoretical interactions. Caution should be exercised when prescribing bicalutamide with other medicines which may inhibit medicine oxidation e.g. cimetidine and ketoconazole. In theory, this could result in increased plasma concentrations of bicalutamide and an increase in adverse effects.

Leuprorelin.

There are no reports of drug interactions with leuprorelin acetate to date.
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of Eligard with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de Pointes such as Class IA (e.g. quinidine, disopyramide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Bicalutamide.

Administration of bicalutamide may lead to inhibition of spermatogenesis. The long-term effects of bicalutamide on male fertility have not been studied. In male rats dosed at 250 mg/kg/day (less than human therapeutic concentrations after the maximum recommended clinical dose of 150 mg), the precoital interval and time to successful mating were increased in the first pairing but no effects on fertility following successful mating were seen. These effects were reversed by 7 weeks after the end of an 11-week period of dosing. A period of subfertility or infertility should be assumed in man.
Antiandrogen therapy may cause morphological changes in spermatozoa. Although the effect of bicalutamide on sperm morphology has not been evaluated and no such changes have been reported for patients who received bicalutamide, patients and/or their partners should follow adequate contraception during bicalutamide therapy and for 130 days after bicalutamide therapy.

Leuprorelin.

Preclinical studies with leuprorelin acetate in rats demonstrated reversible, expected effects (given that leuprorelin acetate has known pharmacological effects on reproductive endocrinology) on the reproductive system of both sexes.
Leuprorelin acetate did not show teratogenicity in rats.
Clinical and pharmacological studies in adults with leuprorelin acetate and similar analogues have shown full reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks.
(Category D)

Bicalutamide.

Bicalutamide is contraindicated in females and must not be given to pregnant women.

Leuprorelin.

(See Section 4.3 Contraindications.)
Although not relevant to the approved indication, leuprorelin acetate is contraindicated in pregnancy due to its embryotoxic effects.

Bicalutamide.

Bicalutamide is contraindicated in females and must not be given to breastfeeding mothers.

Leuprorelin.

Eligard is contraindicated for use in breastfeeding women.

4.7 Effects on Ability to Drive and Use Machines

Bicalutamide.

During treatment with bicalutamide, somnolence has been reported. Those patients who experience this symptom should observe caution when driving or using machines.

Leuprorelin.

No studies on the effects of Eligard on the ability to drive and use machines have been performed. The ability to drive and operate machines may be impaired due to fatigue, dizziness and visual disturbances being possible side effects of treatment or resulting from the underlying disease.

4.8 Adverse Effects (Undesirable Effects)

Bicalutamide.

Bicalutamide 50 mg in general, has been well tolerated with few withdrawals due to adverse events.

Clinical trial data-combination therapy (with medical castration) in advanced prostate cancer.

The following adverse experiences were reported in clinical trials (as possible adverse medicine effects in the opinion of investigating clinicians, with a frequency of ≥ 1%) during treatment with bicalutamide 50 mg plus an LHRH agonist. No causal relationship of these experiences to medicine treatment has been made and some of the experiences reported are those that commonly occur in elderly patients. (See Table 1).

Increased PT/INR.

Accounts of coumarin anticoagulants interacting with bicalutamide have been reported in post marketing surveillance (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.4 Special Warnings and Precautions for Use).

Leuprorelin.

Eligard, like other LH-RH analogues, caused a transient increase in serum testosterone concentrations during the first two weeks of treatment. Therefore, potential exacerbations of signs and symptoms of the disease during the first few weeks of treatment are of concern in patients with vertebral metastases and/or urinary obstruction or haematuria. If these conditions are aggravated, it may lead to neurological problems such as weakness and/or paraesthesia of the lower limbs or worsening of urinary symptoms (see Section 4.4 Special Warnings and Precautions for Use).

'Flare' phenomenon.

The initial increase in circulating levels of pituitary gonadotropins and gonadal steroids leads in some patients to a transient exacerbation of symptoms and signs ('flare' phenomenon). The exacerbation may include worsened bone pain, ureteric obstruction and spinal cord compression. This possibility should be taken into account in deciding to initiate leuprorelin acetate therapy in patients with existing obstructive uropathy or vertebral metastases. Early symptoms of spinal cord compression such as paraesthesia should alert the physician to the need for intensive monitoring and possible treatment.
There is no information available on the clinical effects of interrupting leuprorelin acetate therapy and whether this will produce a withdrawal 'flare'.
Initiating therapy with a non-steroidal anti-androgen at the same time as leuprorelin acetate therapy has proven benefit in reducing flare reactions in 'at risk' patients.
The safety of Eligard was evaluated in open-label, multicentre studies. In Eligard clinical studies conducted, patient injection sites were closely monitored. The adverse reactions from injections sites are summarised in Table 2.
The majority (84%) of transient burning/stinging events for Eligard 1 month were reported as mild. Pain was generally reported as brief in duration and mild in intensity. Erythema were all reported as mild and generally resolved within a few days post-injection.
The majority (86%) of transient burning/stinging events for Eligard 3 month were reported as mild. Pain was generally reported as brief in duration and mild in intensity. One of the reports characterized the erythema as mild and resolved within 7 days. The other was moderate and resolved within 15 days. Neither patient experienced erythema at multiple injections.
The following possibly or probably related systemic adverse events occurred during clinical trials of up to six months of treatment with Eligard 1 month and Eligard 3 month, and were reported in ≥ 2% and < 2% of patients (Tables 3 and 4, respectively). Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug-related were excluded.

More common reactions (incidence ≥ 2%).


Less common reactions (incidence < 2%).


Post-marketing experiences.

Pituitary apoplexy.

During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin releasing hormone agonists, with a majority occurring within two weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as a sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

Other adverse effects.

During post-market surveillance with LH-RH agonists; diabetes mellitus, myocardial infarction, cerebrovascular accident and sudden cardiac death have also been reported (see Section 4.4 Special Warnings and Precautions for Use).
Anaphylactic/anaphylactoid reactions have been reported after GnRH agonist analog administration.
Postmarketing reports of convulsions have been observed in patients on leuprorelin acetate with or without a history of predisposing factors. Convulsions are to be managed according to the current clinical practice.
Muscular atrophy has been observed with long term use of products in this class.
Interstitial lung disease has been reported with an unknown frequency.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Bicalutamide.

There is no human experience of overdosage. There is no specific antidote; treatment should be symptomatic. Dialysis may not be helpful, since bicalutamide is highly protein bound and is not recovered unchanged in the urine. General supportive care, including frequent monitoring of vital signs, is indicated.

Leuprorelin.

In clinical trials using daily subcutaneous leuprorelin acetate in patients with prostate cancer, doses as high as 20 mg/day for up to two years caused no adverse effects differing from those observed with the 1 mg/day dose.
There is no clinical experience with the effects of an acute overdose. Because the acute animal toxicity of the drug is low, adverse effects are not expected. In the event of an overdose the patient should be monitored and supportive treatment given, if considered necessary.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Bicalutamide.

Bicalutamide is a nonsteroidal antiandrogen, devoid of other endocrine activity. It binds to androgen receptors without activating gene expression, and thus inhibits the androgen stimulus. This inhibition impairs the growth and encourages apoptosis in androgen dependent tumour cells and regression of prostatic tumours. In a subset of patients who experience disease progression while receiving bicalutamide, discontinuation of the medicine may result in an 'antiandrogen withdrawal syndrome', which manifests as a fall in prostate specific antigen (PSA) level. It is unknown whether this phenomenon translates to a prolongation of tumour response or survival.
Bicalutamide is a racemate with its anti-androgenic activity being almost exclusively in the (R)-enantiomer.

Leuprorelin.

Leuprorelin acetate, an LH-RH agonist, acts as a potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses. Animal and human studies indicate that after an initial stimulation, chronic administration of leuprorelin acetate results in suppression of testicular steroidogenesis. This effect is reversible upon discontinuation of drug therapy.
Administration of leuprorelin acetate has resulted in inhibition of the growth of certain hormone-dependent tumours (prostatic tumours in Noble and Dunning male rats and DMBA induced mammary tumours in female rats) as well as atrophy of the reproductive organs.
In humans, administration of leuprorelin acetate results in an initial increase in circulating levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestosterone in males, and oestrone and oestradiol in premenopausal females). However, continuous administration of leuprorelin acetate results in decreased levels of LH and FSH. In males, testosterone is reduced to below castrate threshold (≤ 50 nanogram/dL). These decreases occur within two to six weeks after initiation of treatment.
Leuprorelin acetate is not active when given orally.

Clinical trials.

Combination therapy (with medical castration) in advanced prostate cancer.

In a large multicentre, controlled clinical trial, 813 patients with previously untreated advanced prostate cancer were randomized to receive bicalutamide 50 mg once daily (404 patients) or flutamide 250 mg (409 patients) three times a day, each in combination with a luteinising hormone releasing hormone agonist (LH-RH agonist) (either goserelin acetate implant or leuprorelin acetate depot). At the time of analysis, the median time of follow up was 49 weeks. Bicalutamide/ LH-RH agonist therapy was associated with a statistically significant (p = 0.005) improvement in time to treatment failure.
Subjective responses, (including scores for pain, analgesic use and Eastern Oncology Cooperative Group (ECOG) performance status) assessed in patients with symptoms at entry were seen in 95 (52%) patients treated with bicalutamide and in 88 (54%) patients treated with flutamide, each in combination therapy with LH-RH agonists. This small difference was not statistically significant between bicalutamide 50 mg combination therapy and flutamide combination therapy.

Meta-analysis.

There is considerable debate regarding the relative merits of combination versus monotherapy in advanced prostate cancer, summarised by Dalesio et al 19951 in their meta-analysis of trials of maximal androgen blockade (MAB). This analysis showed no statistically significant reduction in the annual odds of death in favour of MAB. The meta-analysis included the effect of MAB only on mortality, and did not measure other endpoints such as time to disease progression.
The majority of the patients (approximately 70%) studied in these clinical trials were age 70 and older.
1 Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of 22 randomised trials with 3283 deaths in 5710 patients. Lancet 1995; 346: 265-269.

5.2 Pharmacokinetic Properties

Absorption.

Bicalutamide.

Bicalutamide is well absorbed following oral administration. There is no evidence of any clinically relevant effect of food on bioavailability.

Leuprorelin.

The absorption pharmacokinetic parameters determined for Eligard are presented in Table 5.
After the initial increase following each injection, mean serum concentrations remained relatively constant; 0.28 - 2.0 nanogram/mL for Eligard 1 month, 0.2 - 2.0 nanogram/mL for Eligard 3 month. There was no evidence of significant accumulation during repeated dosing. Non-detectable leuprorelin serum concentrations have been observed during chronic Eligard administration, but testosterone levels were maintained at castrate levels.
The pharmacokinetics of Eligard in hepatically and renally impaired patients have not been determined.

Distribution.

Bicalutamide.

Bicalutamide is highly protein bound (racemate 96%, R-enantiomer 99.6%).
Steady state plasma concentrations of the (R)-enantiomer of approximately 9 microgram per mL are observed during daily administration of bicalutamide 50 mg. At steady state the predominantly active (R)-enantiomer accounts for 99% of the total circulating enantiomers.

Leuprorelin.

The mean steady-state volume of distribution of leuprorelin following intravenous bolus administration to healthy male volunteers was 27 L. In vitro binding to human plasma proteins ranged from 43% to 49%.

Metabolism.

Bicalutamide.

Bicalutamide undergoes stereospecific metabolism. Bicalutamide is extensively metabolised (via oxidation and glucuronidation).

Leuprorelin.

In healthy male volunteers, a 1 mg bolus of leuprorelin administered intravenously revealed that the mean systemic clearance was 7.6 L/h, with a terminal elimination half-life of approximately 3 hours based on a two compartment model.
Drug metabolism studies were not conducted with Eligard. Upon administration with different leuprorelin acetate formulations, the major metabolite of leuprorelin acetate is a pentapeptide (M-1) metabolite.

Excretion.

Bicalutamide.

Its metabolites are eliminated via the kidneys and bile in approximately equal proportions.
The (S)-enantiomer is rapidly cleared relative to the (R)-enantiomer, the latter having a plasma elimination half-life of about 1 week. On daily administration of bicalutamide, the (R)-enantiomer accumulates about 10 fold in plasma as a consequence of its long half- life.
The pharmacokinetics of the (R)-enantiomer are unaffected by age, renal impairment or mild to moderate hepatic impairment. There is evidence that for subjects with severe hepatic impairment, the (R)-enantiomer is more slowly eliminated from plasma.

Leuprorelin.

Drug excretion studies were not conducted with Eligard.

5.3 Preclinical Safety Data

Genotoxicity.

Bicalutamide.

Bicalutamide was inactive in in vitro tests for gene mutation and in in vitro and in vivo tests for clastogenicity.

Leuprorelin.

Mutagenicity studies have been performed with leuprorelin acetate using bacterial and mammalian systems and with Eligard 1 month in bacterial systems. These studies provided no evidence of a genotoxic potential.

Carcinogenicity.

Bicalutamide.

Two-year oral carcinogenicity studies were conducted in male and female rats and mice at doses of 5, 15 or 75 mg/kg/day of bicalutamide. A variety of tumour target organ effects were identified and were attributed to the antiandrogenicity of bicalutamide, namely, testicular benign interstitial (Leydig) cell tumours in male rats at all dose levels and uterine adenocarcinoma in female rats at 75 mg/kg/day (at these dose levels plasma (R)-bicalutamide concentrations were less than human therapeutic concentrations after the maximum recommended clinical dose of 150 mg). There is no evidence of Leydig cell hyperplasia patients; uterine tumours are not relevant to the indicated patient population.
A small increase in the incidence of hepatocellular carcinoma in male mice given 75 mg/kg/day of bicalutamide (approximately 2 times human therapeutic concentrations after the maximum recommended clinical dose of 150 mg) and an increased incidence of benign thyroid follicular cell adenomas in rats given 5 mg/kg/day (less than the human therapeutic concentrations after the maximum recommended clinical dose of 150 mg) and above were recorded. These neoplastic changes were progressions of non-neoplastic changes related to hepatic enzyme induction observed in animal toxicity studies. Enzyme induction has not been observed following bicalutamide administration in man.

Leuprorelin.

Two-year carcinogenicity studies were conducted with leuprorelin acetate in rats and mice. In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg). There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group). In mice, no leuprorelin acetate-induced tumors or pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years. Patients have been treated with leuprorelin acetate for up to three years with doses as high as 10 mg/day and for two years with doses as high as 20 mg/day without demonstrable pituitary abnormalities.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Bi Eligard cp should be stored between 2-8°C (refrigerate).

Individual components.

Eligard should be stored below 8°C (refrigerate). The patient may store Eligard below 25°C in intact packaging for a period of 8 weeks prior to administration.
MPL-Bicalutamide 50 mg film coated tablets may be stored below 30°C when protected from moisture and light.

6.5 Nature and Contents of Container

Bi Eligard cp 1 month (AUST R 237653).

Consists of:
1 single use kit Eligard 1 month. The kit consists of a two-syringe mixing system, a 20-gauge 5/8 inch needle, a silica desiccant pouch to control moisture uptake, and package insert for constitution and administration procedures. Each syringe is individually packaged. Syringe B, made of cyclic olefin copolymer and sealed with a chlorobutyl closure, contains aseptically filled, lyophilized leuprorelin acetate. Syringe A, constructed of polypropylene and sealed with a polypropylene or polyethylene cap, contains the Atrigel Delivery System; and
28 MPL-Bicalutamide 50 mg film coated tablets supplied in PVC/PVDC/Al blister packs.

Bi Eligard cp 3 month (AUST R 238311).

Consists of:
1 single use kit Eligard 3 month. The kit consists of a two-syringe mixing system, a 20-gauge 5/8 inch needle, a silica desiccant pouch to control moisture uptake, and package insert for constitution and administration procedures. Each syringe is individually packaged. Syringe B, made of cyclic olefin copolymer and sealed with a chlorobutyl closure, contains aseptically filled, lyophilized leuprorelin acetate. Syringe A, constructed of polypropylene and sealed with a polypropylene or polyethylene cap, contains the Atrigel Delivery System; and
28 MPL-Bicalutamide 50 mg film coated tablets supplied in PVC/PVDC/Al blister packs.

Bi Eligard cp 3 month (AUST R 237652).

Consists of:
1 single use kit Eligard 3 month. The kit consists of a two-syringe mixing system, a 20-gauge 5/8 inch needle, a silica desiccant pouch to control moisture uptake, and package insert for constitution and administration procedures. Each syringe is individually packaged. Syringe B, made of cyclic olefin copolymer and sealed with a chlorobutyl closure, contains aseptically filled, lyophilized leuprorelin acetate. Syringe A, constructed of polypropylene and sealed with a polypropylene or polyethylene cap, contains the Atrigel Delivery System; and
84 MPL-Bicalutamide 50 mg film coated tablets supplied in PVC/PVDC/Al blister packs.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Bicalutamide.

Bicalutamide is a fine white to off-white powder. At 37°C it is practically insoluble in water (4.6 mg/litre), acid (4.6 mg/litre at pH 1) and alkali (3.7 mg/litre at pH 8). In organic solvents it is slightly soluble in ethanol, sparingly soluble in methanol and freely soluble in acetone and tetrahydrofuran.
Chemical name: (RS)-4'-Cyano-α', α', α',-trifluoro-3-(4-fluorophenylsulfonyl)-2-hydroxy-2- methylpropiono-m-toluidide.
Molecular formula: C18H14F4N2O4S.
Molecular weight: 430.38 g/mol.

Leuprorelin.

Leuprorelin acetate is a white to near white powder, freely soluble in water and glacial acetic acid.
Chemical name: 5-oxo-L-prolyl-L-histidyl- L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt).
Molecular formula: C59H84N16O12.C2H4O2.
Molecular weight: 1269.45 g/mol.

CAS number.

Bicalutamide.

90357-06-5.

Leuprorelin.

74381-53-6.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes