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PROSTAP 3 LEUPRORELIN ACETATE 11.25MG DEPOT INJECTION

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THE COLOURS SHOWN ON THIS PROOF ARE FOR GENERAL REPRESENTATION PURPOSES ONLY. THEY ARE NOT ACCURATE AND MUST NOT BE
USED AS A COLOUR MATCH FOR THE FINISHED JOB. PLEASE REFER TO THE PANTONE COLOUR GUIDES FOR ACCURATE COLOUR REFERENCES.

PROSTAP® 3 LEUPRORELIN ACETATE 11.25mg DEPOT
INJECTION
(leuprorelin acetate)
Patient Information Leaflet

In this leaflet:
1. What PROSTAP 3 is and what it is used for
2. Before having this medicine
3. How to take PROSTAP 3
4. Possible side effects
5. How to store PROSTAP 3
6. Further information
1. What PROSTAP 3 is and what it is used for
PROSTAP 3 is a synthetic hormone which can be used to reduce the levels of testosterone and estrogen
circulating in the body.
PROSTAP 3 is used to treat prostate cancer in men and endometriosis in women.
2. Before having this medicine
PROSTAP 3 is not recommended for use in children under the age of 18 years.

DT

DATE OF PROOF:

Men only:
• If you are a man with urinary obstruction or spinal cord compression. Your doctor will supervise
you closely for the first few weeks of treatment.
• If you are a man with prostate cancer, and have had injections of a synthetic hormone in the past
that has not worked, or you have had an operation to remove your testicles.

11/05/12

ARTWORKER:

WARNING!

Women only:
• If you are a woman with submucous fibroids (benign tumours in the muscle underneath the lining
of the womb). PROSTAP 3 can cause severe bleeding when the fibroids breakdown. Contact
your doctor immediately if you experience severe or unusual bleeding or pain.
• If you are a woman and continue to have periods (menstruate) after starting treatment with
PROSTAP 3 you should tell your doctor.
• If you are a woman of child-bearing age, you should use non hormonal contraception, whilst
receiving PROSTAP 3. Although PROSTAP 3 causes periods to stop, it is not itself a
contraceptive. If you are unsure about this talk to your doctor.

Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines
obtained without a prescription.

Pregnancy and breastfeeding
You should not take PROSTAP 3 if you are pregnant, planning to become pregnant or are breastfeeding.
INC SAFETY WARNING

UK PIL DATED APRIL 2011

06464/2713D
CODE:

Prostap 3 injection
PRODUCT:

CUSTOMER: Waymade

Taking PROSTAP 3 with food and drink
PROSTAP 3 can be taken with or without food.

Driving and using machines
Do not drive or operate machinery if you experience drowsiness, dizziness or visual disturbances whilst
being treated with PROSTAP 3.
3. How to take PROSTAP 3
The doctor or nurse will give you an injection of PROSTAP 3. The injection will normally be given in your
arm, thigh or abdomen. The injection site should be varied at regular intervals.
You will normally be given an injection once every 3 months.
If you have endometriosis you will be given an injection of PROSTAP 3 for a period of 6 months only and
treatment will be initiated during the first five days of the menstrual cycle.
If you miss an injection
As soon as you realise you have missed an injection, contact your doctor who will be able to give you your
next injection.

Colour
Swatch

Black

WARNING!

DATE:

Take special care with PROSTAP 3:
Both men and women:
• If you are diabetic. PROSTAP 3 can aggravate existing diabetes therefore diabetes patients may
need more frequent monitoring of the blood glucose levels.
• If you are at an increased risk of thinning of the bones (osteoporosis) you should tell your doctor
before taking PROSTAP 3. Risk factors include:
o If you or any of your close family have thinning of the bones
o If you drink excessive amounts of alcohol, and/or smoke heavily
o If you take drugs for epilepsy or have taken steroids such as hydrocortisone or
prednisolone for a long time.
• There have been reports of depression in patients taking PROSTAP 3 which may be severe. If
you are taking PROSTAP 3 and develop depressed mood, inform your doctor.

DATE:

05-0440
PRE-PRESS NO.:

Q.A.
APPROVED:

CUSTOMER
APPROVED:

Do not take PROSTAP 3:
• If you are allergic (hypersensitive) to leuprorelin acetate (PROSTAP SR or PROSTAP 3) or any of
the other ingredients of PROSTAP 3.
• If you are pregnant, planning to become pregnant or are breastfeeding.
• If you have abnormal vaginal bleeding which you have not discussed with your doctor.

WE CANNOT ACCEPT RESPONSIBILITY FOR ANY ERRORS IN THIS PROOF AFTER APPROVAL. THE ARTWORK RECEIVED HAS BEEN SIGNIFICANTLY
ADJUSTED, REVISED OR RESET BY US FROM DISK OR HARD COPY. WHILST WE TAKE EXTREME CARE AT ALL TIMES TO ENSURE ACCURACY, THE FINAL RESPONSIBILITY
MUST BE TAKEN BY OUR CUSTOMER. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

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Notes:

Your medicine is called PROSTAP 3 Leuprorelin Acetate 11.25mg Depot Injection, but will be referred to
as PROSTAP 3 throughout this leaflet.
Read all of this leaflet carefully before you start using this medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their
symptoms are the same as yours.
• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell
your doctor or pharmacist.

PROOF HISTORY:
v.1 - waymade - 11/05/12

Leaflet Flat Size = 148 x 317

27mm

THE COLOURS SHOWN ON THIS PROOF ARE FOR GENERAL REPRESENTATION PURPOSES ONLY. THEY ARE NOT ACCURATE AND MUST NOT BE
USED AS A COLOUR MATCH FOR THE FINISHED JOB. PLEASE REFER TO THE PANTONE COLOUR GUIDES FOR ACCURATE COLOUR REFERENCES.

Women only:
If a PROSTAP 3 injection is missed, breakthrough bleeding or ovulation may occur with the potential for
conception. If you think you may be pregnant you should stop using PROSTAP 3 and contact your doctor
immediately.

Tell your doctor:
• If you get a severe headache which does not get better when you take painkillers.
• If you suffer from any unexplained bruising or bleeding or feel generally unwell whilst taking
PROSTAP 3. Although rare, these could be symptoms of changes in the number of red or white
blood cells.
If any of the following side effects get serious, or if you notice any side effects not listed in this
leaflet, speak to your doctor or pharmacist:

WARNING!

Both men and women:
• PROSTAP 3 can sometimes cause swelling in your ankles, tiredness, nausea or headaches. The
treatment may cause pain in the joints, fever or chills, dizziness, vomiting, loss of appetite,
diarrhoea, pounding heartbeats, tingling in the hands or feet, muscle aching or weakness,
depression, altered vision, changes in weight, jaundice, abnormalities in liver function, thinning of
bones, increase in blood pressure, difficulty sleeping, blood clots in the lungs, spinal fracture,
paralysis or low blood pressure. Sometimes PROSTAP 3 causes redness or discomfort at the
place where the injection is given.
• If you suffer from depression, this may become worse when receiving PROSTAP 3.
• Blood sugar levels may be altered during treatment with PROSTAP 3, which may affect control in
diabetic patients and require more frequent monitoring.
• If you have an existing pituitary lesion, there may be an increased risk of loss of blood to the area,
which may cause permanent damage.
• If you have a blood test your doctor may notice a change in blood lipid (cholesterol) levels or in
values for tests on how the liver is working. These changes do not usually cause any symptoms.
• Mood changes, depression
· In Long term use: Common
· In Short term use: Uncommon

DATE:

5. How to store PROSTAP 3
PROSTAP 3 should not be stored above 25°C.
Store in the original package in order to protect from light.
Do not freeze.
Do not use this medicine after the date stated on the packaging.
If the pack has been damaged, return it to your pharmacist.
If the powder or sterile vehicle become discoloured or show any other signs of deterioration, you
should seek the advice of your pharmacist who will advise you what to do.
Keep out of the reach and sight of children

06464/2713D
CODE:

INC SAFETY WARNING

Prostap 3 injection

6. Further information
What PROSTAP 3 contains:
The active ingredient in PROSTAP 3 Powder is luprorelin acetate.
Each vial of Prostap 3 Powder contains 11.25mg leuprorelin acetate in a prolonged release formulation.
The other ingredients in Prostap 3 are: polylactic acid, which controls the release of the active ingredient
into the body, and mannitol.
The Sterile Vehicle contains carmellose sodium, mannitol, polysorbate 80 and water for Injections.
UK PIL DATED APRIL 2011

DT

11/05/12



PRODUCT:

ARTWORKER:








DATE OF PROOF:

Q.A.
APPROVED:
CUSTOMER: Waymade

PRE-PRESS NO.:

05-0440

Women only:
• In women PROSTAP 3 may cause hot flushes, vaginal dryness or mood changes including
depression. It may cause a change in breast size or breast tenderness and can occasionally
cause hair loss. As can happen naturally when women reach the menopause, PROSTAP 3 can
cause a small amount of bone thinning.

What PROSTAP 3 looks like and contents of the pack:
Each pack contains a vial of Prostap 3 Powder containing 11.25mg of active ingredient and a separate
ampoule containing 2ml of Sterile Vehicle.
The Sterile Vehicle is a clear liquid, which is mixed with the Prostap 3 Powder before injection.
Prostap 3 is available as a pack of one injection for three months.
Each Prostap 3 pack contains a glass vial with a red cap containing a white to off-white powder, a
glass ampoule with 2ml of sterile vehicle containing a clear, colourless liquid for reconstitution of Prostap
3 powder, 2.5ml syringe, two 23G (1") needles and a swab in a sealed sachet.
POM

PL No: 06464/2713 PROSTAP 3 Leuprorelin Acetate 11.25mg depot injection

This product is manufactured by Abbott Laboratories S.A., Avenida de Burgos, 91, 28050 Madrid, Spain
and procured from within the EU and repackaged by the Product Licence holder:
Waymade plc, Miles Gray Road, Basildon Essex SS14 3FR
Leaflet Revision date (Ref.) 8.5.2012
PROSTAP is a registered trademark of Takeda Chemical Industries

Colour
Swatch

Black

WARNING!

DATE:

Men only:
• When men with prostate cancer first start treatment with PROSTAP 3, levels of testosterone can
increase and in some people this may cause a temporary increase in local pain. In some cases,
to prevent this from happening, your doctor may give you another type of drug such as
cyproterone acetate or flutamide before and just after your first PROSTAP 3 injection. If you do
get worsening pain, weakness or loss of feeling in your legs or difficulty passing urine, contact
your doctor immediately.
• PROSTAP 3 can cause a loss of interest in sexual intercourse, hot flushes and occasionally it may
cause a reduction in size and function of the testes or swelling of the breasts.

WE CANNOT ACCEPT RESPONSIBILITY FOR ANY ERRORS IN THIS PROOF AFTER APPROVAL. THE ARTWORK RECEIVED HAS BEEN SIGNIFICANTLY
ADJUSTED, REVISED OR RESET BY US FROM DISK OR HARD COPY. WHILST WE TAKE EXTREME CARE AT ALL TIMES TO ENSURE ACCURACY, THE FINAL RESPONSIBILITY
MUST BE TAKEN BY OUR CUSTOMER. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

ARIAL REGULAR FONT SIZE 8
ARIAL BOLD
FONT SIZE 8
BRIDGED TO
CRESTOR 6464/2069 2070

Leaflet Flat Size = 148 x 317

CUSTOMER
APPROVED:

4. Possible side effects
Like all medicines, PROSTAP 3 can cause side effects, although not everybody gets them.
Contact your doctor immediately or go to hospital:
• If you develop a severe rash, itching or shortness of breath or difficulty breathing. These could be
symptoms of a severe allergic reaction.

PROOF HISTORY:
v.1 - waymade - 11/05/12

Notes:

27mm

CUSTOMER: Waymade

PRE-PRESS NO.:

02-1808

PRODUCT:

Prostap 3 medical info leaf

ARTWORKER:

DT

Q.A.
APPROVED:

CUSTOMER
APPROVED:

CODE:

06464/2713 E

DATE OF PROOF:

11/05/12

DATE:

PROOF HISTORY:
v.1 - waymade - 11/05/12

DATE:

Leaflet Flat Size = 296 x 317
ARIAL REGULAR FONT SIZE 8
ARIAL BOLD FONT SIZE 10
BRIDGED TO
TRANSTEC 6464/2327 2328 2329

UK PIL DATES aPRIL 2011
INC SAFETY WARNING

Pg 4

6.5 Nature and contents of container
Vials containing 11.25mg leuprorelin acetate as microsphere powder.
Ampoule containing 2ml of Sterile Vehicle.
6.6. Instructions for use/handling
See 6.2 above.
7. PRODUCT LICENCE HOLDER AND MANUFACTURER:
This product is manufactured by Abbott Laboratories S.A., Avenida de Burgos, 91, 28050 Madrid, Spain and is
procured from within the EU and repackaged by the Product Licence holder:
Waymade plc, Miles Gray Road, Basildon, Essex SS14 3FR
8. PRODUCT LICENCE NUMBER:

Pg 1

PROSTAP® 3 LEUPRORELIN ACETATE 11.25mg DEPOT
INJECTION
(leuprorelin acetate)
Healthcare Professionals User Leaflet

1. NAME OF THE MEDICINAL PRODUCT

PROSTAP 3 LEUPRORELIN ACETATE 11.25mg DEPOT INJECTION.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION:

Each vial of Prostap 3 powder contains 11.25mg of the active ingredient, Leuprorelin acetate in a prolonged
release formulation.
Each ampoule of Sterile vehicle contains carmellose sodium, mannitol, polysorbate 80 and water for injections

3. PHARMACEUTICAL FORM

PL No: 06464/2713 Prostap 3 Leuprorelin Acetate 11.25mg depot injection

Prolonged release powder for suspension for injection by subcutaneous (advanced prostate cancer) or
intramuscular (endometriosis) administration after reconstitution with the Sterile Vehicle.

Ref.: 8.5.2012
Prostap is a registered trademark of Takeda Chemical Industries

4. CLINICAL PARTICULARS:

Administration:
The vial of Prostap 3 microsphere powder should be reconstituted immediately prior to
administration by subcutaneous or intramuscular injection.
1.
2.

3.
4.
5.

Remove flip-cap from vial of Prostap 3 powder and cap from syringe.
Ensure the supplied 23-gauge needle is fixed securely to the syringe and draw up
2ml of sterile vehicle from the ampoule. Then inject whole contents of syringe into vial of
Prostap 3 powder using an aseptic technique. Remove the syringe/needle and keep aseptic.
Shake vial gently for 15-20 seconds to produce a uniform, cloudy suspension of Prostap 3.
Immediately draw up suspension into syringe taking care to exclude air bubbles.
Change the needle on syringe using a fresh 23-gauge needle if the suspension is to
be administered subcutaneously or alternatively a 21-gauge needle for intramuscular
administration. Twist the needle to ensure it is fully engaged. Having cleaned an
appropriate injection site, administer the suspension immediately by subcutaneous
or intramuscular injection as appropriate, taking care not to enter a blood vessel. Apply
sterile dressing to injection site if required.

No other fluid can be used for reconstitution of Prostap 3 powder

4.1 Therapeutic indications
• Metastatic prostate cancer.
• Locally advanced prostate cancer, as an alternative to surgical castration.
• As an adjuvant treatment to radiotherapy in patients with high-risk localised or locally advanced
prostate cancer.
• As an adjuvant treatment to radical prostatectomy in patients with locally advanced prostate cancer at
high risk of disease progression.
• Management of endometriosis, including pain relief and reduction of endometriotic lesions. (See
Section 5.1).
4.2 Posology and method of administration
Dosage
Prostate Cancer:
The usual recommended dose is 11.25mg presented as a three month depot injection and administered
as a single subcutaneous injection at intervals of three every months. The majority of patients will
respond to this dosage. Prostap 3 therapy should not be discontinued when remission or improvement
occurs. As with other drugs administered regularly by injection, the injection site should be varied
periodically.
Response to Prostap 3 therapy should be monitored by clinical parameters and by measuring
prostate-specific antigen (PSA) serum levels. Clinical studies with leuprorelin acetate shown that
testosterone levels increased during the first 4 days of treatment in the majority of non-orchidectomised
patients. They then decreased and reached castrate levels by 2-4 weeks. Once attained, castrate levels
were maintained as long as drug therapy continued. If a patient's response appears to be sub-optimal,
then it would be advisable to confirm that serum testosterone levels have reached or are remaining
at castrate levels.Transient increases in acid phosphatase levels sometimes occur early in the
treatment period but usually return to normal or near normal values by the 4th week of treatment.
Endometriosis:
The recommended dose is 11.25mg administered as a single intramuscular injection every 3 months for
a period of 6 months only. Treatment should be initiated during the first 5 days of the menstrual cycle.
In women receiving GnRH analogues for the treatment of endometriosis, the addition of hormone
replacement therapy (HRT-an oestrogen and progestogen) has been shown to reduce bone mineral
density loss and vasomotor symptoms. Therefore if appropriate, HRT should be co-administered with
Prostap 3 taking into account the risks and benefits of each treatment.
Elderly: As for adults
Children (under 18 years): Prostap 3 is not recommended in children under 18 years due to insufficient
data on safety and efficacy in this patient group.
Administration
The vial of Prostap 3 microsphere powder should be reconstituted immediately prior to administration by
subcutaneous or intramuscular injection.
Remove the flip-cap from the vial of Prostap 3.
Ensure the supplied 23-gauge needle is fixed securely to the syringe and draw up 2ml of the sterile
vehicle from the ampoule into the syringe. Then Inject whole contents of syringe into vial of Prostap 3
powder using an aseptic technique.
Remove the syringe/needle and keep aseptic. Shake vial gently for 15-20 seconds to produce a uniform
cloudy suspension of Prostap 3. Immediately draw up suspension into syringe taking care to exclude air
bubbles.
Change the needle on the syringe using a fresh 23 gauge needle if the suspension is to be administered
subcutaneously or alternatively a 21 gauge needle for intramuscular administration. Having cleaned an
appropriate injection site and ensured that the needle is fixed securely, administer the suspension by
subcutaneous or intramuscular injection as appropriate taking care not to enter a blood vessel. Apply
sterile dressing to the injection site if required. The injection should be given as soon as possible after
mixing. If any settling of suspension occurs in the vial or syringe, re-suspend by gentle shaking and
administer immediately.
No other fluid can be used for reconstitution of Prostap 3 powder.
4.3 Contra-Indications:
Hypersensitivity to the ingredients, any of the excipients or to synthetic gonadotropin releasing hormone
(Gn-RH) or Gn-RH derivatives.
Women: Prostap 3 is contra-indicated in women who are or may become pregnant while receiving the
drug. Prostap 3 should not be used in women who are breastfeeding or have undiagnosed abnormal
vaginal bleeding.
Men: There are no known contra-indications to the use of Prostap 3 in men.
4.4. Special warnings and special precautions for use
As would be expected with this class of drug, development or aggravation of diabetes may occur,
therefore diabetic patients may require more frequent monitoring of blood glucose during treatment with
Prostap 3. Hepatic dysfunction and jaundice with elevated liver enzyme levels have been reported.
Therefore, close observation should be made and appropriate measures taken if necessary.
Spinal fracture, paralysis, hypotension and worsening of depression have been reported.
Pg 2

WARNING!

WE CANNOT ACCEPT RESPONSIBILITY FOR ANY ERRORS IN THIS PROOF AFTER APPROVAL. THE ARTWORK RECEIVED HAS BEEN SIGNIFICANTLY
ADJUSTED, REVISED OR RESET BY US FROM DISK OR HARD COPY. WHILST WE TAKE EXTREME CARE AT ALL TIMES TO ENSURE ACCURACY, THE FINAL RESPONSIBILITY
MUST BE TAKEN BY OUR CUSTOMER. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

WARNING!

THE COLOURS SHOWN ON THIS PROOF ARE FOR GENERAL REPRESENTATION PURPOSES ONLY. THEY ARE NOT ACCURATE AND MUST NOT BE
USED AS A COLOUR MATCH FOR THE FINISHED JOB. PLEASE REFER TO THE PANTONE COLOUR GUIDES FOR ACCURATE COLOUR REFERENCES.

CUSTOMER: Waymade

PRE-PRESS NO.:

02-1808

PRODUCT:

Prostap 3 medical info leaf

ARTWORKER:

DT

Q.A.
APPROVED:

CUSTOMER
APPROVED:

CODE:

06464/2713 E

DATE OF PROOF:

11/05/12

DATE:

DATE:

PROOF HISTORY:
v.1 - waymade - 11/05/12

Leaflet Flat Size = 296 x 317

ARIAL REGULAR FONT SIZE 8
ARIAL BOLD FONT SIZE 10
BRIDGED TO
TRANSTEC 6464/2327 2328 2329

UK PIL DATES aPRIL 2011
INC SAFETY WARNING

Pg 2

Men: In the initial stages of therapy, a transient rise in levels of testosterone, dihydrotestosterone and acid
phosphatase may occur. In some cases, this may be associated with a ‘flare’ or exacerbation of the
tumour growth resulting in temporary deterioration of the patient’s condition. These symptoms usually
subside on continuation of therapy. ‘Flare’ may manifest itself as systemic or neurological symptoms in
some cases.
In order to reduce the risk of ‘flare’, an anti-androgen may be administered beginning 3 days prior to
leuprorelin acetate 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.
Patients at risk of ureteric obstruction or spinal cord compression should be considered carefully and
closely supervised in the first few weeks of treatment. These patients should be considered for
prophylactic treatment with anti-androgens. Should urological/neurological complications occur, these
should be treated by appropriate specific measures.
If an anti-androgen is used over a prolonged period, due attention should be paid to the contra-indications
and precautions associated with its extended use. Whilst the development of pituitary adenomas has
been noted in chronic toxicity studies at high doses in some animal species, this has not been observed
in long term clinical studies with leuprorelin acetate.
Women: During the early phase of endometriosis therapy, sex steroids temporarily rise above baseline
because of the physiological effect of the drug. Therefore, a worsening of clinical signs and symptoms
may be observed during the initial days of therapy, but these will dissipate with continued therapy.
When receiving GnRH analogues for the treatment of endometriosis, the addition of HRT (an oestrogen
and progestogen) has been shown to reduce bone mineral density loss and vasomotor symptoms (see
‘Posology and Method of Administration’ section 4.2 for further information).
The induced hypo-estrogenic state results in a small loss in bone density over the course of treatment,
some of which may not be reversible. The extent of bone demineralisation due to hypo-estrogenaemia is
proportional to time and, consequently, is the adverse event responsible for limiting the duration of
therapy to 6 months. The generally accepted level of bone loss with LHRH analogues such as Prostap 3
is 5%. In clinical studies with Prostap 3 the levels varied between 2.3% and 15.7% depending on the
method of measurement. During one six month treatment period, this bone loss should not be important.
In patients with major risk factors for decreased bone mineral content such as chronic alcohol and/or
tobacco use, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass
such as anticonvulsants or corticosteroids, Prostap 3 therapy may pose an additional risk. In these
patients, the risks and benefits must be weighed carefully before therapy with Prostap 3 is instituted.
In women with submucous fibroids, there have been reports of severe bleeding following the
administration of Prostap 3 as a consequence of the acute degeneration of the fibroids. Patients should
be warned of the possibility of abnormal bleeding or pain in case earlier surgical intervention is required.
Prostap 3 may cause an increase in uterine cervical resistance, which may result in difficulty in dilating
the cervix for intrauterine surgical procedures.
Precautions
Men: Patients with urinary obstruction and patients with metastatic vertebral lesions should begin Prostap
3 therapy under close supervision for the first few weeks of treatment.
Women: Since menstruation should stop with effective doses of Prostap 3, the patient should notify her
physician if regular menstruation persists.
4.5 Interaction with other medicinal products and other forms of interaction:
None have been reported.
4.6 Pregnancy and Lactation:
Safe use of leuprorelin acetate in pregnancy has not been established clinically. Studies in animals have
shown reproductive toxicity (see section 5.3). Before starting treatment with Prostap 3, pregnancy must
be excluded.
There have been reports of foetal malformation when Prostap 3 has been given during pregnancy.
Prostap 3 should not be used in women who are breastfeeding.
When used 3-monthly at the recommended dose, Prostap 3 usually inhibits ovulation and stops
menstruation. Contraception is not ensured, however, by taking Prostap 3 and therefore patients should
use non-hormonal methods of contraception during treatment. Patients should be advised that if they
miss successive doses of Prostap 3, breakthrough bleeding or ovulation may occur with the potential for
conception. Patients should be advised to see their physician if they believe they may be pregnant. If a
patient becomes pregnant during treatment, the drug must be discontinued. The patient must be apprised
of this evidence and the potential for an unknown risk to the foetus.
4.7 Effects on ability to drive and use machinery:
Prostap 3 can influence the ability to drive and use machines due to visual disturbances and dizziness.
4.8 Undesirable effects:
Side effects seen with Prostap 3 are due mainly to the specific pharmacological action, namely increases
and decreases in certain hormone levels. Adverse events which have been reported infrequently include
peripheral oedema, pulmonary embolism, hypertension, palpitations, fatigue, muscle weakness,
diarrhoea, nausea, vomiting, anorexia, fever/chills, headache (occasionally severe), hot flushes,
arthralgia, myalgia, dizziness, insomnia, depression, paraesthesia, visual disturbances, weight changes,
hepatic dysfunction, jaundice, increases in liver function test values (usually transient) and irritation at the
injection site. Changes in blood lipids and alteration of glucose tolerance, have also been reported which
may affect diabetic control. Thrombocytopenia and leucopenia have been reported rarely. Hypersensitivity
reactions including rash, pruritus, urticaria, and rarely, wheezing or interstitial pneumonitis have also been
reported. Anaphylactic reactions are rare.
Spinal fracture, paralysis, hypotension and worsening of depression have been reported (see ‘Special
Warnings and Precautions for Use’ section 4.4).
A reduction in bone mass may occur with the use of GnRH agonists.
Very rare cases of pituitary apoplexy have been reported following initial administration in patients with
pituitary adenoma.
Men: In cases where a ‘tumour flare’ occurs after Prostap 3 therapy, an exacerbation may occur in any
symptoms or signs due to disease, for example, bone pain, urinary obstruction weakness of the lower
extremities and paraesthesia. These symptoms subside on continuation of therapy.
Impotence and decreased libido will be expected with Prostap 3 therapy.
The administration of Prostap 3 is often associated with hot flushes and sometimes sweating.
Orchiatrophy and gynaecomastia has been reported occasionally.

Pg 3

Women: Those adverse events occurring most frequently with Prostap 3 are associated with
hypo-estrogenism; the most frequently reported are hot flushes, mood swings including depression
(occasionally severe), and vaginal dryness.
Estrogen levels return to normal after treatment is discontinued.
The induced hypo-oestrogenic state results in a small loss of bone density over the course of treatment,
some which may not be reversible (see section 4.4).
Breast tenderness or change in breast size may occur occasionally. Hair loss has also been reported
occasionally.
Vaginal haemorrhage may occur during therapy due to acute degeneration of submucous fibroids (see
section 4.4).
4.9 Overdose:
No case of overdose has been reported. In animal studies, doses up to 500 times the recommended
human dose resulted in dyspnoea, decreased activity and local irritation at the injection site. In cases of
overdose, the patients should be monitored closely and management should be symptomatic and
supportive.

5. PHARMACOLOGICAL PROPERTIES:
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Gonadotrophin-Releasing Hormone Analogues ATC code: L02AE 02
Prostap 3 contains leuprorelin acetate, a synthetic nonapeptide analogue of naturally occurring
gonadotrophin releasing hormone (GnRH), which possesses greater potency than the natural hormone.
Leuprorelin acetate is a peptide and therefore unrelated to the steroids. Chronic administration results in
an inhibition of gonadotrophin production and subsequent suppression of ovarian and testicular steroid
secretion. This effect is reversible on discontinuation of therapy.
Administration of leuprorelin acetate results in an initial increase in circulating levels of gonadotrophins,
which leads to a transient increase in gonadal steroid levels in both men and women. Continued
administration of leuprorelin acetate results in a decrease of gonadotrophin and sex steroid levels. In
men serum testosterone levels, initially raised in response to early luteinising hormone (LH ) release, fall
to castrate levels in about 2-4 weeks.
Leuprorelin acetate is inactive when given orally.
A randomised , open-label, comparative multi-centre study was performed to compare the efficacy and
safety of the 3.75mg and 11.25mg depots of leuprorelin acetate. 48% of patients included had locally
advanced disease (T3N0M0), 52% of patients had metastatic disease. Mean serum testosterone level fell
below the threshold for chemical castration (0/.5ng/ml) at one month of treatment, continuing to decrease
thereafter and stabilising at a value below the castration threshold. The decline in serum PSA mirrored
that of serum testosterone in both groups.
In an open, prospective clinical trial involving 205 patients receiving 3.75mg leuprorelin acetate on a
monthly basis as a treatment for metastatic prostate cancer, the long-term efficacy and safety of
leuprorelin acetate was assessed. Testosterone levels were maintained below the castrate threshold
over the 63-month follow up period. Median survival time exceeded 42.5 months for those receiving
monotherapy and 30.9 months for those receiving leuprorelin acetate in combination with anti-androgens
(this difference relating to baseline differences between groups). In a meta-analysis involving primarily
patients with metastatic disease, no statistically significant difference in survival was found for patients
treated with LHRH analogues compared with patients treated with orchidectomy.
In another randomised, open-label, multi-centre comparative trial, leuprorelin acetate in combination with
flutamide has been shown to significantly improve disease-free survival and overall survival when used
as an adjuvant therapy to radiotherapy in 88 patients with high-risk localised (T1-T2 and PSA of at least
10 ng/mL or a Gleason score of at least 7), or locally advanced (T3-T4), prostate cancer. The optimum
duration of adjuvant therapy has not been established. This US study used a higher dose of leuprorelin
acetate (7.5 mg/month) which is therapeutically equivalent o the European licensed dose.
The use of a LHRH agonist may be considered after prostatectomy in selected patients considered at
high risk of disease progression. There are no disease-free survival data or survival date with leuprorelin
acetate in this setting.
5.2 Pharmacokinetic properties
Leuprorelin acetate well absorbed after subcutaneous or intramuscular injections. It binds to the
luteinising hormone releasing hormone (LHRH) receptors and is rapidly degraded. An initially high
plasma level of leuprorelin peaks at around 3 hours after a Prostap 3 subcutaneous injection, followed by
a decrease to maintenance levels in 7 to 14 days. Prostap 3 provides continuous plasma levels for up to
117 days resulting in the suppression of testosterone to below castration level within 4 weeks of the first
injection in the majority of patients.
The metabolism, distribution and excretion of leuprorelin acetate in humans have not been fully
determined.
5.3 Preclinical safety data
Animal studies have shown that leuprorelin acetate has a high acute safety factor. No major overt
toxicological problems have been seen during repeated administration. Whilst the development of
pituitary adenomas has been noted in chronic toxicity studies at high doses in some animal species, this
has not been observed in long term clinical studies. No evidence of mutagenicity or teratogenicity has
been shown. Animal reproductive studies showed increased foetal mortality and decreased foetal
weights reflecting the pharmacological effects of this LHRH antagonist.
6. PHARMACEUTICAL PARTICULARS:
6.1 List of excipients
Prostap 3: polylactic acid and mannitol.
Sterile vehicle: contains carmellose sodium, mannitol, polysorbate 80 and water for injection.
6.2. Incompatibilities
No other fluid other than the Sterile Vehicle provided for Prostap 3 can be used for the reconstitution of
Prostap 3 powder.
6.3 Shelf-life
36 months unopened.
Once reconstituted with Sterile Vehicle, the suspension should be used immediately.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package and protect from light. Do not freeze.

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