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PROSTAP SR LEUPRORELIN ACETATE 3.75MG 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® SR LEUPRORELIN ACETATE 3.75mg DEPOT INJECTION
(leuprorelin acetate)
Patient Information Leaflet
This product is available as the above name. Throughout this leaflet it will be referred to as Prostap SR.

1. What Prostap SR is and what it is used for
Prostap SR is a synthetic hormone, which can be used to reduce levels of testosterone and estrogen
circulating in the body.
Prostap SR is used to treat prostate cancer in men and endometriosis and uterine fibroids in women. It
can also be used to reduce the thickness of the lining (endometrium) of the womb (uterus) in preparation
for surgery.
2. Before having this medicine
Prostap SR is not recommended for use in children under the age of 18 years

DATE:

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.

15/05/12
DATE OF PROOF:

Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines
obtained without a prescription.
Taking Prostap SR with food and drink
Prostap SR can be taken with or without food.
Pregnancy and breastfeeding
You should not take Prostap SR if you are pregnant, planning to become pregnant or are breastfeeding.
Driving and using machines
Do not drive or operate machinery if you experience drowsiness, dizziness or visual disturbances whilst
being treated with Prostap SR.

You will normally be given an injection once a month. If you are to be given Prostap SR prior to
intrauterine surgery you will receive a single injection 5 – 6 weeks before your surgery.
INC SAFETY WARNING

UK PIL DATED APRIL 2011

06464/2714D

3. How to take Prostap SR
The doctor or nurse will give you an injection of Prostap SR. The injection will normally be given in your
arm, thigh or abdomen. The injection site should be varied at regular intervals.

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Prostap SR 3075mg injection patient leaf
PRODUCT:

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WARNING!

Women only:
• If you are a woman with submucous fibroids (benign tumours in the muscle underneath the lining
of the womb). Prostap SR 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 SR you should tell your doctor
• If you are a woman of child-bearing age, you should use non hormonal contraception, whilst
receiving Prostap SR. Although Prostap SR causes periods to stop, it is not itself a contraceptive.
If you are unsure about this, talk to your doctor.

DATE:

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Take special care with Prostap SR:
Both men and women:
• If you are diabetic Prostap SR 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 SR. 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 which may be severe. If you are
taking Prostap and develop depressed mood, inform your doctor.

Waymade

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Do not take Prostap SR:
• If you are allergic (hypersensitive) to leuprorelin acetate (Prostap SR or Prostap 3) or any of the
other ingredients of Prostap SR.
• 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

If you have endometriosis you will be given an injection of Prostap SR for a period of 6 months only and
treatment will be initiated during the first five days of the menstrual cycle.
If you have uterine fibroids you will be given an injection of Prostap SR once a month usually for 3 – 4
months before surgery.
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.
Women only:
If a Prostap SR 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 SR and contact your doctor
immediately.
4. Possible side effects
Like all medicines, Prostap SR 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.
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 SR. Although rare, these could be symptoms of changes in the number of red or white
blood cells.

Colour
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Leaflet Flat Size = 148 x 400

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Bridged to Crrestor 6464/2069
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In this leaflet:
1. What Prostap SR is and what it is used for
2. Before having this medicine
3. How to take Prostap SR
4. Possible side effects
5. How to store Prostap SR
6. Further information

PROOF HISTORY:
v.1- waymade - 15/05/12

Notes:

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.

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.

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:
• In women Prostap SR 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 SR can
cause a small amount of bone thinning.

WARNING!

5. How to store Prostap SR
Do not store above 25°C.
Store in the original container 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.
Keep out of the reach and sight of children.
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.

What Prostap SR looks like and contents of the pack:
Prostap SR is available as a pack of one injection for one month,
Each Prostap SR pack contains a glass vial with a coloured 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
SR powder, one 2.5ml syringe, two 22G (1½") needles and a swab in a sealed sachet.
The ampoule contains 2ml of sterile vehicle, but 1ml of sterile vehicle will be mixed with Prostap powder
prior to intramuscular or subcutaneous injection.
PL No: 06464/2714 Prostap SR Leuprorelin Acetate 3.75mg depot injection

DATE:

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

DT

15/05/12

ARTWORKER:

DATE OF PROOF:

Prostap SR 3075mg injection patient leaf

06464/2714D

PRODUCT:

CODE:

INC SAFETY WARNING

Prostap is a registered trademark of Takeda Chemical Industries.

UK PIL DATED APRIL 2011

05-0269
PRE-PRESS NO.:
Waymade

Leaflet revision and issue date (Ref.) 8.5.2012

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Q.A.
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POM

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WARNING!

6. Further Information
What Prostap SR contains:
The active ingredient in Prostap SR Powder is leuprorelin acetate.
Each vial of Prostap SR Powder contains 3.75mg leuprorelin acetate in a prolonged release formulation.
The other ingredients in Prostap SR are: gelatin, copolymer (DL-lactic acid/glycolic 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.

DATE:

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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 Crrestor 6464/2069
2070

Notes:

Men only:
• When men with prostate cancer first start treatment with Prostap SR, 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 SR injection. If you do get
worsening pain, weakness or loss of feeling in your legs or difficulty passing urine, contact your
doctor immediately. Prostap SR 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.

PROOF HISTORY:
v.1- waymade - 15/05/12

Leaflet Flat Size = 148 x 400

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:
Both men and women:
• Prostap SR 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 functioning, thinning
of bones, increase in blood pressure, difficulty sleeping, blood clots in the lungs, spinal fracture,
paralysis or low blood pressure. Sometimes Prostap SR causes redness or discomfort at the
place where the injection is given.
• If you suffer from depression, this may become worse when receiving Prostap SR.
• Blood sugar levels may be altered during treatment with Prostap SR, 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

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02-1808

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Prostap 3 medical info leaf

ARTWORKER:

DT

Q.A.
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CODE:

06464/2714 E

DATE OF PROOF:

15/05/12

DATE:

PROOF HISTORY:
v.1 - waymade - 15/05/12

DATE:

Leaflet Flat Size = 296 x 317
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BRIDGED TO
TRANSTEC 6464/2327 2328 2329

UK PIL DATED APRIL 2011
INC SAFETY WARNING

Pg 4

6.3 Shelf-life
36 months unopened.
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.
From a microbiological point of view, once reconstituted with Sterile Vehicle, the product should be used
immediately. If not used immediately, in-use storage times and conditions prior to use are the
responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless
reconstitution has taken place in controlled and validated aseptic conditions.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original container and protect from light. Do not freeze.

Pg 1

PROSTAP® SR LEUPRORELIN ACETATE 3.75mg DEPOT
INJECTION
(leuprorelin acetate)
Healthcare Professionals User Leaflet

1. NAME OF THE MEDICINAL PRODUCT

PROSTAP SR LEUPRORELIN ACETATE 3.75mg DEPOT INJECTION.
The product will be referred to as Prostap SR throughout this leaflet.

6.5 Nature and contents of container
Vials containing 3.75mg leuprorelin acetate as microcapsule powder.
Ampoule containing 2ml of Sterile Vehicle.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION:

6.6. Instructions for use/handling
Prostap SR Powder 3.75mg: A sterile, lyophilised, white, odourless PLGA microcapsule powder for
subcutaneous or intramuscular injection after reconstitution with the Sterile Vehicle (4 week depot
injection).
PLGA = copolymer (DL-lactic acid/glycolic acid) 75:25mol%
Sterile Vehicle: Ampoule containing 2ml of clear, colourless, slightly viscous, sterile vehicle of which 1ml
should be used for reconstitution of the microcapsules.

3. PHARMACEUTICAL FORM

7. PRODUCT LICENCE HOLDER AND MANUFACTURER:
PL No: 06464/2714 Prostap SR Leuprorelin Acetate 3.75mg depot injection
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
Ref.: 8.5.2012
Prostap is a registered trademark of Takeda Chemical Industries
Administration:
The vial of Prostap SR microsphere powder should be reconstituted immediately prior to administration
by subcutaneous or intramuscular injection.
1. Remove flip-cap from vial of Prostap SR powder. Open ampoule of Sterile Vehicle.
2. Fix the needle to the syringe, twist to ensure needle is fully engaged and draw up 1ml of
the sterile vehicle from the ampoule into the syringe. Then inject whole contents of syringe
into vial of Prostap SR powder using an aseptic technique. Remove the syringe/needle and keep
aseptic.
3. Shake vial gently for 15-20 seconds to produce a uniform, cloudy suspension of Prostap SR.
4. Immediately draw up suspension into syringe taking care to exclude air bubbles.
5. 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 by subcutaneous or intramuscular injection as appropriate, taking care
not to enter a blood vessel. Apply sterile dressing to injection site if required.

Each vial of Prostap SR powder contains 3.75mg of the active ingredient, leuprorelin acetate in a prolonged
release formulation.
Prolonged release powder for suspension for injection by subcutaneous or intramuscular administration after
reconstitution with the sterile vehicle.

4. CLINICAL PARTICULARS:

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.
• Endometrial preparation prior to intrauterine surgical procedures including endometrial ablation or
resection.
• Preoperative management of uterine fibroids to reduce their size and associated bleeding.
(See section 5.1)
4.2 Posology and method of administration
Dosage
Prostate Cancer: The usual recommended dose is 3.75mg administered as a single subcutaneous
or intramuscular injection every month. The majority of patients will respond to a 3.75mg dose.
Prostap SR 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 SR therapy may be monitored by clinical parameters and by measuring serum
levels of testosterone and acid phosphotase.
Clinical studies leuprorelin acetate have 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 by the 4th week of treatment.
Endometriosis: The recommended dose is 3.75mg administered as a single subcutaneous or
intramuscular injection every month 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 estrogen and progestogen) has been shown to reduce bone mineral
density loss and vasomotor symptoms.Therefore if appropriate, HRT should be co-administered with
Prostap SR taking into account the risks and benefits of each treatment.
Endometrial preparation prior to intrauterine surgery: A single 3.75mg subcutaneous or
intramuscular injection 5 – 6 weeks prior to surgery. Therapy should be initiated during days 3 to 5 of
the menstrual cycle.
Preparative management of uterine fibroids: The recommended dose is 3.75mg administered as a single
subcutaneous or intramuscular injection every month, usually for 3 – 4 months but for a maximum of 6
months.
Elderly: As for adults
Children: Prostap SR is not recommended in children under 18 years due to insufficient data on safety
and efficacy in this patient group.
4.3 Contraindications:
Hypersensitivity to the active substance, any of the excipients or to synthetic gonadotrophin releasing
hormone (Gn-RH) or Gn-RH derivatives.
Women: Prostap SR is contra-indicated in women who are or may become pregnant while receiving
the drug. Prostap SR should not be used in women who are breast feeding or have undiagnosed
abnormal vaginal bleeding.
Men: There are no known contra-indications to the use of Prostap in men.

The injection should be given as soon as possible after mixing. If any settling of suspension occurs in
via or syringe, re-suspend by gentle shaking and administer immediately.
No other fluid can be used for reconstitution of Prostap SR powder

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 SR.
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.
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.
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:

06464/2714 E

DATE OF PROOF:

15/05/12

DATE:

DATE:

PROOF HISTORY:
v.1 - waymade - 15/05/12

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 DATED APRIL 2011
INC SAFETY WARNING

Pg 2

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 contraindications 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: When considering the preoperative treatment of fibroids it is mandatory to confirm the diagnosis
of fibroids and exclude an ovarian mass, either visually by laparoscopy or by ultrasonography or other
investigative technique, as appropriate, before Prostap SR therapy is instituted.
During the early phase of therapy, sex steroids temporarily rise above baseline because of the
physiological effect of the drug. Therefore, an increase in clinical signs and symptoms may be observed
during the initial days of therapy, but these will dissipate with continued therapy.
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
SR is 5%. In clinical studies with Prostap SR 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 SR therapy may pose an additional risk. In
these patients, the risks and benefits must be weighed carefully before therapy with Prostap SR is
instituted. This is particularly important in women with uterine fibroids where age related bone loss may
have already begun to occur.
Therefore, before using Prostap SR for the preoperative treatment of uterine fibroids, patients with
major risk factors for decreased bone mineral content (see above) should have their bone density
measured and where results are below the normal (5th percentile by DEXA scan) range, Prostap SR
therapy should not be started.
In women with submucous fibroids, there have been reports of severe bleeding following the
administration of Prostap SR 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 SR may cause an increase in uterine cervical resistance, which may result in difficulty in dilating
the cervix for intrauterine surgical procedures.
In women receiving GnRH analogues for the treatment of endometriosis, the addition of HRT (an
estrogen and progestogen) has been shown to reduce bone mineral density loss and vasomotor
symptoms.
Precautions
Men: Patients with urinary obstruction and patients with metastatic vertebral lesions should begin
Prostap SR therapy under close supervision for the first few weeks of treatment.
Women: Since menstruation should stop with effective doses of Prostap SR, the patient should notify her
physician if regular menstruation persists.
4.5 Interaction with other medicinal products and other forms of interaction:
No interaction studies have been performed.
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 SR, pregnancy must be excluded. There have been reports of foetal malformation when
Prostap SR has been given during pregnancy.
Prostap SR should not be used in women who are breast feeding.
When used monthly at the recommended dose, Prostap SR usually inhibits ovulation and stops
menstruation. Contraception is not ensured, however, by taking Prostap SR and therefore patients
should use non-hormonal methods of contraception during treatment.
Patients should be advised that if they miss successive doses of Prostap SR, 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 SR can influence the ability to drive and use machines due to visual disturbances and dizziness.
4.8 Undesirable effects:
Side effects seen with Prostap SR 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 alternation 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 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 SR 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 SR therapy.
The administration of Prostap SR is often associated with hot flushes and sometimes sweating.
Orchiatrophy and gynaecomastia have been reported occasionally.

Pg 3

Women: Those adverse events occurring most frequently with Prostap SR are associated with hypoestrogenism; 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-estrogenic 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 SR contains leuprorelin acetate, a synthetic nonapeptide analogue of naturally occurring
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. Estradiol levels will decrease to postmenopausal levels in
premenopausal women within one month of initiating treatment.
The drug is well absorbed from the subcutaneous or intramuscular route, binds to luteinising hormone
releasing hormone (LHRH) receptors and is rapidly degraded. In this dose form, an initial high level of
leuprorelin acetate in the plasma is achieved within 3 hours followed by a drop over 24-48 hours to
maintenance levels of 0.3-0.8ng/ml and a slow decline thereafter. Effective levels persist for 30-40 days
after a single dose.
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 3.75 mg 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 3.75 mg leuprorelin acetate on a
monthly basis as 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 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 or leuprorelin
acetate (7.5mg/month) which is therapeutically equivalent to 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 data with leuprorelin
acetate in this setting.
5.2 Pharmacokinetic properties
Studies submitted show that single intramuscular or subcutaneous doses of Leuprorelin acetate over the
dose range 3.75 to 15mg results in detectable levels of leuprorelin acetate for more than 28 days, good
bioavailability, a consistent and predictable pharmacokinetic profile, and biological efficacy at plasma
levels of less than 0.5ng/ml. The pharmacokinetic profile is similar to that seen in animal studies using
the compound, with an initial high level of drug released from the microcapsules during reconstitution
and injection followed by a plateau over a 2-3 week period before levels gradually become undetectable.
There appears to be no significant difference between the routes of administration (im vs sc) in biological
effectiveness or pharmacokinetics.
The metabolism, distribution and excretion of leuprorelin acetate in humans have not been fully
determined.
5.3 Preclinical safety data
A teratogenic effect has been observed in rabbits but not in rats.
6. PHARMACEUTICAL PARTICULARS:
6.1 List of excipients
Prostap SR Powder: Gelatin, copolymer (DL-lactic acid/glycolic acid) and mannitol.
Sterile vehicle: contains carmellose sodium, mannitol, polysorbate 80 and water for injection.
6.2. Incompatibilities
None reported

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Source: Medicines and Healthcare Products Regulatory Agency

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