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PROSTAP SR DCS 3.75 MG POWDER AND SOLVENT FOR PROLONGED-RELEASE SUSPENSION FOR INJECTION IN PRE-FILL

Active substance(s): LEUPRORELIN ACETATE / LEUPRORELIN ACETATE / LEUPRORELIN ACETATE

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®

2582
23.08.16[9]

Prostap SR DCS 3.75 mg Powder and
Solvent for Prolonged-release
Suspension for Injection in Pre-filled
Syringe
(leuprorelin acetate)
PATIENT INFORMATION LEAFLET
Read all of this leaflet carefully before you start using this medicine
because it contains important information for you.
- 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 signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed in this leaflet. See section 4.
Your medicine will be referred to as PROSTAP SR throughout the following
leaflet.
In this leaflet:
1. What PROSTAP SR is and what it is used for
2. What you need to know before you use PROSTAP SR
3. How to take PROSTAP SR
4. Possible side effects
5. How to store PROSTAP SR
6. Contents of the pack and other information
1. WHAT PROSTAP SR IS AND WHAT IT IS USED FOR
PROSTAP SR is a synthetic hormone which can be used to reduce the
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.
Use in children:
PROSTAP SR is a synthetic hormone which can be used to reduce the
levels of testosterone and estrogen circulating in the body. Leuprorelin 1
Month Depot is used to treat premature puberty which is caused by a
release of certain hormones from the pituitary gland (central precocious
puberty) in girls under 9 years of age and boys under 10 years of age.
2. WHAT YOU NEED TO KNOW BEFORE YOU USE PROSTAP SR
Use in children: Your doctor will make a precise diagnosis of central
precocious puberty.
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 (listed in
section 6).
- 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.
- In girls with central precocious puberty
- if the girl to be treated is pregnant or breast-feeding.
- if the girl has undiagnosed vaginal bleeding.
Warnings and precautions:
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 have diabetes or suffer from heart problems you should tell your
doctor.
- 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:
- If you or any of your close family have thinning of the bones.
- If you drink excessive amounts of alcohol, and/or smoke heavily.
- 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 SR
which may be severe. If you are taking PROSTAP SR and develop
depressed mood, inform your doctor.
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 break-down. 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.
Men only:
- In the rare event of an abscess occurring at the injection site your doctor
may measure your testosterone levels as there could be reduced
absorption of leuprorelin from the injection site.
- 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 you should tell your doctor.
- Please tell your doctor if you have any of the following: Any heart or blood
vessel conditions, including heart rhythm problems (arrhythmia), or are
being treated with medicines for these conditions. The risk of heart rhythm
problems may be increased when using PROSTAP SR.
In children:
- In the event of a sterile abscess at the injection site (mostly reported after
injection into the muscle) your doctor will monitor your hormone levels as
there could be reduced absorption of leuprorelin from the injection site.
- If the child has progressive brain tumour your doctor will decide if
treatment with leuprorelin is appropriate.
In girls with central precocious puberty:
- After the first injection vaginal bleeding (spotting) and discharge may
occur as a sign of hormone withdrawal. Vaginal bleeding beyond the
first/second month of treatment needs to be investigated.
- Bone density may decrease during treatment of central precocious
puberty with Leuprorelin 1 Month Depot. However, after treatment is
stopped, subsequent bone mass growth is preserved and peak bone
mass in late adolescence does not seem to be affected by treatment.
- Often sterile abscesses at the injection site occurred when Leuprorelin 1
Month Depot is administered in higher dosages than recommended and
when it is administered into the muscle. Your doctor will therefore
administer the medicinal product under the skin of e.g. abdomen, bottom
or thigh.

- Discontinuation of treatment may lead to a slipping of the growth plate of
the thigh bone. A possible cause could be a weakness of the growth plate
due to a lower concentration of female sexual hormones during treatment.
Other medicines and PROSTAP SR
Please tell your doctor or pharmacist if you are taking or have recently taken
any other medicines, including medicines obtained without a prescription.
PROSTAP SR might interfere with some medicines used to treat heart
rhythm problems (e.g. quinidine, procainamide, amiodarone and sotalol) or
might increase the risk of heart rhythm problems when used with some
other drugs (e.g. methadone (used for pain relief and part of drug addiction
detoxification), moxifloxacin (an antibiotic), antipsychotics used for serious
mental illnesses).
PROSTAP SR with food and drink
PROSTAP SR can be taken with or without food.
Pregnancy and breastfeeding
PROSTAP SR must not be administered in pregnant or breast-feeding
women or girls (see also section “Do not use PROSTAP SR).
Driving and using machines
Do not drive or operate machinery if you experience drowsiness, dizziness
or visual disturbances whilst being treated with PROSTAP SR.
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.
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.
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.
Use in children
Treatment of children should be under the overall supervision of the
paediatric endocrinologist.
The dosing scheme needs to be adapted individually.
The recommended starting dose is dependent on the body weight:
a) Children with a body weight 20 kg or more
Unless prescribed otherwise, 1 ml PROSTAP SR (3.75 mg leuprorelin
acetate) is administered once a month under the skin of e.g. abdomen,
bottom or thigh as a single injection.
b) Children with a body weight less than 20 kg
Taking into account the clinical activity of the central precocious puberty in
these rare cases, the following applies:
Unless prescribed otherwise, 0.5 ml PROSTAP SR (1.88 mg leuprorelin
acetate) are administered once a month under the skin of e.g. abdomen,
bottom or thigh as a single injection. The remainder of the suspension
should be discarded. Your doctor will monitor the child’s weight gain.
Depending on the central precocious puberty activity, your doctor may
increase the dosage in the presence of inadequate suppression (e.g.
vaginal bleeding). Your doctor will determine the minimal effective dose with
the help of a blood test.
The duration of treatment depends on the clinical signs at the start of
treatment or during the course of treatment and is decided by your doctor
together with the legal guardian and, if appropriate, the treated child. Your
doctor will determine the bone age of the child in regular intervals.
In girls with bone maturation of older than 12 years and boys with bone
maturation of older than 13 years your doctor will consider discontinuing the
treatment, depending on the clinical effects in your child.
In girls, pregnancy should be excluded before the start of treatment. The
occurrence of pregnancy during treatment cannot be generally excluded. In
such cases, please talk to your doctor.
The therapy is a long-term treatment, adjusted individually. Please arrange
with your doctor that PROSTAP SR is administered as precisely as possible
in regular monthly periods. An exceptional delay of the injection date for a
few days (30 ± 2 days) does not influence the result of the therapy.
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.
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:
Men:
- 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.
- 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. This is
very rare (may affect more than 1 in 10,000 people).
- 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 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.

6. CONTENTS OF THE PACK AND OTHER INFORMATION
What PROSTAP SR contains:
The active ingredient in Prostap SR Powder is leuprorelin acetate (3.75 mg)

Very common (may affect more than 1 in 10 people)
Weight changes, hot flushes, sweating, muscle weakness, bone pain, loss
of interest in sexual intercourse, inability to have an erection, a reduction in
size and function of the testes, tiredness or skin reactions at the injection
site (these include skin hardening, redness, pain, abscesses, swelling,
nodules, ulcers and skin damage).

The other ingredients are:
Powder- gelatin, copoly (DL lactic acid/glycolic acid) 72:25 mol%, mannitol

Common (may affect up to 1 in 10 people)
Loss of appetite, difficulty sleeping, depression, mood changes (with longterm use), headache, nausea, abnormalities in liver function or liver blood
tests, joint pain, swelling of the breast tissue or swelling in your ankles.
Uncommon (may affect more than 1 in 100 people)
Mood changes (with short-term use), dizziness, tingling in the hands or feet,
diarrhoea, vomiting, muscle ache or weakness in the legs.
Not known (frequency cannot be estimated from the available data)
Blood tests may show anaemia (low red cell counts), low counts in white
cells or platelets, allergic reactions (may include symptoms of rash, itching,
wheals or a serious allergic reaction which causes difficulty breathing or
dizziness), changes in blood lipids (cholesterol) or blood sugar, paralysis,
seizure, altered vision, pounding heartbeats, changes in ECG (QT
prolongation), blood clots in lungs, high or low blood pressure, jaundice,
fracture of the spine, thinning of bone, difficulty passing urine, fever or chills.
Women:
- Many of the side effects of PROSTAP SR are related to the decrease in
oestrogen level. Oestrogen level returns to normal after treatment is
stopped. Common side effects include hot flushes, mood swings,
depression and vaginal dryness. As can happen naturally when women
reach the menopause, PROSTAP SR can cause a small amount of bone
thinning. Vaginal bleeding may occur during treatment.
- 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. This is
very rare (may affect more than 1 in 10,000 people).
- 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 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.
Very common (may affect more than 1 in 10 people)
Difficulty sleeping, headaches or hot flushes
Common (may affect up to 1 in 10 people)
Weight changes, mood changes, depression, tingling in hands or feet,
dizziness, nausea, joint pain, muscle weakness, breast tenderness,
changes in breast size, vaginal dryness, swelling in ankles or skin reactions
at the injection site (these include skin hardening, redness, pain, abscesses,
swelling, nodules, ulcers and skin damage)
Uncommon (may affect more than 1 in 100 people)
Loss of appetite, changes in blood lipids (cholesterol), altered vision,
pounding heartbeats, diarrhoea, vomiting, abnormalities in liver blood tests,
hair loss, muscle aches, fever, chills or tiredness
Not known (frequency cannot be estimated from the available data)
Blood tests may show anaemia (low red cell counts), low counts in white
cells or platelets, allergic reactions (may include symptoms of rash, itching,
wheals or a serious allergic reaction causing difficulty breathing or
dizziness), changes in blood sugar, paralysis, blood clots in the lungs, high
or low blood pressure, jaundice, abnormalities in liver function, fracture of
the spine, seizure, thinning of bone or vaginal bleeding.
Children
In the initial phase of treatment, a short-term rise in the sex hormone levels
occurs, followed by a fall to values within the prepuberty range. Due to this
effect, side effects may occur particularly at the start of treatment.
Common (may affect up to 1 in 10 people):
- mood swings
- headache
- abdominal pain / abdominal cramps
- feeling sick / vomiting
- acne
- vaginal bleeding
- spotting
- discharge
- injection site reactions
Very rare (may affect less than 1 in 10,000 people):
- general allergic reactions (fever, rash, itching)
- serious allergic reaction which causes difficulty in breathing or dizziness
- As with other medicinal products of this class: 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.
Not known (frequency cannot be estimated from the available data)
- Seizure
Notes:
In general, if vaginal bleeding (spotting) occurs with continued treatment
(after possible withdrawal bleeding in the first month of treatment), this may
be a sign of potential underdosage. Please tell your doctor if vaginal
bleeding occurs.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed in this leaflet. You can also report side
effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.
By reporting side effects you can help provide more information on the
safety of this medicine.
5. HOW TO STORE PROSTAP SR
Keep out of the sight and reach of children
o
Do not store above 25 C.
Do not refrigerate or freeze.
Store in the original container in order to protect from light.
Do not use this medicine after the date stated on the packaging.
Once mixed with the Sterile Solvent, the suspension must be used
immediately.
If the pack has been opened or damaged, return it to your pharmacist.
If the medicines become discoloured or show any other signs of
deterioration, consult your pharmacist who will tell you what to do.
Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. These
measures will help to protect the environment.

Sterile solvent- carboxymethylcellulose sodium, mannitol, polysorbate 80,
glacial acetic acid (for pH adjustment), water for injections.
What PROSTAP SR looks like and contents of the pack:
The product is a dual chamber glass cartridge with orange base assembled
as a single unit in a disposable delivery device. The cartridge contains a
sterile, lyophilised, white powder in the transparent front chamber and a
clear, odourless, slightly viscous, sterile solvent in the rear chamber.
The pack also contains a 1 x syringe needle, 1 x syringe plunger and
alcohol swab.
MANUFACTURER AND PRODUCT LICENCE HOLDER
Manufactured by
Abbott Laboratoires S.A., Apartado De Correos, 967, Avenida De Burgos,
91, Madrid, E-28050, Spain.
AbbVie Logistics BV, Meeuwenlaan 4, Zwolle, NL-8011 BZ, The
Netherlands.
Procured from within EU by Product Licence holder: Star Pharmaceuticals
Ltd., 5 Sandridge Close, Harrow, Middlesex, HA1 1XD. Repackaged by
Servipharm Ltd.
POM

PL 20636/2582

Leaflet revision and issue date (Ref): 23.08.16[9]
Prostap is a trademark of Takeda Pharmaceutical Company Limited.

2582
23.08.16[H-9]

HEALTH PROFESSIONALS’ USER LEAFLET
®

Prostap SR DCS 3.75 mg Powder and Solvent for Prolonged-release Suspension for Injection in Pre-filled
Syringe
(leuprorelin acetate)
1. NAME OF THE MEDICINAL PRODUCT
PROSTAP SR DCS 3.75 mg Powder and Solvent for Suspension for Injection
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
PROSTAP SR Powder: contains 3.75 mg leuprorelin acetate (equivalent to 3.57 mg base).
Sterile Solvent: carboxymethylcellulose sodium, mannitol, polysorbate 80, glacial acetic acid (for pH adjustment),
water for injections.
When reconstituted with Sterile Solvent, the suspension contains 3.75 mg/ml leuprorelin acetate.
For the full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Powder and solvent for suspension for injection in pre-filled syringe
Powder: A sterile, lyophilised, white powder.
Solvent: A clear, odourless, slightly viscous, sterile solvent.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
(i)
Metastatic prostate cancer.
(ii) Locally advanced prostate cancer, as an alternative to surgical castration.
(iii) As an adjuvant treatment to radiotherapy in patients with high-risk localised or locally advanced prostate
cancer.
(iv) As an adjuvant treatment to radical prostatectomy in patients with locally advanced prostate cancer at high
risk of disease progression.
(v) As neo-adjuvant treatment prior to radiotherapy in patients with high-risk localised or locally advanced
prostate cancer.
(vi) Management of endometriosis, including pain relief and reduction of endometriotic lesions.
(vii) Endometrial preparation prior to intrauterine surgical procedures including endometrial ablation or resection.
(viii) Preoperative management of uterine fibroids to reduce their size and associated bleeding.
In children:
Treatment of central precocious puberty (girls under 9 years of age, boys under 10 years of age).
(See Section 5.1)
4.2 Posology and method of administration
Posology
Prostate Cancer: The usual recommended dose is 3.75 mg presented as a one month depot injection and
administered as a single subcutaneous or intramuscular injection every month. The majority of patients will respond to
a 3.75 mg dose. PROSTAP SR therapy should not be discontinued when remission or improvement occurs. As with
other drugs administered chronically 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 phosphatase. Clinical studies with 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 values by the 4th week of
treatment.
In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of
castrate-resistant prostate cancer. Reference should be made to relevant guidelines.
Endometriosis: The recommended dose is 3.75 mg 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 3.75 mg subcutaneous or intramuscular injection 5-6
weeks prior to surgery. Therapy should be initiated during days 3 to 5 of the menstrual cycle.
Preoperative management of uterine fibroids: The recommended dose is 3.75 mg administered as a single
subcutaneous or intramuscular injection every month, usually for 3-4 months but for a maximum of six months.
Elderly: As for adults.
Paediatric population:
The treatment of children with leuprorelin acetate should be under the overall supervision of the paediatric
endocrinologist.
The dosing scheme needs to be adapted individually.
The recommended starting dose is dependent on the body weight.
Children with a body weight ≥ 20 kg 1 ml (3.75 mg leuprorelin acetate) suspension of 44.1 mg sustained-release
microcapsules in 1 ml vehicle solution are administered once a month as a single subcutaneous injection.
Children with a body weight < 20 kg In these rare cases the following dosage should be administered according to the
clinical activity of the central precocious puberty:
0.5 ml (1.88 mg leuprorelin acetate) is administered once a month as a single subcutaneous injection.
The remainder of the suspension should be discarded. The child’s weight gain should be monitored.
Depending on the activity of the central precocious puberty, it may be necessary to increase the dosage in the
presence of inadequate suppression (clinical evidence e.g. spotting or inadequate gonadotropin suppression in the
LHRH test). The minimal effective monthly dose to be administered should then be determined by means of the
LHRH test.
Sterile abscesses at the injection site often occurred when leuprorelin acetate was administered intramuscularly at
higher than the recommended dosages. Therefore, in such cases, the medicinal product should be administered
subcutaneously (see 4.4).
It is recommended to use the lowest volumes possible for injections in children in order to decrease the
inconvenience which is associated with the intramuscular/subcutaneous injection.
The duration of treatment depends on the clinical parameters at the start of treatment or during the course of
treatment (final height prognosis, growth velocity, bone age and/or bone age acceleration) and is decided by the
treating paediatrician together with the legal guardian and, if appropriate, the treated child. The bone age should be
monitored during treatment at 6-12 month intervals.
In girls with bone maturation of older than 12 years and boys with bone maturation of older than 13 years
discontinuation of treatment should be considered taking into account the clinical parameters.
In girls, pregnancy should be excluded before the start of treatment. The occurrence of pregnancy during treatment
cannot be generally excluded. In such cases, medical advice should be sought.
Note:
The administration interval should be 30 ± 2 days in order to prevent the recurrence of precocious puberty symptoms.
Administration
INSTRUCTIONS ON HOW TO MIX AND ADMINISTER

4.4 Special warnings and 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.
Epidemiological data have shown that during androgen deprivation therapy changes in the metabolic condition (e.g.
reduction in glucose tolerance or aggravation of pre-existing diabetes) as well as an increased risk for cardiovascular
diseases may occur. However, prospective data did not confirm the link between treatment with GnRH analogues and
an increase in cardiovascular mortality. Patients at high risk for metabolic or cardiovascular diseases should be
appropriately monitored.
Hepatic dysfunction and jaundice with elevated liver enzyme have been reported. Therefore, close observation should
be made and appropriate measures taken if necessary.
Spinal fracture, paralysis and hypotension have been reported.
There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH
agonists, such as leuprorelin. Patients should be informed accordingly and treated as appropriate if symptoms occur.
Postmarketing reports of seizures have been observed in patients treated with leuprorelin acetate and these events
have been reported in both children and adults, and in those with or without a history of epilepsy, seizure disorders or
risk disorders for seizures.
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.
In the rare event of an abscess occurring at the injection site, testosterone level should be monitored as there may be
inadequate absorption of leuprorelin from the depot formulation.
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.
Long-term androgen deprivation either by bilateral orchiectomy or administration of GnRH analogues is associated
with increased risk of bone loss which, in patients with additional risk factors, may lead to osteoporosis and increased
risk of bone fracture.
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.
Androgen deprivation therapy may prolong the QT interval.
In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal
products that might prolong the QT interval (see section 4.5) physicians should assess the benefit risk ratio including
the potential for Torsade de pointes prior to initiating PROSTAP SR.
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.
In girls with central precocious puberty: Before starting the therapy, a precise diagnosis of idiopathic and/or
neurogenic central precocious puberty is necessary.
The therapy is a long-term treatment, adjusted individually. PROSTAP SR should be administered as precisely as
possible in regular monthly periods. An exceptional delay of the injection date for a few days (30 ± 2 days) does not
influence the results of the therapy.
In the event of a sterile abscess at the injection site (mostly reported after i.m. injection of higher than the
recommended dosage) the absorption of leuprorelin acetate from the depot can be decreased. In this case the
hormonal parameters (testosterone, oestradiol) should be monitored at 2-week intervals (see 4.2).
The treatment of children with progressive brain tumours should follow a careful individual appraisal of the risks and
benefits.
The occurrence of vaginal bleeding, spotting and discharge after the first injection may occur as a sign of hormone
withdrawal in girls.
Vaginal bleeding beyond the first/second month of treatment needs to be investigated.
Bone mineral density (BMD) may decrease during GnRH therapy for central precocious puberty. However, after
cessation of treatment subsequent bone mass accrual is preserved and peak bone mass in late adolescence does
not seem to be affected by treatment.
Slipped femoral epiphysis can be seen after withdrawal of GnRH treatment. The suggested theory is that the low
concentrations of estrogen during treatment with GnRH agonists weakens the epiphysial plate. The increase in
growth velocity after stopping the treatment subsequently results in a reduction of the shearing force needed for
displacement of the epiphysis.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of PROSTAP SR 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, dofetilide, ibutilide) antiarrhythmic
medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4).
4.6 Fertility, 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 breastfeeding.
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.
In girls with central precocious puberty: See section 4.3 Contraindications.
4.7 Effects on ability to drive and use machines
PROSTAP SR can influence the ability to drive and use machines due to visual disturbances and dizziness.

1. To prepare for
injection, screw the
plunger rod into the
end stopper until the
stopper begins to
turn.

2. Remember to check if
the needle is tight by
twisting the needle cap
clockwise. Do not
overtighten.

3. Holding the syringe upright, release the
diluents by SLOWLY PUSHING the
plunger until the middle stopper is at the
blue line in the middle of the barrel.
NOTE: Pushing the plunger rod quickly or
over the blue line will cause leakage of the
suspension from the needle.

4. Gently tap the syringe on the
palm keeping the syringe upright
to thoroughly mix the particles to
form a uniform suspension. The
suspension will appear milky.
NOTE: Avoid hard tapping to
prevent the generation of
bubbles.

5. Remove the
needle cap and
advance the
plunger to expel
the air from the
syringe.

4.8 Undesirable effects
Adverse reactions seen with PROSTAP SR are due mainly to the specific pharmacological action, namely increases
and decreases in certain hormone levels.
The following tables list adverse reactions with leuprorelin based on experience from clinical trials as well as from
post-marketing experience.
Adverse reactions are grouped by MedDRA System Organ Classes and frequency classification. Frequencies are
defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to
<1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
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.
Tabulated list of adverse reactions
SOC

4.3 Contraindications
Hypersensitivity to the active substance, any of the excipients listed in section 6.1 or to synthetic gonadotrophin
releasing homone (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 breastfeeding or have undiagnosed abnormal vaginal bleeding.
Men: There are no known contra-indications to the use of PROSTAP SR in men.
In girls with central precocious puberty:
- Pregnancy and lactation
- Undiagnosed vaginal bleeding.

Uncommon

Rare

Very rare

Not known
anaemia (reported in
medicinal products
of this class),
thrombocytopaenia,
leucopenia

Immune system
disorders

hypersensitivity
reactions
(including rash,
pruritus,
urticaria and rarely,
wheezing
or interstitial
pneumonitis,
anaphylactic
reactions)
Lipids abnormal,
glucose
tolerance abnormal

weight
fluctuation

decreased
appetite

Psychiatric
disorders

insomnia,
depression
(see Section
4.4),
mood changes
(long-term
use)**

mood
changes
(short term
use)**

Nervous system
disorders

headache
(occasionaly
severe)

dizziness,
parasthesiae

Withdraw the needle from the patient.

Note: The suspension settles out very quickly following reconstitution and
therefore the product should be mixed and used immediately.

Common

Blood and
lymphatic
system
disorders

Metabolism and
nutrition
disorders
6. At the time of injection, check the direction as illustrated, and inject the
entire contents of the syringe. Inject the entire contents of the syringe
subcutaneously or intramuscularly as you would for a normal injection.

Very
common

pituitary
apoplexy
has been
reported
following
initial
administration
in patients
with
pituitary
adenoma

paralysis (see
Section 4.4),
seizure

Eye disorders
Cardiac
disorders

Vascular
disorders

hot flush

Gastrointestinal
disorders
Hepatobiliary
disorders

Skin and
subcutaneous
tissue disorders
Musculoskeletal,
connective
tissue and bone
disorders

nausea

visual impairment
palpitations,
electrocardiogram
QT prolonged
(see Sections
4.4 and 4.5)
pulmonary
embolism,
hypertension,
hypotension
(see Section 4.4)

Gastrointestinal
disorders

abdominal pain /
abdominal
cramps,
nausea/vomiting

Skin and
subcutaneous
tissue disorders
Reproductive
system and
breast disorders

acne

jaundice

General disorders
and
administration
site conditions
** In general, the occurrence of vaginal spotting with continued treatment (subsequent to possible withdrawal bleeding
in the first month of treatment) should be assessed as a sign of potential underdosage. The pituitary suppression
should then be determined by an LHRH test.

diarrhoea,
vomiting

hepatic
function
abnormal, liver
function test
abnormal
(usually
transient)
hyperhydrosis

muscle
weakness,
bone pain

arthralgia

myalgia,
weakness
of lower
extremities

spinal fracture
(see Section
4.4), reduction in
bone mass
which may occur
with the use
of GnRH agonists
urinary tract
obstruction

Renal and
urinary
disorders
Reproductive
system and
breast disorders

Libido
gynaecomastia
decreased,
erectile
dysfunction,
testicular
atrophy
General
Fatigue,
oedema
pyrexia
disorders and
injection
peripheral
administration
site reaction,
site conditions
e.g.,
induration,
erythema,
pain,
abscesses,
swelling,
nodules,
ulcers and
necrosis
** mood changes (long term use: frequency of ‘common’ and short term use: frequency of ‘uncommon’)
Women: Those adverse events occurring most frequently with PROSTAP SR 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-estrogenic state results in a small loss in bone density over the course of treatment, some of which
may not be reversible (see Section 4.4).
Vaginal haemorrhage may occur during therapy due to acute degeneration of submucous fibroids (see Section 4.4).
Tabulated list of adverse reactions
SOC
Very
Common
Uncommon
Rare
Very rare
Not known
common
Blood and
Anaemia (reported
lymphatic
in medicinal
system
products of this
disorders
class),
thrombocytopaenia,
leucopenia
Immune system
disorders

Metabolism and
nutrition
disorders

weight
fluctuation

Psychiatric
disorders

insomnia

Nervous system
disorders

headache
(occasionally
severe)

Gastrointestinal
disorders
Hepatobiliary
disorders

Skin and
subcutaneous
tissue disorders
Musculoskeletal,
connective
tissue and bone
disorders

Reproductive
system and
breast disorders

General
disorders and
administration
site conditions

decreased
appetite,
lipids
abnormal

mood altered
depression
(see Section
4.4)
parasthesiae,
dizziness

Eye disorders
Cardiac
disorders
Vascular
disorders

hypersensitivity
reactions
(including rash,
pruritus,
urticaria and rarely,
wheezing
and interstitial
pneumonitis,
anaphylactic
reactions)
glucose
tolerance
abnormal, which
may affect diabetic
control

pituitary
haemorrhage
has been
reported
following
initial
administration
in patients
with
pituitary
adenoma

paralysis (see
Section 4.4),
seizure

pulmonary
embolism,
hypertension,
hypotension
(see Section 4.4)
nausea

arthralgia,
muscle
weakness

breast
tenderness,
breast
atrophy,
vulvovaginal
dryness
Oedema
peripheral,
injection site
reaction
e.g.injection
site
induration,
erythema,
pain,
abscesses,
swelling,
nodules,
ulcers and
necrosis

diarrhoea,
vomiting
liver function
test
abnormal
(usually
transient)
hair loss

Psychiatric
disorders
Nervous system
disorders

myalgia

spinal fracture (see
section
4.4), reduction in
bone mass
which may occur
with the use
of GnRH agonists
vaginal
haemorrhage

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 11.25 mg 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 (0.5 ng/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 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 (7.5mg/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
Neoadjuvant leuprorelin acetate prior to radiotherapy has been shown to reduce prostate volume.
In children:
Reversible suppression of pituitary gonadotropin release occurs, with a subsequent decrease in oestradiol (E2) or
testosterone levels to values in the pre-pubertal range.
Initial gonadal stimulation (flare-up) may cause vaginal bleeding in girls who are already post-menarchal at start of
treatment. Withdrawal bleeding may occur at the start of treatment. The bleeding normally stops as treatment
continues.
The following therapeutic effects can be demonstrated:
- Suppression of basal and stimulated gonadotropin levels to pre-pubertal levels.
- Suppression of prematurely increased sexual hormone levels to pre-pubertal levels and arrest of premature
menstruation;
- Arrest/involution of somatic pubertal development (Tanner stages);
- Improvement/normalisation of the ratio of chronological age to bone age;
- Prevention of progressive bone age acceleration;
- Decrease of growth velocity and its normalization;
- Increase in final height.
Treatment result is the suppression of the pathologically, prematurely activated hypothalamic-pituitary-gonadal axis
according to prepubertal age.
In a long-term clinical trial in children treated with leuprorelin at doses up to 15mg monthly for > 4 years resumption of
pubertal progression were observed after cessation of treatment. Follow up of 20 female subjects to adulthood
showed normal menstrual cycles in 80% and 12 pregnancies in 7 of the 20 subjects including multiple pregnancies for
4 subjects.

In children:
Figure 1 presents leuprorelin serum levels after a single s.c. administration of leuprorelin acetate depot at a dosage of
30 μg/kg body weight.
Peak serum levels are reached sixty minutes after administration (7.81 ± 3.59 ng/m)l. The AUC 0-672 is 105.78 ± 52.40
ng x hr/ml.

Figure 1: Leuprorelin serum levels after single s.c. administration of 30 μg/kg body weight of leuprorelin acetate as
depot formulation (n=6) (Mean ± SD)
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
The other ingredients are:
Powder- gelatin, copoly (DL lactic acid/glycolic acid) 72:25 mol%, mannitol
Sterile solvent- carboxymethylcellulose sodium, mannitol, polysorbate 80, glacial acetic acid (for ph adjustment),
water for injections.

pyrexia,
fatigue

6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years unopened.
Once reconstituted with sterile solvent, the suspension should be administered immediately.

Uncommon

Rare

Very rare

Not known

Hypersensitivity
(fever, rash, e.g.
itching,
anaphylactic
reactions)

pituitary
haemorrhage
following
initial
administration
in patients with
pituitary
adenoma

6.4 Special precautions for storage
Do not store above 25o C.
Do not refrigerate or freeze.
Store in the original container in order to protect from light.
6.5 Nature and contents of container
The product is a dual chamber glass cartridge with orange base assembled as a single unit in a disposable delivery
device. The cartridge contains a sterile, lyophilised, white powder in the transparent front chamber and a clear,
odourless, slightly viscous, sterile solvent in the rear chamber.
The pack also contains a 1 x syringe needle, 1 x syringe plunger and alcohol swab.
6.6 Special precautions for disposal and other handling
Any unused product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
Procured from within EU by Product Licence holder: Star Pharmaceuticals Ltd., 5 Sandridge Close, Harrow,
Middlesex, HA1 1XD. Repackaged by Servipharm Ltd.

emotional lability
headache

4.9 Overdose
No case of overdose has been reported.
In animal studies, doses of 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.

hepatic function
abnormal, jaundice

In Children: In the initial phase of therapy, a short-term increase as flare-up of the sex hormone level occurs,
followed by a decrease to values within the pre-pubertal range. Due to this pharmacological effect, adverse events
may occur particularly at the beginning of treatment.
Tabulated list of adverse reactions
SOC
Very
Common
common
Immune system
disorders

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued
monitoring of the benefit/risk balance of the medicinal product. Healthcare professional s are asked to report any
suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

5.2 Pharmacokinetic properties
Studies submitted show that single intramuscular or subcutaneous doses of leuprorelin acetate over the dose range
3.75 to 15 mg 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 0.5 ng/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.

visual
impairment
palpitations
hot flush

vaginal
haemorrhage,
spotting**,
vaginal
discharge
injection
site reactions

seizure

8. MARKETING AUTHORISATION NUMBER(S): PL 20636/2582
Leaflet revision and issue date (Ref): 23.08.16[H-9]

®

2582
23.08.16[9]

LUCRIN SR DCS 3.75 mg Powder and
Solvent for Prolonged-release
Suspension for Injection in Pre-filled
Syringe
(leuprorelin acetate)
PATIENT INFORMATION LEAFLET
Read all of this leaflet carefully before you start using this medicine
because it contains important information for you.
- 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 signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed in this leaflet. See section 4.
Your medicine will be referred to as LUCRIN SR throughout the following
leaflet.
In this leaflet:
1. What LUCRIN SR is and what it is used for
2. What you need to know before you use LUCRIN SR
3. How to take LUCRIN SR
4. Possible side effects
5. How to store LUCRIN SR
6. Contents of the pack and other information
1. WHAT LUCRIN SR IS AND WHAT IT IS USED FOR
LUCRIN SR is a synthetic hormone which can be used to reduce the levels
of testosterone and estrogen circulating in the body.
LUCRIN 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.
Use in children:
LUCRIN SR is a synthetic hormone which can be used to reduce the levels
of testosterone and estrogen circulating in the body. Leuprorelin 1 Month
Depot is used to treat premature puberty which is caused by a release of
certain hormones from the pituitary gland (central precocious puberty) in
girls under 9 years of age and boys under 10 years of age.
2. WHAT YOU NEED TO KNOW BEFORE YOU USE LUCRIN SR
Use in children: Your doctor will make a precise diagnosis of central
precocious puberty.
Do not take LUCRIN SR:
- If you are allergic (hypersensitive) to leuprorelin acetate (LUCRIN SR or
LUCRIN 3) or any of the other ingredients of LUCRIN SR (listed in section
6).
- 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.
- In girls with central precocious puberty
- if the girl to be treated is pregnant or breast-feeding.
- if the girl has undiagnosed vaginal bleeding.
Warnings and precautions:
Both men and women:
- If you are diabetic LUCRIN SR can aggravate existing diabetes therefore
diabetes patients may need more frequent monitoring of the blood glucose
levels.
- If you have diabetes or suffer from heart problems you should tell your
doctor.
- If you are at an increased risk of thinning of the bones (osteoporosis) you
should tell your doctor before taking LUCRIN SR. Risk factors include:
- If you or any of your close family have thinning of the bones.
- If you drink excessive amounts of alcohol, and/or smoke heavily.
- 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 LUCRIN SR
which may be severe. If you are taking LUCRIN SR and develop
depressed mood, inform your doctor.
Women only:
- If you are a woman with submucous fibroids (benign tumours in the
muscle underneath the lining of the womb), LUCRIN SR can cause severe
bleeding when the fibroids break-down. 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 LUCRIN SR you should tell your doctor.
- If you are a woman of child-bearing age, you should use non hormonal
contraception whilst receiving LUCRIN SR. Although LUCRIN SR causes
periods to stop, it is not itself a contraceptive. If you are unsure about this
talk to your doctor.
Men only:
- In the rare event of an abscess occurring at the injection site your doctor
may measure your testosterone levels as there could be reduced
absorption of leuprorelin from the injection site.
- 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 you should tell your doctor.
- Please tell your doctor if you have any of the following: Any heart or blood
vessel conditions, including heart rhythm problems (arrhythmia), or are
being treated with medicines for these conditions. The risk of heart rhythm
problems may be increased when using LUCRIN SR.
In children:
- In the event of a sterile abscess at the injection site (mostly reported after
injection into the muscle) your doctor will monitor your hormone levels as
there could be reduced absorption of leuprorelin from the injection site.
- If the child has progressive brain tumour your doctor will decide if
treatment with leuprorelin is appropriate.
In girls with central precocious puberty:
- After the first injection vaginal bleeding (spotting) and discharge may
occur as a sign of hormone withdrawal. Vaginal bleeding beyond the
first/second month of treatment needs to be investigated.
- Bone density may decrease during treatment of central precocious
puberty with Leuprorelin 1 Month Depot. However, after treatment is
stopped, subsequent bone mass growth is preserved and peak bone
mass in late adolescence does not seem to be affected by treatment.
- Often sterile abscesses at the injection site occurred when Leuprorelin 1
Month Depot is administered in higher dosages than recommended and
when it is administered into the muscle. Your doctor will therefore
administer the medicinal product under the skin of e.g. abdomen, bottom
or thigh.

- Discontinuation of treatment may lead to a slipping of the growth plate of
the thigh bone. A possible cause could be a weakness of the growth plate
due to a lower concentration of female sexual hormones during treatment.
Other medicines and LUCRIN SR
Please tell your doctor or pharmacist if you are taking or have recently taken
any other medicines, including medicines obtained without a prescription.
LUCRIN SR might interfere with some medicines used to treat heart rhythm
problems (e.g. quinidine, procainamide, amiodarone and sotalol) or might
increase the risk of heart rhythm problems when used with some other
drugs (e.g. methadone (used for pain relief and part of drug addiction
detoxification), moxifloxacin (an antibiotic), antipsychotics used for serious
mental illnesses).
LUCRIN SR with food and drink
LUCRIN SR can be taken with or without food.
Pregnancy and breastfeeding
LUCRIN SR must not be administered in pregnant or breast-feeding women
or girls (see also section “Do not use LUCRIN SR).
Driving and using machines
Do not drive or operate machinery if you experience drowsiness, dizziness
or visual disturbances whilst being treated with LUCRIN SR.
3. HOW TO TAKE LUCRIN SR
The doctor or nurse will give you an injection of LUCRIN SR. 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 a month. If you are to be given
LUCRIN SR prior to intrauterine surgery you will receive a single injection 56 weeks before your surgery.
If you have endometriosis you will be given an injection of LUCRIN 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 LUCRIN SR
once a month usually for 3-4 months before surgery.
Use in children
Treatment of children should be under the overall supervision of the
paediatric endocrinologist.
The dosing scheme needs to be adapted individually.
The recommended starting dose is dependent on the body weight:
a) Children with a body weight 20 kg or more
Unless prescribed otherwise, 1 ml LUCRIN SR (3.75 mg leuprorelin acetate)
is administered once a month under the skin of e.g. abdomen, bottom or
thigh as a single injection.
b) Children with a body weight less than 20 kg
Taking into account the clinical activity of the central precocious puberty in
these rare cases, the following applies:
Unless prescribed otherwise, 0.5 ml LUCRIN SR (1.88 mg leuprorelin
acetate) are administered once a month under the skin of e.g. abdomen,
bottom or thigh as a single injection. The remainder of the suspension
should be discarded. Your doctor will monitor the child’s weight gain.
Depending on the central precocious puberty activity, your doctor may
increase the dosage in the presence of inadequate suppression (e.g.
vaginal bleeding). Your doctor will determine the minimal effective dose with
the help of a blood test.
The duration of treatment depends on the clinical signs at the start of
treatment or during the course of treatment and is decided by your doctor
together with the legal guardian and, if appropriate, the treated child. Your
doctor will determine the bone age of the child in regular intervals.
In girls with bone maturation of older than 12 years and boys with bone
maturation of older than 13 years your doctor will consider discontinuing the
treatment, depending on the clinical effects in your child.
In girls, pregnancy should be excluded before the start of treatment. The
occurrence of pregnancy during treatment cannot be generally excluded. In
such cases, please talk to your doctor.
The therapy is a long-term treatment, adjusted individually. Please arrange
with your doctor that LUCRIN SR is administered as precisely as possible in
regular monthly periods. An exceptional delay of the injection date for a few
days (30 ± 2 days) does not influence the result of the therapy.
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 LUCRIN 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 LUCRIN SR and contact your doctor immediately.
4. POSSIBLE SIDE EFFECTS
Like all medicines, LUCRIN 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 LUCRIN SR. 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:
Men:
- When men with prostate cancer first start treatment with LUCRIN 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 LUCRIN
SR injection. If you do get worsening pain, weakness or loss of feeling in
your legs or difficulty passing urine, contact your doctor immediately.
- 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. This is
very rare (may affect more than 1 in 10,000 people).
- Blood sugar levels may be altered during treatment with LUCRIN SR,
which may affect control in diabetic patients and require more frequent
monitoring.
- 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.

Very common (may affect more than 1 in 10 people)
Weight changes, hot flushes, sweating, muscle weakness, bone pain, loss
of interest in sexual intercourse, inability to have an erection, a reduction in
size and function of the testes, tiredness or skin reactions at the injection
site (these include skin hardening, redness, pain, abscesses, swelling,
nodules, ulcers and skin damage).

6. CONTENTS OF THE PACK AND OTHER INFORMATION
What LUCRIN SR contains:
The active ingredient in LUCRIN SR Powder is leuprorelin acetate (3.75 mg)

Common (may affect up to 1 in 10 people)
Loss of appetite, difficulty sleeping, depression, mood changes (with longterm use), headache, nausea, abnormalities in liver function or liver blood
tests, joint pain, swelling of the breast tissue or swelling in your ankles.

Sterile solvent- carboxymethylcellulose sodium, mannitol, polysorbate 80,
glacial acetic acid (for pH adjustment), water for injections.

Uncommon (may affect more than 1 in 100 people)
Mood changes (with short-term use), dizziness, tingling in the hands or feet,
diarrhoea, vomiting, muscle ache or weakness in the legs.
Not known (frequency cannot be estimated from the available data)
Blood tests may show anaemia (low red cell counts), low counts in white
cells or platelets, allergic reactions (may include symptoms of rash, itching,
wheals or a serious allergic reaction which causes difficulty breathing or
dizziness), changes in blood lipids (cholesterol) or blood sugar, paralysis,
seizure, altered vision, pounding heartbeats, changes in ECG (QT
prolongation), blood clots in lungs, high or low blood pressure, jaundice,
fracture of the spine, thinning of bone, difficulty passing urine, fever or chills.
Women:
- Many of the side effects of LUCRIN SR are related to the decrease in
oestrogen level. Oestrogen level returns to normal after treatment is
stopped. Common side effects include hot flushes, mood swings,
depression and vaginal dryness. As can happen naturally when women
reach the menopause, LUCRIN SR can cause a small amount of bone
thinning. Vaginal bleeding may occur during treatment.
- 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. This is
very rare (may affect more than 1 in 10,000 people).
- Blood sugar levels may be altered during treatment with LUCRIN SR,
which may affect control in diabetic patients and require more frequent
monitoring.
- 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.
Very common (may affect more than 1 in 10 people)
Difficulty sleeping, headaches or hot flushes
Common (may affect up to 1 in 10 people)
Weight changes, mood changes, depression, tingling in hands or feet,
dizziness, nausea, joint pain, muscle weakness, breast tenderness,
changes in breast size, vaginal dryness, swelling in ankles or skin reactions
at the injection site (these include skin hardening, redness, pain, abscesses,
swelling, nodules, ulcers and skin damage)
Uncommon (may affect more than 1 in 100 people)
Loss of appetite, changes in blood lipids (cholesterol), altered vision,
pounding heartbeats, diarrhoea, vomiting, abnormalities in liver blood tests,
hair loss, muscle aches, fever, chills or tiredness
Not known (frequency cannot be estimated from the available data)
Blood tests may show anaemia (low red cell counts), low counts in white
cells or platelets, allergic reactions (may include symptoms of rash, itching,
wheals or a serious allergic reaction causing difficulty breathing or
dizziness), changes in blood sugar, paralysis, blood clots in the lungs, high
or low blood pressure, jaundice, abnormalities in liver function, fracture of
the spine, seizure, thinning of bone or vaginal bleeding.
Children
In the initial phase of treatment, a short-term rise in the sex hormone levels
occurs, followed by a fall to values within the prepuberty range. Due to this
effect, side effects may occur particularly at the start of treatment.
Common (may affect up to 1 in 10 people):
- mood swings
- headache
- abdominal pain / abdominal cramps
- feeling sick / vomiting
- acne
- vaginal bleeding
- spotting
- discharge
- injection site reactions
Very rare (may affect less than 1 in 10,000 people):
- general allergic reactions (fever, rash, itching)
- serious allergic reaction which causes difficulty in breathing or dizziness
- As with other medicinal products of this class: 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.
Not known (frequency cannot be estimated from the available data)
- Seizure
Notes:
In general, if vaginal bleeding (spotting) occurs with continued treatment
(after possible withdrawal bleeding in the first month of treatment), this may
be a sign of potential underdosage. Please tell your doctor if vaginal
bleeding occurs.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed in this leaflet. You can also report side
effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.
By reporting side effects you can help provide more information on the
safety of this medicine.
5. HOW TO STORE LUCRIN SR
Keep out of the sight and reach of children
o
Do not store above 25 C.
Do not refrigerate or freeze.
Store in the original container in order to protect from light.
Do not use this medicine after the date stated on the packaging.
Once mixed with the Sterile Solvent, the suspension must be used
immediately.
If the pack has been opened or damaged, return it to your pharmacist.
If the medicines become discoloured or show any other signs of
deterioration, consult your pharmacist who will tell you what to do.
Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. These
measures will help to protect the environment.

The other ingredients are:
Powder- gelatin, copoly (DL lactic acid/glycolic acid) 72:25 mol%, mannitol

What LUCRIN SR looks like and contents of the pack:
The product is a dual chamber glass cartridge with orange base assembled
as a single unit in a disposable delivery device. The cartridge contains a
sterile, lyophilised, white powder in the transparent front chamber and a
clear, odourless, slightly viscous, sterile solvent in the rear chamber.
The pack also contains a 1 x syringe needle, 1 x syringe plunger and
alcohol swab.
MANUFACTURER AND PRODUCT LICENCE HOLDER
Manufactured by
Abbott Laboratoires S.A., Apartado De Correos, 967, Avenida De Burgos,
91, Madrid, E-28050, Spain.
AbbVie Logistics BV, Meeuwenlaan 4, Zwolle, NL-8011 BZ, The
Netherlands.
Procured from within EU by Product Licence holder: Star Pharmaceuticals
Ltd., 5 Sandridge Close, Harrow, Middlesex, HA1 1XD. Repackaged by
Servipharm Ltd.
POM

PL 20636/2582

Leaflet revision and issue date (Ref): 23.08.16[9]
LUCRIN is a trademark of AbbVie AG.

2582
23.08.16[H-9]

HEALTH PROFESSIONALS’ USER LEAFLET

LUCRIN® SR DCS 3.75 mg Powder and Solvent for Prolonged-release Suspension for Injection in Pre-filled
Syringe
(leuprorelin acetate)
1. NAME OF THE MEDICINAL PRODUCT
LUCRIN SR DCS 3.75 mg Powder and Solvent for Suspension for Injection
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
LUCRIN SR Powder: contains 3.75 mg leuprorelin acetate (equivalent to 3.57 mg base).
Sterile Solvent- carboxymethylcellulose sodium, mannitol, polysorbate 80, glacial acetic acid (for pH adjustment),
water for injections.
When reconstituted with Sterile Solvent, the suspension contains 3.75 mg/ml leuprorelin acetate.
For the full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Powder and solvent for suspension for injection in pre-filled syringe
Powder: A sterile, lyophilised, white powder.
Solvent: A clear, odourless, slightly viscous, sterile solvent.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
(i)
Metastatic prostate cancer.
(ii) Locally advanced prostate cancer, as an alternative to surgical castration.
(iii) As an adjuvant treatment to radiotherapy in patients with high-risk localised or locally advanced prostate
cancer.
(iv) As an adjuvant treatment to radical prostatectomy in patients with locally advanced prostate cancer at high
risk of disease progression.
(v) As neo-adjuvant treatment prior to radiotherapy in patients with high-risk localised or locally advanced
prostate cancer.
(vi) Management of endometriosis, including pain relief and reduction of endometriotic lesions.
(vii) Endometrial preparation prior to intrauterine surgical procedures including endometrial ablation or resection.
(viii) Preoperative management of uterine fibroids to reduce their size and associated bleeding.
In children:
Treatment of central precocious puberty (girls under 9 years of age, boys under 10 years of age).
(See Section 5.1)
4.2 Posology and method of administration
Posology
Prostate Cancer: The usual recommended dose is 3.75 mg presented as a one month depot injection and
administered as a single subcutaneous or intramuscular injection every month. The majority of patients will respond to
a 3.75 mg dose. LUCRIN SR therapy should not be discontinued when remission or improvement occurs. As with
other drugs administered chronically by injection, the injection site should be varied periodically.
Response to LUCRIN SR therapy may be monitored by clinical parameters and by measuring serum levels of
testosterone and acid phosphatase. Clinical studies with 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 values
by the 4th week of treatment.
In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of
castrate-resistant prostate cancer. Reference should be made to relevant guidelines.
Endometriosis: The recommended dose is 3.75 mg 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 LUCRIN SR taking into account the risks and benefits of
each treatment.
Endometrial preparation prior to intrauterine surgery: A single 3.75 mg subcutaneous or intramuscular injection 5-6
weeks prior to surgery. Therapy should be initiated during days 3 to 5 of the menstrual cycle.
Preoperative management of uterine fibroids: The recommended dose is 3.75 mg administered as a single
subcutaneous or intramuscular injection every month, usually for 3-4 months but for a maximum of six months.
Elderly: As for adults.
Paediatric population:
The treatment of children with leuprorelin acetate should be under the overall supervision of the paediatric
endocrinologist.
The dosing scheme needs to be adapted individually.
The recommended starting dose is dependent on the body weight.
Children with a body weight ≥ 20 kg 1 ml (3.75 mg leuprorelin acetate) suspension of 44.1 mg sustained-release
microcapsules in 1 ml vehicle solution are administered once a month as a single subcutaneous injection.
Children with a body weight < 20 kg In these rare cases the following dosage should be administered according to the
clinical activity of the central precocious puberty:
0.5 ml (1.88 mg leuprorelin acetate) is administered once a month as a single subcutaneous injection.
The remainder of the suspension should be discarded. The child’s weight gain should be monitored.
Depending on the activity of the central precocious puberty, it may be necessary to increase the dosage in the
presence of inadequate suppression (clinical evidence e.g. spotting or inadequate gonadotropin suppression in the
LHRH test). The minimal effective monthly dose to be administered should then be determined by means of the LHRH
test.
Sterile abscesses at the injection site often occurred when leuprorelin acetate was administ ered intramuscularly at
higher than the recommended dosages. Therefore, in such cases, the medicinal product should be administered
subcutaneously (see 4.4).
It is recommended to use the lowest volumes possible for injections in children in order to decrease the inconvenience
which is associated with the intramuscular/subcutaneous injection.
The duration of treatment depends on the clinical parameters at the start of treatment or during the course of treatment
(final height prognosis, growth velocity, bone age and/or bone age acceleration) and is decided by the treating
paediatrician together with the legal guardian and, if appropriate, the treated child. The bone age should be monitored
during treatment at 6-12 month intervals.
In girls with bone maturation of older than 12 years and boys with bone maturation of older than 13 years
discontinuation of treatment should be considered taking into account the clinical parameters.
In girls, pregnancy should be excluded before the start of treatment. The occurrence of pregnancy during treatment
cannot be generally excluded. In such cases, medical advice should be sought.
Note:
The administration interval should be 30 ± 2 days in order to prevent the recurrence of precocious puberty symptoms.
Administration
INSTRUCTIONS ON HOW TO MIX AND ADMINISTER

4.4 Special warnings and 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 LUCRIN SR.
Epidemiological data have shown that during androgen deprivation therapy changes in the metabolic condition (e.g.
reduction in glucose tolerance or aggravation of pre-existing diabetes) as well as an increased risk for cardiovascular
diseases may occur. However, prospective data did not confirm the link between treatment with GnRH analogues and
an increase in cardiovascular mortality. Patients at high risk for metabolic or cardiovascular diseases should be
appropriately monitored.
Hepatic dysfunction and jaundice with elevated liver enzyme have been reported. Therefore, close observation should
be made and appropriate measures taken if necessary.
Spinal fracture, paralysis and hypotension have been reported.
There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH
agonists, such as leuprorelin. Patients should be informed accordingly and treated as appropriate if symptoms occur.
Postmarketing reports of seizures have been observed in patients treated with leuprorelin acetate and these events
have been reported in both children and adults, and in those with or without a history of epilepsy, seizure disorders or
risk disorders for seizures.
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.
In the rare event of an abscess occurring at the injection site, testosterone level should be monitored as there may be
inadequate absorption of leuprorelin from the depot formulation.
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.
Long-term androgen deprivation either by bilateral orchiectomy or administration of GnRH analogues is associated
with increased risk of bone loss which, in patients with additional risk factors, may lead to osteoporosis and increased
risk of bone fracture.
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.
Androgen deprivation therapy may prolong the QT interval.
In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products
that might prolong the QT interval (see section 4.5) physicians should assess the benefit risk ratio including the
potential for Torsade de pointes prior to initiating LUCRIN SR.
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 LUCRIN 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 LUCRIN SR is 5%. In clinical studies with LUCRIN 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, LUCRIN SR therapy may pose an additional risk. In these patients,
the risks and benefits must be weighed carefully before therapy with LUCRIN 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 LUCRIN 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, LUCRIN SR therapy should not be started.
In women with submucous fibroids there have been reports of severe bleeding following the administration of LUCRIN
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.
LUCRIN 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 LUCRIN SR therapy
under close supervision for the first few weeks of treatment.
Women: Since menstruation should stop with effective doses of LUCRIN SR, the patient should notify her physician if
regular menstruation persists.
In girls with central precocious puberty: Before starting the therapy, a precise diagnosis of idiopathic and/or neurogenic
central precocious puberty is necessary.
The therapy is a long-term treatment, adjusted individually. LUCRIN SR should be administered as precisely as
possible in regular monthly periods. An exceptional delay of the injection date for a few days (30 ± 2 days) does not
influence the results of the therapy.
In the event of a sterile abscess at the injection site (mostly reported after i.m. injection of higher than the
recommended dosage) the absorption of leuprorelin acetate from the depot can be decreased. In this case the
hormonal parameters (testosterone, oestradiol) should be monitored at 2-week intervals (see 4.2).
The treatment of children with progressive brain tumours should follow a careful individual appraisal of the risks and
benefits.
The occurrence of vaginal bleeding, spotting and discharge after the first injection may occur as a sign of hormone
withdrawal in girls.
Vaginal bleeding beyond the first/second month of treatment needs to be investigated.
Bone mineral density (BMD) may decrease during GnRH therapy for central precocious puberty. However, after
cessation of treatment subsequent bone mass accrual is preserved and peak bone mass in late adolescence does not
seem to be affected by treatment.
Slipped femoral epiphysis can be seen after withdrawal of GnRH treatment. The suggested theory is that the low
concentrations of estrogen during treatment with GnRH agonists weakens the epiphysial plate. The increase in growth
velocity after stopping the treatment subsequently results in a reduction of the shearing force needed for displacement
of the epiphysis.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of LUCRIN SR 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, dofetilide, ibutilide) antiarrhythmic medicinal
products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4).
4.6 Fertility, 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 LUCRIN SR,
pregnancy must be excluded. There have been reports of foetal malformation when LUCRIN SR has been given
during pregnancy.
LUCRIN SR should not be used in women who are breastfeeding.
When used monthly at the recommended dose, LUCRIN SR usually inhibits ovulation and stops menstruation.
Contraception is not ensured, however, by taking LUCRIN SR and therefore patients should use non-hormonal
methods of contraception during treatment.
Patients should be advised that if they miss successive doses of LUCRIN 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.
In girls with central precocious puberty: See section 4.3 Contraindications.
4.7 Effects on ability to drive and use machines
LUCRIN SR can influence the ability to drive and use machines due to visual disturbances and dizziness.

1. To prepare for
injection, screw the
plunger rod into the
end stopper until the
stopper begins to
turn.

2. Remember to check if
the needle is tight by
twisting the needle cap
clockwise. Do not
overtighten.

3. Holding the syringe upright, release the
diluents by SLOWLY PUSHING the
plunger until the middle stopper is at the
blue line in the middle of the barrel.
NOTE: Pushing the plunger rod quickly or
over the blue line will cause leakage of the
suspension from the needle.

4. Gently tap the syringe on the
palm keeping the syringe upright
to thoroughly mix the particles to
form a uniform suspension. The
suspension will appear milky.
NOTE: Avoid hard tapping to
prevent the generation of
bubbles.

5. Remove the
needle cap and
advance the
plunger to expel
the air from the
syringe.

4.8 Undesirable effects
Adverse reactions seen with LUCRIN SR are due mainly to the specific pharmacological action, nam ely increases and
decreases in certain hormone levels.
The following tables list adverse reactions with leuprorelin based on experience from clinical trials as well as from post marketing experience.
Adverse reactions are grouped by MedDRA System Organ Classes and frequency classification. Frequencies are
defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to
<1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Men: In cases where a “tumour flare” occurs after LUCRIN 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.
Tabulated list of adverse reactions
SOC

Very
common

Common

Uncommon

Rare

Very rare

Blood and
lymphatic
system
disorders

anaemia (reported in
medicinal products
of this
class),
thrombocytopaenia,
leucopenia
hypersensitivity
reactions
(including rash,
pruritus,
urticaria and rarely,
wheezing
or interstitial
pneumonitis,
anaphylactic
reactions)
Lipids abnormal,
glucose
tolerance abnormal

Immune system
disorders

6. At the time of injection, check the direction as illustrated, and inject the
entire contents of the syringe. Inject the entire contents of the syringe
subcutaneously or intramuscularly as you would for a normal injection.
Withdraw the needle from the patient.
Note: The suspension settles out very quickly following reconstitution
and therefore the product should be mixed and used immediately.

4.3 Contraindications
Hypersensitivity to the active substance, any of the excipients listed in section 6.1 or to synthetic gonadotrophin
releasing homone (Gn-RH) or Gn-RH derivatives.
Women: LUCRIN SR is contra-indicated in women who are or may become pregnant while receiving the drug.
LUCRIN SR 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 LUCRIN SR in men.
In girls with central precocious puberty:
- Pregnancy and lactation
- Undiagnosed vaginal bleeding.

Metabolism and
nutrition
disorders

weight
fluctuation

Not known

decreased
appetite

Psychiatric
disorders

insomnia,
depression
(see Section
4.4),
mood changes
(long-term
use)**

mood
changes
(short term
use)**

Nervous system
disorders

headache
(occasionaly
severe)

dizziness,
parasthesiae

pituitary
apoplexy
has been
reported
following
initial
administration
in patients
with
pituitary
adenoma

paralysis (see
Section 4.4),
seizure

Eye disorders
Cardiac
disorders

Vascular
disorders

hot flush

Gastrointestinal
disorders
Hepatobiliary
disorders

Skin and
subcutaneous
tissue disorders
Musculoskeletal,
connective
tissue and bone
disorders

nausea

visual impairment
palpitations,
electrocardiogram
QT prolonged
(see Sections
4.4 and 4.5)
pulmonary
embolism,
hypertension,
hypotension
(see Section 4.4)

Gastrointestinal
disorders

abdominal pain /
abdominal
cramps,
nausea/vomiting

Skin and
subcutaneous
tissue disorders
Reproductive
system and
breast disorders

acne

jaundice

General disorders
and
administration
site conditions
** In general, the occurrence of vaginal spotting with continued treatment (subsequent to possible withdrawal bleeding
in the first month of treatment) should be assessed as a sign of potential underdosage. The pituitary suppression
should then be determined by an LHRH test.

diarrhoea,
vomiting

hepatic
function
abnormal, liver
function test
abnormal
(usually
transient)
hyperhydrosis

muscle
weakness,
bone pain

arthralgia

myalgia,
weakness
of lower
extremities

spinal fracture
(see Section
4.4), reduction in
bone mass
which may occur
with the use
of GnRH agonists
urinary tract
obstruction

Renal and
urinary disorders
Reproductive
system and
breast disorders

Libido
gynaecomastia
decreased,
erectile
dysfunction,
testicular
atrophy
General
Fatigue,
oedema
pyrexia
disorders and
injection
peripheral
administration
site reaction,
site conditions
e.g.,
induration,
erythema,
pain,
abscesses,
swelling,
nodules,
ulcers and
necrosis
** mood changes (long term use: frequency of ‘common’ and short term use: frequency of ‘uncommon’)
Women: Those adverse events occurring most frequently with LUCRIN SR 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-estrogenic state results in a small loss in bone density over the course of treatment, some of which
may not be reversible (see Section 4.4).
Vaginal haemorrhage may occur during therapy due to acute degeneration of submucous fibroids (see Section 4.4).
Tabulated list of adverse reactions
SOC

Very
common

Common

Uncommon

Rare

Very rare

Not known

Blood and
lymphatic
system
disorders

Anaemia (reported
in medicinal
products of this
class),
thrombocytopaenia,
leucopenia

Immune system
disorders

hypersensitivity
reactions
(including rash,
pruritus,
urticaria and rarely,
wheezing
and interstitial
pneumonitis,
anaphylactic
reactions)
glucose
tolerance
abnormal, which
may affect diabetic
control

Metabolism and
nutrition
disorders

weight
fluctuation

Psychiatric
disorders

insomnia

Nervous system
disorders

headache
(occasionally
severe)

Gastrointestinal
disorders
Hepatobiliary
disorders

Skin and
subcutaneous
tissue disorders
Musculoskeletal,
connective
tissue and bone
disorders

Reproductive
system and
breast disorders

General
disorders and
administration
site conditions

decreased
appetite,
lipids
abnormal

mood altered
depression
(see Section
4.4)
parasthesiae,
dizziness

Eye disorders
Cardiac
disorders
Vascular
disorders

pituitary
haemorrhage
has been
reported
following
initial
administration
in patients
with
pituitary
adenoma

paralysis (see
Section 4.4),
seizure

visual
impairment
palpitations
hot flush

pulmonary
embolism,
hypertension,
hypotension
(see Section 4.4)
nausea

arthralgia,
muscle
weakness

breast
tenderness,
breast
atrophy,
vulvovaginal
dryness
Oedema
peripheral,
injection site
reaction
e.g.injection
site
induration,
erythema,
pain,
abscesses,
swelling,
nodules,
ulcers and
necrosis

diarrhoea,
vomiting
liver function
test
abnormal
(usually
transient)
hair loss

Tabulated list of adverse reactions
SOC
Very
Common
common
Immune system
disorders

4.9 Overdose
No case of overdose has been reported.
In animal studies, doses of 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
LUCRIN 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 11.25 mg 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 (0.5 ng/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 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 (7.5mg/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
Neoadjuvant leuprorelin acetate prior to radiotherapy has been shown to reduce prostate volume.
In children:
Reversible suppression of pituitary gonadotropin release occurs, with a subsequent decrease in oestradiol (E2) or
testosterone levels to values in the pre-pubertal range.
Initial gonadal stimulation (flare-up) may cause vaginal bleeding in girls who are already post-menarchal at start of
treatment. Withdrawal bleeding may occur at the start of treatment. The bleeding normally stops as treatment
continues.
The following therapeutic effects can be demonstrated:
- Suppression of basal and stimulated gonadotropin levels to pre-pubertal levels.
- Suppression of prematurely increased sexual hormone levels to pre-pubertal levels and arrest of premature
menstruation;
- Arrest/involution of somatic pubertal development (Tanner stages);
- Improvement/normalisation of the ratio of chronological age to bone age;
- Prevention of progressive bone age acceleration;
- Decrease of growth velocity and its normalization;
- Increase in final height.
Treatment result is the suppression of the pathologically, prematurely activated hypothalamic-pituitary-gonadal axis
according to prepubertal age.
In a long-term clinical trial in children treated with leuprorelin at doses up to 15mg monthly for > 4 years resumption of
pubertal progression were observed after cessation of treatment. Follow up of 20 female subjects to adulthood showed
normal menstrual cycles in 80% and 12 pregnancies in 7 of the 20 subjects including multiple pregnancies for 4
subjects.

In children:
Figure 1 presents leuprorelin serum levels after a single s.c. administration of leuprorelin acetate depot at a dosage of
30 μg/kg body weight.
Peak serum levels are reached sixty minutes after administration (7.81 ± 3.59 ng/m)l. The AUC 0-672 is 105.78 ± 52.40
ng x hr/ml.

hepatic function
abnormal, jaundice

myalgia

spinal fracture (see
section
4.4), reduction in
bone mass
which may occur
with the use
of GnRH agonists
vaginal
haemorrhage

Figure 1: Leuprorelin serum levels after single s.c. administration of 30 μg/kg body weight of leuprorelin acetate as
depot formulation (n=6) (Mean ± SD)
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
The other ingredients are:
Powder- gelatin, copoly (DL lactic acid/glycolic acid) 72:25 mol%, mannitol
Sterile solvent- carboxymethylcellulose sodium, mannitol, polysorbate 80, glacial acetic acid (for ph adjustment), water
for injections.

pyrexia,
fatigue

6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years unopened.
Once reconstituted with sterile solvent, the suspension should be administered immediately.
6.4 Special precautions for storage
Do not store above 25o C.
Do not refrigerate or freeze.
Store in the original container in order to protect from light.

Uncommon

Rare

Very rare

Not known

pituitary
haemorrhage
following
initial
administration
in patients with
pituitary
adenoma

6.5 Nature and contents of container
The product is a dual chamber glass cartridge with orange base assembled as a single unit in a disposable delivery
device. The cartridge contains a sterile, lyophilised, white powder in the transparent front chamber and a clear,
odourless, slightly viscous, sterile solvent in the rear chamber.
The pack also contains a 1 x syringe needle, 1 x syringe plunger and alcohol swab.
6.6 Special precautions for disposal and other handling
Any unused product or waste material should be disposed of in accordance with local requirements.

Hypersensitivity
(fever, rash, e.g.
itching,
anaphylactic
reactions)

7. MARKETING AUTHORISATION HOLDER
Procured from within EU by Product Licence holder: Star Pharmaceuticals Ltd., 5 Sandridge Close, Harrow,
Middlesex, HA1 1XD. Repackaged by Servipharm Ltd.

emotional lability
headache

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued
monitoring of the benefit/risk balance of the medicinal product. Healthcare professional s are asked to report any
suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

5.2 Pharmacokinetic properties
Studies submitted show that single intramuscular or subcutaneous doses of leuprorelin acetate over the dose range
3.75 to 15 mg 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 0.5 ng/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.

In Children: In the initial phase of therapy, a short-term increase as flare-up of the sex hormone level occurs, followed
by a decrease to values within the pre-pubertal range. Due to this pharmacological effect, adverse events may occur
particularly at the beginning of treatment.

Psychiatric
disorders
Nervous system
disorders

vaginal
haemorrhage,
spotting**,
vaginal
discharge
injection
site reactions

seizure

8. MARKETING AUTHORISATION NUMBER(S): PL 20636/2582
Leaflet revision and issue date (Ref): 23.08.16[H-9]

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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