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LUCRIN SR DCS 3.75 MG POWDER AND SOLVENT FOR PROLONGED-RELEASE SUSPENSION FOR INJECTION IN PRE-FILLE

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

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®

2582
22.06.15[6]

Prostap SR DCS 3.75 mg Powder and
Solvent for Prolonged-release
Suspension for Injection in Pre-filled
Syringe
(leuprorelin acetate)

- 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.

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.
The safety and efficacy of PROSTAP SR in children has not yet been
established.
2. WHAT YOU NEED TO KNOW BEFORE YOU USE PROSTAP SR
PROSTAP SR is not recommended for use in children under the age of 18
years.
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.
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.

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
You should not take PROSTAP SR if you are pregnant, planning to become
pregnant or are breastfeeding.
Driving and using machines
Do not drive or operate machinery if you experience drowsiness, dizziness
or visual disturbances whilst being treated with PROSTAP SR.
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.
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:
Both men and women:
PROSTAP SR can sometimes cause swelling in your ankles, tiredness,
nausea or headaches. The treatment may cause pain in the joints,
anaemia, fever or chills, dizziness, vomiting, loss of appetite, diarrhoea,
pounding heartbeats, tingling in the hands or feet, muscle aching or
weakness, mood changes, depression, altered vision, changes in weight,
jaundice, abnormalities in liver function, thinning of bones, increase in blood
pressure, difficulty sleeping, blood clots in the lungs, spinal fracture,
paralysis or low blood pressure. Skin reactions at the injection site have
been reported rarely following injection of leuprorelin. These include: skin
hardening, redness, pain, abscesses, swelling, nodules, ulcers and skin
damage.

Blood sugar levels may be altered during treatment with PROSTAP SR,
which may affect control in diabetic patients and require more frequent
monitoring.
If you have an existing pituitary lesion, there may be an increased risk of
loss of blood to the area, which may cause permanent damage.
If you have a blood test your doctor may notice a change in blood lipid
(cholesterol) levels or in values for tests on how the liver is working. These
changes do not usually cause any symptoms.
Men only:
- When men with prostate cancer first start treatment with PROSTAP SR,
levels of testosterone can increase and in some people this may cause a
temporary increase in local pain. In some cases, to prevent this from
happening, your doctor may give you another type of drug such as
cyproterone acetate or flutamide before and just after your first
PROSTAP SR injection. If you do get worsening pain, weakness or loss
of feeling in your legs or difficulty passing urine, contact your doctor
immediately.
- PROSTAP SR can cause a loss of interest in sexual intercourse, hot
flushes and occasionally it may cause a reduction in size and function of
the testes or swelling of the breasts.
- Frequency unknown: changes in ECG (QT prolongation)
Women only:
- In women PROSTAP SR may cause hot flushes and vaginal dryness. It
may cause a change in breast size or breast tenderness and can
occasionally cause hair loss. As can happen naturally when women
reach the menopause, PROSTAP SR can cause a small amount of bone
thinning.
Additional effects in Children:
In children PROSTAP SR may cause abdominal pain/abdominal cramps.
Very rarely general allergic reactions (fever, rash, itching or a serious
allergic reaction which causes difficulty in breathing or dizziness) may
occur.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. 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
Do not store above 25oC.
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.
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)
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.
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): 22.06.15[6]
Prostap is a trademark of Takeda Pharmaceutical Company Limited.

HEALTH PROFESSIONALS’ USER LEAFLET

2582
22.06.15[H-6]

3.

®

Prostap SR DCS 3.75 mg Powder and Solvent for Prolongedrelease Suspension for Injection in Pre-filled Syringe
(leuprorelin acetate)

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.

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. (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.

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.

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.
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.

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.

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.

Withdraw the needle from the patient.

Paediatric population
The safety and efficacy of PROSTAP SR in children has not yet been established.
Administration
INSTRUCTIONS ON HOW TO MIX AND ADMINISTER
1.

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

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: 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.
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.

2.

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

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.
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.
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.
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.
4.8 Undesirable effects
Side effects seen with PROSTAP SR are due mainly to the specific pharmacological action, namely increases
and decreases in certain hormone levels.
Adverse events which have been reported infrequently include peripheral oedema, pulmonary embolism,
hypertension, palpitations, fatigue, muscle weakness, diarrhoea, nausea, vomiting, anorexia, fever/chills,
headache (occasionally severe), hot flushes, arthralgia, myalgia, dizziness, insomnia, mood changes,
depression, paraesthesia, visual disturbances, weight changes, hepatic dysfunction, jaundice and increases in
liver function test values (usually transient). Reactions at the injection site e.g. induration, erythema, pain,
abscesses, swelling, nodules, ulcers and necrosis have been rarely reported. Changes in blood lipids and
alteration of glucose tolerance have also been reported which may affect diabetic control. Thrombocytopenia
and leucopenia have been reported rarely. Anaemia has been reported in patients receiving GnRH analogues.
Hypersensitivity reactions including rash, pruritus, urticaria, and rarely, wheezing or interstitial pneumonitis
have also been reported. Anaphylactic reactions are rare.

In Children: Commonly reported adverse events are emotional lability, headache, abdominal pain/abdominal
cramps, nausea/vomiting. General allergic reactions (fever, rash e.g. itching, anaphylactic reactions) are very
rare. As with other medicinal products of this class, very rare cases of pituitary apoplexy have been reported
following initial administration in patients with pituitary adenoma.
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 professionals are asked
to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
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
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.
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.
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.

Spinal fracture, paralysis, hypotension and worsening of depression have been reported (see Section 4.4).
A reduction in bone mass may occur with the use of GnRH agonists.
Very rare cases of pituitary apoplexy have been reported following initial administration in patients with
pituitary adenoma.
Men: In cases where a “tumour flare” occurs after PROSTAP SR therapy, an exacerbation may occur in any
symptoms or signs due to disease, for example, bone pain, urinary obstruction, weakness of the lower
extremities and paraesthesia. These symptoms subside on continuation of therapy.
Impotence and decreased libido will be expected with PROSTAP SR therapy.
The administration of PROSTAP SR is often associated with hot flushes and sometimes sweating.
Orchiatrophy and gynaecomastia have been reported occasionally.
Frequency unknown: QT prolongation (see sections 4.4 and 4.5)
Women: Those adverse events occurring most frequently with PROSTAP SR are associated with hypoestrogenism; the most frequently reported are hot flushes, mood swings including depression (occasionally
severe), and vaginal dryness. Estrogen levels return to normal after treatment is discontinued.
The induced hypo-estrogenic state results in a small loss in bone density over the course of treatment, some
of which may not be reversible (see Section 4.4).
Breast tenderness or change in breast size may occur occasionally. Hair loss has also been reported
occasionally.
Vaginal haemorrhage may occur during therapy due to acute degeneration of submucous fibroids (see Section
4.4).

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 25oC.
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.
8. MARKETING AUTHORISATION NUMBER(S): PL 20636/2582
Leaflet revision and issue date (Ref): 22.06.15[H-6]

®

2582
22.06.15[6]

LUCRIN SR DCS 3.75 mg Powder and
Solvent for Prolonged-release
Suspension for Injection in Pre-filled
Syringe
(leuprorelin acetate)

- 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.

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.
The safety and efficacy of LUCRIN SR in children has not yet been
established.
2. WHAT YOU NEED TO KNOW BEFORE YOU USE LUCRIN SR
LUCRIN SR is not recommended for use in children under the age of 18
years.
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.
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.

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
You should not take LUCRIN SR if you are pregnant, planning to become
pregnant or are breastfeeding.
Driving and using machines
Do not drive or operate machinery if you experience drowsiness, dizziness
or visual disturbances whilst being treated with 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
5-6 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.
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:
Both men and women:
LUCRIN SR can sometimes cause swelling in your ankles, tiredness,
nausea or headaches. The treatment may cause pain in the joints,
anaemia, fever or chills, dizziness, vomiting, loss of appetite, diarrhoea,
pounding heartbeats, tingling in the hands or feet, muscle aching or
weakness, mood changes, depression, altered vision, changes in weight,
jaundice, abnormalities in liver function, thinning of bones, increase in blood
pressure, difficulty sleeping, blood clots in the lungs, spinal fracture,
paralysis or low blood pressure. Skin reactions at the injection site have
been reported rarely following injection of leuprorelin. These include: skin
hardening, redness, pain, abscesses, swelling, nodules, ulcers and skin
damage.

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 an existing pituitary lesion, there may be an increased risk of
loss of blood to the area, which may cause permanent damage.
If you have a blood test your doctor may notice a change in blood lipid
(cholesterol) levels or in values for tests on how the liver is working. These
changes do not usually cause any symptoms.
Men only:
- 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.
- LUCRIN SR can cause a loss of interest in sexual intercourse, hot
flushes and occasionally it may cause a reduction in size and function of
the testes or swelling of the breasts.
- Frequency unknown: changes in ECG (QT prolongation)
Women only:
- In women LUCRIN SR may cause hot flushes and vaginal dryness. It
may cause a change in breast size or breast tenderness and can
occasionally cause hair loss. As can happen naturally when women
reach the menopause, LUCRIN SR can cause a small amount of bone
thinning.
Additional effects in Children:
- In children LUCRIN SR may cause abdominal pain/abdominal cramps.
Very rarely general allergic reactions (fever, rash, itching or a serious
allergic reaction which causes difficulty in breathing or dizziness) may
occur.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. 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
Do not store above 25oC.
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.
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)
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.
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): 22.06.15[6]
LUCRIN is a trademark of AbbVie AG.

HEALTH PROFESSIONALS’ USER LEAFLET

2582
22.06.15[H-6]

3.

®

LUCRIN SR DCS 3.75 mg Powder and Solvent for Prolongedrelease Suspension for Injection in Pre-filled Syringe
(leuprorelin acetate)

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.

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. (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.

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.

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.
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.

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.

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.

Withdraw the needle from the patient.

Paediatric population
The safety and efficacy of LUCRIN SR in children has not yet been established.
Administration
INSTRUCTIONS ON HOW TO MIX AND ADMINISTER
1.

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

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.
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.

2.

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

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.
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.

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 professionals are asked
to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
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.

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.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Gonadotrophin Releasing Hormone Analogues

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.

The drug is well absorbed from the subcutaneous or intramuscular route, binds to luteinising hormone
releasing hormone (LHRH) receptors and is rapidly degraded.

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.

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.

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.

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.
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 nonhormonal 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.
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.
4.8 Undesirable effects
Side effects seen with LUCRIN SR are due mainly to the specific pharmacological action, namely increases
and decreases in certain hormone levels.
Adverse events which have been reported infrequently include peripheral oedema, pulmonary embolism,
hypertension, palpitations, fatigue, muscle weakness, diarrhoea, nausea, vomiting, anorexia, fever/chills,
headache (occasionally severe), hot flushes, arthralgia, myalgia, dizziness, insomnia, mood changes,
depression, paraesthesia, visual disturbances, weight changes, hepatic dysfunction, jaundice and increases in
liver function test values (usually transient). Reactions at the injection site e.g. induration, erythema, pain,
abscesses, swelling, nodules, ulcers and necrosis have been rarely reported. Changes in blood lipids and
alteration of glucose tolerance have also been reported which may affect diabetic control. Thrombocytopenia
and leucopenia have been reported rarely. Anaemia has been reported in patients receiving GnRH analogues.
Hypersensitivity reactions including rash, pruritus, urticaria, and rarely, wheezing or interstitial pneumonitis
have also been reported. Anaphylactic reactions are rare.
Spinal fracture, paralysis, hypotension and worsening of depression have been reported (see Section 4.4).
A reduction in bone mass may occur with the use of GnRH agonists.
Very rare cases of pituitary apoplexy have been reported following initial administration in patients with
pituitary adenoma.
Men: In cases where a “tumour flare” occurs after 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.
Impotence and decreased libido will be expected with LUCRIN SR therapy.
The administration of LUCRIN SR is often associated with hot flushes and sometimes sweating.
Orchiatrophy and gynaecomastia have been reported occasionally.

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.
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.
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.
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 25oC.
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.

Frequency unknown: QT prolongation (see sections 4.4 and 4.5)
6.6 Special precautions for disposal and other handling
Any unused product or waste material should be disposed of in accordance with local requirements.

Women: Those adverse events occurring most frequently with LUCRIN SR are associated with hypoestrogenism; the most frequently reported are hot flushes, mood swings including depression (occasionally
severe), and vaginal dryness. Estrogen levels return to normal after treatment is discontinued.
The induced hypo-estrogenic state results in a small loss in bone density over the course of treatment, some
of which may not be reversible (see Section 4.4).
Breast tenderness or change in breast size may occur occasionally. Hair loss has also been reported
occasionally.

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.

Vaginal haemorrhage may occur during therapy due to acute degeneration of submucous fibroids (see Section
4.4).

Leaflet revision and issue date (Ref): 22.06.15[H-6]

In Children: Commonly reported adverse events are emotional lability, headache, abdominal pain/abdominal
cramps, nausea/vomiting. General allergic reactions (fever, rash e.g. itching, anaphylactic reactions) are very
rare. As with other medicinal products of this class, very rare cases of pituitary apoplexy have been reported
following initial administration in patients with pituitary adenoma.

8. MARKETING AUTHORISATION NUMBER(S): PL 20636/2582

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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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