Document: label-and-leaflet MAH BRAND_PLPI 16378-0582 change

• label-and-leaflet MAH BRAND_PLPI 16378-0582
• leaflet MAH BRAND_PLPI 16378-0582

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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:

at 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.

bt 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.

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).

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.aov.uk/vellowcard.

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 use this medicine after the expiry date which is stated on the packaging.

The expiry date refers to the last day of that month.

Do not store above 25°C.

Do not refrigerate or freeze.

Store in the original container in order to protect from light.

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.

Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION What Prostap® SR contains:

•    Each syringe contains 3.75 mg leuprorelin acetate. When reconstituted with the solvent, the solution contains 3.75mg/2ml of leuprorelin acetate.

•    The excipients in Prostap® SR are: Gelatin, copolymer (DL-lactic acid/glycolic acid 75:25), mannitol.

•    The Sterile Solvent contains carmellose sodium, mannitol (E421), polysorbate 80 and water for injections.

What Prostap® SR looks like and contents of the pack:

Prostap® SR is a prolonged release powder for use in an injection.

The Sterile Solvent is a clear liquid, which is mixed with the Prostap® SR Powder before injection.

One dual chamber pre-filled syringe containing a sterile white powder in the front chamber and a clear sterile solvent in the rear chamber. The syringe contains a syringe plunger and a 23 gauge syringe needle fitted with a safety device. The pack contains 2 swabs soaked in alcohol.

Product Licence Holder and Manufacturer:

Manufactured by Takeda Pharmaceutical Company Ltd., Japan and Procured from the EU and repackaged by Product Licence Holder: Beachcourse Limited., 20 Alliance Court, Alliance Road,

London W3 ORB, UK.

PL 16378/0582    |POM|

Revision date: 10.10.2016 Leaflet reference: PROSTSR PIL

Prostap® is a registered trademark of Takeda Pharmaceutical Company Limited.

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)    Administration

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.

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

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.

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.

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.

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.

SEE MIL-2 FOR THE REST OF INFORMATION

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 pre-pubertal 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.

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:

Figure 1 presents leuprorelin serum levels after a single s.c. administration of leuprorelin acetate depot at a dosage of 30 p g/kg body weight. Peak serum levels are reached sixty minutes after administration (7.81 ± 3.59 ng/ml). The AUC0-672 is 105.78 ± 52.40 ng x hr/ml.

Figure 1: Leuprorelin serum levels after single s.c. administration of 30 pg/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

Prostap® SR Powder

Gelatin, Copolymer (DL lactic acid/glycolic acid) 72:25 mol%, Mannitol (E421)

Sterile Solvent

Carmellose sodium, Mannitol (E421), Polysorbate 80, 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 25^oC.

Do not refrigerate or freeze.

Store in the original container in order to protect from light.

6.5    Nature and contents of container

One dual chamber pre-filled syringe containing a sterile white powder in the front chamber and a clear sterile solvent in the rear chamber. The syringe contains a syringe plunger and a 23 gauge syringe needle fitted with a safety device. The pack contains 2 swabs soaked in alcohol.

6.6    Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local requirements.

Product Licence Holder and Manufacturer:

Manufactured by Takeda Pharmaceutical Company Ltd., Japan and Procured from the EU and repackaged by Product Licence Holder: Beachcourse Limited., 20 Alliance Court, Alliance Road, London W3 0RB, UK.

PL 16378/0582    |POM|

Revision date: 10.10.2016 Leaflet reference: PROSTSR MIL-2

Prostap^® is a registered trademark of Takeda Pharmaceutical Company Limited.

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