PROSTAP PD DCS 1.88 MG POWDER & SOLVENT FOR PROLONGED-RELEASE SUSPENSION FOR INJECTION IN PRE-FILLED - patient leaflet, side effects, dosage

1. what prostap pd dcs is and what it is used for

PROSTAP PD DCS is a synthetic hormone which can be used to reduce the levels of testosterone and oestrogen (sex steroids) circulating in the body.

PROSTAP PD DCS is used to treat premature puberty which is caused by a release of certain hormones from the pituitary gland (central precocious puberty) in girls under 9 years of age and boys under 10 years of age with a body weight of less than 20 kg.

Your doctor will make a precise diagnosis of central precocious puberty.

2. what you need to know before your child is given prostap pd dcs

Do not use PROSTAP PD DCS:

• If your child is allergic (hypersensitive) to leuprorelin or any of the other ingredients of PROSTAP PD DCS (listed in section 6).
• In girls with central precocious puberty

if the girl to be treated is pregnant or breast-feeding.

if the girl has abnormal vaginal bleeding which has not been discussed with her doctor (see Warnings and Precautions section below).

Warnings and Precautions:

When your child begins treatment with PROSTAP PD DCS, existing symptoms may initially get worse as a result of levels of sex steroids in the body increasing. These worsening symptoms usually subside with continued use of PROSTAP PD DCS (see section 4 for further information).

Talk to your doctor or nurse before your child is given PROSTAP PD DCS:

• If your child has a seizure (fit), tell your doctor. There have been reports of seizures in patients receiving PROSTAP PD DCS. These occurred in patients with or without epilepsy or other reasons that increase the risk of having seizures.
• If your child develops depressed mood, tell your doctor. There have been reports of depression in patients receiving PROSTAP PD DCS, which may be severe.
• In the event of a sterile abscess at the injection site (mostly reported after injection into the muscle) your doctor will monitor hormone levels as there could be reduced absorption of leuprorelin from the injection site.
• Often sterile abscesses at the injection site occurred when PROSTAP PD DCS is administered in higher dosages than recommended and when it is administered into the muscle. Your doctor will therefore administer the medicinal product under the skin of e.g. abdomen, bottom or thigh.
• If your child has a progressive brain tumour, the doctor will decide if treatment with leuprorelin is appropriate.
• Bone density may decrease during treatment of central precocious puberty with PROSTAP PD DCS. However, after treatment is stopped, subsequent bone mass growth is preserved and peak bone mass in late adolescence does not seem to be affected by treatment.

In girls with central precocious puberty:

• After the first injection vaginal bleeding (spotting) and discharge may occur as a sign of hormone withdrawal. Vaginal bleeding beyond the first/second month of treatment needs to be investigated.
• Discontinuation of treatment may lead to a slipping of the growth plate of the thigh bone. A possible cause could be a weakness of the growth plate due to a lower concentration of female sexual hormones during treatment.

Other medicines and PROSTAP PD DCS

Please tell your doctor or pharmacist if your child is taking or has recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

PROSTAP PD DCS must not be given to pregnant or breast-feeding girls (see also section “Do not use PROSTAP PD DCS’).

Driving and using machines

Your child may feel dizzy, have blurred vision or difficulty focussing his/her eyes. If these happen it may be dangerous to do things such as use machines, ride a bike or a horse or climb trees.

PROSTAP PD DCS contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per injection, that is to say it is essentially ‘sodium-free’.

3. how to use prostap pd dcs

Your doctor or nurse will give your child an injection of PROSTAP PD DCS. The injection should be given immediately after it has been prepared. The injection will normally be given in the arm, thigh or abdomen. The injection site should be varied at regular intervals.

Your child will normally be given an injection once a month.

The dosing scheme needs to be adapted individually. The

recommended starting dose is dependent on body weight:

• a) 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, 1 ml PROSTAP PD DCS (1.88 mg leuprorelin acetate) is administered once a month under the skin of e.g. abdomen, bottom or thigh as a single injection. Your doctor will monitor your child’s weight ga­in.

• b) Children with a body weight 20 kg or more

Other forms of leuprorelin may be more suitable, such as 1 ml PROSTAP SR (3.75 mg leuprorelin acetate) administered once a month under the skin.

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 may be decided by your doctor together with the legal guardian and, if appropriate, child being treated. Your doctor will determine the bone age of your child at regular intervals.

In girls with bone age of older than 12 years and boys with bone age of older than 13 years your doctor will consider discontinuing the treatment, depending on the clinical effects.

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 PD DCS 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 your child has missed an injection, contact your doctor who will be able to give your child the next injection.

If you stop using PROSTAP PD DCS

Your doctor will talk to you and your child before stopping treatment.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. possible side effects

Like all medicines, PROSTAP PD DCS can cause side effects, although not everybody gets them.

Contact your doctor immediately or go to hospital:

• If your child develops a severe rash, itching or shortness of breath or difficulty breathing. These could be symptoms of a severe allergic reaction.

Tell your doctor:

• If your child gets a severe headache which does not get better when they take painkillers.

At the beginning of treatment, a temporary 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
• depression
• headache
• abdominal pain/abdominal cramps
• feeling sick/vomiting
• acne
• vaginal bleeding
• vaginal spotting
• vaginal discharge
• injection site reactions (these include hardening, redness, pain, abscesses,

swelling, nodules, ulcers and skin damage)

Very rare (may affect up to 1 in 10,000 people):

• general allergic reactions (symptoms include fever, rash, itching, wheals or chills)
• serious allergic reaction which causes difficulty in breathing or dizziness. If this happens, contact your doctor immediately or go to the hospital.
• in patients with existing tumours of the pituitary gland, bleeding of the pituitary gland may occur.

Not known (frequency cannot be estimated from the available data):

• □ seizure

• inflammation of lungs or lung disease.

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. Websiteor search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. how to store prostap pd dcs

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 refrigerate or freeze.

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 any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other informationwhat

PROSTAP PD DCS contains:

• The active ingredient in PROSTAP PD DCS powder is leuprorelin acetate (1.88 mg).
• The other ingredients in PROSTAP PD DCS powder are: copolymer (DL-lactic acid/glycolic acid)and mannitol (E421).
• The Solvent contains carmellose sodium, mannitol (E421), polysorbate 80, water for injections and acetic acid, glacial.

What PROSTAP PD DCS looks like and contents of the pack:

PROSTAP PD DCS should only be administered by your doctor or a nurse who will also take care of the preparation of the product.

PROSTAP PD DCS is a prolonged release powder for use in an injection.

The solventis a clear liquid, which is mixed with the PROSTAP PD DCS Powder before injection.

Each pack contains a pre-filled dual chamber syringe containing 1.88 mg leuprorelin acetate powder in the front chamber and 1 ml of solvent in the rear chamber, a syringe needle fitted with a safety device and one syringe plunger.

Marketing Authorisation Holder:

Takeda UK Limited

1 Kingdom Street

London

W2 6BD

UK

Manufacturer:

Delpharm Novara S.r.l.,

Via Crosa 86

28065 Cerano

Italy

This leaflet does not contain the complete information about your medicine. If you have any questions or you are not sure about anything you should ask your doctor or nurse who can give you more information. The information in this leaflet applies only to PROSTAP PD DCS.

This leaflet was last revised in March 2021.

* Registered Trademark of Takeda

[Takeda logo]

This leaflet can be made available in large print, audio or Braille on request. Contact 0800 198 5000 to request this, quoting the following number: 16189/0038

HEALTH PROFESSIONALS’ USER LEAFLET

PROSTAP PD DCS leuprorelin acetate depot injection 1.88 mg

• 1. NAME OF THE MEDICINAL PRODUCT

PROSTAP PD DCS 1.88 mg powder and solvent for prolonged-release suspension for injection in prefilled syringe

• 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

PROSTAP Powder: Each pre-filled syringe 1.88 mg leuprorelin acetate (equivalent to 1.79 mg base).

After reconstitution each ml of suspension contains 1.88 mg leuprorelin acetate.

For the full list of excipients, see section 6.1.

• 3. PHARMACEUTICAL FORM

Powder and solvent for prolonged-release suspension for injection in pre-filled syringe.

Powder: A lyophilised, white powder in front chamber of the pre-filled syringe.

Solvent: A slightly viscous, odourless solvent in rear chamber of the pre-filled syringe.

• 4. CLINICAL PARTICULARS

  • 4.1 Therapeutic indications

Treatment of central precocious puberty (girls under 9 years of age, boys under 10 years of age with a body weight of less than 20 kg) (see section 5.1).

• 4.2 Posology and method of administration

Posology

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

In these rare cases, the following dosage should be administered according to the clinical activity of the central precocious puberty:

1 ml (1.88 mg leuprorelin acetate) is administered once a month as a single subcutaneous injection.

Children with a body weight > 20 kg

Use a higher strength preparation (e.g. 3.75 mg powder and solvent for prolonged-release suspension for injection in pre-filled syringe administered once a month).

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 GnRH test). The minimal effective monthly dose to be administered should then be determined by means of the GnRH 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 section 4.4).

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.

Method of administration

PROSTAP PD DCS should be prepared, reconstituted and administered only by healthcare professionals who are familiar with these procedures.

The pre-filled syringe of PROSTAP PD DCS powder and solvent should be reconstituted immediately prior to administration by subcutaneous injection.

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

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

Holding the syringe UPRIGHT, release the solvent 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.

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.

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

At the time of injection, check the direction of the safety device (with round mark face up) and inject the entire contents of the syringe. Inject the entire contents of the syringe subcutaneously as you would for a normal injection.

Withdraw the needle from the patient. Immediately activate the safety device by pushing the arrow forward with the thumb or finger until the device is fully extended and a CLICK is heard or felt.

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

INSTRUCTIONS ON HOWTO MIX AND ADMINISTER

Note; The suspension settles out very quiddy 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 other synthetic gonadotrophin releasing hormone (GnRH) analogues or GnRH derivatives.

In girls :

Pregnancy and breastfeeding.

Undiagnosed vaginal bleeding.

• 4.4 Special warnings and precautions for use

PROSTAP PD DCS suspension must be prepared at the time of use and, after reconstitution, used immediately (see section 4.2).

Depression

There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH agonists, such as leuprorelin acetate. Patients should be informed accordingly and treated as appropriate if symptoms occur.

Seizure

Postmarketing reports of seizures have been observed in patients treated with leuprorelin acetate. These events have been reported in those with or without a history of epilepsy, seizure disorders or risk disorders for seizures.

Before starting the therapy, a precise diagnosis of idiopathic and/or neurogenic central precocious puberty is nscessary and, in girls, pregnancy must be excluded (see section 4.3).

The therapy is a long-term treatment, adjusted individually. PROSTAP PD DCS 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, estradiol) should be monitored at 2-week intervals (see section 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 GnRHa 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 GnRHa 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.

PROSTAP PD DCS contains sodium. This medicine contains less than 1 mmol sodium (23 mg) per injection, that is to say it is essentially ‘sodium free’.

• 4.5 Interaction with other medicinal products and other forms of

interaction No interaction studies have been performed.

• 4.6 Fertility, pregnancy and lactation

Pregnancy

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 PD DCS, pregnancy must be excluded. There have been reports of foetal malformation when PROSTAP PD DCS has been given during pregnancy.

PROSTAP PD DCS must not be used in girls who are pregnant (see section 4.3).

When used monthly at the recommended dose, PROSTAP PD DCS usually inhibits ovulation and stops menstruation. Contraception is not ensured, however, by taking PROSTAP PD DCS and therefore patients should use non-hormonal methods of contraception during treatment and after cessation of treatment until the return of menses.

Patients should be advised that if they miss successive doses of PROSTAP PD DCS, 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.

Breastfeeding

PROSTAP PD DCS must not be used in girls who are breastfeeding (see section 4.3).

• 4.7 Effects on ability to drive and use machines

Leuprorelin acetate can influence the ability to drive and use machines due to visual disturbances and dizziness.

• 4.8 Undesirable effects

Adverse reactions seen with leuprorelin acetate are due mainly to the specific pharmacological action, namely increases and decreases in certain hormone levels.

The following table lists 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).

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

Tabulated list of adverse reactions in children

SOC	V ery common	Common	Uncommon	Rare	V ery rare	Not known
Immune system disorders					Hypersensitivity (rash, pruritus, urticaria, wheezing, fever, chills and anaphylactic

					reactions)
Psychiatric disorders		Depression (see Section 4.4), emotional lability
Nervous system disorders		Headache			Pituitary apoplexy has been reported following initial administration in patients with pituitary adenoma, pituitary haemorrhage	Seizure
Gastrointestinal disorders		Abdominal pain / abdominal cramps, nausea/vomiting
Skin and subcutaneous tissue disorders		Acne
Respiratory, thoracic and mediastinal disorders						Interstitial lung disease
Reproductive system and breast disorders		Vaginal haemorrhage, spotting, vaginal discharge
General disorders and administration site conditions		Injection site reactions (e.g. induration, erythema, pain, abscess, swelling, nodules and necrosis)

In general, the occurrence of vaginal spotting with continued treatment (subsequent to possible withdrawal bleeding in the first month of treatment), should be assessed as a sign of potential underdosage. Pituitary suppression should then be determined by gonadotropin releasing hormone (GnRH) stimulation test.

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. Website:

or search for MHRA Yellow Card in the Google Play or Apple App Store.

• 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 PD DCS 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. Continued administration of leuprorelin acetate results in a decrease of gonadotrophin and sex steroid levels.

The drug is well absorbed from the subcutaneous or intramuscular route, binds to gonadotropin releasing hormone (GnRH) 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.

Leuprorelin acetate is inactive when given orally.

In children, reversible suppression of pituitary gonadotropin release occurs, with a subsequent decrease in estradiol (E2) or testosterone levels to values in the pre-pubertal range.

Initial gonadal stimulation (flare-up) may cause vaginal bleeding in girls who are already postmenarchal at start of treatment. Withdrawal bleeding may occur at the start of treatment. The bleeding normally stops as treatment continues.

The following therapeutic effects can be demonstrated:

• – Suppression of basal and stimulated gonadotropin levels to pre-pubertal levels;

• – Suppression of prematurely increased sexual hormone levels to pre-pubertal levels and arrest of

premature menstruation;

• – Arrest/involution of somatic pubertal development (Tanner stages);

• – Improvement/nor­malisation of the ratio of chronological age to bone age; – Prevention of

progressive bone age acceleration; – Decrease of growth velocity and its normalization; –

Increase in final height.

Treatment result is the suppression of the pathologically, prematurely activated hypothalamic-pituitarygonadal axis according to pre-pubertal age.

In a long-term clinical trial in children treated with leuprorelin at doses up to 15 mg 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

In a study with the 1.88 mg leuprorelin formulation administered subcutaneously (s.c.) in children with central precocious puberty, leuprorelin serum levels rose rapidly following the first injection declining gradually over the next 3 days, remaining in the range 0.02 to 0.03 ng/mL for 3 weeks and declining to 0.01 ng/mL at 4 weeks after administration.

During 4 weekly repeated treatment for 12 months, plasma leuprorelin concentrations before each dose and at 4 weeks after the 12th dose were 0.01 ± 0.02 ng/mL indicating sustained release of leuprorelin over the dosing interval and no accumulation.

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

Figure 1 : Leuprorelin serum levels after single s.c. administration of 30 |Lig/kg body weight of leuprorelin acetate as depot formulation (n=6) (Mean □ SD)

• 5.3 Preclinical safety data

Animal studies have shown that leuprorelin acetate has a high acute safety factor. No major overt toxicological problems have been seen during repeated administration. Whilst the development of pituitary adenomas has been noted in chronic toxicity studies at high doses in some animal species, this has not been observed in long-term clinical studies. No evidence of mutagenicity or teratogenicity has been shown. Animal reproductive studies showed increased foetal mortality and decreased foetal weights reflecting the pharmacological effects of this GnRH agonist.

• 6. PHARMACEUTICAL PARTICULARS

  • 6.1 List of excipients

Powder

Copolymer (DL-lactic acid/glycolic acid) (75:25 mol%)

Mannitol (E421)

Sterile solvent

Carmellose sodium

Mannitol (E421)

Polysorbate 80

Acetic acid, glacial

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 refrigerate or freeze.

• 6.5 Nature and contents of container

One dual chamber pre-filled syringe containing 1.88 mg leuprorelin acetate powder in the front chamber and 1 ml of sterile solvent in the rear chamber.

1 × 25 gauge syringe needle fitted with safety device

1 x syringe plunger

• 6.6 Special precautions for disposal and other handling

Prepare the injectable suspension at the time of use and, after reconstituting, use immediately. Always ensure the safety device to prevent needle-stick injury is deployed after injection.

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

• 7. MARKETING AUTHORISATION HOLDER

Takeda UK Limited,

1 Kingdom Street

London

W2 6BD

United Kingdom

• 8. MARKETING AUTHORISATION NUMBER(S)

PL 16189/0038

• 9. DATE OF FIRST AUTHORISATION/RE­NEWAL OF THE AUTHORISATION

04/06/2021

• 10. DATE OF REVISION OF THE TEXT