Consumer medicine information

Lucrin Injection [9149]

Leuprorelin acetate

BRAND INFORMATION

Brand name

Lucrin Solution for injection

Active ingredient

Leuprorelin acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lucrin Injection [9149].

What is in this leaflet

This leaflet answers some common questions about Lucrin Injection.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given this medicine against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet.

You may need to read it again.

What Lucrin is used for

Lucrin is used to treat prostate cancer.

It belongs to a group of medicines called gonadotropin releasing hormone agonists.

It works by blocking the secretion of hormones from testes. In some types of cancer, these hormones help the cancer cells to grow. By blocking these hormones, Lucrin may slow or stop the growth of prostate cancer.

Ask your doctor or pharmacist if you have any questions about why it has been prescribed for you.

Your doctor may have prescribed it for another purpose.

Lucrin is available only with a doctor's prescription.

Lucrin should not be given to children.

Before you are given Lucrin

When you must not be given it

Do not receive Lucrin if you have an allergy to:

  • any medicine similar to Lucrin
  • any of the ingredients listed at the end of this leaflet

Some symptoms of an allergic reaction include skin rash, itching, shortness of breath or swelling of the face, lips or tongue, which may cause difficulty in swallowing or breathing.

Pregnancy and Breastfeeding
Although not relevant to prostate cancer patients, Lucrin should not be used during pregnancy or while breastfeeding.

Do not receive it after the expiry date printed on the pack or if the packaging is damaged or shows signs of tampering.

If it has expired or is damaged return it to your pharmacist for disposal.

Before are given Lucrin

Tell your doctor if you have any allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • if your cancer has spread to your spine
  • difficulty or pain when passing urine
  • history of convulsions, fits or seizures
  • history of diabetes
  • history of heart problems

Fertility
Lucrin may impair fertility in men. Use of this medicine for a short time has shown a full return to fertility after stopping the medicine. Fertility suppression may or may not be permanent when the medicine is given for a long time.

Children
Certain strengths of Lucrin have not been tested in children so the safety and effectiveness in children is not fully known.

If you have not told your doctor about any of the above, tell them before you are given Lucrin.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food store.

Lucrin has not been found to interact with other commonly used medicines. If you have any questions or concerns, discuss them with your doctor or pharmacist.

Tell your doctor or pharmacist if you are taking any of the following medicines:

  • medicines used to treat abnormal heart rhythms, e.g. quinidine, disopyramide, procainamide, amiodarone, sotalol, dofetilide or ibutilide
  • methadone, a medicine used to reduce withdrawal symptoms associated with drug addiction
  • certain antibiotics such as moxifloxacin, a medicine used to treat infections caused by certain bacteria
  • antipsychotic medicines

Taking these medicines together with Lucrin may increase the risk of abnormal heart rhythms.

How Lucrin is given

Lucrin should only be given by a doctor or nurse.

Your doctor will tell you which formulation of Lucrin will be given and for how long. This may differ from the information contained in this leaflet

How often Lucrin is given

Lucrin Injection
Recommended dose is 1mg (0.2mL) injected daily under the skin.

Lucrin Depot 7.5mg, 22.5mg, 30mg and 45mg PDS injection should be mixed with the diluent before use according to the manufacturer's instructions provided.

Lucrin Depot 7.5mg PDS is injected into a muscle once every 4 weeks.

Lucrin Depot 22.5mg PDS is injected into a muscle once every 12 weeks.

Lucrin Depot 30mg PDS is injected into a muscle once every 16 weeks.

Lucrin Depot 45mg PDS is injected into a muscle once every 24 weeks.

The site of injection should be varied from time to time.

If the microspheres are not in suspension, the injection must not be administered.

How to take it

This medicine is given as an injection, usually into your muscle by a doctor or trained nurse with experienced in the administration of such injections.

How long to take it

Continue taking your medicine for as long as your doctor tells you.

The medicine helps control your condition, but it does not cure it. It is important to keep taking your medicine even if you feel well.

If you forget to have your injection

If you missed your injection or are not sure what to do, check with your doctor or pharmacist.

Overdose

As Lucrin is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any side effects after being given this medicine, telephone your doctor, or the Poisons Information Centre (telephone Australia 13 11 26), or go to Accident and Emergency at your nearest hospital.

There have not been any unwanted side effects seen with the overdosage of Lucrin.

While you are being given Lucrin

Things you must do

When Lucrin is first started, there may be a temporary increase in some hormones. This may cause an increase in pain or other symptoms of the cancer in the first weeks. If this happens, see your doctor.

If symptoms include difficulty urinating, a feeling of weakness or numbness in the lower limbs, you should notify your doctor immediately.

These symptoms usually only happen with the first treatment with this medicine; you should not experience them with future treatments.

Your doctor may continue to monitor your testosterone levels to ensure that acceptable suppression of the secretion of hormones from the testes is maintained throughout your course of treatment.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Lucrin.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon that you are taking this medicine.

If you are about to have any blood tests, tell your doctor that you are taking this medicine.

It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your progress can be checked.

If you do not feel well or your condition worsens, tell your doctor.

Things you must not do

Do not use this medicine to treat any other complaints unless your doctor or pharmacist tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Do not use fractional doses or combinations of doses to substitute any depot formulations.

Due to different release characteristics of each presentation of Lucrin Depot, a fractional dose of the 3-month depot, 4-month depot or 6-month depot formulation is not equivalent to the same dose of the monthly formulation (Lucrin Depot 7.5 mg PDS) and should not be given. Similarly, fractional doses of the 30 mg or 45 mg formulations should not be used as a substitute for the 30 mg or 22.5 mg and multiples of the 7.5 mg presentation should not be used as a substitute for the 22.5 mg, 30 mg or 45 mg formulations.

Things to be careful of

Be careful driving or operating machinery until you know how Lucrin affects you.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.

Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Lucrin.

It helps most people with prostate cancer, but it may have unwanted side effects in a few people. All medicines have some unwanted side effects. Sometimes they are serious, but most of the time they are not. You may need medical attention if you get some of the side-effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • pain, swelling or redness at the injection site
  • cough
  • unusual tiredness or weakness
  • tiredness, sleepiness or drowsiness
  • difficulty sleeping
  • mild muscle, back or joint pain
  • changes in testicular size
  • change in your sexual drive
  • inability to get or maintain an erection
  • sweating and body odour
  • hot flushes
  • general pain
  • nausea/vomiting
  • buzzing, hissing, whistling, ringing or other persistent noise in the ear
  • mild skin problems such as rash, itching, hives, dry skin or acne
  • headache
  • dizziness or light-headedness
  • diarrhoea
  • constipation

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

  • swelling in limbs
  • problems with your eyesight
  • difficulty breathing
  • thirst
  • frequent passing of urine
  • numbness or tingling of hands or feet
  • blood in your urine
  • difficulty or pain when passing urine
  • changes in breast size
  • chest pain
  • feeling of weakness in arms(s) or leg(s)
  • speech problems

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • swelling of the face, lips, mouth, throat or neck which may cause difficulty in swallowing or breathing or sudden collapse
  • unsteadiness when walking

The above list includes very serious side effects. You may need urgent medical attention. These side effects are rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Other side effects not listed above may occur in some people.

Storage

Lucrin injection should be stored in a refrigerator (2°C to 8°C). Do not freeze. Protect from light.

Lucrin PDS Injections should be kept in a cool, dry place where the temperature stays below 25°C.

Do not store it or any other medicine in the bathroom, near a sink, or on a windowsill. Do not leave it in the car.

Heat and dampness can destroy some medicines.

Keep it where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor or pharmacist tells you to stop taking this medicine, or the medicine has passed its expiry date, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

MULTI-DOSE VIAL

Description:
Lucrin 5 mg/mL Injection is a clear colourless liquid in a multidose glass vial.

Lucrin 5 mg/mL Injection may also be supplied as an injection kit, which consists of a multidose glass vial containing a clear colourless liquid, alcohol swabs and syringes with needles.

PREFILLED DUAL-CHAMBER SYRINGES

Description:
Lucrin Depot 7.5 mg PDS Injection, Lucrin Depot - 3 Month PDS Injection, Lucrin Depot - 4 Month and Lucrin Depot - 6 Month PDS Injection is a dual-chamber syringe containing active ingredient (white powder) in the front chamber and diluent (colourless solution) in the rear chamber.

Ingredients

Lucrin multidose vial contains leuprorelin acetate 5 mg/mL as the active ingredient.

It also contains sodium chloride, sodium hydroxide, acetic acid, and water for injections.

It also contains the preservative: benzyl alcohol.

Lucrin Depot 7.5mg PDS contains 7.5mg leuprorelin acetate as the active ingredient.

It also contains gelatine, mannitol and polyglactin.

Lucrin Depot 22.5mg PDS contains 22mg leuprorelin acetate as the active ingredient.

It also contains polylactic acid and mannitol.

Lucrin Depot 30mg PDS contains 30mg leuprorelin acetate as the active ingredient.

It also contains polylactic acid and mannitol.

The diluent contains carmellose sodium, mannitol, polysorbate 80 and water for injections.

Lucrin Depot 45mg PDS contains 45mg leuprorelin acetate as the active ingredient.

It also contains polylactic acid, stearic acid and mannitol.

The diluent contains carmellose sodium, mannitol, polysorbate 80, glacial acetic acid and water for injections.

Supplier

Lucrin multidose vial is made in France.

Lucrin Depot PDS is made in Japan.

Lucrin is supplied in Australia by:

AbbVie Pty Ltd
241 O'Riordan Street
Mascot NSW 2020
1800 043 460
ABN: 48 156384262

This leaflet was prepared in May 2015.

Australian Registration Number(s)

Lucrin 5 mg/mL Injection: AUST R 29658

Lucrin Depot 7.5mg 1 Month PDS Injection: AUST R 114302

Lucrin Depot 22.5mg 3-Month PDS Injection: AUST R 114303

Lucrin Depot 30mg 4-Month PDS Injection: AUST R 114304

Lucrin Depot 45mg 6-Month PDS Injection: AUST R 222375

Version 11

BRAND INFORMATION

Brand name

Lucrin Solution for injection

Active ingredient

Leuprorelin acetate

Schedule

S4

 

1 Name of Medicine

Leuprorelin acetate.

6.7 Physicochemical Properties

Leuprorelin acetate is a hygroscopic, white or almost white powder. It has a molecular formula of C59H84N16O12.C2H4O2 and a molecular weight of 1269.47. The solubility of leuprorelin acetate in water is more than 75% and less than 0.0001% in ether and hexane. The chemical name is 5-oxoL-prolyl-L- histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D- leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt).

Chemical structure.


CAS number.

53714-56-0 (leuprorelin free peptide).
74381-53-6 (leuprorelin acetate).

2 Qualitative and Quantitative Composition

Lucrin Depot 7.5 mg PDS Injection.

Each prefilled dual chamber syringe contains 7.5 mg leuprorelin acetate in the front chamber and 1 mL of diluent in the rear chamber.

Lucrin Depot 3-Month PDS Injection.

Each prefilled dual chamber syringe contains 22.5 mg leuprorelin acetate in the front chamber and 1.5 mL of diluent in the rear chamber.

Lucrin Depot 4-Month PDS Injection.

Each prefilled dual chamber syringe contains 30 mg leuprorelin acetate in the front chamber and 1.5 mL of diluent in the rear chamber.

Lucrin Depot 6-Month PDS Injection.

Each prefilled dual chamber syringe contains 45 mg leuprorelin acetate in the front chamber and 1.5 mL of diluent in the rear chamber.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Prefilled dual chamber syringe consisting of powder for injection and diluent.

Powder for injection.

White lyophilised powder once reconstituted becomes a milky suspension.

Diluent.

The diluent is a clear colourless solution.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Leuprorelin acetate is a synthetic nonapeptide analogue of naturally occurring gonadotropin releasing hormone (GnRH or LH-RH). The analogue possesses greater potency than the natural hormone.
Leuprorelin acetate acts as a potent inhibitor of gonadotropin secretion when given continuously and in therapeutic doses. Animal and human studies indicate that following an initial stimulation, chronic administration of leuprorelin acetate results in suppression of testicular steroidogenesis.
Administration of leuprorelin acetate has resulted in inhibition of the growth of certain hormone dependent tumours (prostatic tumours in Noble and Dunning male rats and DMBA induced mammary tumours in female rats) as well as atrophy of the reproductive organs.
In humans, administration of leuprorelin acetate results in an initial increase in circulating levels of luteinizing hormone (LH), leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestosterone). However, continuous administration of leuprorelin acetate results in decreased levels of LH. In 93.7% of males, androgens are reduced to castrate levels. These decreases occur within a month of initiating treatment and are maintained as long as treatment continues. During the course of treatment, testosterone levels should be monitored to ensure there has been adequate suppression, as treatment effects are not always maintained.

Clinical trials.

Lucrin Depot 7.5 mg.

In an open label, noncomparative, multicenter clinical study of Lucrin Depot 7.5 mg, 56 patients with stage D2 prostatic adenocarcinoma and no prior systemic treatment were enrolled. The objectives were to determine if a 7.5 mg depot formulation of leuprorelin injected once every 4 weeks would reduce and maintain serum testosterone to castrate range (≤ 50 nanogram/dL), to evaluate objective clinical response, and to assess the safety of the formulation. During the initial 24 weeks, serum testosterone was measured weekly, biweekly, or every four weeks and objective tumour response assessments were performed at weeks 12 and 24. Once the patient completed the initial 24 week treatment phase, treatment continued at the investigator's discretion. Data from the initial 24 week treatment phase are summarised in this section.
In the majority of patients, serum testosterone increased by 50% or more above baseline during the first week of treatment. Serum testosterone suppressed to the castrate range within 30 days of the initial depot injection in 94% (51/54) of patients for whom testosterone suppression was achieved (2 patients withdrew prior to onset of suppression) and within 66 days in all 54 patients. Mean serum testosterone suppressed to castrate level by week 3. The median dosing interval between injections was 28 days. One escape from suppression (2 consecutive testosterone values greater than 50 nanogram/dL after achieving castrate level) was noted at week 18, associated with a substantial dosing delay. In this patient, serum testosterone returned to the castrate range at the next monthly measurement. Serum testosterone was minimally above the castrate range on a single occasion for 4 other patients. No clinical significance was attributed to these rises in testosterone. See Figure 1.
Secondary efficacy endpoints evaluated included objective tumour response, assessed by clinical evaluations of tumour burden (complete response, partial response, objectively stable, and progression), as well as changes in local disease status, assessed by digital rectal examination, and changes in prostatic acid phosphatase (PAP). These evaluations were performed at weeks 12 and 24. The objective tumour response analysis showed a "no progression" (i.e. complete or partial response, or stable disease) in 77% (40/52) of patients at week 12, and in 84% (42/50) of patients at week 24. Local disease improved or remained stable in all (42) patients evaluated at week 12 and in 98% (41/42) of patients elevated at week 24. PAP normalised or decreased at week 12 and/or 24 in the majority of patients with elevated baseline PAP.
Periodic monitoring of serum testosterone and PSA levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. It should be noted that results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.

Lucrin Depot 3-Month 22.5 mg.

In clinical studies, serum testosterone was suppressed to castrate within 30 days in 87 of 92 (95%) patients and within an additional two weeks in three patients. Two patients did not suppress for 15 and 28 weeks, respectively. Suppression was maintained in all of these patients with the exception of transient minimal testosterone elevations in one of them, and in another an increase in serum testosterone to above the castrate range was recorded during the 12 hour observation period after a subsequent injection. This represents stimulation of gonadotropin secretion. See Figure 2.
An 85% rate of "no progression" was achieved during the initial 24 weeks of treatment. A decrease from baseline in serum PSA of ≥ 90% was reported in 71% of the patients and a change to within the normal range (≤ 3.99 nanogram/mL) in 63% of the patients.
Periodic monitoring of serum testosterone and PSA levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. It should be noted that results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.

Lucrin Depot 4-Month 30 mg.

In an open label, noncomparative, multicenter clinical study of Lucrin Depot 30 mg, 49 patients with stage D2 prostatic adenocarcinoma (with no prior treatment) were enrolled. The objectives were to determine whether a 30 mg depot formulation of leuprorelin injected once every 16 weeks would reduce and maintain serum testosterone levels at castrate levels (≤ 50 nanogram/dL), and to assess the safety of the formulation. The study was divided into an initial 32 week treatment phase and a long-term treatment phase. Serum testosterone levels were determined biweekly or weekly during the first 32 weeks of treatment. Once the patient completed the initial 32 week treatment period, treatment continued at the investigator's discretion with serum testosterone levels being done every 4 months prior to the injection.
In the majority of patients, testosterone levels increased 50% or more above the baseline during the first week of treatment. Mean serum testosterone subsequently suppressed to castrate levels within 30 days of the first injection in 94% of patients and within 43 days in all 49 patients during the initial 32 week treatment period. The median dosing interval between injections was 112 days. One escape from suppression (two consecutive testosterone values greater than 50 nanogram/dL after castrate levels achieved) was noted at week 16. In this patient, serum testosterone increased to above the castrate range following the second depot injection (week 16) but returned to the castrate level by week 18. No adverse reactions were associated with this rise in serum testosterone. A second patient had a rise in testosterone at week 17, then returned to the castrate level by week 18 and remained there through week 32. In the long-term treatment phase two patients experienced testosterone elevations, both at week 48. Testosterone for one patient returned to the castrate range at week 52, and one patient discontinued the study at week 48 due to disease progression.
Secondary efficacy endpoints evaluated in the study were the objective tumour response as assessed by clinical evaluations of tumour burden (complete response, partial response, objectively stable and progression) and evaluations of changes in prostatic involvement and prostate specific antigen (PSA). These evaluations were performed at weeks 16 and 32 of the treatment phase. The long-term treatment phase monitored PSA at each visit (every 16 weeks). The objective tumour response analysis showed "no progression" (i.e. complete or partial response, or stable disease) in 86% (37/43) of patients at week 16, and in 77% (37/48) of patients at week 32. Local disease improved or remained stable in all patients evaluated at week 16 and/or 32. For patients with elevated baseline PSA, 50% (23/46) had a normal PSA (less than 4.0 nanogram/mL) at week 16, and 51% (19/37) had a normal PSA at week 32.
Periodic monitoring of serum testosterone and PSA levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. It should be noted that results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.
Using historical comparisons, the safety and efficacy of Lucrin Depot 30 mg injection appear similar to the other Lucrin Depot formulations. See Figure 3.

Lucrin Depot 6-Month 45 mg.

An open label, noncomparative, multicenter clinical study of Lucrin Depot 45 mg injection enrolled 151 patients with prostate cancer. The study drug was administered as two intramuscular injections of Lucrin Depot 45 mg at 24 week intervals (139/151 received 2 injections), and patients were followed for a total of 48 weeks.
Among 148 patients who had testosterone value at week 4, serum testosterone was suppressed to castrate levels (< 50 nanogram/dL) from week 4 through week 48 in an estimated 93.4% (two sided 95% CI: 89.2%, 97.6%) of patients. One patient failed to achieve testosterone suppression by week 4, and eight patients had escapes from suppression (any testosterone value > 50 nanogram/dL after castrate levels were achieved). Mean testosterone levels increased to 608 nanogram/dL from a baseline of 435 nanogram/dL during the first week of treatment. By week 4, the mean testosterone concentration had decreased to below castrate levels (16 nanogram/dL).
Periodic monitoring of serum testosterone levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. Testosterone determinations are dependent on assay methodology and it is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.
Figure 4 shows the mean testosterone concentration at various time points.
Patients at risk of spinal cord compression and urinary tract obstruction were excluded from this study.

5.2 Pharmacokinetic Properties

Leuprorelin acetate is not active when given orally. Intramuscular injection of the depot formulation provides plasma concentrations of leuprorelin acetate over a period of one month with Lucrin Depot 7.5 mg PDS Injection and over three months for Lucrin Depot 3-Month PDS Injection, over four months for Lucrin Depot 4-Month PDS Injection and over six months for Lucrin Depot 6-Month PDS Injection.

Absorption.

A mean peak plasma leuprorelin acetate concentration of 48.9 nanogram/mL was observed at 4 hours following a single injection of the three month formulation of Lucrin Depot 22.5 mg Injection. It then declined to 0.67 nanogram/mL at 12 weeks. Leuprorelin acetate appeared to be released at a constant rate following the onset of steady-state levels during the third week after dosing, providing steady plasma concentrations through the 12 week dosing interval. However, intact leuprorelin and an inactive major metabolite could not be distinguished by the assay that was employed in the study. Detectable levels of leuprorelin acetate were present at all measurement points in all patients. The initial burst, followed by a decline to a steady-state level, was similar to the release pattern seen with the monthly formulation.
Following a single injection of the four month formulation of Lucrin Depot 30 mg Injection in patients, a mean peak plasma leuprorelin concentration of 59.3 nanogram/mL was observed at 4 hours and the mean concentration then declined to 0.30 nanogram/mL at 16 weeks. Leuprorelin appeared to be released at a constant rate following the onset of steady-state levels during the fourth week after dosing, providing steady plasma concentrations throughout the 16 week dosing interval. Again, intact leuprorelin and an inactive major metabolite could not be distinguished by the assay that was employed in the study. The initial burst, followed by the rapid decline to a steady-state level, was similar to the release pattern seen with the other depot formulations.
Following a single injection of leuprorelin acetate depot 6 month 45 mg in 26 prostate cancer patients, mean peak plasma leuprorelin concentration of 6.7 nanogram/mL was observed at 2 hours and the mean concentration then declined to 0.07 nanogram/mL at 24 weeks. Leuprorelin appeared to be released continuously following the onset of steady-state levels during the third week after dosing providing steady plasma concentrations through the 24 week dosing interval. The initial burst, followed by the rapid decline to a steady-state level, was similar to the release pattern seen with the other depot formulations. In this study, mean leuprorelin plasma concentration time profiles were similar after the first and second dose.

Distribution.

The mean steady-state volume distribution of leuprorelin following intravenous bolus administration to healthy male volunteers was 27 L. In vitro binding to human plasma proteins ranged from 43% to 49%.

Metabolism and excretion.

In healthy male volunteers, a 1 mg bolus of leuprorelin administered intravenously revealed that the mean systemic clearance was 7.6 L/h, with a terminal elimination half-life of approximately 3 hours based on a two compartment model.

Special populations.

The pharmacokinetics of the drug in patients with hepatic and renal impairment have not been determined.

5.3 Preclinical Safety Data

Genotoxicity.

Genotoxicity studies have been performed with leuprorelin acetate using bacterial and mammalian systems. These studies provided no evidence of a genotoxic potential.

Carcinogenicity.

A two year carcinogenicity study was conducted in rats and mice. In rats, a dose related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg). This study also revealed an increased incidence of pancreatic islet cell adenomas, but their incidence showed a negative trend with dose, suggesting that it may not be drug related. In mice, no pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years. In short-term toxicity studies in mice treated for 3 months with 20-200 mg/kg, hypertrophic and castration cells were found in the anterior pituitary. Neither pituitary nor pancreatic changes were found in cynomolgus monkeys treated for 12 months with 10 mg/kg daily.

4 Clinical Particulars

4.1 Therapeutic Indications

Lucrin is indicated for the palliative treatment of metastatic or locally advanced prostate cancer.

4.3 Contraindications

Although not relevant to the approved indication, leuprorelin acetate is contraindicated in pregnancy due to its embryotoxic effects. (See Section 4.6 Fertility, Pregnancy and Lactation).
Although not relevant to the approved indication, Lucrin Depot PDS Injection should not be administered to a nursing mother as it is not known whether leuprorelin acetate is excreted into human milk. (See Section 4.6 Fertility, Pregnancy and Lactation).
Lucrin Depot PDS Injection is contraindicated in patients with known hypersensitivity to leuprorelin acetate or similar nonapeptides or any of the excipients. Isolated cases of anaphylaxis have been reported with the monthly formulation of Lucrin Depot 7.5 mg Injection.

4.4 Special Warnings and Precautions for Use

Tumour flare.

Initially, Lucrin Depot PDS Injections, like other LHRH agonists, cause increases in serum levels of testosterone to approximately 50% above baseline during the first week of treatment. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostate cancer, may occasionally develop during the first few weeks of Lucrin Depot treatment. A small number of patients may experience a temporary increase in bone pain, which can be managed symptomatically. As with other LHRH agonists, isolated cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications.
Initiating therapy with a nonsteroidal antiandrogen at the same time as leuprorelin acetate therapy has proven benefit in reducing flare reactions in 'at risk' patients (e.g. those with thecal indentation, or at risk of cord compression, and patients with bladder neck obstruction).
Patients with metastatic vertebral lesions and/or with urinary tract obstructions should be closely observed during the first few weeks of therapy.
For patients at risk, the physician may consider initiating therapy with daily Lucrin (leuprorelin acetate) injection for the first two weeks to facilitate withdrawal of treatment if that is considered necessary.

Castration resistant prostate cancer.

In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of castrate-resistant prostate cancer. Reference should be made to relevant guidelines.

Hyperglycaemia and diabetes.

Hyperglycaemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycaemia may represent development of diabetes mellitus or worsening of glycaemic control in patients with diabetes. Monitor blood glucose and/or glycosylated haemoglobin (HbA1c) periodically in patients receiving GnRH agonists and manage with current practice for treatment of hyperglycaemia or diabetes.

Cardiovascular diseases.

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with the use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving GnRH agonists should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Effect on QT/ QTc 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 physicians should assess the benefit/ risk ratio including the potential for Torsades de pointes prior to initiating leuprorelin acetate.
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of leuprorelin acetate with medicinal products known to prolong the QT interval or medicinal products able to induce Torsades de pointes such as class IA (e.g. quinidine, disopyramide, procainamide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated.

Bone mineral density.

Bone mineral density changes can occur during any hypoestrogenic state. Bone mineral density loss may be reversible after withdrawal of leuprorelin acetate.

Convulsions.

Postmarketing reports of convulsions have been observed in patients on leuprorelin acetate therapy. These included patients in the female and paediatric populations, patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumours, and in patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above.

Use in the elderly.

No data available.

Paediatric use.

Safety and effectiveness in children have not been established for this formulation and dose.

Effect on laboratory tests.

Response to leuprorelin acetate therapy may be monitored by measuring serum levels of testosterone, as well as prostate specific antigen and acid phosphatase. In the majority of nonorchiectomized patients, testosterone levels increased during the first week of treatment. They then decreased and by day 14 had returned to baseline levels or below. Castrate levels were reached in 2 to 4 weeks. Once achieved, castrate levels were maintained as long as the patient received their injections. Transient increases in acid phosphatase levels may occur early in the treatment period; however, by the fourth week the elevated levels usually decreased to values at or near normal. Due to the suppression of the pituitary gonadal system by Lucrin Depot, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and for up to three months after discontinuation of Lucrin Depot may be affected.
Serum testosterone levels should be checked periodically in order to assure appropriate suppression, since not all patients achieved testosterone levels below 50 nanogram/dL and some escaped suppression prior to the end of the 24 week treatment period. In addition, PSA levels should be monitored to identify potential disease progression.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No pharmacokinetic based drug-drug interaction studies have been conducted with Lucrin Depot PDS Injection. However, because leuprorelin acetate is a peptide that is primarily degraded by peptidase, and the drug is only about 46% bound to plasma proteins, drug interactions would not be expected to occur.
See Section 4.4 Special Warnings and Precautions, Effect on QT/QTc interval.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Clinical and pharmacological studies in adults with leuprorelin acetate and similar analogues have shown full reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks.
(Category D)
Although not relevant to the approved indication, leuprorelin acetate is contraindicated in pregnancy due to its embryotoxic effects. (See Section 4.3 Contraindications.)
Although not relevant to the approved indication, Lucrin Depot PDS Injection should not be administered to a nursing mother, as it is not known whether leuprorelin acetate is excreted into human milk. (See Section 4.3 Contraindications.)

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.
Side effects seen with Lucrin Depot are due to specific pharmacological action; namely, increases and decreases in certain hormone levels.
In the majority of patients, testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment.

'Flare' phenomenon.

The initial increase in circulating levels of pituitary gonadotropins and gonadal steroids leads in some patients to a transient exacerbation of symptoms and signs ('flare' phenomenon). The exacerbation may include worsened bone pain, ureteric obstruction and spinal cord compression. This possibility should be taken into account in deciding to initiate leuprorelin acetate therapy in patients with existing obstructive uropathy or vertebral metastases. Early symptoms of spinal cord compression, such as paraesthesia, should alert the physician to the need for intensive monitoring and possible treatment.
There is no information available on the clinical effects of interrupting leuprorelin acetate therapy with whether this will produce a withdrawal 'flare'.
Initiating therapy with a nonsteroidal antiandrogen at the same time as leuprorelin acetate therapy has proven benefit in reducing flare reactions in 'at risk' patients.
The 4 month formulation of Lucrin Depot 30 mg was utilised in clinical trials that studied the drug in 49 nonorchiectomized prostate cancer patients for 32 weeks or longer and in 24 orchiectomized prostate cancer patients for 20 weeks.
In the majority of nonorchiectomized patients, testosterone levels increased 50% or more above baseline during the first week of treatment with Lucrin Depot, declining thereafter to baseline levels or below by the end of the second week of treatment. Therefore, potential exacerbations of signs and symptoms during the first few weeks of treatment are of concern in patients with vertebral metastases and/or urinary obstruction or haematuria which, if aggravated, may lead to neurological problems, such as temporary weakness and/or paraesthesia of the lower limbs, or worsening of urinary symptoms.
One open label, multicentre study was conducted with Lucrin Depot 45 mg for 6 month administration in 151 prostate cancer patients. Patients were treated for 48 weeks, with 139/151 receiving two injections 24 weeks apart.
In a clinical trial of Lucrin Depot 7.5 mg Injection and in two clinical trials with Lucrin Depot 3-Month 22.5 mg Injection and the abovementioned clinical trials with Lucrin Depot 4-Month 30 mg Injection and Lucrin Depot 6-Month 45 mg Injection, reactions were reported to have a possible or probable relationship to drug as ascribed by the treating physician in 5% or more of the patients receiving the drug. Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug related are excluded. (See Table 1.)

Laboratory abnormalities.

Lucrin Depot 7.5 mg and Lucrin Depot 3-Month 22.5 mg.

Abnormalities of certain parameters were observed, but are difficult to assess in this population. The following were recorded in 5% or more of patients: increased urea nitrogen, hyperglycaemia, hyperlipidaemia (total cholesterol, LDL cholesterol, triglycerides), hyperphosphatemia, abnormal liver function tests, increased prothrombin time (PT), increased partial thromboplastin time (PTT). Additional laboratory abnormalities reported were: decreased platelets, decreased potassium and increased WBC.

Lucrin Depot 4-Month 30 mg.

In 5% or more of patients who took part in the Lucrin Depot 4-Month 30 mg study, the following abnormalities were observed: decreased bicarbonate, decreased haemoglobin/ haematocrit/ RBC, hyperlipidaemia (total cholesterol, LDL cholesterol, triglycerides), decreased HDL cholesterol, eosinophilia, increased glucose, increased liver function tests (ALT, AST, GGTP, LDH), increased phosphorus. Additional laboratory abnormalities were reported: increased BUN and PT, leukopenia, thrombocytopenia, uricaciduria.

Lucrin Depot 6-Month 45 mg.

Abnormalities of certain parameters were observed, but their relationship to drug treatment is difficult to assess in this population. The following abnormalities were recorded in ≥ 5% of patients: decreased haemoglobin, decreased haematocrit, decreased red blood cells, increased eosinophils, increased AST, increased GGT, increased BUN, increased phosphorus, increased creatinine, increased glucose, increased LDL cholesterol, increased total cholesterol, increased triglycerides, decreased HDL cholesterol, and decreased eGFR. Additional laboratory abnormalities reported were: increased ALT, increased LDH.
In these same clinical trials the following adverse reactions were reported in less than 5% of the patients on Lucrin Depot Injections.

Body as a whole.

Enlarged abdomen, fever, chills, weight gain, hypothermia, abscess4, accidental injury4, allergic reaction4, cyst4, generalised oedema4, hernia4, neck pain4, 6, neoplasm4 , asthenia6, feeling hot*6, injection site discomfort6, injection site erythema6, injection site induration6, injection site nodule6, injection site swelling6, injection site warmth6, oedema peripheral6, pain6, pitting oedema6, injection site cellulites6, sinusitis6, metastases to bone6.

Cardiovascular system.

Cardiac arrhythmia, bradycardia, heart failure, angina pectoris, hypertension, hypotension, varicose vein, migraine, postural hypotension, atrial fibrillation4, deep thrombophlebitis4, tachycardia6, mitral valve incompetence6, tricuspid valve incompetence6.

Digestive system.

Anorexia, diarrhoea, duodenal ulcer, increased appetite, thirst/dry mouth, dyspepsia, rectal disorder, eructation4, gastrointestinal haemorrhage4, gingivitis4, gum haemorrhage4, hepatomegaly4, intestinal obstruction4, periodontal abscess4, abdominal pain upper6, colonic pseudo-obstruction6, constipation6, flatulence6, haematochezia6, retching6, nausea6.

Musculoskeletal system.

Bone pain, myalgia, leg cramps4, pathological fracture4, ptosis4, arthralgia6, rib fracture6, bursitis6, joint stiffness6, muscle fatigue6, muscle spasm6, osteoarthritis6, pain in extremity6.

Central/ peripheral nervous system.

Paraesthesia, anxiety, delusions, depression, hypaesthesia, decreased libido*, nervousness, hyperkinesia, ataxia, hypertonia, abnormal thinking4, amnesia4, convulsion4, dementia4, confusion4, insomnia/sleep disorders4,6, neuromuscular disorders4, neuropathy4, paralysis4, depressed mood6, loss of libido6, dizziness6, headache6, lethargy6, memory impairment6.

Respiratory system.

Haemoptysis, epistaxis, pharyngitis, pleural effusion, pneumonia, increased cough, rhinitis, hiccup4, voice alteration4, asthma4, bronchitis4, dyspnoea6, dyspnoea exertional6.

Skin and appendages.

Dermatitis, hair growth, dry skin, macropapular rash, pruritus, skin discolouration, actinic keratosis6, cold sweat6, erythema6, hyperhidrosis6, night sweats6, pruritic6, rash6, rash pruritic6.

Urogenital system.

Dysuria, frequency/urgency/impaired, haematuria, testicular pain, gynaecomastia, impotence, penis disorders, testis disorders, nocturia, urinary incontinence4, 6, testicular atrophy4, 6, bladder carcinoma4, epididymitis4, prostate disorder4, 6, bladder spasm6, hydronephrosis6, hypertonic bladder6, renal failure6, urinary hesitation6, urinary retention6, urine flow decreased6, pelvic pain6.

Haemic and lymphatic system.

Anaemia, lymphoedema, decreased thromboplastin, leucocytosis, leukopenia, thrombocytopenia, lymphadenopathy4.

Metabolic and nutritional disorders.

Dehydration, oedema, libido decrease, hypercholesteremia, hypokalaemia, healing abnormal4, hypoxia4, weight loss4, central obesity6, gout6, hyperkalemia6.

Special senses.

Abnormal vision, amblyopia, dry eyes, tinnitus.

Laboratory.

Increased calcium, increased uric acid, alanine amino transferase (SGPT) increased, aspartate aminotransferase increased (SGOT)6, blood alkaline phosphatase increased6, blood glucose increased6, gamma-glutamyltransferase increased (GGT)6, heart rate irregular6, hepatic enzyme increased6, liver function test abnormal6.

Miscellaneous.

Hard nodule in throat.
* Physiological effect of decreased testosterone.
4 These adverse reactions were only experienced by patients on Lucrin Depot 4-Month 30 mg study.
6 These adverse reactions were only experienced by patients on Lucrin Depot 6-Month 45 mg study.
In clinical trials and postmarketing surveillance, the following adverse events have been observed with this or other formulations of leuprorelin acetate. As leuprorelin has multiple indications and, therefore, patient populations, some of these adverse events may not be applicable to every patient. For a majority of these adverse events, a cause and effect relationship has not been established.

Body as a whole.

Infection/ inflammation, abdomen enlarged, asthenia, chills, fever, general pain, headache, photosensitivity reactions, swelling (temporal bone), jaundice.

Cardiovascular system.

Congestive heart failure, ECG changes/ ischaemia, hypertension, hypotension, myocardial infarction, murmur, phlebitis/ thrombosis, pulmonary emboli, sudden cardiac death, transient ischaemic attack/ stroke, angina, bradycardia, cardiac arrhythmia, varicose veins, tachycardia.

Digestive system.

Constipation, dysphagia, gastrointestinal bleeding, gastrointestinal disturbance, hepatic dysfunction, peptic ulcer, rectal polyps, diarrhoea, dry mouth, duodenal ulcer, increased appetite, liver function tests abnormal, nausea, thirst, vomiting, serious liver injury.

Endocrine.

Diabetes, thyroid enlargement.

Metabolic and nutritional system.

BUN increased, calcium increased, creatinine increased, dehydration, oedema, hyperlipidaemia (total cholesterol, LDL cholesterol, triglycerides), hyperphosphatemia, hypoglycaemia, hypoproteinemia, potassium decreased, uric acid increased, bilirubin increased.

Haemic and lymphatic system.

Anaemia, decreased WBC, ecchymosis, lymphedema, PT increased, PTT increased, platelets decreased, increased WBC.

Musculoskeletal system.

Ankylosing spondylosis, joint pain, pelvic fibrosis, tenosynovitis-like symptoms, joint disorders, myalgia, spinal fracture, paralysis.

Nervous system.

Anxiety, convulsion, dizziness/ lightheadedness, headache, hearing disorder, sleep disorders, lethargy, memory disorder, mood swings, nervousness, numbness, peripheral neuropathy, depression, delusion, hypasthenia, hypoesthesia, insomnia, libido increase, neuromuscular disorders, paraesthesia, syncope/ blackouts.

Respiratory system.

Cough, pleural rub, pneumonia, pulmonary fibrosis, pulmonary infiltrate, respiratory disorders, sinus congestion, dyspnoea, epistaxis, haemoptysis, pharyngitis, pleural effusion, interstitial lung disease.

Skin and appendages.

Carcinoma of skin/ ear, dry skin, hair loss, pigmentation, skin lesions, dermatitis, hair growth, hard nodule in throat, pruritus, rash, urticaria, itching.

Urogenital system.

Bladder spasms, incontinence, penile swelling, prostate pain, urinary obstruction, urinary tract infection, breast pain, breast tenderness, gynaecomastia, haematuria, menstrual disorders including breakthrough and sustained vaginal bleeding, penile disorders, testicular atrophy, testicular pain, testicular size decrease, urinary disorders, urinary frequency, urinary urgency.

Special senses.

Ophthalmologic disorders, abnormal vision, amblyopia, blurred vision, dry eyes, hearing disorders, taste disorders, tinnitus.
Injection site reactions including pain, infection, inflammation, sterile abscess, induration and hematoma have been reported.
There have been very rare reports of suicidal ideation and attempt.
As with other agents in this class, very rare cases of pituitary apoplexy have been reported following initial administration in patients with pituitary adenoma.
Isolated cases of anaphylaxis have been reported.

Changes in bone density.

Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with an LHRH agonist analogue. In a clinical trial, 25 men with prostate cancer, 12 of whom had been treated previously with leuprorelin acetate for at least six months, underwent bone density studies as a result of pain. The leuprorelin treated group had lower bone density scores than the nontreated control group. It can be anticipated that long periods of medical castration in men will have effects on bone density.

4.2 Dose and Method of Administration

Overall treatment with Lucrin must be done under the supervision of a physician; however administration of the drug product may be done by a healthcare professional experienced in the administration of intramuscular injections.
Serum testosterone concentrations may rise if a dose is omitted or delayed, and waning of effect was observed in 3% of patients at week 24, just prior to repeat the injection. It is recommended that testosterone levels are checked in patients, particularly those whose PSA rises towards the end of the treatment interval.

Lucrin Depot 7.5 mg 1-Month, 22.5 mg 3-Month, 30 mg 4-Month and 45 mg 6-Month Prefilled Dual Chamber Syringe (PDS) Injections.

Lucrin Depot 1-Month 7.5 mg.

The recommended dose of Lucrin Depot 1-Month administration is one injection every 4 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted and should be administered every 4 weeks as a single intramuscular injection.

Lucrin Depot 3-Month 22.5 mg.

The recommended dose of Lucrin Depot 3-Month administration is one injection every 12 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted and should be administered every 12 weeks as a single intramuscular injection.

Lucrin Depot 4-Month 30 mg.

The recommended dose of Lucrin Depot 4-Month administration is one injection every 16 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted and should be administered every 16 weeks as a single intramuscular injection.

Lucrin Depot 6-Month 45 mg.

The recommended dose of Lucrin Depot 6-Month administration is one injection every 24 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted and should be administered every 24 weeks as a single intramuscular injection.
Lucrin Depot is to be used as an intramuscular injection.

Method of administration.

For optimal performance of the prefilled dual chamber syringe (PDS) read and follow the following instructions.
1. To prepare for injection screw the white plunger into the end stopper until the stopper begins to turn.
2. Hold the syringe upright. Release the diluent by slowly pushing (6-8 seconds) the plunger until the first stopper is at the blue line in the middle of the barrel.
3. Keep the syringe upright. Gently mix the microspheres (powder) with the diluent thoroughly to form a uniform suspension by gently swirling the syringe. The suspension will appear milky. If the powder adheres to the stopper or caking/ clumping is present, tap the syringe with your finger to disperse.
4. Hold the syringe upright. With the opposite hand pull the needle cap upward without twisting.
5. Keep the syringe upright. Advance the plunger to expel the air from the syringe.
6. Inject the entire contents of the syringe intramuscularly at the time of the reconstitution. The suspension settles very quickly following reconstitution; therefore, leuprorelin acetate should be mixed and used immediately. Reshake the suspension if settling occurs. Lucrin Depot should not be used if the microspheres are not in suspension.

Note.

Aspirated blood would be visible just below the luer lock connection if the blood vessel is accidentally penetrated. If present, blood can be seen through the transparent hub of the needle.
Although the solution has been shown to be stable for 24 hours following reconstitution, the suspension should be discarded if not used immediately, as the product does not contain a preservative.
As with other drugs administered by injection, the injection site should be varied periodically.
Product contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.

4.7 Effects on Ability to Drive and Use Machines

There are no known effects on the ability to drive and use machines.

4.9 Overdose

In rats, subcutaneous administration of 250 to 500 times the recommended human dose, expressed on a per bodyweight basis, results in dyspnoea, decreased activity and local irritation at the injection site. There is no evidence at present that there is a clinical counterpart of this phenomenon. In early clinical trials with daily subcutaneous leuprorelin acetate in patients with prostate cancer, doses as high as 20 mg/day for up to two years caused no adverse effects differing from those observed with the 1 mg/day dose.
For advice on the management of overdose please contact the Poisons Information Centre, phone 131126.

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lucrin Depot 7.5 mg PDS Injection contains leuprorelin acetate (7.5 mg), gelatin (1.3 mg), polyglactin (66.2 mg) and mannitol (13.2 mg). The accompanying diluent contains carmellose sodium (5 mg), mannitol (50 mg), polysorbate 80 (1 mg), water for injections (1 mL) and glacial acetic acid to control pH.
Lucrin Depot 3-Month PDS Injection contains leuprorelin acetate (22.5 mg), polylactic acid (198.6 mg) and mannitol (38.9 mg). The accompanying diluent contains carmellose sodium (7.5 mg), mannitol (75 mg), polysorbate 80 (1.5 mg), water for injections (1.5 mL) and glacial acetic acid to control pH.
Lucrin Depot 4-Month PDS Injection contains leuprorelin acetate (30 mg), polylactic acid (264.8 mg) and mannitol (51.9 mg). The accompanying diluent contains carmellose sodium (7.5 mg), mannitol (75 mg), polysorbate 80 (1.5 mg), water for injections USP (1.5 mL) and glacial acetic acid USP to control pH.
Lucrin Depot 6-Month PDS Injection contains leuprorelin acetate (45.0 mg equivalent to 42.9 mg of leuprorelin), polylactic acid (169.9 mg), mannitol (39.7 mg) and stearic acid (10.1 mg). The accompanying diluent contains carmellose sodium (7.5 mg), mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injections USP (1.5 mL) and glacial acetic acid Ph. Eur. to control pH.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Lucrin Depot 7.5 mg PDS Injection is available as sterile lyophilised microspheres, which, when mixed with diluent, becomes a suspension, intended for administration as a monthly intramuscular injection. Clear, colourless type I glass cartridge with rubber stopper. Front chamber with 7.5 mg powder for solution for injection, rear chamber containing 1 mL diluent.
Lucrin Depot 3-Month PDS Injection is available as sterile lyophilised microspheres, which, when mixed with diluent, becomes a suspension, for administration as a single intramuscular injection every three months. Clear, colourless type I glass cartridge with rubber stopper. Front chamber with 22.5 mg powder for solution for injection, rear chamber containing 1.5 mL diluent.
Lucrin Depot 4-Month PDS Injection is available as sterile lyophilised microspheres, which when mixed with diluent, become a suspension which is intended as an intramuscular injection to be given every four months. Clear, colourless type I glass cartridge with rubber stopper. Front chamber with 30 mg powder for solution for injection, rear chamber containing 1.5 mL diluent.
Lucrin Depot 6-Month PDS Injection is available as sterile lyophilised microspheres, which when mixed with diluent, become a suspension which is intended as an intramuscular injection to be given every six months. Clear, colourless type I glass cartridge with rubber stopper. Front chamber with 45 mg powder for solution for injection, rear chamber containing 1.5 mL diluent.

6.6 Special Precautions for Disposal

No data available.

Summary Table of Changes