Consumer medicine information

DECAPEPTYL

Triptorelin acetate

BRAND INFORMATION

Brand name

Decapeptyl Solution for subcutaneous injection

Active ingredient

Triptorelin acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DECAPEPTYL.

What is in this leaflet

This leaflet answers some common questions about Decapeptyl.

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 Decapeptyl against the benefits she/he expects it will have for you.

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

Keep this leaflet with the medicine.

You may need to read it again.

What Decapeptyl is used for

Decapeptyl contains triptorelin, which is a synthetic version of the natural gonadotropin releasing hormone (GnRH). GnRH regulates the release of two gonadotropins that are involved in the development of follicles and release of eggs from the ovaries: follicle-stimulating hormone (FSH) and luteinising hormone (LH).

Assisted Reproductive Technology (ART) include gonadotropins that replace the activities of naturally produced FSH and LH. Occasionally, in response to ART treatment, the release of eggs may occur too early due to an early surge in LH levels and this may lead to that ART cycle being cancelled, without retrieval of any eggs. Decapeptyl blocks the action of GnRH and is therefore intended to prevent an LH surge, thereby lessening the chances of premature ovulation and a cancelled ART cycle.

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

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

This medicine is not expected to affect your ability to drive a car or operate machinery.

Before you use Decapeptyl

When you must not use it

Do not use Decapeptyl if you are allergic to:

  • triptorelin acetate, the active ingredient in Decapeptyl
  • any of the other ingredients listed at the end of this leaflet
  • GnRH or synthetic versions of GnRH (medicines similar to Decapeptyl).

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not use Decapeptyl if:

  • you are pregnant
  • you are breast feeding
  • you are prone to allergies.

Do not use Decapeptyl after the expiry date printed on the pack.

Do not use Decapeptyl if the packaging is torn or shows signs of tampering.

If you are not sure whether you should have this medicine, talk to your doctor.

Before you use it

Tell your doctor if you have allergies to:

  • any other medicines
  • any other substances such as foods, preservatives or dyes.

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

  • if you are possibly pregnant
  • if you have a mild to severe liver disease
  • if you have an active allergic condition or if you are prone to allergic reactions
  • if you administer Decapeptyl yourself. You should be aware of possible allergic reactions (e.g. itching, skin rash, fever).

If you have not told your doctor about any of the above, tell him/her before you are given Decapeptyl.

Taking other medicines

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

There are some medicines which may interfere with the action of Decapeptyl. These include medicines affecting secretion of gonadotropins.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while you are receiving this medicine.

How to use Decapeptyl

This medicine contains a solution of triptorelin provided in a pre-filled disposable syringe for single use. It is given as an injection under the skin (subcutaneous) of the lower abdomen.

If your doctor or nurse decides you can give the injections to yourself, they will train you appropriately on the injection technique.

Do not self-inject Decapeptyl until you are sure of how to do it.

The first injection of Decapeptyl should be under medical supervision.

Follow all instructions given to you by your doctor carefully.

An instruction leaflet is supplied with your medicine and the following information is included:

Injecting your medicine

  • Remove the protective foil and take the syringe out of the blister packaging.
  • Keep the syringe upright with the grey protective cap facing up.
  • Remove the grey protective cap.
  • Gently push the plunger until the first drops of liquid appear at the needle tip.
  • The medicine is to be injected under the skin of the lower abdomen. Clean the injection site with an antiseptic swab immediately prior to injection.
  • Lift up a fold of skin between the thumb and forefinger. With your free hand hold the syringe at a right angle to the skin like a dart and quickly insert the needle all the way into the skin fold. Press down slowly on the plunger to inject the contents of the syringe.
  • Remove the syringe and needle from the skin and discard this immediately into a sharps disposal unit.
  • For each dose, choose a different injection site along the lower abdomen.

Other important information

  • Each pre-filled syringe is for single use only.
  • Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you experience sign/symptoms of an allergic reaction (e.g. difficulty in breathing or swelling of the lips).
  • The first injection of this medicine should be supervised by your doctor or nurse.
  • The syringe should be disposed into a sharps disposal unit.

How much to use

Always use this medicine exactly as your doctor has told you. You should check with your doctor if you are not sure.

The usual dosage of Decapeptyl is one injection under the skin of your lower abdomen once-daily.

Treatment can be started on day 2 or 3, or on day 21 to 23, of the menstrual cycle.

After 2 to 4 weeks of Decapeptyl treatment, other hormones (gonadotropins) will be given in order to stimulate follicle growth.

In general, Decapeptyl treatment will continue until follicles have reached a suitable size, usually 4 to 7 weeks.

If enough follicles are present, Decapeptyl treatment will be stopped and you will be given a medicine to induce ovulation.

Your doctor will closely monitor your progress for at least another 2 weeks.

How long to use it

Usually one dose of Decapeptyl is used each day. The length of Decapeptyl treatment is usually from 4-7 weeks. However, your doctor will be able to answer this question more precisely.

If you forget to use it

It is important that you do not miss a dose of Decapeptyl.

If you do miss a dose, contact your doctor or nurse. Do not take a double dose to make up for the dose that you missed.

If you use too much (overdose)

As your treatment will be closely monitored it is unlikely you will be prescribed too large a dose of Decapeptyl. However, Decapeptyl can be associated with some symptoms (see Side effects). If you use more than the prescribed dose contact a doctor immediately.

While you are using Decapeptyl

In case you suffer from a reaction after injecting Decapeptyl you should contact your doctor immediately. Symptoms of a reaction can include:

  • pain in the abdomen
  • swelling in the abdomen
  • nausea
  • vomiting
  • diarrhoea
  • weight gain
  • difficulty breathing
  • decreased urination.

Tell your doctor straight away, even if the symptoms develop some days after the last injection has been given. These can be signs of high levels of activity in the ovaries which might become severe (see also section Side effects).

If these symptoms become severe, the infertility treatment should be stopped and you should receive treatment in hospital.

Undergoing infertility treatment with hormones, like this medicine, has been associated with increased risk of:

  • ectopic pregnancy (pregnancy outside of the womb) if you have a history of fallopian tube disease
  • miscarriage
  • multiple pregnancy (twins, triplets, etc.)
  • congenital malformations (physical defects present in baby at birth).

Things you must do

Tell your doctor immediately if you become pregnant while using Decapeptyl.

Tell your doctor if you have abnormal vaginal bleeding while using Decapeptyl.

Be sure to keep all your doctor's appointments so your progress can be checked.

Your doctor will normally arrange for you to have ultrasound scans and sometimes blood tests to monitor your response to treatment.

Tell any other doctors, dentists, and pharmacists who are treating you that you are using Decapeptyl.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are using Decapeptyl.

If you are going to have surgery, tell the surgeon or anaesthetist that you are using Decapeptyl.

Things to be careful of

Decapeptyl should not normally interfere with your ability to drive or operate machinery.

Take special care with Decapeptyl

Decapeptyl can lead to mood changes (including depression).

Long-term use (over many months or years) of Decapeptyl for other conditions can lead to thinning of bones, which may increase risk of bone fracture.

If you are at additional risk of thinning of the bones (osteoporosis) you should tell you doctor before taking Decapeptyl.

Side effects

Tell your doctor or nurse or pharmacist as soon as possible if you do not feel well after you use Decapeptyl.

This medicine may have unwanted side effects in some people. All medicines can have side effects. Sometimes they are serious. Most of the time they are not. You may need medical attention if you experience side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

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

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

  • headache
  • abdominal pain
  • vaginal bleeding/spotting
  • nausea
  • inflammation at the injection site.

These are mild side effects and are usually short-lived.

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

  • cold
  • sore throat
  • flu-like symptoms
  • pharyngitis
  • mood alterations
  • dizziness
  • hot flushes
  • vomiting
  • abdominal bloating
  • back pain
  • abortion
  • pelvic pain
  • overstimulation of the ovaries
  • ovarian-cysts (at the beginning of the Decapeptyl treatment)
  • pain during menstruation
  • heavy, prolonged and/or irregular periods
  • vulvovaginal dryness
  • painful sexual intercourse
  • decreased libido
  • breast pain
  • joint pain
  • pain or other reactions at the injection site
  • tiredness.

The above list includes serious side effects which may require medical attention.

Contact your doctor immediately if you experience sudden headache, vomiting or visual disturbances while using Decapeptyl.

Medicines like Decapeptyl can uncover a rare pituitary condition that a person may not be aware of and use of the medicine in this case may lead to these symptoms.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if any of the following happen.

  • allergic reactions
  • angioedema (swelling of the face, lips, mouth, tongue or throat, which may cause difficulty in swallowing or breathing)
  • abdominal discomfort
  • swelling in the abdomen
  • blurred eye vision
  • visual impairment
  • diarrhoea
  • excessive sweating
  • weight gain
  • difficulty breathing, shortness of breath
  • decreased urination.

These are very serious side effects. You may need urgent medical attention or hospitalisation.

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

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

After using Decapeptyl

Storage

Keep Decapeptyl where children cannot reach it.

Keep Decapeptyl in the original pack until it is time for it to be used.

Store Decapeptyl in a refrigerator (2°C to 8°C). Do not freeze.

Disposal

If you are self-injecting, you should discard all sharps into a disposal unit.

If you have any Decapeptyl that has expired or is left over from your treatment refer this to your clinic.

Product description

What it looks like

This medicine is supplied as a colourless solution in a glass syringe of 1 mL to which a needle is connected. The syringe and needle are closed with a rubber stopper and a needle shield. This product is supplied as a pack of 7 or 28 pre-filled syringes.

Not all pack sizes may be marketed in Australia.

Ingredients

Each 1 mL pre-filled syringe of Decapeptyl contains, as the active ingredient, 100 micrograms triptorelin acetate (equivalent to 95.6 micrograms triptorelin).

The other ingredients are:

  • sodium chloride
  • glacial acetic acid
  • water for injections.

This medicine does not contain sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Decapeptyl is distributed in Australia by:

Ferring Pharmaceuticals Pty Ltd
Suite 2, Level 1, Building 1,
20 Bridge Street, Pymble NSW 2073

This leaflet was prepared in August 2015.

#36096-v2A

Australian Register Number:
AUST R 219857

Decapeptyl 100 micrograms/1 mL solution for injection

BRAND INFORMATION

Brand name

Decapeptyl Solution for subcutaneous injection

Active ingredient

Triptorelin acetate

Schedule

S4

 

1 Name of Medicine

Triptorelin acetate.

6.7 Physicochemical Properties

L-pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-tryptophyl-L-leucyl-L-arginyl-L-prolyl-glycinamide, acetate salt.
Molecular formula: C64H82N18O13 (free base); C64H82N18O13.C2H4O2 (triptorelin acetate).
Molecular weight: 1311.5 (net) + 60.1 (acetate) = 1371.6 (triptorelin acetate).

Chemical structure.


CAS number.

160296-12-8.

2 Qualitative and Quantitative Composition

Decapeptyl is for subcutaneous (s.c.) injection.
It consists of a clear, colourless solution containing 100 microgram of triptorelin acetate (equivalent to 95.6 microgram of triptorelin free base) in a prefilled syringe. The concentration of triptorelin is 95.6 microgram/1 mL (equivalent to triptorelin acetate 100 microgram/1 mL).
Decapeptyl contains sodium chloride, glacial acetic acid and water for injections.

3 Pharmaceutical Form

Triptorelin is a white to off-white powder, freely soluble in acetic acid, and soluble in water and in diluted acids and bases.
Appearance of the injection: Clear colourless solution.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Pharmacotherapeutic group: Gonadotropin releasing hormone analogues, ATC code: L02AE04.
Triptorelin, a gonadotropin releasing hormone (GnRH) agonist, inhibits gonadotropin secretion when given continuously and in therapeutic doses. After the administration of triptorelin there is an initial and transient increase in circulating follicle stimulating hormone (FSH) and luteinising hormone (LH) levels (flare up). Continued administration of triptorelin then results in decreased FSH and LH secretion with a consequent marked reduction in gonadal hormone production. The exact duration of action of Decapeptyl has not been established, but pituitary suppression is maintained for at least 6 days after stopping administration. After discontinuation of Decapeptyl, a further drop in circulating LH levels should be expected, with LH levels returning to baseline after approximately 2 weeks.
Decapeptyl induced down regulation of the pituitary can prevent the LH surge and thereby prevent premature ovulation and/or follicular luteinisation. The adoption of a down regulation agent is intended to reduce the cycle cancellation rate and improve the pregnancy rate in assisted reproductive technology (ART) cycles.

Clinical trials.

MFK/IVF/0399E and FE999906 CS003 were large randomised, multicentre studies comparing highly purified human menopausal gonadotrophin (HP-hMG) and recombinant follicle stimulating hormone (rFSH) in patients (18-38 years) undergoing controlled ovarian hyperstimulation for in vitro fertilisation/ intracytoplasmic sperm injection (IVF/ICSI) following the long GnRH agonist protocol starting in the midluteal phase (see Table 3). These clinical studies were not prospectively designed to test the efficacy of triptorelin.
In MFK/IVF/0399E, several GnRH agonists were used for down regulation. A total of 781 patients started down regulation, of whom 117 were given Decapeptyl 100 microgram. Adequate down regulation was established by serum estradiol < 200 picomol/L (56 picogram/mL) and no ovarian cysts.
In FE999906 CS003, patients (21-37 years) diagnosed with tubal or unexplained infertility, including endometriosis stage III/IV and mild male factor eligible for IVF, were enrolled. In this study, 781 patients started down regulation and all received Decapeptyl 100 microgram s.c. daily. Confirmation of down regulation prior to randomisation to HP-hMG or rFSH was defined as menstrual bleeding and transvaginal ultrasound showing a shedded endometrium with a thickness of < 5 mm and no ovarian cysts or serum estradiol (E2) < 50 picogram/mL and no ovarian cysts.
A total of 898 patients were exposed to Decapeptyl 100 microgram s.c. in these two studies. The primary endpoint in MFK/IVF/0399E and FE999906 CS003 was ongoing pregnancy rates (defined as at least one viable foetus at 10-11 weeks after embryo transfer) after one cycle. In FE999906 CS003, a strict protocol and treatment approach were implemented to minimize sources of variation in the study, including harmonisation of concomitant fertility treatments, a prespecified stimulation goal and homogeneity of other major prerandomisation and postrandomisation interventions.
The treatment outcome associated with different types of GnRH agonists can be derived from MFK/IVF/00399E. Comparative data with respect to ongoing pregnancy rate are shown in Table 4.
Among the 113 patients who were down regulated with Decapeptyl 100 microgram and underwent COH, the ongoing pregnancy rate was 24% (27/113). By comparison, the ongoing pregnancy rate was 21% for patients down regulated with Decapeptyl Depot 3.75 mg, and 25% for those who had used other GnRH agonists (daily or depot). Although this study was not designed to draw comparisons between different down regulation agents, these results suggest that the ongoing pregnancy rate when Decapeptyl 100 microgram s.c. daily was used is not different from the rates observed with the use of other GnRH agonists.

5.2 Pharmacokinetic Properties

Absorption.

Pharmacokinetic data suggest that after s.c. administration of the product, the systemic bioavailability of triptorelin is close to 100%. Following a single dose of triptorelin 250 microgram s.c. in healthy male subjects (n = 4), the mean maximum plasma concentration of triptorelin was 5.68 (range: 4.76 to 7.14) nanogram/mL (n = 4). Maximum plasma concentrations were reached approximately 45 minutes after s.c. administration.

Distribution.

Following an intravenous (i.v.) bolus injection of 500 microgram triptorelin to 19 female subjects, the drug is distributed and eliminated according to a 3-compartment model and the corresponding half-lives are 3.2 (range: 1.4 to 10.9) minutes, 46.1 (range: 20.2 to 138.1) minutes and 5.1 (range: 2.5 to 13.8) hours. The estimated volume of distribution at steady state of triptorelin was 28.9 (range: 13.1 to 78.6) L. Protein binding has not been investigated.

Metabolism.

Metabolites of triptorelin have not been determined in humans. However, human pharmacokinetic data suggest that C-terminal fragments produced by tissue degradation are either completely degraded within tissues or are rapidly further degraded in plasma, or cleared by the kidneys.

Excretion.

Triptorelin is either completely degraded within tissue or rapidly further degraded in plasma, or cleared by the kidneys. Following i.v. bolus injection of 500 microgram triptorelin to 19 female subjects the drug was distributed and eliminated according to a 3 compartment model. The mean terminal half-life was 5.1 (range: 2.5 to 13.8) hours. Average total clearance was estimated to 107 (range: 89 to 188) mL/min. Urinary excretion was investigated in 8 of the female subjects. Renal clearance over 24 hours was on average 25.3 (range: 5.3 to 45.4) mL/min. The mean percentage of the dose recovered in urine over the 24 hours was 16.7 (range: 3.4 to 34.6) %.

Special populations.

Patients with renal and liver impairment have also been studied after i.v. administration. This pharmacokinetic data is only available in male volunteers. Compared to young healthy adult males, mean triptorelin clearance was reduced by 43% in subjects with moderate renal impairment (mean creatinine clearance 40 mL/min), by 58% in subjects with severe renal impairment (mean creatinine clearance 8.9 mL/min) and by 73% in subjects with combined hepatic impairment (Child Pugh score 5-9) and a lower mean creatinine clearance (90 mL/min) than that of young healthy adult males.
These clinical studies indicate a risk of accumulation of triptorelin in patients with severe liver and renal impairment. However, the risk of accumulation appears to be small, given that the triptorelin terminal half-life is approximately 8 hours in these patients.
The effects of age and race on triptorelin pharmacokinetics have not been systematically studied.

5.3 Preclinical Safety Data

Genotoxicity.

In vitro tests for gene mutations in bacterial and mammalian cells and for chromosomal damage in vitro and in vivo (mouse micronucleus test) revealed no genotoxic activity for triptorelin.

Carcinogenicity.

Carcinogenicity studies were conducted in mice (18 months) and rats (up to 23 months) with microparticles containing triptorelin, administered once monthly by intramuscular injection. No carcinogenic effect was observed in mice with treatment at up to 6000 microgram/kg/month (equivalent to 214 microgram/kg/day), estimated to yield almost 4 times the clinical exposure at the maximum recommended human dose. In rats, pituitary adenomas and carcinomas were increased with treatment at all dose levels tested (≥ 120 microgram/kg/month; equivalent to 4.3 microgram/kg/day, and estimated to yield less than a sixth of clinical exposure at the maximum recommended human dose). Rats are recognised to be particularly sensitive to such effects of luteinising hormone releasing hormone (LHRH) analogues compared with other species. The clinical relevance of the finding is unknown, but considered likely to be low.

4 Clinical Particulars

4.1 Therapeutic Indications

Decapeptyl 100 microgram/1 mL is indicated for down regulation and prevention of premature luteinising hormone (LH) surges in women undergoing controlled ovarian hyperstimulation for assisted reproductive technologies (ART).
In clinical trials Decapeptyl 100 microgram/1 mL has been used in cycles where urinary and recombinant human follicle stimulating hormone (FSH) as well as human menopausal gonadotrophin (HMG) were used for stimulation.

4.3 Contraindications

Decapeptyl 100 microgram/1 mL is contraindicated in cases of:
hypersensitivity to triptorelin or to any of the excipients in Decapeptyl;
hypersensitivity to gonadotropin releasing hormone (GnRH) or any other GnRH analogue;
pregnancy and lactation;
women of childbearing potential should be examined carefully before treatment to exclude pregnancy.

4.4 Special Warnings and Precautions for Use

Identified precautions.

ART is associated with an increased risk of multiple pregnancies, pregnancy loss, ectopic pregnancies and congenital malformations. These risks are also valid with usage of Decapeptyl as adjunct therapy in controlled ovarian hyperstimulation.
Follicular recruitment, induced by the use of GnRH analogues and gonadotropins, may be markedly increased in a minority of predisposed patients, particularly in case of polycystic ovarian syndrome (PCOS).
Ovarian stimulation should be conducted under strict medical supervision.

Ovarian hyperstimulation syndrome.

The use of Decapeptyl in controlled ovarian hyperstimulation may increase the risk of ovarian hyperstimulation syndrome (OHSS) and ovarian cysts. As with other GnRH analogues there have been reports of OHSS associated with the use of triptorelin in combination with gonadotropins.
OHSS is a medical event distinct from uncomplicated ovarian enlargement. OHSS is a syndrome that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities.
The following symptoms may be observed in severe cases of OHSS: abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhoea. Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, haemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events.
Excessive ovarian response to gonadotropin treatment seldom gives rise to OHSS unless hCG is administered to trigger ovulation. Therefore in cases of OHSS it is prudent to withhold hCG and advise the patient to refrain from coitus or to use barrier methods for at least 4 days. OHSS may progress rapidly (within 24 hours to several days) to become a serious medical event, therefore patients should be followed for at least two weeks after the hCG administration.
OHSS may be more severe and more protracted if pregnancy occurs. This syndrome occurs with higher incidence in patients with polycystic ovarian disease. Most often, OHSS occurs after hormonal treatment has been discontinued and reaches its maximum severity at about seven to ten days following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If severe OHSS occurs, gonadotropin treatment should be stopped if still ongoing, the patient hospitalised and specific therapy for OHSS started, e.g. with rest, intravenous infusion of electrolyte solutions or colloids and heparin.
The risk of OHSS might be higher with use of GnRH agonists in combination with gonadotropins than with use of gonadotropins alone. In two clinical studies (MFK/IVF/0399E and FE999906 CS003), GnRH agonists, including Decapeptyl, were used in combination with gonadotropins, OHSS was reported in 6.5% and 3.1% of patients respectively.

Ovarian cysts.

Ovarian cysts may occur during the initial phase of treatment with GnRH agonists. They are usually asymptomatic and nonfunctional.

Bone loss.

Long term use of GnRH agonists may cause reduction in bone mineral density. Patients with known risk of osteopenia should discuss this with the treating physician.

Drugs/ conditions affecting pituitary secretion.

Rarely, treatment with GnRH agonists may reveal the presence of a previously unknown gonadotroph cell pituitary adenoma. These patients may present with a pituitary apoplexy characterised by sudden headache, vomiting, visual impairment and ophthalmoplegia. When triptorelin is coadministered with drugs affecting pituitary secretion of gonadotropins caution should be exercised and it is recommended that the patient's hormonal status should be supervised.

Mood changes.

Mood changes, including depression have been reported during long-term use. Patients with known depression should be monitored closely during therapy.

Use in atopic patients.

Special care should be taken in women with signs and symptoms of active allergic conditions or known history of allergic predisposition. Treatment with Decapeptyl is not advised in women with severe allergic conditions.

Use in hepatic impairment.

In patients with hepatic impairment, triptorelin has a mean terminal half-life of 7-8 hours compared to 3-5 hours in healthy subjects (see Section 5.2 Pharmacokinetic Properties). Despite this prolonged exposure, triptorelin is not expected to be present in circulation at the time of embryo transfer.

Use in renal impairment.

In patients with renal impairment, triptorelin has a mean terminal half-life of 7-8 hours compared to 3-5 hours in healthy subjects (see Section 5.2 Pharmacokinetic Properties). Despite this prolonged exposure, triptorelin is not expected to be present in circulation at the time of embryo transfer.

Use in the elderly.

Decapeptyl, a product for use in ART, is not indicated for use in the elderly.

Paediatric use.

Decapeptyl, a product for use in ART, is not indicated for use in the paediatric population.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions of Decapeptyl 100 microgram/1 mL with other medicines have not been investigated for this indication.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Decapeptyl is indicated for use in assisted reproductive technologies (see Section 4.1 Therapeutic Indications).
(Category D)
Decapeptyl 100 microgram/1 mL is contraindicated during pregnancy (see Section 4.3 Contraindications). Pregnancy must be excluded before initiation of fertilisation treatment. Nonhormonal methods of contraception should be employed during therapy until menses resume. If a patient becomes pregnant while receiving triptorelin, therapy should be discontinued.
When triptorelin is used for fertilisation treatment, there is no nonclinical or clinical evidence to suggest a causal connection between triptorelin and any subsequent abnormalities of oocyte development or pregnancy or outcome.
Very limited clinical data on the use of triptorelin during pregnancy does not indicate an increased risk of congenital malformations. Treatment of pregnant rats with triptorelin acetate at 10 microgram/kg/day by subcutaneous administration during early pregnancy resulted in retardation of fetal development and treatment in midpregnancy resulted in inhibition of parturition with frequent stillbirths. Administration of the drug during the period of organogenesis revealed no evidence of teratogenicity in rats or rabbits at subcutaneous doses up to 10 and 50 microgram/kg/day, respectively (0.9 and 9 times the clinical dose on a body surface area basis). Based on the pharmacological effects, disadvantageous influence on the pregnancy and the offspring cannot be excluded.
Decapeptyl is contraindicated for use during lactation (see Section 4.3 Contraindications).

4.8 Adverse Effects (Undesirable Effects)

The information presented in Table 1 is based on adverse events (AEs) and adverse drug reactions (ADRs), and their frequencies, reported in 7 clinical trials of Decapeptyl 100 microgram daily in down regulation and prevention of premature LH surges (N = 1329) combined with the postmarketing experience (presented in the not known category).
The following criteria were used in the selection of AEs/ ADRs that are presented throughout this section.
1. Clinical trials: treatment emergent AEs reported by at least 1% of the ART subjects receiving Decapeptyl 100 microgram daily.
2. Postmarketing safety surveillance: > 3 ADR reports of the ART subjects receiving Decapeptyl 100 microgram daily.
The most frequent adverse events reported in clinical trials and from postmarketing use are headache (5%), abortion (4%), dysmenorrhoea (2%), ovarian hyperstimulation syndrome (2%), injection site inflammation (1%) and nausea.
No anaphylactic reactions have been seen in clinical trials, and only very few cases of hypersensitivity reactions have been reported from postmarketing use.
Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug related adverse events and for approximating rates.
Studies MFK/IVF/0399E and FE999906 CS003 listed in Table 2 were not prospectively designed to test triptorelin and AEs reported during stimulation may not reflect events associated with triptorelin.

Postmarketing experience.

This postmarketing safety summary provides information on the daily dosing of triptorelin, formulation for ART indication, covering the period 1 January 1989 to 31 December 2013.
A total of 91 adverse drug reaction cases have been reported to Ferring Pharmaceuticals in this period. Out of 91 cases, 45 were reported as serious (14 unlisted and 29 listed) and 46 cases nonserious. Among the serious unlisted cases reported, there were two cases of OHSS reported in which other serious unlisted events were also reported (cerebral artery thrombosis, and ovarian haemorrhage). Also two serious unlisted cases each comprising ectopic pregnancy and paraesthesia were reported. In the remaining 10 serious unlisted cases, the following preferred terms were reported: pulmonary oedema, drug ineffective, pelvic inflammatory disease, exposure during pregnancy, genital pain, bundle branch block, hyperemesis gravidarum, cerebellar syndrome, thrombocytopenia, and blood pressure increased.
In three cases the subjects were exposed to daily dosing of triptorelin during the pregnancy. In two of these cases, the outcome of the pregnancy was a normal healthy baby was delivered. One case was confounded by the cosuspected drug clomipramine, used for obsessive compulsive disorder during pregnancy. The baby was discovered to have Down syndrome and an abortion was chosen.
In general, injection site reactions (inflammation and pain) were reported as non-serious, mild and reversible.

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 www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

The dosage regimen of Decapeptyl is 100 microgram given once daily as a 1 mL subcutaneous injection into the lower abdominal wall. Treatment with Decapeptyl 100 microgram/1 mL should be initiated under the supervision of a physician experienced in the treatment of infertility. Following the first administration, it is advised that the patient be kept under medical supervision for 30 minutes to ensure there is no allergic/ pseudoallergic reaction to the injection.
Subsequent injections of Decapeptyl may be self administered by the patient. In this instance the patient should first be instructed on appropriate self injection technique and be made aware of the signs and symptoms that may indicate hypersensitivity, the consequences of such a reaction and the need for immediate medical intervention should such a reaction occur. For detailed information on how to inject Decapeptyl, the patient should refer to the "Patient Instructions for Use Leaflet" provided with the product.

Injecting the medicine.

1. Remove the protective foil and take the syringe out of the blister packaging.
2. Keep the syringe upright with the grey protective cap facing up.
3. Remove the grey protective cap.
4. Gently push the plunger until the first drops of liquid appear at the needle tip.
5. The medicine is to be injected under the skin of the lower abdomen. Clean the injection site with an antiseptic swab immediately prior to injection.
6. Lift up a fold of skin between thumb and forefinger. With your free hand hold the syringe at a right angle to the skin like a dart and quickly insert the needle all the way into the skin fold. Press down slowly on the plunger to inject the contents of the syringe.
7. Remove the syringe and needle from the skin and discard this immediately into a sharps disposal unit.
8. For each dose, choose a different injection site along the lower abdomen.
Treatment can be started in the early follicular phase (day 2 or 3 of the menstrual cycle) or in the midluteal phase (day 21-23 of the menstrual cycle or 5-7 days before expected start of menses). Controlled ovarian hyperstimulation with gonadotropins should be started after approximately 2-4 weeks of Decapeptyl treatment. Ovarian response should be monitored clinically (including ovarian ultrasound alone or preferably in combination with measurement of oestradiol levels) and the dose of gonadotropins adjusted accordingly.
When a suitable number of follicles have reached an appropriate size, treatment with Decapeptyl and gonadotropin is stopped and a single injection of human chorionic gonadotrophin (hCG) is administered to induce the final follicular maturation. If down regulation is not confirmed after 4 weeks (determined by ultrasound documentation of a shedded endometrium alone or preferably in combination with measurement of oestradiol levels), discontinuation of Decapeptyl should be considered. The total duration of treatment is usually 4-7 weeks.
When using Decapeptyl, luteal phase support should be provided according to the reproductive medical centre's practice.
No specific dose recommendations are given for subjects with renal or hepatic impairment. A clinical study indicated that the risk of accumulation of triptorelin in patients with severe liver and renal impairment is small (see Section 5.2 Pharmacokinetic Properties).

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects of the ability to drive and use machines have been performed. However, due to its pharmacological profile Decapeptyl 100 microgram/1 mL is likely to have no or negligible influence on the patient's ability to drive and use machines.

4.9 Overdose

Overdose in humans may result in a prolonged duration of action. In the case of overdose, Decapeptyl treatment should be (temporarily) discontinued. No adverse reaction has been reported as a consequence of overdose.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

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 in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package, to protect from light.

6.5 Nature and Contents of Container

Each 1 mL syringe of Decapeptyl contains a solution of 100 microgram of triptorelin acetate equivalent to 95.6 microgram triptorelin free base.
1 mL solution in a pre-filled syringe (glass) with plunger stopper (chlorobutyl rubber), plunger rod (polystyrene), integrated needle and rigid needle shield in pack sizes of 7 or 28.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes