Ipsen Pharmaceuticals Ltd

Decapeptyl 3-month, 11.25mg

Powder and solvent for suspension for injection

Triptorelin (INN) 11.25 mg as triptorelin pamoate.

For excipients, see 6.1.

Powder and solvent for suspension for injection.

Slightly yellow lyophilised cake.

Solvent for suspension for injection:

Clear, colourless solution free of suspended particles.

Prostatic carcinoma.

In the management of advanced prostatic carcinoma.

Genital and extragenital endometriosis.

Precocious puberty ( onset before 8 years in girls and 9 years in boys)

-see section 5.1

For intramuscular injection only.

Prostatic carcinoma:

Male Adults only: one injection every three months.

Endometriosis:

Female adults only: one injection every three months.

The treatment must be started in the first five days of the menstrual cycle.

Treatment duration: this depends on the initial severity of the endometriosis and the changes observed in the clinical features (functional and anatomical) during treatment. In principle, the treatment should be administered for at least 3 months and for at most 6 months (see Section 4.8 Undesirable Effects). It is not recommended to start a second treatment course with triptorelin or another GnRH analogue.

Elderly patients:

No special requirements are needed in the elderly.

Precocious puberty

One intramuscular injection of Decapeptyl SR 11.25mg repeated every 3 months.

Treatment should be stopped around the physiological age of puberty in boys and girls and should not be continued in girls with a bone maturation of more than 12 years. There are limited data available in boys relating to the optimum time to stop treatment based on bone age, however it is advised that treatment is stopped in boys with a bone maturation age of 13-14 years.

Patients with liver disease or renal insufficiency:

No dosage reduction is required in patients with liver disease or renal insufficiency.

Hypersensitivity to the peptide or related peptides, or any other ingredient of the formulation.

This medication should never be used during pregnancy. Confirm that the patient is not pregnant before starting the treatment.

Prostatic carcinoma:

Initially, Decapeptyl 3-month like other GnRH analogues causes a transient increase in serum testosterone and consequent worsening of symptoms. These may include increased pain or activity in vertebral lesions, or in tumours giving urinary tract obstruction. Serum acid phosphatase levels may rise. Patients with such lesions should be closely monitored.

Consideration should be given to the use of an anti-androgen for several weeks at the beginning of Decapeptyl 3-month treatment, to counteract the effects of this initial rise in serum testosterone levels. The product should only be used under the supervision of an appropriate specialist having requisite facilities for regular monitoring of response. Initial treatment should be in hospital.

Endometriosis:

The administration of one Decapeptyl 3-month vial results in constant hypogonadotrophic amenorrhoea. During the first month of treatment a non-hormonal contraceptive should be given. The onset of metrorrhagia in the course of treatment is abnormal, apart from the first month. If this occurs, plasma oestradiol levels should be verified. Should oestradiol be less than 50 pg/ml possible associated organic lesions should be investigated.

Ovarian function resumes after the treatment is withdrawn. The return of menses after cessation of therapy with Decapeptyl 3-month may be delayed; the first menses occur on average 134 days after the last injection. If required, it may therefore be necessary to provide for contraception, three months after last injection.

No known interactions.

Data currently available concerning the effects of this type of product during pregnancy are summarised below:

- animal studies have not shown the product to have any teratogenic effects. No malformations are therefore expected in humans with this product as substances that cause malformations in humans have been found to be teratogenic in well-conducted animals studies.

- in clinical studies conducted to date, the use of GnRH analogues in a limited number of pregnant women has not resulted in any malformations or foetotoxicity. Nevertheless, further studies are required to study the consequences of exposure during pregnancy.

There is no evidence that Decapeptyl 3-month has any effect on the patient's ability to drive or operate machinery.

Decapeptyl 3-month is generally well-tolerated.

Undesirable effects in men:

The most frequent side-effects of hot flushes, decreased libido and impotence are a result of the decrease in testosterone levels. Bone pain and worsening of existing haematuria or urinary obstruction may occur occasionally as a result of "disease flare".

Transient secondary neuropathy, loss of hair, gastrointestinal disturbances, sweating, gynaecomastia, vertigo, and transient hypertension may occur.

Undesirable effects in women:

At the start of treatment:

Endometriosis-related symptoms (pelvic pain, dysmenorrhoea) may be exacerbated, during the initial and transient increase in plasma oestradiol levels, and should disappear in one or two weeks.

Metrorrhagia may occur in the month following the first injection.

During the treatment:

The most frequently reported effects, such as hot flushes, vaginal dryness, decreased libido and dyspareunia are related to pituitary-ovarian blockade.

A few rare cases of headache, arthralgia and myalgia have been reported.

In both men and women:

Allergic reactions such as urticaria, rash, pruritus and very occasionally, Quincke's oedema have been reported.

A few cases of nausea, vomiting, weight gain, hypertension, mood disorders, transient visual disturbances, pain and erythema at the injection site and fever have been reported.

Use of GnRH analogues may lead to bone loss, a risk factor for potential osteoporosis. On cessation of therapy, some recovery of bone mineral density may occur, but generally not to baseline levels.

In children

Mild or moderate withdrawal bleeding ( common) may occur in girls in the first month of treatment. Additional common adverse reactions may be observed such as injection site reactions and arthralgia.

According to the cumulative safety experience with triptorelin in children treated for precocious puberty, in addition the following rare reactions have been reported from post-marketing surveillance: allergic reactions, headache, weight gain, increased blood pressure, episodes of blurred or abnormal vision, gastrointestinal tract discomfort with abdominal pain and vomiting, epistaxis, malaise, myalgia , emotional lability, nervousness.

There is no human experience of overdosage. Animal data do not predict any effects other than those related to sex hormone concentration and consequent effect on the reproductive tract. If overdosage occurs, symptomatic management is indicated.

ATC Classification: Gonadotrophin-releasing hormone Analogue, L02AE04: antineoplasic and immunomodulator.

Triptorelin is a synthetic decapeptide (D-Trp6 GnRH) analogue of natural GnRH. Studies in animals and man have shown that continued administration of triptorelin exerts, after a short initial stimulation, an inhibitory effect on the gonadotrophin secretion with consequent suppression of testicular and ovarian function.

The first administration of Decapeptyl 3-month stimulates the release of pituitary gonadotrophins with a transient increase in testosterone levels ("flare-up"). Prolonged administration leads to a suppression of gonadotrophins and a fall in plasma testosterone to castrate levels after approximately 20 days and which continues for as long as the product is administered.

The treatment suppresses oestradiol secretion in women and thus enables resting of ectopic endometrial tissue.

One, non-comparative, open label study was undertaken in children with central precocious puberty to assess the efficacy of Decapeptyl SR 11.25mg to suppress pubertal development as defined by onset of development of sex characteristics before the age of 8 years for girls and 9 years for boys and a pubertal response of LH to luteinizing hormone releasing hormone ( LHRH ) 7 IU/L.

Sixty four patients ( 54 girls and 10 boys) were enrolled and received the first injection, with 61 (51 girls and 10 boys) receiving all four injections and completing study visits up to month 12.

53 children ( 45 girls (83%) and 8 boys (80%)) had suppressed LH response ( LH 3 IU/L) to LHRH challenge, three months after the injection. At 6 months the corresponding proportions were 51 girls (94%) and 9 boys (90%) and at 12 months 49 girls (91%) and 7 boys (70%).

Stabilisation of the height standard deviation score was observed in 35/51 (69%) and 7/10 (70%) boys at month 12. Stabilisation of the difference in bone age – chronological age and a decrease in the growth velocity were also observed at month 12.

Most patients (51/54 girls and 10/10 boys) achieved a regression or stabilisation of their secondary sex characteristics: all girls had stable or decreased breast development at month 12 (69% regression) and all boys had decreased or stable genital development at month 12 (70% regression).

Nine children (14%) experienced side-effects, four patients with local reaction at the injection site and five patients with withdrawal bleeding. Two patients experienced injection site pain.

Following intramuscular injection of Decapeptyl 3-month in patients (men and women), a peak in plasma triptorelin is observed approximately 3 hours after injection. After a phase of decrease, which continues during the first month, the circulating triptorelin levels remain stable until day 90.

In vitro and animal toxicology studies have not shown any specific toxic potential for triptorelin. The observed effects are related to the pharmacological properties of triptorelin on the endocrine system.

The resorption of Decapeptyl 3-month is complete in 120 days.

D, L Lactide coglycolide polymers

Mannitol

Sodium carmellose

Polysorbate 80,

Water for injections.

Not applicable. The product is not intended for admixture.

3 years. The product should be used immediately after reconstitution. Any remaining product should be discarded.

The shelf life expiry date of the solvent shall not exceed five years from the date of its manufacture.

Store below 25 °C.

Powder for suspension for injection:

Type I, clear slightly tinted glass vial (4 ml capacity)

Solvent for suspension for injection:

2 ml Type 1 clear glass ampoule

Box containing 1 vial and 1 ampoule with 1 syringe and 2 needles. The injection needle is equipped with a safety shield.

The solvent should be drawn into the syringe provided and transferred to the vial containing the powder for injection. The vial should be gently shaken and the mixture then drawn back into the syringe without inverting the vial. The needle should then be changed and the green needle used to administer the injection immediately.

Immediately following the injection procedure, lock the safety needle shield.

Only grasp the coloured hub to disconnect needle from the syringe.

Dispose of used needles in a designated sharps container.

Ipsen Pharmaceuticals Ltd

7 Upper Leeson Street

Dublin 4

Ireland

Trading as:

Ipsen Pharmaceuticals

PA 869/3/2

2^nd October 1998/ 2^nd October 2003

August 2008