SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Novgos 3.6 mg Implant

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

One implant contains 3.6 mg goserelin (as goserelin acetate)

Excipients:

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Implant, pre-filled syringe.

The sterile, cylindrical, white to cream coloured implant is placed in a sterile injection needle.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Novgos is a luteinization hormone releasing hormone (LHRH)- Agonist (analogue of the natural LHRH).

Novgos is used for treatment of patients with advanced prostate cancer where endocrine treatment is indicated.

4.2 Posology and method of administration

1 implant every month.

Novgos is injected subcutaneously into the anterior abdominal wall.

Generally treatment of prostate cancer with Goserelin is a long-term treatment. Regular control examinations as performed usually in prostate cancer patients are recommended to assess the therapeutic effect.

Remarks for injection technique:

1.    The implant consists of two bags, the sterile injection needle and the sterile applicator. Note that the implant is visibly fixed in the injection needle. Open both bags and connect the injection needle to the applicator via the Luer lock. Make sure that the connection is tight and that the plunger remains unchanged in its position.

2.    Check that the implant is visible in the control window in the needle.

3.    Remove the locking device from the plunger. Insert the cannula into the anterior abdominal wall and insert the implant by depressing the plunger completely.

Paediatric Patients

Novgos is contraindicated in children and adolescents (see section 4.3).

Special Patient Groups

No dosage or interval adjustment is necessary for patients with renal or hepatic impairment or in the elderly.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Novgos is not indicated for use in children and adolescents, as efficacy and tolerability for this group of patients has not been investigated.

4.4 Special warnings and precautions for use

Special caution should be given to patients at particular risk of developing ureteric obstruction or spinal cord compression. Administration of Novgos should be carefully judged and closely monitored during the first months of therapy.

If spinal cord compression or renal impairment due to ureteric obstruction are present or develop, specific standard treatment of these complications should be instituted.

Consideration should be given to the initial use of an anti-androgen at the start of Novgos therapy since this has been reported to prevent the possible sequelae.

Continuous suppression of sexual hormone production leads to infertility in men.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6 Fertility, Pregnancy and lactation

Not applicable as Novgos is intended for male patients only.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects

The adverse events are listed by system organ class and frequency using the

following convention:

very common (>1/10)

common (>1/100 to <1/10)

uncommon (>1/1,000 to <1/100)

rare (>1/10,000 to <1/1,000)

very rare (<1/10,000), not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

General

Cardiac disorders:

uncommon:    changes in blood pressure (hypotension or

hypertension)

Nervous system disorders:

very common:    non-specific paraesthesias

very rare:    pituitary apoplexy following initial    administration

Skin and subcutaneous tissue disorders:

common:    mild skin rash

Musculoskeletal and connective tissue disorders:

very rare:    arthralgia/bone pain

General disorders and administration site conditions:

rare:    local reactions at the injection site

Immune system disorders:

rare:    hypersensitivity reactions, including    symptoms of

anaphylaxis

At the beginning of the therapy

Initially, there is a short-term increase in serum testosterone inducing a temporary increase of specific symptoms:

Nervous system disorders:

very rare:    spinal cord compression

Renal and urinary disorders:

very rare:    ureteric obstruction (due to obstruction of the urinary

tract passage)

Musculoskeletal and connective tissue disorders: common:    bone pain

In these cases, the patients must be closely monitored and treated symptomatically during the first month of treatment.

During the therapy

Due to the decrease in serum testosterone during the treatment the use of LHRH-agonists causes loss in bone mineral density. For this reason, during long-term therapy with Novgos an increased fracture risk cannot be excluded, although no increased fracture rates have been observed so far.

Nervous system disorders:

very rare:    pituitary adenomas

Endocrine disorders:

very common:    hot flushes and sweating

Reproductive system and breast disorders:

very common:    decrease in libido and potency, testicular atrophy

common:    breast swelling

very rare:    breast tenderness

Pituitary adenomas occur more often in prostate cancer patients. However, as no medical reports on the initial state of the pituitary gland were available for these few cases monitored under treatment, it cannot be excluded with certainty that their development was favoured by the use of Novgos.

4.9 Overdose

There is only limited experience of overdosage in humans. In cases where goserelin has unintentionally been re-administered early or given at a higher dose, no clinically relevant adverse reactions have been seen.

Animal tests suggest that no effect other than the intended therapeutic effects on sex hormone concentrations and on the reproductive tract will be evident with higher doses.

In case of toxication symptomatic treatment is required.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: LHRH-agonist ATC code: L02A E03

The treatment with Novgos in men leads to fall of serum testosterone to the castration range.

Treatment with Novgos causes inhibition of growth or regression of hormone dependent cancer of the prostatic gland (oestradiol and/or progesterone receptor positive tumours).

Biosynthesis and secretion of the male and female sexual hormones (testosterone and oestradiol, respectively) are controlled by the hypothalamic LHRH and by luteinization hormone (LH) and follicle stimulating hormone (FSH) which are produced in the pituitary gland. The pulsating release of the natural LHRH from the hypothalamus triggers synthesis and excretion of LH and FSH from the anterior lobe of the pituitary gland.

Goserelin acetate, the active substance of Novgos, is a LHRH analogue with higher activity and longer half life as the natural hormone.

Long-term treatment with goserelin acetate leads to a receptor-down-regulation of the pituitary gland. The number of LHRH- receptors decreases. Thereby LH and FSH secretion and biosynthesis of oestradiol and testosterone in the gonads is suppressed.

After an initial increase during the first 3-5 days in men testosterone levels decrease. Castration range is normally achieved between the second and third week after the beginning of treatment with Novgos. Suppression of serum testosterone with Novgos is equal to the results of orchiectomy.

5.2 Pharmacokinetic properties

The active substance is spread in a completely biodegradable matrix of Poly(D,L-lactide-co-glycolide). An average of 120 pg goserelin per day is released from Novgos. Seven to14 days after administration of Novgos, the maximum serum levels of goserelin are achieved. Subsequently they slowly fall during the third and fourth week of therapy. No accumulation occurs.

Goserelin slightly binds to serum protein (25 %). After subcutaneous administration of a single dose (aqueous solution of 250 pg) of goserelin in patients with normal renal function, elimination half time of 4.2 h in men was observed.

The influence of impaired renal function on goserelin serum levels and total body clearance has been investigated in male patients suffering from prostate cancer. With increasing renal impairment elimination of the substance was delayed. In this case, a close correlation between creatinine clearance and total body clearance could be shown.

However, goserelin was eliminated relatively fast (half-life 12.1h) in patients with severe renal impairment (creatinine-clearance <20ml/min), leading to the conclusion of an additional non-renal elimination pathway possibly located in the liver. Accumulation of goserelin associated with chronic application can therefore not be expected in patients with limited renal impairment.

There is no significant change in pharmacokinetics in patients with hepatic failure.

5.3 Preclinical safety data

Preclinical studies with LHRH agonists revealed in both sexes effects on the reproductive system, which were expected from the known pharmacological properties. These effects were shown to be reversible after discontinuation of the treatment and a due period of regeneration.

Goserelin acetate did not show teratogenicity in rats and rabbits. Based on the pharmacological effects of LHRH agonists on the reproductive system, embryotoxicity and -lethality was observed in rabbits.

Goserelin acetate was not mutagenic in a set of in vitro and in vivo assays.

Carcinogenicity studies were performed with other LHRH analogues in rats and mice over 24 months. In rats, a dose-related increase in pituitary adenomas was observed after subcutaneous administration at doses of 0.6 to 4 mg/kg/day. No such effect was observed in mice, allowing to regard the effect in rats as species-specific, having no relevance for humans.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Poly(D,L-lactide-co-glycolide) (1:1).

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

Do not store above 25 °C.

Store in the original package.

6.5 Nature and contents of container

Each implant is placed in a sterile, siliconised stainless steel injection needle closed with a Luer-Lock screw cap and a needle cover. The needle unit is packaged together with a desiccant in a polyester/aluminium/polyethylene pouch. A sterilised applicator is provided packed in a separate pouch.

Novgos is available in packs of 1, 3 and 6 implants.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Acino AG Am Windfeld 35 D-83714 Miesbach Germany

8    MARKETING AUTHORISATION NUMBER(S)

PL 21806/0044

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

02/04/2009

10 DATE OF REVISION OF THE TEXT

27/02/2013