2017-6-2
`
`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
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`Ipsen Pharmaceuticals Ltd
`Blanchardstown Industrial Park, Blanchardstown, Dublin 15,
`Telephone: 00441753 627 777
`Telephone: 01 8098256
`Fax: + 353 1 8098450
`Medical Information e-mail: medical.information.uk@ipsen.com
`
`SPC
`
`Decapeptyl (tr iptorelin) SR
`
`Table of Contents
`
`Summary of Product Characteristics last updated on medicines.ie: 6/1/2017
`
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`Legal Categories
`Product subject to medical
`prescription which may not
`be renewed (A)
`
`Active Ingredients
`
`triptorelin acetate
`
`1. NAME OF THE MEDICINAL PRODUCT
`2. QUALITATIVE AND QUANTITATIVE COMPOSmON
`3. PHARMACEUTICAL FORM
`4. CUNICAL PARTICUlARS
`4.1 Therapeutic indications
`4.2 Posology and method of administration
`4.3 Contraindications
`4.4 Special warnings and precautions for use
`4.5 Interaction with other medicinal products and other forms of interaction
`4.6 Fertility, pregnancy and lactation
`4.7 Effects on ability to drive and use machines
`4.8 Undesirable effects
`4.9 Overdose
`5. PHARMACOLOGICAL PROPERTIES
`5.1 Pharmacodynamic properties
`5.2 Pharmacokinetic properties
`5.3 Preclinical safety data
`6. PHARMACEUTICAL PARTICULARS
`6.1 List of excipient(s)
`6.2 Incompatibilities
`6.3 Shelf life
`6.4 Special precautions for storage
`6.5 Nature and contents of container
`6.6 Special precautions for disposal and other handling
`7. MARKETING AUTHORISATION HOLDER
`8. MARKETING AUTHORISATION NUMBER(S)
`9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
`10. DATE OF REVISION OF THE TEXT
`
`11. NAME OF THE MEDICINAL PRODUCT
`Decapeptyl SR, 3 mg powder and solvent for suspension for injection
`
`12. QUALITATIVE AND QUANTITATIVE COMPOSITION
`
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`
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`
`Each vial contains the quantity of triptorelin (as triptorelin acetate) to ensure that the minimum quantity injected is 3 mg.
`
`A 2 ml ampoule of solvent for suspension is provided in each pack.
`
`Once reconstituted, 1 ml of the suspension contains 1.5 mg triptorelin at a minimum.
`
`For a full list of excipients, see section 6.1.
`
`I 3. PHARMACEUTICAL FORM
`
`Powder and solvent for suspension for injection.
`
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`
`A sterile, white to off-white, lyophilised powder which, when reconstituted as directed with the clear, colourless, sterile
`liquid, yields a sterile suspension for injection.
`
`14. CUNICAL PARTICULARS
`
`14.1 Therapeutic indications
`
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`2017-6-2
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`Prostatic carcinoma
`
`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`In the management of advanced prostatic carcinoma
`
`Uterine fibromyomas
`
`Treatment of uterine fibromyomas
`
`Endometriosis
`
`Genital and extragenital endometriosis
`
`Breast cancer
`
`As adjuvant treatment in combination with tamoxifen or an aromatase inhibitor, of endocrine responsive early stage
`breast cancer in women at high risk of recurrence who are confirmed as pre-menopausal after completion of
`chemotherapy (see Sections 4.3, 4.4, 4.8 and 5.1),
`
`Female infertility
`
`Complementary treatment in association with the gonadotropins (hMG, FSH and hCG) in the course of ovulation
`induction in view of in-vitro fertilisation and embryo transfer (I.V.F.E.T.).
`
`14.2 Posology and method of administration
`
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`
`Prostatic cancer:
`
`Male adults only:
`
`One intramuscular injection of Decapeptyl SR (3 mg) every 28 days.
`
`No special requirements are needed for the elderly.
`
`In patients with metastatic castration resistant prostate cancer not surgically castrated receiving triptorelin and eligible
`for treatment with androgen biosynthesis inhibitors, treatment with triptorelin needs to be continued.
`
`Uterine fibromyomas:
`
`The treatment must be initiated in the first five days of the cycle. The recommended dose is one intramuscular injection
`every 28 days.
`
`Injection schedule: this depends on the change in volume of the fibromyomas, assessed by ultrasonography.
`
`In principle, fibromyomas should be treated for at least 4 months and for a maximum of 6 months. A second course of
`treatment by Decapeptyl SR or by other GnRH analogues should not be undertaken.
`
`Breast cancer
`
`One intramuscular injection every 4 weeks in combination with tamoxifen or an aromatase inhibitor. Triptorelin should be
`commenced after completion of chemotherapy, once pre-menopausalstatus has been confirmed (see section 4.4). The
`treatment with triptorelin must be initiated at least 6-8 weeks weeks before starting aromatase inhibitor treatment. A
`minimum of two injections of triptorelin (with an interval of 4 weeks between injections) should be administered before
`commencement of aromatase inhibitor treatment.
`
`During treatment with an aromatase inhibitor, triptorelin must not be interrupted in order to avoid rebound increases in
`circulating oestrogens in premenopausal women.
`
`The recommended treatment duration for adjuvant treatment in combination with other hormonotherapy is up to 5
`years.
`
`Since Decapeptyl SR 3.75 mg is a suspension of microparticles, inadvertent intravascular injection must be strictly
`avoided.
`
`Endometriosis:
`
`The treatment must be initiated in the first five days of the cycle.
`
`Injection schedule: one intramuscular injection of Decapeptyl SR every 28 days.
`
`Duration of treatment: this depends on the initial severity of endometriosis and the change in clinical manifestations
`(functional and anatomical) during treatment.
`
`In principle, endometriosis should be treated for at least 4 months and for a maximum of 6 months.
`
`A second course of treatment by Decapeptyl SR or by other GnRH analogues should not be undertaken.
`
`Female infertility:
`
`One intramuscular injection of Decapeptyl SR administered on the second day of the cycle. In general, the stimulation by
`gonadotropins should be performed when the blood level of oestrogens are less than 50 pg/ml (usually around the 15th
`day of the cycle).
`
`14.3 Contraindications
`
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`2017-6-2
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`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`Hypersensitivity to GnRH (gonadotropin releasing hormone), its analogues or to any of the excipients listed in section
`6.1.
`
`Pregnancy and lactation
`
`In the pre-menopausal breast cancer setting: Initiation of aromatase inhibitor treatment before adequate ovarian
`suppression with triptorelin has been achieved (see sections 4.2 and 4.4).
`
`14.4 Special warnings and precautions for use
`
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`
`The use of GnRH agonists may cause a reduction in bone mineral density. In men, preliminary data suggest that the use
`of a bisphosphonate in combination with an GnRH agonist may reduce bone mineral loss. No specific data is available for
`patients with established osteoporosis or with risk factors for osteoporosis (e.g. chronic alcohol abuse, smokers, long-
`term therapy with drugs that reduce bone mineral density, e.g. anticonvulsants or corticosteroids, family history of
`osteoporosis, malnutrition, e.g. anorexia nervosa). Particular caution is therefore necessary since reduction in bone
`mineral density is likely to be more detrimental in these patients. Treatment with Decapeptyl SR should be considered on
`an individual basis and only be initiated if the benefits of treatment outweigh the risk following a very careful appraisal.
`Consideration should be given to additional measures in order to counteract loss of bone mineral density.
`
`Adjustment of antihypertensive therapy may be required in patients receiving such medication.
`
`It should be confirmed that the patient is not pregnant before prescription of triptorelin.
`
`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.
`
`There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH
`agonists, such as triptorelin. Patients should be informed accordingly and treated as appropriate if symptoms occur.
`Patients with known depression should be monitored closely during therapy.
`
`This medicinal product contains less than 1 mmol of sodium (23 mg) per dose and is considered essentially 'sodium-
`free'.
`
`Prostate cancer
`
`Initially, Decapeptyl SR, like other GnRH agonists, causes a transient increase in serum testosterone levels. As a
`consequence, isolated cases of transient worsening of signs and symptoms of prostate cancer may occasionally develop
`during the first weeks of treatment. During the initial phase of treatment, consideration should be given to the additional
`administration of a suitable anti-androgen to counteract the initial rise in serum testosterone levels and the worsening of
`clinical symptoms.
`
`A small number of patients may experience a temporary worsening of signs and symptoms of their prostate cancer
`(tumour flare) and temporary increase in cancer related pain (metastatic pain), which can be managed symptomatically.
`
`As with other GnRH agonists, isolated cases of spinal cord compression or urethral obstruction have been observed. If
`spinal cord compression or renal impairment develops, standard treatment of these complications should be instituted,
`and in extreme cases an immediate orchidectomy (surgical castration) should be considered. Careful monitoring is
`indicated during the first weeks of treatment, particularly in patients suffering from vertebral metastasis, at the risk of
`spinal cord compression, and in patients with urinary tract obstruction.
`
`After surgical castration, Decapeptyl SR does not induce any further decrease in serum testosterone levels.
`
`Long-term androgen deprivation either by bilateral orchidectomy or administration of GnRH agonists is associated with
`increased risk of bone loss and may lead to osteoporosis and increased risk of bone fracture.
`
`Androgen deprivation therapy may prolong the QT 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 (see section 4.5) physicians should assess the benefit risk ratio including the potential
`for Torsade de pointes prior to initiating Decapeptyl SR.
`
`In addition, from epidemiological data, it has been observed that patients may experience metabolic changes (e.g.
`glucose intolerance), or an increased risk of cardiovascular disease during androgen deprivation therapy. However,
`prospective data did not confirm the link between treatment with GnRH analogues and an increase in cardiovascular
`mortality. Patients at high risk for metabolic or cardiovascular diseases should be carefully assessed before commencing
`treatment and during androgen deprivation therapy.
`
`Administration of triptorelin in therapeutic doses result in suppression of the pituitary gonadal system. Normal function is
`usually restored after treatment is discontinued. Diagnostic tests of pituitary gonadal function conducted during
`treatment and after discontinuation of therapy with GnRH agonists may therefore be misleading.
`
`Endometriosis and Uterine Fibromyomas
`
`The use of GnRH agonists is likely to cause reduction in bone mineral density averaging 1% per month during a six
`month treatment period. Every 10% reduction in bone mineral density is linked with about a two to three times
`increased fracture risk.
`
`In the majority of women, currently available data suggest that recovery of bone loss occurs after cessation of therapy.
`
`Used at the recommended dose, Decapeptyl SR causes constant hypogonadotropic amenorrhoea. If vaginal
`haemorrhage occurs after the first month, plasma oestradiol levels should be measured and if levels are below 50
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`LUYE1027
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`IPR2016-01096
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`

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`2017-6-2
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`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`pg/ml1 possible organic lesions should be investigated.
`
`After withdrawal of treatment1 ovarian function resumes and ovulation occurs approximately 2 months after the last
`injection. A non-hormonal method of contraception should be used throughout treatment including for 1 month after the
`duration of the last injection.
`
`Since menses should stop during Decapeptyl SR treatment/ the patient should be instructed to notify her physician if
`regular menstruation persists.
`
`It is recommended that during treatment of uterine fibroids1 the size of the fibroid is determined regularly. There have
`been a few reports of bleeding in patients with submucous fibroids following GnRH analogue therapy. Typically the
`bleeding has occurred 6 - 10 weeks after the initiation of therapy.
`
`Breast cancer
`
`In order to ensure adequate ovarian suppression in premenopausal women/ treatment with triptorelin should be
`administered for at least 6-8 weeks prior to commencement of an aromatase inhibitor and monthly triptorelin injections
`should be administered on schedule and without interruption throughout aromatase inhibitor treatment.
`
`Women who are premenopausal at diagnosis and who become amenorrhoeic with chemotherapy may have continued
`oestrogen production from the ovaries without menses. Serial assessment of circulating FSH 1 and oestradiol to assure a
`true postmenopausal status is required if this subset of women is to be considered for therapy with an aromatase
`inhibitor (NCCN Guidelines for Breast Cancer). Accordingly/ ovarian suppression should be confirmed by low blood
`concentrations of FSH and oestradiol prior to starting aromatase inhibitor treatment and measurements should be
`repeated every three months during this combination therapy with triptorelin and an aromatase inhibitor. This is to avoid
`aromatase inhibitor-induced rebound increase in circulating oestrogen/ with consequential implications for breast cancer.
`Of note1 circulating FSH levels are lowered in response to gonadotrophin analogue-induced ovarian suppression1 unlike
`in a natural menopause where FSH levels are elevated.
`
`Triptorelin1when used as adjuvant therapy in combination with tamoxifen or anaromatase inhibitor/ is associated with a
`high risk of osteoporosis. Osteoporosis has been reported with a higher frequency following the use of triptorelin in
`combination with aromatase inhibitor than in the combination with tamoxifen (39% vs 25%).
`
`Bone mineral density should be assessed before starting treatment with triptorelin1 especially in women who have
`multiple risk factors for osteoporosis. These patients should be closely monitored and treatment for1 or prophylaxis of1
`osteoporosis should be initiated when appropriate.
`
`Treatment of premenopausal women with endocrine responsive early stage breast cancer with triptorelin in combination
`with tamoxifen or an aromatase inhibitor should follow a careful individual appraisal of the risks and benefits.
`
`Patients who have discontinued triptorelin treatment should also discontinue aromatase inhibitors within 1 month of the
`last triptorelin administration (1 month formulation).
`
`The risk of musculoskeletal disorders (including joint or musculoskeletal pain) when triptorelin is used in combination
`with either an aromatase inhibitor or tamoxifen is approximately 89% with the AI and approximately 76% with
`tamoxifen.
`
`Hypertension was reported as a targeted adverse event at a very common frequency with triptorelin in combination with
`either exemestane or tamoxifen (see section 4.8). Premenopausal women with breast cancer receiving triptorelin in
`combination with either exemestane or tamoxifen should have regular monitoring of cardiovascular risk factors and
`blood pressure.
`
`Hyperglycaemia and diabetes were reported as targeted adverse events at a common frequency with triptorelin in
`combination with either exemestane or tamoxifen (see section 4.8). Premenopausal women with breast cancer receiving
`triptorelin in combination with either exemestane or tamoxifen should have regular monitoring of risk factors for diabetes
`with blood glucose monitoring on a regular basis and appropriate anti-diabetic treatment initiated1 if appropriate/
`according to national guidelines.
`
`Depression occurred in approximately 50% of patients treated with triptorelin in combination with either tamoxifen or
`exemestane in all treatment groups in the TEXT and SOFT studies1 but less than 5% of patients had severe depression
`(grade 3-4). Patients should be informed accordingly and treated as appropriate if symptoms occur. Patients with known
`depression or depression history should be carefully monitored during therapy.
`
`Particular attention should also be paid to the exemestane and tamoxifen prescribing information for relevant safety
`information when administered in combination with triptorelin.
`
`Chemotherapy can induce temporary amenorrhoea or a permanent loss of ovarian function due to cytotoxic damage of
`gonadal tissue. Retention of pre-menopausal status following completion of chemotherapy should be confirmed as
`recommended by clinical guidelines (NCCN Guidelines for Breast Cancer) by blood concentrations of oestradiol and FSH
`within the reference ranges for pre-menopausal women.
`
`Female infertilitv
`
`The induction of ovulation should be monitored under rigorous medical supervision with strict and regular biological and
`clinical control by fast plasma oestrogen assay and ultrasonography. As with other GnRH analogues there have been
`reports of ovarian hyperstimulation syndrome (OHSS) associated with the use of triptorelin in combination with
`gonadotropins.
`
`In cases of excessive ovarian response/ interruption of the stimulation cycle by stopping the injections of gonadotropins
`is recommended.
`
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`4/15
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`Luye Pharma Group Ltd., et al. v. Alkermes Pharma Ireland Ltd.
`IPR2016-01096
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`

`

`2017-6-2
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`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`The increase in the follicular retrieval induced by injection of Decapeptyl SR when associated with gonadotropins may be
`great in some predisposed patients and particularly in cases of polycystic ovarian disease. The ovarian response to the
`triptorelin-gonadotropin treatment may differ with the same doses from one patient to another, and in certain cases,
`from one cycle to another in the same patient.
`
`In patients with renal or hepatic impairment, triptorelin has a mean terminal half life of 7-8 hours compared to 3-5 hours
`in healthy subjects. Despite this prolonged exposure, triptorelin is not expected to be present in circulation at the time of
`embryo transfer.
`
`14.5 Interaction with other medicinal products and other forms of interaction
`
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`
`Hyperprolactinemic drugs should not be prescribed concomitantly as they reduce the level of GnRH receptors in the
`pituitary.
`
`When Decapeptyl SR is co-administered with drugs affecting pituitary secretion of gonadotropins, caution should be
`exercised and it is recommended that the patient's hormonal status be supervised.
`
`Since androgen deprivation treatment may prolong the QT interval, the concomitant use of Decapeptyl SR with medicinal
`products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g.
`quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products,
`methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4).
`
`14.6 Fertility, pregnancy and lactation
`
`Decapeptyl SR should not be used during pregnancy since concurrent use of GnRH agonists is associated with a
`theoretical risk of abortion or foetal abnormality. Prior to treatment, potentially fertile women should be examined
`carefully to exclude pregnancy. Non-hormonal methods of contraception should be employed during therapy until
`menses resume.
`
`Pregnancy should be excluded before triptorelin is used for fertilisation treatment. When Decapeptyl SR is used in this
`setting, there is no clinical evidence to suggest a causal connection between Decapeptyl SR and any subsequent
`abnormalities of oocyte development or pregnancy or outcome.
`
`Decapeptyl SR should not be used during breast-feeding.
`
`14.7 Effects on ability to drive and use machines
`
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`
`No studies on the effects on the ability to drive and use machines have been performed. However, the ability to drive
`and use machines may be impaired should the patient experience dizziness, somnolence and visual disturbances (being
`possible undesirable effects of treatment), or resulting from the underlying disease.
`
`14.8 Undesirable effects
`
`Clinical trials experience
`
`General tolerance in men
`
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`
`Since patients suffering from locally advanced or metastatic, hormone-dependent prostate cancer are generally old and
`have other diseases frequently encountered in this aged population, more than 90% of the patients included in clinical
`trials reported adverse events, and often the causality is difficult to assess. As seen with other GnRH agonist therapies
`or after surgical castration, the most commonly observed adverse events related to triptorelin treatment were due to its
`expected pharmacological effects. These effects included hot flushes and decreased libido.
`
`With the exception of immuno-allergic (rare) and injection site ( < 5%) reactions, all adverse events are known to be
`related to testosterone changes.
`
`The following adverse reactions considered as at least possibly related to triptorelin treatment were reported. Most of
`these events are known to be related to biochemical or surgical castration.
`
`The frequency of the adverse reactions is classified as follows: very common (2::1/10); common (2::1/100, < 1/10);
`uncommon (2::1/1000, < 1/100); rare (2:: 1/10000, < 1/1000).
`
`System Organ
`Class
`
`Infections and
`infestations
`
`Very common
`
`Common
`
`Uncommon
`
`Rare
`
`Nasopharyngitis
`
`Additional
`post-
`marketing
`AEs
`
`Frequency not
`known
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`2017-6-2
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`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`Blood and
`lymphatic
`system
`disorders
`
`Immune system
`disorders
`
`Metabolism and
`nutrition
`disorders
`
`Psychiatric
`disorders
`
`Thrombocytosis
`
`Hypersensitivity
`
`Anaphylactic
`reaction
`
`Anaphylactic
`shock
`
`Anorexia
`
`Diabetes mellitus
`
`Gout
`
`Hyperlipidaemia
`
`Increased appetite
`
`Libido decreased Depression*
`
`Insomnia
`
`Confusional state Anxiety
`
`Loss of libido
`
`Irritability
`
`Decreased activity
`
`Mood change*
`
`Euphoric mood
`
`Nervous system Paraesthesia in
`lower limbs
`disorders
`
`Dizziness
`
`Headache
`
`Paraesthesia
`
`Memory
`impairment
`
`Eye disorders
`
`Ear and
`labyrinth
`disorders
`
`Cardiac
`Disorders
`
`Vascular
`disorders
`
`Respiratory,
`thoracic and
`mediastinal
`disorders
`
`Visual impairment Abnormal
`sensation in eye
`
`Visual disturbance
`
`llnnitus
`
`Vertigo
`
`Palpitations
`
`QT prolongation
`(see sections
`4.4 and 4.5)
`
`Hot flush
`
`Hypertension
`
`Hypotension
`
`Dyspnoea
`
`Epistaxis
`
`Orthopnoea
`
`Gastrointestinal
`disorders
`
`Dry mouth
`
`Abdominal pain
`
`Nausea
`
`Constipation
`
`Skin and
`subcutaneous
`tissue disorders
`
`Hyperhidrosis
`
`Diarrhoea
`
`Vomiting
`
`Acne
`
`Alopecia
`
`Erythema
`
`Pruritus
`
`Rash
`
`Urticaria
`
`Abdominal
`distension
`
`Dysgeusia
`
`Flatulence
`
`Blister
`
`Purpura
`
`Angioneurotic
`oedema
`
`Musculoskeletal Back pain
`
`Musculoskeletal
`
`Arthralgia
`
`Joint stiffness
`
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`LUYE1027
`Luye Pharma Group Ltd., et al. v. Alkermes Pharma Ireland Ltd.
`IPR2016-01096
`
`

`

`2017-6-2
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`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`and connective
`tissue disorders
`
`Renal and
`urinary
`disorders
`
`Erectile
`Reproductive
`dysfunction
`system and
`breast disorders (including
`ejaculation failure,
`ejaculation
`disorder)
`
`Asthenia
`
`General
`disorders and
`administration
`site conditions
`
`Investigations
`
`pain
`
`Bone pain
`
`Joint swelling
`
`Musculoskeletal
`stiffness
`
`Osteoarthritis
`
`Pain in extremity Muscle cramp
`
`Muscular
`weakness
`
`Myalgia
`
`Nocturia
`
`Urinary retention
`
`Pelvic pain
`
`Breast pain
`
`Gynaecomastia
`
`Testicular atrophy
`
`Testicular pain
`
`Lethargy
`
`Injection site
`reaction (including
`Oedema
`erythema,
`inflammation and peripheral
`pain)
`Pain
`
`Chest pain
`
`Dysstasia
`
`Influenza like
`illness
`
`Oedema
`
`Rigors
`
`Pyrexia
`
`Somnolence
`
`Blood alkaline
`Weight increased Alanine
`aminotransferase phosphatase
`increased
`increased
`
`Urinary
`incontinence
`
`Malaise
`
`Aspartate
`aminotransferase
`increased
`
`Blood creatinine
`increased
`
`Blood pressure
`increased
`
`Blood urea
`increased
`
`Gamma-glutamyl
`transferase
`increased
`
`Weight decreased
`
`* This frequency is based on class-effect frequencies common for all GnRH agonists
`Triptorelin causes a transient increase in circulating testosterone levels within the first week after the initial injection of
`the sustained release formulation. With this initial increase in circulating testosterone levels, a small percentage of
`patients (:5 5%) may experience a temporary worsening of signs and symptoms of their prostate cancer (tumour flare),
`usually manifested by an increase in urinary symptoms ( < 2%) and metastatic pain (5%), which can be managed
`symptomatically. These symptoms are transient and usually disappear in one to two weeks.
`
`Isolated cases of exacerbation of disease symptoms, either urethral obstruction or spinal cord compression by
`metastasis have occurred. Therefore, patients with metastatic vertebral lesions and/or with upper or lower urinary tract
`obstruction should be closely observed during the first few weeks of therapy (see section 4.4).
`
`The use of GnRH agonists, to treat prostate cancer may be associated with increased bone loss and may lead to
`osteoporosis and increases the risk of bone fracture.
`
`General tolerance in women (see section 4.4)
`
`As a consequence of decreased oestrogen levels, the most commonly reported adverse events (expected in 10% of
`women or more) were headache, libido decreased, sleep disorder, mood altered, dyspareunia, dysmenorrhoea, genital
`haemorrhage, ovarian hyperstimulation syndrome, ovarian hypertrophy pelvic pain, abdominal pain, vulvovaginal
`dryness, hyperhidrosis, hot flushes and asthenia.
`
`The following adverse reactions, considered as at least possibly related to triptorelin treatment, were reported. Most of
`these are known to be related to biochemical or surgical castration.
`
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`

`

`2017-6-2
`The frequency of the adverse reactions is classified as follows: very common (:::1/10); common (:::1/1001 < 1/10);
`uncommon (:::1/10001 < 1/100); rare (:::1/100001 < 1/1000).
`
`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`System Organ
`Class
`
`Immune system
`disorders
`
`Metabolism and
`nutrition disorders
`
`Psychiatric
`disorders
`
`Very common
`
`Common
`
`Uncommon
`
`Additional post-
`marketing AEs
`
`Frequency not
`known
`
`Hypersensitivity
`
`Anaphylactic shock
`
`Decreased appetite
`
`Fluid retention
`
`Ubido decreased
`
`Depression*
`
`Affect lability
`
`Confusional state
`
`Mood disorder
`
`Nervousness
`
`Anxiety
`
`Sleep disorder
`(including insomnia)
`
`Nervous system
`disorders
`
`Headache
`
`Dizziness
`
`Eye disorders
`
`Ear and labyrinth
`disorders
`
`Cardiac Disorders
`
`Vascular disorders Hot flushes
`
`Respiratory,
`thoracic and
`mediastinal
`disorders
`
`Gastrointestinal
`disorders
`
`Skin and
`subcutaneous
`tissue disorders
`
`Acne
`
`Hyperhidrosis
`
`Seborrhoea
`
`Depression**
`
`Disorientation
`
`Dysgeusia
`
`Hypoasthesia
`
`Syncope
`
`Memory impairment
`
`Disturbance in
`attention
`
`Paraesthesia
`
`Tremor
`
`Dry eye
`
`Visual Impairment
`
`Vertigo
`
`Palpitations
`
`Dyspnoea
`
`Epistaxis
`
`Visual disturbance
`
`Hypertension
`
`Abdominal pain
`
`Abdominal distension Diarrhoea
`
`Abdominal discomfort Dry mouth
`
`Nausea
`
`Flatulence
`
`Angioneurotic oedema
`
`Urticaria
`
`Mouth ulceration
`
`Vomiting
`
`Alopecia
`
`Dry skin
`
`Hirsutism
`
`Onychoclasis
`
`Pruritus
`
`Rash
`
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`Luye Pharma Group Ltd., et al. v. Alkermes Pharma Ireland Ltd.
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`

`

`2017-6-2
`
`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`Musculoskeletal
`and connective
`tissue disorders
`
`Reproductive
`system and breast
`disorders
`
`Arthralgia
`
`Back pain
`
`Muscular weakness
`
`Muscle spasms
`
`Myalgia
`
`Pain in extremities
`
`Breast disorder
`
`Breast pain
`
`Coital bleeding
`
`Amenorrhoea
`
`Dyspareunia
`
`Genital bleeding
`(including vaginal
`bleeding withdrawal
`bleed)
`
`Ovarian
`hyperstimulation
`syndrome
`
`Ovarian hypertrophy
`
`Pelvic pain
`
`Vulvovaginal dryness
`
`Cystocele
`
`Menstrual disorder
`(including
`dysmenorrhoea,
`metrorrhagia and
`menorrhagia)
`
`Ovarian cyst
`
`Vaginal discharge
`
`General disorders Asthenia
`and administration
`site conditions
`
`Injection site reaction
`(including pain,
`swelling, erythema
`and inflammation)
`
`Oedema peripheral
`
`Investigations
`
`Weight increased
`
`Weight decreased
`
`Malaise
`
`Pyrexia
`
`Blood alkaline
`phosphatase
`increased
`
`Blood pressure
`increased
`
`*Long term use: This frequency is based on class-effect frequencies common for all GnRH agonists
`
`** Short term use: This frequency is based on class-effect frequencies common for all GnRH agonists
`
`At the beginning of treatment, the symptoms of endometriosis including pelvic pain and dysmenorrhoea may be very
`commonly exacerbated(;?: 10%) during the initial transient increase in plasma oestradiol levels. These symptoms are
`transient and usually disappear in one or two weeks.
`
`Genital haemorrhage including menorrhagia, metrorrhagia may occur in the month following the first injection.
`
`When used to treat infertility, the combination with gonadotropins may result in ovarian hyperstimulation syndrome.
`Ovarian hypertrophy, pelvic and/or abdominal pain may be observed.
`
`Breast Cancer
`
`The most commonly observed adverse reactions associated with triptorelin treatment for up to 5 years in combination
`with either tamoxifen or an aromatase inhibitor in the TEXT and SOFT studies were hot flushes, musculoskeletal
`disorder, fatigue, insomnia, hyperhidrosis, vulvovaginal dryness and depression.
`The frequencies of the adverse reactions reported with triptorelin in combination with tamoxifen (N = 2325) or
`exemestane (N = 2318) are shown in the following table. The classifications are as follows: very common (;?:1/10);
`common (;?:1/100 to <1/10); uncommon (;?:1/1,000 to <1/100), rare (;?:1/10,000 to <1/1000).
`
`System Organ Classes Very Common
`
`Common
`
`Uncommon
`
`Rare
`
`~1/10
`
`~1/100 to <1/10 ~1/1000 to
`<1/100
`
`~1/10,000 to
`<1/1000
`
`Cardiac disorders
`
`Endocrine disorders
`
`Myocardial
`Ischaemia
`
`QT prolongation
`
`Diabetes mellitus
`(glucose
`intolerance)
`
`Hyperglycaemia
`
`Gastrointestinal disorders Nausea
`
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`LUYE1027
`Luye Pharma Group Ltd., et al. v. Alkermes Pharma Ireland Ltd.
`IPR2016-01096
`
`

`

`2017-6-2
`
`Decapeptyl (triptorelin) SR- Summary of Product Characteristics (SPC)
`
`General disorders and
`administration site
`conditions
`
`Fatigue
`
`Injection site
`reaction
`
`Immune system disorders
`
`Hypersensitivity
`
`Musculoskeletal and
`connective tissue
`disorders
`
`Mus