No case of overdose has been reported. Animal data do not predict any effects other than those on sex hormone concentration and consequent effect on the reproductive tract. If overdose occurs, symptomatic management is indicated.
2 years.
The product should be used immediately after reconstitution.
This medicinal product must not be mixed with other medicinal products except the one mentioned in 6.6.
D,L lactide-glycolide copolymer
Mannitol
Carmellose sodium
Polysorbate 80.
Clinical trials experience
General tolerance in men
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 (>1/10); common (>1/100, < 1/10); uncommon (>1/1000, < 1/100); rare (>1/10000, < 1/1000).
| System Organ Class | Very Common | Common | Uncommon | Rare | Additional post-marketing AEs Frequency not known |
| Infections and infestations | Nasopharyngitis | ||||
| Blood and lymphatic system disorders | Thrombocytosis | ||||
| Immune system disorders | Hypersensitivity | Anaphylactic reaction | Anaphylactic shock | ||
| Metabolism and nutrition disorders | Anorexia Diabetes mellitus Gout Hyperlipidaemia Increased appetite | ||||
| Psychiatric disorders | Libido decreased | Depression* Loss of libido Mood change* | Insomnia Irritability | Confusional state Decreased activity Euphoric mood | Anxiety |
| Nervous system disorders | Paraesthesia in lower limbs | Dizziness Headache | Paraesthesia | Memory impairment | |
| Eye disorders | Visual impairment | Abnormal sensation in eye Visual disturbance | |||
| Ear and labyrinth disorders | Tinnitus Vertigo | ||||
| Cardiac Disorders | Palpitations | QT prolongation | |||
| Vascular disorders | Hot flush | Hypertension | Hypotension | ||
| Respiratory, thoracic and mediastinal disorders | Dyspnoea Epistaxis | Orthopnoea | |||
| Gastrointestinal disorders | Dry mouth Nausea | Abdominal pain Constipation Diarrhoea Vomiting | Abdominal distension Dysgeusia Flatulence | ||
| Skin and subcutaneous tissue disorders | Hyperhidrosis | Acne Alopecia Erythema Pruritus Rash Urticaria | Blister Purpura | Angioneurotic oedema | |
| Musculoskeletal and connective tissue disorders | Back pain | Musculoskeletal pain Pain in extremity | Arthralgia Bone pain Muscle cramp Muscular weakness Myalgia | Joint stiffness Joint swelling Musculoskeletal stiffness Osteoarthritis | |
| Renal and urinary disorders | Nocturia Urinary retention | Urinary incontinence | |||
| Reproductive system and breast disorders | Erectile dysfunction (including ejaculation failure, ejaculation disorder) | Pelvic pain | Breast pain Gynaecomastia Testicular atrophy Testicular pain | ||
| General disorders and administration site conditions | Asthenia | Injection site reaction (including erythema, inflammation and pain) Oedema | Lethargy Oedema peripheral Pain Rigors Somnolence | Chest pain Dysstasia Influenza like illness Pyrexia | Malaise |
| Investigations | Weight increased | Alanine aminotransferase increased Aspartate aminotransferase increased Blood creatinine increased Blood pressure increased Blood urea increased Gamma-glutamyl transferase increased Weight decreased | Blood alkaline phosphatase increased |
* 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%) 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.
The use of GnRH agonists to treat prostate cancer may be associated with increased bone loss and may lead to osteoporosis and increases in the risk of bone fracture.
General tolerance in women
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 changes, 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.
The frequency of the adverse reactions is classified as follows: very common (>1/10); common (>1/100, < 1/10); uncommon (>1/1000, < 1/100); rare (>1/10000, < 1/1000).
| System Organ Class | Very Common | Common | Uncommon | Additional post-marketing AEs Frequency not known |
| Immune system disorders | Hypersensitivity | Anaphylactic shock | ||
| Metabolism and nutrition disorders | Decreased appetite Fluid retention | |||
| Psychiatric disorders | Libido decreased Mood disorder Sleep disorder (including insomnia) | Depression* Nervousness | Affect lability Anxiety Depression** Disorientation | Confusional state |
| Nervous system disorders | Headache | Dizziness | Dysgeusia Hypoasthesia Syncope Memory impairment Disturbance in attention Paraesthesia Tremor | |
| Eye disorders | Dry eye Visual Impairment | Visual disturbance | ||
| Ear and labyrinth disorders | Vertigo | |||
| Cardiac Disorders | Palpitations | |||
| Vascular disorders | Hot flush | Hypertension | ||
| Respiratory, thoracic and mediastinal disorders | Dyspnoea Epistaxis | |||
| Gastrointestinal disorders | Abdominal pain Abdominal discomfort Nausea | Abdominal distension Dry mouth Flatulence Mouth ulceration Vomiting | Diarrhoea | |
| Skin and subcutaneous tissue disorders | Acne Hyperhidrosis Seborrhoea | Alopecia Dry skin Hirsutism Onychoclasis Pruritus Rash | Angioneurotic oedema Urticaria | |
| Musculoskeletal and connective tissue disorders | Arthralgia Muscle spasms Pain in extremities | Back pain Myalgia | Muscular weakness | |
| Reproductive system and breast disorders | Breast disorder Dyspareunia Genital bleeding (including vaginal bleeding withdrawal bleed) Ovarian hyperstimulation syndrome Ovarian hypertrophy Pelvic pain Vulvovaginal dryness | Breast pain | Coital bleeding Cystocele Menstrual disorder (including dysmenorrhoea, metrorrhagia and menorrhagia) Ovarian cyst Vaginal discharge | Amenorrhoea |
| General disorders and administration site conditions | Asthenia | Injection site reaction (including pain, swelling, erythema and inflammation) Oedema peripheral | Malaise Pyrexia | |
| Investigations | Weight increased | Weight decreased | 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 to two weeks.
Genital haemorrhage including menorrhagia and metrorrhagia may occur in the month following the first injection.
General tolerance in children
The frequency of the adverse reactions is classified as follows: very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1000, < 1/100).
| System Organ Class | Very Common | Common | Uncommon | Additional post-marketing AEs Frequency not known |
| Immune system disorders | Hypersensitivity | Anaphylactic shock (seen in adult men and women) | ||
| Metabolism and Nutrition Disorders | Obesity | |||
| Psychiatric disorders | Mood altered | Affect lability Depression Nervousness | ||
| Nervous system disorders | Headache | |||
| Eye disorders | Visual impairment | Visual disturbance | ||
| Vascular disorders | Hot flush | Hypertension | ||
| Respiratory, thoracic and mediastinal disorders | Epistaxis | |||
| Gastrointestinal disorders | Abdominal pain | Vomiting Constipation Nausea | ||
| Skin and subcutaneous tissue disorders | Acne | Pruritus Rash Urticaria | Angioneurotic oedema | |
| Musculoskeletal and connective tissue disorders | Neck pain | Myalgia | ||
| Reproductive system and breast disorders | Vaginal bleeding (including vaginal haemorrhage withdrawal bleed, uterine haemorrhage, vaginal discharge, vaginal bleeding including spotting) | Breast pain | ||
| General disorders and administration site conditions | Injection site reaction (including injection site pain, injection site erythema and injection site inflammation) | Malaise | ||
| Investigations | Weight increased | Blood prolactin increased Blood pressure increased |
General
Increased lymphocytes count has been reported with patients undergoing GnRH agonist treatment. This secondary lymphocytosis is apparently related to GnRH induced castration and seems to indicate that gonadal hormones are involved in thymic involution.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via the
Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
The compound did not demonstrate any specific toxicity in animal toxicological studies. The effects observed are related to the pharmacological properties of triptorelin on the endocrine system.
Pharmacotherapeutic group:
Gonadotropin-Releasing Hormone analogue
L 02 A E 04: Antineoplastic and immunomodulator
Triptorelin is a synthetic decapeptide analogue of natural GnRH.
Prostate cancer
The first administration of Decapeptyl SR 11.25 mg stimulates the release of pituitary gonadotropins with a transient increase in testosterone levels (“flare-upâ€) in men. Prolonged administration leads to a suppression of gonadotropins and a fall in plasma testosterone or oestradiol to castrate levels after approximately 20 days, which is maintained for as long as the product is administered.
The efficacy and safety of triptorelin has been determined in clinical studies involving 645 patients with locally advanced or metastatic prostate cancer.
Of these, three long term controlled studies compared the efficacy and safety of triptorelin to bilateral orchidectomy as an initial therapy in patients with locally advanced or metastatic prostate cancer (stage C or D). In one of these three long term studies, 7 patients in the triptorelin group and 7 patients in the orchidectomy group had also undergone prostatectomy. Triptorelin induced biochemical castration at least as rapidly as surgical pulpectomy and was as effective as surgical castration in the long term palliative treatment of locally advanced or metastatic prostate cancer. Both the triptorelin and orchidectomy groups showed improvements in dysuria and pain, and reduction in volume of prostate. Analysis after six and eight years in two of the studies showed that there was no significant difference in the median survival rates in the triptorelin group versus the orchidectomy group.
A study assessing the pharmacodynamic equivalence between triptorelin 3-month and 28-day prolonged release formulations in patients with locally advanced or metastatic prostate cancer, found that equivalent testosterone suppression was achieved, whether 3 doses of Decapeptyl SR 3 mg (n=68) or a single dose of Decapeptyl SR 11.25 mg (n=63) was given. The percentage of patients who achieved a testosterone castrate level ≤ 0.5 ng/mL at D84 was similar in the two treatment groups (98% and 96% in the 3-month and 28-day formulation groups, respectively). The time to achieve chemical castration was not significantly different between the two groups.
In a phase III randomized clinical trial including 970 patients with locally advanced prostate cancer (mainly T2c-T4 with some T1c to T2b patients with pathological regional nodal disease) of whom 483 were assigned to short-term androgen suppression (6 months) in combination with radiation therapy and 487 to long-term therapy (3 years), a non-inferiority analysis compared the short-term to long-term concomitant and adjuvant hormonal treatment with triptorelin (62.2%) or goserelin (30.1%). The 5-year overall mortality was 19.0% and 15.2%, in the short-term and long-term groups, respectively. The observed Hazard Ratio of 1.42 with an upper one-sided 95.71% CI of 1.79 or two-sided 95.71% CI of 1.09; 1.85 (p = 0.65 for non inferiority), demonstrate that the combination of radiotherapy plus 6 months of androgen deprivation therapy provides inferior survival as compared with radiotherapy plus 3 years of androgen deprivation therapy. Overall survival at 5 years of long-term treatment and short-term treatment shows 84.8% survival and 81.0%, respectively.
Overall quality of life using QLQ-C30 did not differ significantly between the two groups (P= 0.37).
Neoadjuvant triptorelin prior to radiotherapy has been shown to significantly reduce prostate volume.
The use of a GnRH agonist may be considered after radical prostatectomy in selected patients considered at high risk of disease progression. There are no disease-free survival data or survival data with triptorelin in this setting.
Endometriosis
The first administration of Decapeptyl SR 11.25 mg stimulates the release of pituitary gonadotropins with a transient increase in oestradiol levels in women. Prolonged administration leads to a suppression of gonadotropins and a fall in plasma testosterone or oestradiol to castrate levels after approximately 20 days, which is maintained for as long as the product is administered.
Continued administration of Decapeptyl SR 11.25 mg induces suppression of oestrogen secretion and thus enables resting of ectopic endometrial tissue.
Precocious puberty
Inhibition of the increased hypophyseal gonadotropic activity in children with precocious puberty leads to suppression of oestradiol and testosterone secretion in girls and boys, respectively, and to lowering of the LH peak due to the GnRH stimulation test. The consequence is a regression or stabilisation of secondary sex characteristics and an improvement in median predicted adult height of 2.3cm after one year's treatment.
Following intramuscular injection of Decapeptyl SR 11.25 mg in patients (men and women), a peak of plasma triptorelin is observed in the first 3 hours after injection. After a phase of decrease, the circulating triptorelin levels remain stable at around 0.04-0.05ng/mL in endometriosis patients and around 0.1ng/mL in prostate cancer patients until day 90.
28 April 2016
Ipsen Limited,
190 Bath Road,
Slough,
SL1 3XE,
United Kingdom.
Do not store above 25°C. Keep container in the outer carton.
A type I, 4mL capacity glass vial with an elastomer stopper and an aluminium cap containing the powder.
A type I, 3mL capacity glass ampoule containing 2mL of the suspension vehicle.
Box containing 1 vial and 1 ampoule with 1 syringe and 2 needles.
PL 34926/0003
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.
The suspension for injection must be reconstituted using an aseptic technique and only using the ampoule of solvent for injection.
The instructions for reconstitution hereafter and in the leaflet must be strictly followed.
The solvent should be drawn into the syringe provided using the reconstituion needle (20 G, without safety device) and transferred to the vial containing the powder. The suspension should be reconstituted by swirling the vial gently from side to side for long enough until a homogeneous, milky suspension is formed. Do not invert the vial.
It is important to check there is no unsuspended powder in the vial. The suspension obtained should then be drawn back into the syringe, without inverting the vial. The reconstitution needle should then be changed and the injection needle (20 G, with safety device) used to administer the product.
As the product is a suspension, the injection should be administered immediately after reconstitution to prevent precipitation.
For single use only.
Used needles, any unused suspension or other waste materials should be disposed of in accordance with local requirements.
Date of first authorisation: 16 October 2002
Date of last renewal: 16 March 2009
