- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical 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 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 excipients
- 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
Prostate cancerOne intramuscular injection should be administered every 4 weeks (28 days). No dosage adjustment is necessary in the elderly.Decapeptyl is also available as a 3-month treatment (Decapeptyl SR 11.25 mg) and as a 6-month treatment (Decapeptyl SR 22.5 mg) for prostate cancer. In patients treated with GnRH analogues for metastatic prostate cancer, treatment is usually continued upon development of castrate-resistant prostate cancer.Reference should be made to relevant guidelines.Endometriosis and uterine fibroids One intramuscular injection every 28 days. For the treatment of endometriosis and uterine fibroids the treatment must be initiated in the first five days of the cycle. The maximum duration of treatment should be 6 months. For patients with uterine fibroids Decapeptyl SR 3 mg should be administered for a minimum of 3 months.A further course of treatment by Decapeptyl SR 3 mg or by other GnRH agonists beyond 6 months should not be undertaken due to concerns about bone density losses.Decapeptyl is also available as a 3-month treatment (Decapeptyl SR 11.25 mg) for endometriosis.
Prostate cancerInitially, Decapeptyl SR 3 mg, 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 3 mg 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 3 mg.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 their glucose, cholesterol and blood pressure adequately monitored during androgen deprivation therapy.Metabolic changes may be more severe in these high risk patients. Patients at high risk of metabolic or cardiovascular disease and receiving androgen deprivation therapy should be monitored at appropriate intervals not exceeding 3 months. Administration of triptorelin in therapeutic doses results 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 FibromyomasThe 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 3 mg causes constant hypogonadotropic amenorrhoea. If vaginal haemorrhage occurs after the first month, plasma oestradiol levels should be measured and if levels are below 50 pg/mL, possible organic lesions should be investigated.After withdrawal of treatment, 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 3 mg treatment, the patient should be instructed to notify her physician if regular menstruation persists.It is recommended that during treatment of uterine fibroids, the size of the fibroid is determined regularly. There have been a few reports of bleeding in patients with submucous fibroids following GnRH agonist therapy. Typically the bleeding has occurred 6 - 10 weeks after the initiation of therapy.
General tolerance in menSince 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 (see sections 4.4 and 4.5)|
|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|
|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|
|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|
GeneralIncreased 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 reactionsReporting 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
Patients with prostate cancerThis results in an increase in peripheral circulating levels of testosterone and dihydrotestosterone. Continued administration (over 7 days) however, leads to suppression of gonadotropins and a consequent fall in plasma testosterone. In patients with prostate cancer, plasma testosterone levels fall to castrate levels after 2 - 3 weeks of treatment, frequently resulting in an improvement of function and objective symptoms.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.
Patients with endometriosis and uterine fibroidsContinued administration of Decapeptyl SR 3 mg induces suppression of oestrogen secretion and thus enables resting of ectopic endometrial tissue. In pre-operative therapy for uterine fibroids there appears to be a beneficial effect on the blood loss at surgery. Studies have demonstrated a consistent and marked reduction in uterine and/or fibroid volume becoming maximal in a three to six month treatment period. Clinical studies have shown that 90-100% of patients with fibroids become amenorrhoeic within two months of treatment and triptorelin provides relief from the symptoms of abdominal pain, dysmenorrhoea and menorrhagia associated with uterine fibroids.
In healthy volunteersSubcutaneously administered triptorelin (100 μg) is rapidly absorbed (Tmax = 0.63 ± 0.26 hr for peak plasma concentration = 1.85 ± 0.23 ng/mL). Elimination is effected with a biological half-life of 7.6 ± 1.6 hr, after a 3 to 4 hr distribution phase. Total plasma clearance is: 161 ± 28 mL/min. Distribution volume is 104.1 ± 11.7 litres.
In patients with prostate cancerWith subcutaneous administration (100 μg), triptorelin blood levels oscillate between maximum values of 1.28 ± 0.24 ng/mL (Cmax) obtained in general one hour after injection (Tmax) and minimum values of 0.28 ± 0.15 ng/mL (Cmin) obtained 24hrs after injection.The biological half-life is on average 11.7 ± 3.4 hr but varies according to patients. Plasma clearance (118 ± 32 mL/min) reflects slower elimination in patients, whilst distribution volumes are close to those of healthy volunteers (113.4 ± 21.6 litres).SUSTAINED RELEASE FORM
In patients with prostate cancerFollowing intramuscular injection of the sustained release form, an initial phase of release of the active principle present on the surface of the microspheres is observed, followed by further fairly regular release (Cmax = 0.32 ± 0.12 ng/mL), with a mean rate of release of triptorelin of 46.6 ± 7.1 μg/day. The bioavailability of the microparticles is approximately 53% at one month.
In patients with endometriosis and uterine fibroidsAfter intramuscular injection of Decapeptyl SR 3 mg in patients with endometriosis and uterine fibroids the maximum blood level of triptorelin is obtained between 2 to 6 hours after injection, the peak value reached is 11 ng/mL. There was no evidence of accumulation of the product following monthly injections over six months. The minimum blood level oscillates between 0.1 and 0.2 ng/mL. The bioavailability of the sustained release product is approximately 50%.
Product Information – Amended handling instructions for Decapeptyl®
Amended handling instructions for Decapeptyl SR including the addition of a safety needle have been approved and can be found in the Summary of Product Characteristics (SPCs) and the package leaflets (PILs). Existing stocks in the supply chain may take some months to run down. To check that these instructions apply to your Decapeptyl SR pack, ensure that the contents listed on the tray inside the pack include one safety injection needle. Packs including these needles contain the revised handling process.
This information is not applicable to Decapeptyl SR without the safety injection needle. For the SPC/PIL for Decapeptyl SR without the safety needle please contact Ipsen Medical Information on 01753 627777.
190 Bath Road, Slough, Berkshire, SL1 3XE
+44 (0)1753 627 778
+44 (0)1753 627 777
+44 (0)1753 627 777
+44 (0)1753 627 627