Decapeptyl

Decapeptyl

triptorelin

Manufacturer:

Ferring

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Triptorelin actetate.
Description
Each syringe with 1 mL solution contains: DECAPEPTYL 0.1 mg/mL, 100 μg triptorelin acetate equivalent to 95.6 micrograms triptorelin free base.
Each syringe contains injectable amount of triptorelin (D-Trp6-LHRH) 3.75 mg encapsulated in a biodegradable polymer, poly(DL-lactide-co-glycolide). Each syringe of suspension medium contains polysorbate 80, dextran 70, sodium chloride, sodium dihydrogen phosphate dihydrate, sodium hydroxide solution to adjust the pH and water for injection 1 mL.
Action
Pharmacotherapeutic Group: Gonadotropin releasing hormone analogues. ATC Code: L02AE04.
Pharmacology: Pharmacodynamics: Decapeptyl: Triptorelin is a synthetic decapeptide analogue of the natural gonadotrophin-releasing hormone (GnRH). GnRH is a decapeptide, which is synthesised in the hypothalamus and regulates the biosynthesis and release of the gonadotrophins LH (luteinising hormone) and FSH (follicle stimulating hormone) by the pituitary. Triptorelin gives a greater stimulation of the pituitary to secrete LH and FSH than a comparable dose of gonadorelin, and has a longer duration of action. The increase of LH and FSH levels will initially lead to an increase of serum testosterone concentrations in men or serum estrogen concentrations in women. Chronic administration of a GnRH agonist results in an inhibition of pituitary LH- and FSH-secretion. This inhibition leads to a reduction in steroidogenesis, by which the serum estradiol concentration in women and the serum testosterone concentration in men fall to within the postmenopausal or castrate range, respectively, i.e. a hypogonadotrophic hypogonadal state.
Plasma DHEAS (dihydroepiandrostenedione sulphate) levels are not influenced. Therapeutically, this leads to a decrease in growth of testosterone-sensitive prostate tumours in men, and to reduction of endometriosis foci and estrogen-dependent uterus myomas in women.
The exact duration of action of DECAPEPTYL has not been established, but pituitary suppression is maintained for at least 6 days after stopping administration.
The DECAPEPTYL-induced downregulation of the pituitary can prevent the LH surge and thereby premature ovulation and/or follicular luteinization. The use of the downregulation with GnRH agonist reduces the cycle cancellation rate and improves the pregnancy rate in ART cycles.
After discontinuation of DECAPEPTYL, a further drop in circulating LH levels should be expected, with LH levels returning to baseline after approximately 2 weeks.
Pharmacokinetics: The pharmacokinetic data suggest that after subcutaneous administration of DECAPEPTYL the systemic bioavailability of triptorelin is close to 100%. The elimination half-life of triptorelin is approximately 3 hours, indicating that triptorelin is eliminated within 24 hours and therefore will not be present in circulation at the time of embryo transfer. Metabolism to smaller peptides and amino acids primarily occurs in the liver and kidneys. Triptorelin is predominantly excreted in the urine.
The clinical studies indicated that the risk of accumulation of triptorelin in patients with severe liver and renal impairment is small (i.e. half-life of approximately 8 hours in these patients).
Absorption: Triptorelin is not active when given orally. Following a single dose of DECAPEPTYL 0.25 mg SC in healthy male subjects, the mean maximum plasma concentration of triptorelin was 5.68 ng/mL. Maximum plasma concentrations were reached approximately 45 minutes after SC administration. The mean terminal elimination half-life was approximately 3 hours and the total clearance was 9.24 L/hour and these parameters were quite similar to those determined after IV administration.
Distribution & Metabolism: Human distribution and metabolism after administration of DECAPEPTYL have not been studied. It is known that after injection, GnRH agonist progressively accumulate in the anterior pituitary and the main inactivating organs, the liver and kidneys. In the pituitary, GnRH agonists are inactivated by N-terminal cleavage by peptidases. In the liver and kidneys, GnRH agonists are degraded to biologically inactive C-terminal metabolites.
Following IV infusion of DECAPEPTYL 0.1 mg, disappearance of triptorelin from the plasma has two components: an initial fast component of approximately 19 minutes and a second slower component of approximately 50 minutes. Protein binding has not been investigated.
Excretion: Triptorelin, as all other GnRH agonists, is predominantly excreted in urine. Information on the elimination of triptorelin is available in female subjects. DECAPEPTYL 0.5 mg was administered as an IV bolus to 19 female subjects. The mean half-life for terminal elimination was 5.1 hours (range: 2.5-13.81 hours). The elimination of triptorelin in urine was investigated in eight of the female subjects. Renal clearance over 24 hours was on average 25.3 mL/min (range: 5.3-45.4 mL/min). The mean percentage of the dose recovered in urine over the 24 hours was 16.7% (range: 3.4-34.6%). This indicates that approximately 17% of the dose is eliminated unchanged in the urine within 24 hours. This figure is similar to that reported for other GnRH agonists.
Decapeptyl CR: Triptorelin is a synthetic analogue of gonadorelin (GnRH). As a result of the substitution of the 6th amino acid residue in the native molecule, the agonistic effect is more pronounced and the plasma half-life prolonged.
Injection of Decapeptyl CR initially results in a stimulation of the pituitary release of LH and FSH. After prolonged stimulation, the pituitary becomes refractory, the gonadotropin release declines, resulting in a decrease of the sex steroids (testosterone or estrogen) to castrate levels. These effects are reversible.
Depot Injection: After a single injection, plasma levels remains at a therapeutic level for 30 days.
Indications/Uses
Decapeptyl: Down regulation and prevention of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation for assisted reproductive technologies (ART).
Preoperative reduction of myoma size to reduce the symptoms of bleeding and pain in women with symptomatic uterine myomas.
Symptomatic endometriosis confirmed by laparoscopy when suppression of the ovarian hormonogenesis is indicated to the extent that surgical therapy is not primarily indicated.
Decapeptyl CR: In situations where lowering of sex steroid serum levels to castrate level is desired eg, prostate cancer, endometriosis, uterine myoma and/or assisted reproduction techniques (ART) eg, in vitro fertilization (IVF).
Treatment of confirmed central precocious puberty (pre-term sexual development) (girls <9 years, boys <10 years).
Dosage/Direction for Use
Decapeptyl: DECAPEPTYL is intended for subcutaneous injection once daily into the lower abdominal wall. Following the first administration, it is advised that the patient be kept under medical supervision for 30 minutes to ensure there is no allergic/pseudo-allergic reaction to the injection. Facilities for the treatment for such reactions should be immediately available. The following injections may be self-administered as long as the patient is made aware of the signs and symptoms that may indicate hypersensitivity, the consequences of such a reaction and the need for immediate medical intervention. The injection site should be varied to prevent lipoatrophy.
Down Regulation and Prevention of Premature LH Surges: Treatment with DECAPEPTYL should be initiated under the supervision of a physician experienced in the treatment of infertility. Treatment can be started in the early follicular phase (day 2 or 3 of the menstrual cycle) or in the mid-luteal phase (day 21-23 of the menstrual cycle or 5-7 days before expected start of menses). Controlled ovarian hyperstimulation with gonadotrophins should be started after approximately 2-4 weeks of DECAPEPTYL treatment. Ovarian response should be monitored clinically (including ovarian ultrasound alone or in combination with measurement of oestradiol levels) and the dose of gonadotrophins adjusted accordingly. When a suitable number of follicles have reached an appropriate size, treatment with DECAPEPTYL and gonadotrophin is stopped and a single injection of hCG is administered to induce the final follicular maturation. If downregulation is not confirmed after 4 weeks (determined by oestradiol levels or ultrasound documentation of a shedded endometrium), discontinuation of DECAPEPTYL should be considered. The total duration of treatment is usually 4-7 weeks.
When using DECAPEPTYL, luteal phase support should be provided. Luteal phase support should be given according to the reproductive medical centre's practice.
Uterine Myomas and Endometriosis: The duration of treatment depends on the initial degree of severity of endometriosis and on the evolution of its clinical manifestations (functional and anatomical) and on the evolution of the volume of the uterine myomas, determined by ultrasonography during treatment. Normally, the maximum attainable result is expected after 3 to 4 months.
In view of the possible effect on bone density, DECAPEPTYL therapy without add-back therapy should not exceed duration of 6 months (see Precautions).
Special Patient Populations: No specific dose recommendations are given for subjects with renal or hepatic impairment. A clinical study indicated that the risk of accumulation of triptorelin in patients with severe liver and renal impairment is small.
Decapeptyl CR: Decapeptyl CR (contents of 1 disposable syringe following addition of the suspension medium) is injected once every 28 days either SC (eg, in the skin of the abdomen, the buttock or upper thigh) or IM. The injection should be given in a different place each time.
Reconstituted solutions must be used immediately.
Therapy of Prostate Carcinoma: It is important that the 4-week cycle be observed.
As a Diagnostic: It can be generally clarified after 3 months of treatment whether the prostate cancer is androgen-dependent or not. If so, administration can be continued.
Uterine Myoma and Endometriosis: In view of the possible effect on bone density, therapy should not exceed 6-month period.
Assisted Reproduction Techniques: Single administration on cycle days 2 or 3 (follicular phase) or cycle day 22 (luteal phase).
Children: The dosage regimen is based on body weight. Treatment is commenced with the appropriate dose administered on days 0, 14 and 28. Thereafter, the same dose should be repeated every 4 weeks. Should the effect be insufficient, the dose may be repeated every 3 weeks. The doses are as follows: Body weight <20 kg: 1.875 mg (½ dose); 20-30 kg: 2.5 mg (2/3 dose); >30 kg: 3.75 mg (full dose).
Treatment should be stopped if a bone maturation of >12 years in girls and >13 years in boys has been achieved.
Overdosage
Overdose in humans may result in a prolonged duration of action. In case of overdose, DECAPEPTYL treatment should be (temporarily) discontinued, and symptomatic treatment should be initiated.
Contraindications
Decapeptyl: DECAPEPTYL is contraindicated in cases of hypersensitivity to Triptorelin acetate or to any of the excipients; Hypersensitivity to gonadotrophin-releasing hormone (GnRH) or any other GnRH analogue; Pregnancy or lactation; Severe osteoporosis.
Decapeptyl CR: Pregnancy and lactation; hypersensitivity to the constituents of Decapeptyl CR; hormone-insensitive carcinoma or after prostectomy, surgical castration, clinically manifest osteoporosis or risk of osteoporosis.
ART: Particularly in patients with polycystic ovaries, the use of Decapeptyl CR should be considered with great precaution, when the number of ultrasonography-detected follicles exceeds 10. Progressive brain tumours in children.
Special Precautions
Decapeptyl: When triptorelin is co-administered with drugs affecting pituitary secretion of gonadotrophins, caution should be given and the patient's hormonal status should be supervised.
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. For the IVF indication; despite this prolonged exposure, triptorelin is not expected to be present in circulation at the time of embryo transfer.
Women of childbearing potential should be examined carefully before treatment to exclude pregnancy.
Downregulation and prevention of premature LH surges: ART is associated with an increased risk of multiple pregnancies, pregnancy wastage, ectopic pregnancies and congenital malformations. These risks are also valid with usage of DECAPEPTYL as adjunct therapy in controlled ovarian hyperstimulation. The use of DECAPEPTYL in controlled ovarian hyperstimulation may increase the risk of ovarian hyperstimulation syndrome (OHSS) and ovarian cysts.
Ovarian Hyperstimulation Syndrome (OHSS):
OHSS is a medical event distinct from uncomplicated ovarian enlargement. OHSS is a syndrome that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities.
The following symptoms may be observed in severe cases of OHSS: abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhoea. Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, haemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events.
Excessive ovarian response to gonadotrophin treatment seldom gives rise to OHSS unless hCG is administered to trigger ovulation. Therefore in cases of OHSS it is prudent to withhold hCG and advise the patient to refrain from coitus or to use barrier methods for at least 4 days. OHSS may progress rapidly (within 24 hours to several days) to become a serious medical event, therefore patients should be followed for at least two weeks after the hCG administration.
OHSS may be more severe and more protracted if pregnancy occurs. Most often, OHSS occurs after hormonal treatment has been discontinued and reaches its maximum severity at about seven to ten days following treatment.
Usually, OHSS resolves spontaneously with the onset of menses.
If severe OHSS occurs, gonadotrophin treatment should be stopped. The patient should be hospitalised and specific therapy for OHSS should be started e.g. with rest, intravenous infusion of electrolyte solutions or colloids and heparin.
This syndrome occurs with higher incidence in patients with polycystic ovarian disease. The risk of OHSS might be higher with use of GnRH agonists in combination with gonadotrophins than with use of gonadotrophins alone.
Ovarian cysts: Ovarian cysts may occur during the initial phase of treatment with GnRH agonist. They are usually asymptomatic and non-functional.
Uterine Myomas and Endometriosis: Menstruation does not occur during treatment. A supervening metrorrhagia in the course of treatment is abnormal (apart from the first month), and should lead to verification of plasma estrogen level. Should this level be less than 50 pg/mL, possible associated organic lesions should be sought. After withdrawal of treatment, ovarian function resumes, e.g. menstrual bleeding will resume after 7-12 weeks after the final injection.
Non-hormonal contraception should be used during the initial month of treatment as ovulation may be triggered by the initial release of gonadotrophins. It should also be used from 4 weeks after the last injection until resumption of menstruation or until another contraceptive method has been established.
During treatment of uterine myomas the size of uterus and myoma should be determined regularly, e.g. by means of ultrasonography. Disproportionally fast reduction of uterus size in comparison with the reduction of myoma tissue has in isolated cases led to bleeding and sepsis.
Treatment with DECAPEPTYL over several months can lead to a decrease of bone density. For this reason, treatment without add-back therapy should not exceed duration of 6 months. After withdrawal of treatment, the bone loss is generally reversible within 6-9 months. Particular caution is therefore advised in patients with additional risk factors in view of osteoporosis.
Decapeptyl CR: Monitoring of the therapy should be performed according to the sex steroid serum levels.
Men: The initial transient increase of serum testosterone has, in a few patients, been associated with a temporary aggravation of secondary symptoms of the disease eg, urinary obstruction, skeletal pain due to metastases, compression of the spinal cord, muscular fatigue and lymphatic oedema of the legs. The patient should be advised to consult the physician, if any of these symptoms aggravates. In the initial phase of therapy, supplementary administration of an appropriate antiandrogen agent should be considered as a means of diminishing the initial rise in testosterone and the deterioration in clinical symptoms.
Women: Potentially fertile women should be examined carefully before treatment to exclude pregnancy. Nonhormonal methods of contraception should be employed during therapy and in case of endometriosis or myoma, should be continued until menses are resumed. Women should not use preparations containing estrogens during the period of Decapeptyl CR therapy.
During treatment of uterine myoma, uterus and myoma size should be measured regularly by means of ultrasonography. Unproportionally rapid reduction of uterus volume in comparison with myoma tissue has, in a few cases, caused bleeding and sepsis.
Since menses should stop during Decapeptyl/Decapeptyl CR treatment, the patient should be instructed to notify the physician if regular menstruation persists.
Children: The chronological age at the beginning of therapy should be <9 years in girls and <10 years in boys. After completion of therapy, development of puberty characteristics will occur. Information with regards to future fertility is still limited. In most girls, menses will start on average 1 year after ending the therapy, which in most cases is regular. Special forms of precocious puberty (pseudoprecocious puberty and gonadotropin-independent precocious puberty) should be precluded.
Use in Pregnancy & Lactation: In animal tests, no teratogenic effects have been detected. In humans, there is insufficient experience. Therefore, a state of nonpregnancy should be established prior to initiation of therapy (see also Contraindications). There are insufficient data relating to the use of Decapeptyl CR during lactation.
Use In Pregnancy & Lactation
Decapeptyl: Very limited data on the use of triptorelin during pregnancy do not indicate an increased risk of congenital malformations. However, long-term follow-up studies on development are far too limited. Animal data do not indicate direct or indirect harmful effects with respect to pregnancies or postnatal developments, but there are indications for foetotoxicity and delayed parturition. Based on the pharmacological effects disadvantageous influence on the pregnancy and the offspring cannot be excluded and DECAPEPTYL should not be used during pregnancy.
Women of childbearing potential should use effective non-hormonal contraception except when undergoing ART. It is not known whether triptorelin is excreted in human milk. Because of the potential for adverse reactions from triptorelin in nursing infants, breastfeeding should be discontinued prior to and throughout administration.
Decapeptyl CR: In animal tests, no teratogenic effects have been detected. In humans, there is insufficient experience. Therefore, a state of nonpregnancy should be established prior to initiation of therapy (see also Contraindications). There are insufficient data relating to the use of Decapeptyl CR during lactation.
Adverse Reactions
Decapeptyl: Safety information is presented separately according to the indications. Due to limited data from clinical trial program and from the post-marketing period for female population with uterine myoma and endometriosis, safety information was extrapolated from the safety experience with DECAPEPTYL CR 3.75 mg.
Downregulation and prevention of premature LH surges: Frequently (≥2%) reported adverse events during treatment with DECAPEPTYL 0.1 mg/mL in clinical trials, either before or during co-administration with gonadotrophins, are listed in the table. The most frequent adverseevents are headache (27%), vaginal bleeding/spotting (24%), abdominal pain (15%), injection site inflammation (12%) and nausea (10%). (See Table 1.)

Click on icon to see table/diagram/image

Ovarian cysts have been reported to occur commonly (1%) during the initial phase of treatment with DECAPEPTYL.
Single cases of allergic reactions, localized or generalized, have been reported after injection of DECAPEPTYL.
Uterine Myomas and Endometriosis: As a consequence of decreased estrogen level, most patients are expected to experience adverse reactions, such as hot flushes being reported in 75-100% of patients. Additionally, bleeding/spotting, sweating, vaginal dryness and dyspaeunia, decreased libido and mood changes are expected in more than 10% women. (See Table 2.)

Click on icon to see table/diagram/image

Weight changes have been reported following administration of DECAPEPTYL. Dizziness, tremor and headache can be seen in some of the patients. Slight trabecular bone loss may occur. This is generally reversible within 6-9 months after treatment discontinuation (see Precautions).
At the start of therapy, withdrawal bleeding may occur. In general, menstruation starts again ca. 3 months after the last injection but may be later in individual cases. As a consequence of the lowered oestrogen levels, slight trabecular bone loss may occur. However, this is generally reversible within 6-9 months after treatment has been discontinued.
Decapeptyl CR: The pharmacological side effects owing to the suppression of hormone production include in men: Hot flushes, impotence and loss of libido, and in rare cases, gynaecomastia and testicular atrophy; in women: Hot flushes, bleeding or spotting, vaginal dryness and/or dyspareunia. As a consequence of the lowered estrogen levels, slight trabecular bone loss may occur. However, this is recovered generally within 6-9 months after treatment has been discontinued.
Other possible side effects include in men: Depressive mood, increased enzyme activity (LDH, γGT, SGOT, SGPT), and thrombophlebitis. One patient suffered a pulmonary embolism. In women: Depressive mood, loss of libido, sporadically elevated enzyme levels (LDH, γGT, SGOT, SGPT), slight rise in serum cholesterol, paraesthesia and visual disturbances.
In men and women: Hypersensitivity reactions (eg, itching, skin rash, fever, anaphylaxis) may occur in individual cases. Hypersensitivity reactions have also been observed after the administration of dextran. In rare cases, there may be temporary pain at the injection site.
ART: Since exogenous gonadotropins are also injected, the symptoms of hormonal deprivation do not last >2 days. In order to recognize ovarian hyperstimulation as soon as possible, careful monitoring of follicular growth is necessary.
Children: In children, occasional bleedings and discharge, vomiting, nausea and anaphylaxis may occur.
Drug Interactions
Interactions of DECAPEPTYL with other medicines have not been investigated for these indications. The possibility of interactions with commonly used medicinal products, including histamine liberating products, cannot be excluded.
Storage
Store between 2-8°C. Disposable syringes should be stored in original packages, protected from light.
Decapeptyl: Do not freeze.
Shelf-Life: Decapeptyl: 3 years.
ATC Classification
L02AE04 - triptorelin ; Belongs to the class of gonadotropin releasing hormone analogues. Used in endocrine therapy.
Presentation/Packing
Decapeptyl Inj (pre-filled syringe) 0.1 mg/mL x 7's, 28's. Decapeptyl CR Inj 3.75 mg x 1 single-dose kit.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in