Active ingredients: Triptorelin
DECAPEPTYL 0.1 mg / ml Powder and solvent for solution for injection
Decapeptyl package inserts are available for pack sizes:- DECAPEPTYL 0.1 mg / ml Powder and solvent for solution for injection
- DECAPEPTYL 3.75 mg / 2 ml powder and solvent for prolonged-release suspension for injection
- Decapeptyl 11.25 mg / 2 ml powder and solvent for prolonged-release suspension for injection
Why is Decapeptyl used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Endocrine therapy, analogue of the hormone releasing gonadotropins
THERAPEUTIC INDICATIONS
Treatment of infertility in women in association with gonadotropins in ovulation induction protocols, in the context of in vitro fertilization followed by embryo transfer (F.I.V.E.T.) and in other techniques for assisted procreation.
Contraindications When Decapeptyl should not be used
Hypersensitivity to GnRH, its analogues or to any of the excipients of the medicinal product (see 4.8). Pregnancy and breastfeeding.
Precautions for use What you need to know before taking Decapeptyl
The use of GnRH agonists can cause reduction in bone mineral density.
Particular care should be taken in the case of patients with additional risk factors for osteoporosis (eg chronic alcohol abuse, smoking, long-term therapy with drugs that reduce bone mineral density, such as anticonvulsants or coticoids, family history of osteoporosis , malnutrition)
Before prescribing triptorelin, verification of the patient's non-pregnant status is required.
Rarely, treatment with GnRH agonists may reveal the presence of an unknown pre-existing gonadotropic cell pituitary adenoma. These patients may present with pituitary apoplexy characterized by sudden headache, vomiting, visual impairment and ophthalmoplegia.
There have been reports of mood alterations, including depression, which can be severe, in patients taking Decapeptyl. If you are taking Decapeptyl and develop depressed mood, please inform your doctor. Patients should be monitored closely during therapy. with known depression.
Androgen deprivation therapy can prolong the QT interval.
In patients with a history of QT interval prolongation or with risk factors for QT interval prolongation and in patients receiving concomitant medications that can prolong the QT interval (see Interactions section), before starting treatment with Decapeptyl 0.1 mg Physicians should evaluate the benefit-risk ratio including the possibility of Torsade de Pointes.
Women
Reduction in bone mineral density
The use of GnRH agonists is likely to cause, on average, a reduction in bone mineral density of 1% / per month over a 6 month treatment period. Every 10% reduction in bone mineral density increases the risk of fractures by 2 to 3 times.
Currently available data suggest that restoration of bone density occurs after cessation of therapy in most women.
No specific data are available for patients with confirmed osteoporosis or with risk factors for osteoporosis (eg chronic alcohol abuse, smokers, long-term therapies with drugs that reduce bone mineral density, such as anticonvulsants or corticoids, family history of osteoporosis, malnutrition, e.g. anorexia nervosa) Since the reduction in bone mineral density is likely to be more harmful in these patients, triptorelin treatment should be considered on an individual basis and initiated, after very careful evaluation, only if the benefits of treatment outweigh the risks Additional measures should be considered to counteract the loss of bone mineral density.
Female infertility
Before prescribing triptorelin 0.1mg, verification of the patient's non-pregnancy status is required.
Follicular stimulation, induced by the use of GnRH analogues and gonadotropins, can be significantly increased in a minority of predisposed patients, particularly in the case of Polycystic Ovary Syndrome.
The ovarian response to the Decapeptyl - gonadotropin combination can vary, even with the same dosage, from one patient to another and, in some cases, from one cycle to another, in the same patient.
Ovulation must be closely monitored with regular clinical and biological checks: ultrasound examinations and evaluation of plasma estrogens
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 case of ovarian hyper-response that may occur in predisposed patients or in case of polycystic disease of the ovary, it is recommended to stop the administration of gonadotropins, while the administration of Decapeptyl 0.1 mg is continued for a few days in order to avoid a possible spontaneous LH surge.
Interactions Which drugs or foods can modify the effect of Decapeptyl
Care should be taken when triptorelin is administered concomitantly with other drugs that affect the pituitary secretion of gonadotropins and it is recommended that the patient's hormonal status be monitored.
Since androgen deprivation treatment may prolong the QT interval, concomitant use of Decapeptyl 0.1mg with medicinal products known to prolong the QT interval or with medicinal products capable of inducing Torsade de Pointes such as antiarrhythmic medicinal products should be carefully considered. class IA (eg quinidine, disopyramide) or class III (eg amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin, antipsychotics, etc. (see section Precautions for use).
Warnings It is important to know that:
Pregnancy and breastfeeding
Pregnancy
Triptorelin should not be used during pregnancy as concomitant use of GnRH agonists is associated with a theoretical risk of abortion or fetal abnormalities. Women of childbearing potential should be carefully examined before starting treatment to rule out pregnancy Non-hormonal methods of contraception should be used during therapy until the menstrual cycle returns.
Pregnancy must be ruled out before using triptorelin for the treatment of infertility. When triptorelin is used in this setting, there is no clinical evidence to suggest a causal relationship between triptorelin and any subsequent abnormalities in oocyte development. , in pregnancy or in the outcome of pregnancy.
Feeding time
Triptorelin should not be used during breastfeeding.
Driving and using machines
Considering the pharmacological profile of triptorelin, triptorelin is likely to have no or negligible effects on the patient's ability to drive or use machines.
For those who carry out sporting activities
The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Dosage and method of use How to use Decapeptyl: Dosage
Strictly follow the medical prescription.
Short protocol: administer 1 vial of Decapeptyl 0.1 mg per day subcutaneously starting from the second day of the menstrual cycle (coinciding with the start of ovarian stimulation) until the day before the administration of hCG, for an average duration of 10-12 days.
Long protocol: administer 1 vial of Decapeptyl 0.1 mg per day subcutaneously, starting from the second day of the menstrual cycle. After pituitary desensitization is achieved (plasma estrogen concentration less than 50 pg / ml usually around the 15th day of treatment), start gonadotropin stimulation simultaneously with Decapeptyl 0.1 mg up to the day before hCG administration.
The drug is administered subcutaneously after extemporaneous preparation.
Withdraw the contents of the vial with the syringe and transfer all the liquid from the vial into the vial. Shake the vial gently without turning it upside down to ensure a homogeneous solution. Proceed to the injection immediately.
N.B .: It is important that the injection is carried out in strict accordance with the instructions for use.
Overdose What to do if you have taken too much Decapeptyl
No adverse reactions have been reported as a consequence of overdose. In case of accidental intake of a higher dosage than recommended, consult your doctor without delay.
Side Effects What are the side effects of Decapeptyl
Increased lymphocyte counts have been reported in patients receiving GnRH analogues
Experience in clinical trials
The adult population enrolled in clinical studies and treated with triptorelin, the immediate release formulation, included 127 men with prostate cancer treated daily for 3 months and approximately 1,000 women undergoing in vitro fertilization protocols. Detailed safety experience gained during clinical trials performed in men and women with the 3.75mg and 11.25mg triptorelin formulations was also included.
The overall analysis of safety experience from clinical trials included drug class related adverse reactions as a result of hypogonadotropic hypogonadism or, occasionally, initial pituitary-gonadal stimulation.
The frequency of adverse reactions is classified as follows: very common (≥1 / 10) - Common (≥1 / 100-
General tolerability in adults
Very common: Mild to severe hot flashes which usually do not require discontinuation of therapy. Common: psychiatric disorders (mood swings, depression) *
Uncommon: psychiatric disorders (mood changes, depression) **
Not known: QT interval prolongation (see Precautions for use and Interactions sections)
* Long-term use. This frequency is based on the frequency of the class effect, common to all GnRH agonists
** Short term use. This frequency is based on the frequency of the class effect, common to all GnRH agonists
General tolerability in women
Very common at the start of treatment: in the treatment of infertility triptorelin, used in combination with gonadotropins, can give ovarian hyperstimulation syndrome. Ovarian hypertrophy, dyspnoea, pelvic and / or abdominal pain may occur
Very common at the start of triptorelin treatment in the monthly and quarterly formulations: Genital haemorrhage including menorrhagia or metrorrhagia may occur in the month following the first injection.
Very common during triptorelin treatment in the monthly and quarterly formulations: these adverse reactions show a series of hypo-estrogenic events related to pituitary-ovarian block, such as sleep disorders, headache, mood alteration, vulvo-vaginal dryness and dyspareunia, decreased libido.
Common during triptorelin treatment in the monthly formulation: breast pain, muscle spasms, arthralgia, weight gain, nausea, abdominal discomfort / pain, asthenia. Mood changes and depression have been reported with long-term use.
Local tolerability
Very rare: pain, erythema and inflammation at the injection site.
Post-marketing information
During post-marketing surveillance, other undesirable effects have been reported in women being treated for IVF. Undesirable effects are classified by systemic organic categories and in decreasing order of frequency of the reported effects:
Skin and subcutaneous tissue disorders: hypersensitivity reactions, including itching, hives, rash, angioneurotic edema (refer to the "Contraindications" section)
Nervous system disorders: headache
Eye disorders: episodes of blurred vision or visual disturbances.
If you get any side effects, including any possible side effects not listed in this leaflet, contact your doctor or pharmacist. Side effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety of this drug
Expiry and Retention
Expiry: see the expiry date indicated on the package.
Warning: do not use the medicine after the expiry date indicated on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored.
No special storage conditions
Keep this medicine out of the reach and sight of children.
COMPOSITION
The vial of powder contains:
Active ingredient: Triptorelin 0.1 mg
Excipients: mannitol
The solvent vial contains:
sodium chloride, water for injections
PHARMACEUTICAL FORM AND CONTENT
Powder and solvent for solution for injection.
Subcutaneous use.
The pack contains 7 powder vials, 7 solvent vials of 1 ml
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
DECAPEPTYL 0.1 MG / ML POWDER AND SOLVENT FOR SOLUTION FOR INJECTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial of powder contains:
Active ingredient: Triptorelin 0.1 mg
For excipients, see 6.1.
03.0 PHARMACEUTICAL FORM
Powder and solvent for solution for injection.
Subcutaneous use.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of infertility in women in association with gonadotropins (hMG, hCG, FSH) in ovulation induction protocols, in the context of in vitro fertilization followed by embryo transfer (F.I.V.E.T.) and in other techniques for assisted reproduction.
04.2 Posology and method of administration
Short protocol: administer 1 vial of Decapeptyl 0.1 mg per day subcutaneously starting from the second day of the menstrual cycle (coinciding with the start of ovarian stimulation) until the day before the administration of hCG, for a mean duration of 10- 12 days.
Long protocol: administer 1 vial of Decapeptyl 0.1 mg per day subcutaneously, starting from the second day of the menstrual cycle. After pituitary desensitization is achieved (plasma estrogen concentration less than 50 pg / ml usually around the 15th day of treatment), start gonadotropin stimulation simultaneously with Decapeptyl 0.1 mg up to the day before hCG administration.
The drug is administered subcutaneously after extemporaneous preparation.
Withdraw the contents of the vial with the syringe and transfer the liquid from the vial into the vial. Shake the vial gently to ensure a homogeneous solution, without turning it upside down. Proceed to the injection immediately.
N.B .: It is important that the injection is carried out strictly respecting the instructions for use.
04.3 Contraindications
Hypersensitivity to GnRH, its analogues or to any of the excipients of the medicinal product (see 4.8). Pregnancy and breastfeeding.
04.4 Special warnings and appropriate precautions for use
The use of GnRH agonists can cause reduction in bone mineral density.
Particular care should be taken in the case of patients with additional risk factors for osteoporosis (eg chronic alcohol abuse, smoking, long-term therapy with drugs that reduce bone mineral density, such as anticonvulsants or corticoids, family history of osteoporosis , malnutrition).
Before prescribing triptorelin, verification of the patient's non-pregnant status is required.
Rarely, treatment with GnRH agonists may reveal the presence of an unknown pre-existing gonadotropic cell pituitary adenoma. These patients may present with pituitary apoplexy characterized by sudden headache, vomiting, visual impairment and ophthalmoplegia.
Mood alterations, including depression, have been reported. There is an increased risk of the incidence of depression (which may be severe) in patients receiving treatment with GnRH agonists, such as triptorelin.
Patients should be informed and treated appropriately in the event of symptoms appearing.
Patients with known depression should be closely monitored during therapy.
Women
Reduction in bone mineral density
The use of GnRH agonists is likely to cause, on average, a reduction in bone mineral density of 1% / per month over a 6 month treatment period. Every 10% reduction in bone mineral density increases the risk of fractures by 2 to 3 times.
Currently available data suggest that restoration of bone density occurs after cessation of therapy in most women.
No specific data are available for patients with confirmed osteoporosis or with risk factors for osteoporosis (eg chronic alcohol abuse, smokers, long-term therapies with drugs that reduce bone mineral density, such as anticonvulsants or corticoids, family history of osteoporosis, malnutrition, e.g. anorexia nervosa) Since decreased bone mineral density is likely to be more harmful in these patients, triptorelin treatment should be considered on an individual basis and initiated, after very careful evaluation, only if the benefits of treatment outweigh the risks Additional measures should be considered to counteract the loss of bone mineral density.
Female infertility
Before prescribing triptorelin 0.1mg, verification of the patient's non-pregnancy status is required.
Follicular stimulation, induced by the use of GnRH analogues and gonadotropins, can be significantly increased in a minority of predisposed patients, particularly in the case of Polycystic Ovary Syndrome.
The ovarian response to the Decapeptyl - gonadotropin combination can vary, even with the same dosage, from one patient to another and, in some cases, from one cycle to another, in the same patient.
Ovulation must be closely monitored with regular clinical and biological checks: ultrasound examinations and evaluation of plasma estrogens
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 case of ovarian hyper-response that may occur in predisposed patients or in case of polycystic disease of the ovary, it is recommended to stop the administration of gonadotropins, while the administration of Decapeptyl 0.1 mg is continued for a few days in order to avoid a possible spontaneous LH surge.
04.5 Interactions with other medicinal products and other forms of interaction
Care should be taken when triptorelin is administered concomitantly with other drugs that affect the pituitary secretion of gonadotropins and it is recommended that the patient's hormonal situation is monitored.
04.6 Pregnancy and lactation
Pregnancy
Triptorelin should not be used during pregnancy as concomitant use of GnRH agonists is associated with a theoretical risk of abortion or fetal abnormalities. Women of childbearing potential should be carefully examined before starting treatment to rule out pregnancy Non-hormonal methods of contraception should be used during therapy until the menstrual cycle returns.
Pregnancy must be ruled out before using triptorelin for the treatment of infertility. When triptorelin is used in this setting, there is no clinical evidence to suggest a causal relationship between triptorelin and any subsequent abnormalities in oocyte development. , in pregnancy or in the outcome of pregnancy.
Feeding time
Triptorelin should not be used during breastfeeding.
04.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. However, considering the pharmacological profile of triptorelin, triptorelin is likely to have no or negligible effect on the patient's ability to drive or use machines.
04.8 Undesirable effects
Increased lymphocyte counts have been reported in patients receiving GnRH analogues.
Experience in clinical trials
The adult population enrolled in clinical studies and treated with triptorelin, the immediate release formulation, included 127 men with prostate cancer treated daily for 3 months and approximately 1,000 women undergoing in vitro fertilization protocols. Detailed safety experience gained during clinical trials performed in men and women with the 3.75mg and 11.25mg triptorelin formulations was also included.
The overall analysis of safety experience from clinical trials included drug class related adverse reactions as a result of hypogonadotropic hypogonadism or, occasionally, initial pituitary-gonadal stimulation.
The frequency of adverse reactions is classified as follows: very common (≥1 / 10) - Common (≥1 / 100-
General tolerability in adults
Very common: Mild to severe hot flashes which usually do not require discontinuation of therapy.
Common: psychiatric disorders (mood changes, depression) *
Uncommon: psychiatric disorders (mood changes, depression) **
* Long-term use. This frequency is based on the frequency of the class effect, common to all GnRH agonists
** Short term use. This frequency is based on the frequency of the class effect, common to all GnRH agonists
General tolerability in women
Very common at the start of treatment: in the treatment of infertility triptorelin, used in combination with gonadotropins, can give ovarian hyperstimulation syndrome. Ovarian hypertrophy, dyspnoea, pelvic and / or abdominal pain may occur (see section 4.4)
Very common at the start of treatment with tritorelin in the monthly and quarterly formulations:
genital bleeding including menorrhagia or metrorrhagia may occur in the month following the first injection.
Very common during treatment with tritorelin in the monthly and quarterly formulations:
these adverse reactions show a series of hypo-estrogenic events related to pituitary-ovarian block, such as sleep disorders, headache, mood alteration, vulvo-vaginal dryness and dyspareunia, decreased libido.
Common during treatment with tritorelin in the monthly formulation:
breast pain, muscle spasms, arthralgia, weight gain, nausea, abdominal discomfort / pain, asthenia. Mood changes and depression have been reported with long-term use.
Local tolerability
Very rare: pain, erythema and inflammation at the injection site.
Post-marketing information
During post-marketing surveillance, other undesirable effects have been reported in women being treated for IVF. Undesirable effects are classified by systemic organic categories and in decreasing order of frequency of the reported effects:
Skin and subcutaneous tissue disorders: hypersensitivity reactions, including itching, hives, rash, angioneurotic edema (refer to the "Contraindications" section)
Nervous system disorders: headache
Eye disorders: episodes of blurred vision or visual disturbances.
04.9 Overdose
No adverse reactions have been reported as a consequence of overdose.
On the basis of the toxicological data in the animal, no effects other than those on the concentration of sex hormones are foreseeable, with consequent repercussions on the reproductive system. In the event of overdose, symptomatic treatment is advised.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: endocrine therapy; gonadotropin releasing hormone analogues
ATC code: L02AE04
Triptorelin is a synthetic decapeptide (D-Trp-6-LHRH), analogue of the natural peptide.The substitution of glycine in position 6 with D-tryptophan confers a remarkable agonist power and a more marked resistance to enzymatic degradation.
Triptorelin has in fact shown, in various in vitro and in vivo studies, a variable potency, depending on the experimental model, up to 100 times greater than the natural neuropeptide. Studies conducted in animals and in women have shown that the administration of triptorelin, after a short phase of stimulation of the secretion of gonadotropins [(FSH and LH) - with consequent secretion of estradiol - lasting about a week] exerts an inhibitory effect with suppression of ovarian function.
Triptorelin ensures suppression of intercurrent LH peaks, allowing better control of folliculogenesis induced by gonadotropins. This translates into an increase in follicular recruitment, as well as an increase in the number of embryos generated and pregnancies per cycle.
05.2 Pharmacokinetic properties
In healthy volunteers: after subcutaneous administration triptorelin (0.1 mg) is rapidly absorbed (the plasma peak, equal to 1.85 ± 0.23 ng / ml is reached after 0.63 ± 0.26 hours). The distribution phase lasting 3-4 hours follows, resulting in a volume of distribution equivalent to 1562.7 ± 158.8 ml / kg. Elimination occurs with a biological half-life of 7.6 ± 1.6 hours and total plasma clearance is 161.7 ± 28.6 ml / min.
05.3 Preclinical safety data
Acute toxicity was evaluated intraperitoneally and subcutaneously in rats and mice.
As regards the intraperitoneal route, the LD 50 is very low and in the rat it is equal to 100 mg / kg, while in the mouse it is equal to 160-200 mg / kg.
Following subcutaneous administration, in both species the LD50 is not measurable at significantly higher doses (150,000 times in the rat and 250,000 times in the mouse) compared to the usual therapeutic dose.
Chronic toxicity studies have shown that repeated administrations do not induce changes in organs and systems other than the reproductive one. Animal studies have not shown teratogenic effects.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Mannitol, Sodium chloride, Water for injections
06.2 Incompatibility
There are no data of incompatibility with other drugs.
06.3 Period of validity
24 months in intact packaging.
06.4 Special precautions for storage
No special storage conditions
06.5 Nature of the immediate packaging and contents of the package
Pack of 7 vials of powder and 7 solvent vials of 1ml
06.6 Instructions for use and handling
None
07.0 MARKETING AUTHORIZATION HOLDER
IPSEN S.p.A. - Via A. Figino 16 - Milan.
08.0 MARKETING AUTHORIZATION NUMBER
026999045
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 08.05.1996
Last renewal date: 01.12.2009
10.0 DATE OF REVISION OF THE TEXT
Determination V&A 674 of 2 April 2014
