Active ingredients: Triptorelin (Triptorelin acetate)
FERTIPEPTIL, solution for injection
Why is Fertipeptil used? What is it for?
This medicine is supplied as a solution for injection in a disposable syringe. It is given as a subcutaneous injection in the lower abdomen.
This medicine contains triptorelin, which is a synthetic analogue of the natural gonadotropin-releasing hormone (GnRH). GnRH regulates the release of gonadotropins (sex hormones: luteinizing hormone (LH) and follicle stimulating hormone (FSH)). FERTIPEPTIL blocks the action. GnRH therapy reduces LH and FSH levels (downregulation). This leads to premature ovulation prevention (egg release).
This drug is used to treat women who are undergoing assisted reproductive techniques (ART). In ART, ovulation can occasionally occur early, causing a significant decrease in the chances of becoming pregnant. FERTIPEPTIL is used for downregulation and for the prevention of a premature increase in LH which could therefore cause premature egg release.
Contraindications When Fertipeptil should not be used
Do not use FERTIPEPTIL:
- If you are allergic (hypersensitive) to triptorelin acetate or to any of the other ingredients of FERTIPEPTIL (See section 6 - Further information)
- If you are allergic (hypersensitive) to GnRH or other GnRH analogues (drugs similar to FERTIPEPTIL)
- If you are pregnant or breastfeeding. Read the section "Pregnancy and breastfeeding"
Precautions for use What you need to know before taking Fertipeptil
Pay particular attention to treatment with FERTIPEPTIL
- There have been reports of depression in patients taking FERTIPEPTIL which can be severe. If you are taking FERTIPEPTIL and develop a depressed mood, please tell your doctor.
- Because it can cause mood swings.
- Because treatment can in rare cases cause cerebral hemorrhage (pituitary apoplexy). Contact your doctor immediately if you experience sudden headache, vomiting or vision disturbances.
- Because the treatment can cause thinning of the bones which increases the risk of fractures.
- If you are at additional risk of bone thinning (osteoporosis) please tell your doctor before using FERTIPEPTIL. Risk factors include:
- Some of his family members suffer from thinning of the bones
- He drinks excessively alcohol, has a poor diet and / or smokes a lot
- You are being treated with medicines that can affect the strength of your bones.
Tell your doctor if any of the following warnings apply to you or have been in the past.
- If you have a mild or severe liver disorder.
- If you have an active allergic reaction or if you have often suffered from allergic reactions in the past.
- If you administer FERTIPEPTIL alone, you must be informed of the possible allergic reactions that may occur (itching, rash, fever). (See section 4 "Possible Side Effects").
Contact your doctor immediately if you experience any reactions after the injection of Fertipeptil.
If you suffer from:
- Abdominal pain
- Abdominal swelling
- Nausea
- He retched
- Diarrhea
- Weight gain
- Breathing difficulty
- Decreased urine production.
Tell your doctor right away, even if symptoms appear a few days after the last injection. Those described may be signs of high ovarian activity which can become severe (See also section 4 "Possible Side Effects"). symptoms become severe, infertility treatment must be stopped and you must go to a hospital.
While you are being treated with this medicine, your doctor will have an ultrasound scan and sometimes blood tests to check your response to treatment.
Hormone treatment for infertility such as this drug may increase the risk of:
- Ectopic pregnancy (pregnancy outside the uterus) in case of previous problems with the fallopian tubes
- Miscarriage
- Multiple pregnancy (twins, triplets, etc.)
- Congenital malformations (physical defects of the newborn present at birth).
Interactions Which drugs or foods can modify the effect of Fertipeptil
Tell your doctor what medicines you are using or have recently used, including medicines bought without a prescription.
Warnings It is important to know that:
Pregnancy and breastfeeding
FERTIPEPTIL should not be used during pregnancy or breastfeeding.
Do not use FERTIPEPTIL if you suspect that you are pregnant. Pregnancy must first be ruled out by your doctor.
Do not continue to use FERTIPEPTIL if you discover that you are pregnant during treatment.
Non-hormonal contraception, such as a condom or diaphragm, should be used during treatment with FERTIPEPTIL.
Effects on ability to drive and use machines
The drug is unlikely to affect the ability to drive and use machines.
For those who carry out sports activities
The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Important information about some of the ingredients of FERTIPEPTIL
This drug contains less than 1 mmol sodium (23 mg) per maximum dosage dose, so it is essentially "sodium free".
Dosage and method of use How to use Fertipeptil: Dosage
This drug should always be used as directed by the doctor. If you are not sure about its use, check with your doctor how to do it.
The commonly used dose is a subcutaneous injection into the lower abdomen, once a day. Treatment can be started on the 2nd or 3rd day or from the 21st to 23rd day of the menstrual cycle (or 5-7 days before). of the hypothetical day of the start of the menstrual cycle). After 2-4 weeks, other hormones will be given to promote follicle growth (growth of the sac containing the egg). Normally, FERTIPEPTIL treatment continues until the follicle has reached the right size, usually 4 to 7 weeks.
If enough follicles are obtained, you will be given a medicine called human chorionic gonadotropin (hCG) in a single injection to induce ovulation (release of an egg).
Your doctor will monitor your progress for at least 2 weeks after the hCG injection.
INSTRUCTIONS FOR ADMINISTRATION
If you have been asked to administer this medicine yourself, carefully follow all instructions given to you.
The first injection of this drug should be done under the supervision of a doctor.
- Remove the protective film and take the syringe out of the package. Hold the syringe with the needle pointing up, keeping the gray protective cap. Remove the gray protective cap. Gently push the piston until the first drop of liquid comes out.
- Lift the skin between thumb and forefinger. Push the plunger of the syringe and slowly inject the contents of the syringe.
If you have forgotten to take FERTIPEPTIL
Tell your doctor or nurse.
If you have stopped using FERTIPEPTIL
Do not stop taking FERTIPEPTIL on your own but strictly follow your doctor's instructions. Stopping the treatment too soon will decrease the likelihood of becoming pregnant.
If you have any questions about the use of this product, ask your doctor.
Overdose What to do if you have taken too much Fertipeptil
If you have taken more FERTIPEPTIL than you should, please tell your doctor or nurse.
Side Effects What are the side effects of Fertipeptil
Like all medicines, this drug can cause side effects, although they do not occur in all people.
The following are the very common side effects that occur in more than 1 in 10 patients treated:
- headache
- abdominal pain
- vaginal bleeding / Spotting
- nausea
- inflammation at the injection site
The following are common side effects that occur in 1 to 10 out of 100 patients treated:
- cooler
- flu symptoms
- pharyngitis
- dizziness
- hot flashes
- He retched
- abdominal bloating
- back pain
- abortion
- pelvic pain
- hyperstimulation of the ovaries (hyperactivity), (see paragraph 2 "Pay particular attention to treatment with FERTIPEPTIL")
- ovarian cysts (at the start of treatment)
- pain during menstruation
- pain or other reactions at the injection site
- fatigue
Uncommon, occurring in 1 to 10 patients in 1000 patients treated:
- mood swings, depression.
Not known: the frequency cannot be calculated from the available data:
- abdominal discomfort
- enlarged ovaries
- excessive sweating
- vaginal discharge between menstruation
- allergic reactions (see section 2 "Pay particular attention to treatment with FERTIPEPTIL")
- redness at the injection site
- sleep disorders
- decreased sexual desire
- weight gain
- shortness of breath
- blurred vision
- vision disturbances
- itch
- heavy, prolonged and / or irregular menstruation
- rash
- vaginal dryness
- angioedema (swelling immediately under the skin)
- pain during sexual intercourse
- weakness
- breast pain
- muscle spasms
- joint pain
In the event of occurrence or aggravation of one or more of the undesirable effects described or the occurrence of undesirable effects not described, please inform your doctor.
Expiry and Retention
Store in a refrigerator (2 ° C - 8 ° C). Do not freeze.
Store in the original package, to protect it from light.
Keep out of the reach and sight of children.
Do not use FERTIPEPTIL after the expiry date indicated on the package. The expiry date refers to the last day of the month indicated.
Medicines should not be disposed of along with regular garbage. Ask your pharmacist how to throw away the unused drug. These measures are adopted to protect the environment.
Deadline "> Other information
What FERTIPEPTIL contains
- The active substance is triptorelin acetate. Each pre-filled syringe of 1 ml solution for injection contains 100 micrograms of triptorelin acetate equivalent to 95.6 micrograms of free base triptorelin.
- The other ingredients are sodium chloride, acetic acid (glacial) and water for injections.
What FERTIPEPTIL looks like and what is the contents of the pack
This medicine is a clear colorless solution in a 1 ml glass syringe to which a needle is attached.
The syringe and needle are closed by a rubber stopper and a needle cap.
The carton contains 7 or 28 pre-filled syringes.
Not all packs may be on the market.
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 -
FERTIPEPTIL 0.1 MG / 1 ML SOLUTION FOR INJECTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each pre-filled syringe with 1 ml of solution for injection contains 100 micrograms of triptorelin acetate, equivalent to 95.6 micrograms of free base triptorelin.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Injectable solution.
Clear colorless solution.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Fertipeptil is indicated for the downregulation and prevention of premature luteinizing hormone (LH) peaks in women undergoing controlled ovarian hyperstimulation in assisted reproductive techniques (ART).
In clinical studies, Fertipeptil was used in cycles in which stimulation was induced with either urinary or recombinant follicle stimulating hormone (FSH) or human menopausal gonadotropin (HMG).
04.2 Posology and method of administration -
Dosage
Treatment can be started in the first follicular phase (day 2 or 3 of the menstrual cycle) or in the middle luteal phase (day 21-23 of the menstrual cycle or 5-7 days before the expected start of menstruation). Controlled ovarian hyperstimulation with gonadotropins should be started approximately 2-4 weeks after treatment with Fertipeptil. Ovarian response should be clinically monitored (by ovarian ultrasound alone or, preferably, in combination with estradiol level dosing) and the gonadotropin dose adjusted accordingly. Once a sufficient number of follicles of the appropriate size have been obtained, treatment with Fertipeptil and gonadotropins should be discontinued and a single injection of hCG administered to induce final follicle maturation. If after 4 weeks the downregulation is not confirmed (by ultrasound evidence of a flaking endometrium or, preferably in combination with measurement of estradiol levels), discontinuation of Fertipeptil treatment should be considered. The total duration of treatment is usually 4-7 weeks During treatment with Fertipeptil, adequate support of the luteal phase should be provided, according to the protocol of the referring medical center.
Patients with renal or hepatic impairment
There are no specific dosage recommendations in patients with hepatic or renal impairment. A clinical study found that the risk of triptorelin accumulation in patients with hepatic impairment and severe renal impairment is low (see section 5.2).
Pediatric population
No data are available on the use of Fertipeptil in the pediatric population for the indication: downregulation and prevention of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation in assisted reproductive techniques (ART).
Method of administration
Treatment with Fertipeptil should be initiated under the supervision of a specialist in the treatment of infertility. Fertipeptil is used as a daily subcutaneous injection into the lower abdominal wall. After the first administration, it is recommended that the patient be monitored for 30 minutes for medical attention to ensure that there are no allergic / pseudo-allergic reactions to the injection.
The necessary equipment to treat such reactions must be readily available. Subsequent injections can be performed by the patient herself provided she has been well informed about the signs and symptoms of possible hypersensitivity, the consequences of such reactions and the need for immediate medical attention. To avoid lipoatrophy, it is recommended to vary the injection site. For instructions on use and handling, see section 6.6.
04.3 Contraindications -
Fertipeptil is contraindicated in the following cases:
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
- Hypersensitivity to gonadotropin releasing hormone (GnRH) or its analogues.
- Pregnancy and breastfeeding.
04.4 Special warnings and appropriate precautions for use -
The use of GnRH agonists may cause reduction in bone mineral density. Preliminary data in humans suggest that the use of bisphosphonates in combination with GnRH agonists may reduce bone mineral loss.
Particular care should be taken in patients with additional risk factors for osteoporosis (e.g. chronic alcohol abuse, smoking, long-term therapy with drugs known to reduce bone mineral density such as anticonvulsants or corticoids, family history of osteoporosis , malnutrition).
Loss of bone mineral density
Use of GnRH agonists is likely to cause a reduction in bone mineral density by an average of 1% per month over a six-month treatment period. Every 10% reduction in bone mineral density is associated with an approximately two to threefold increase in fracture risk.
Currently available data suggest that in the majority of women the recovery of lost bone mass occurs after cessation of treatment.
No specific data are available in patients with overt osteoporosis or with risk factors for osteoporosis (e.g. chronic alcohol abuse, smokers, long-term therapies with drugs known to reduce bone mineral density such as anticonvulsants or corticoids, medical history family member for osteoporosis, malnutrition, e.g. anorexia nervosa). Since the loss of bone mineral density in these patients can be particularly harmful, triptorelin treatment should be evaluated on an individual basis and started only if careful analysis of the case considers the expected benefits greater than the associated risks. They should be taken. consider additional measures to counteract the loss of bone mineral density.
Confirmation that the patient is not pregnant should be confirmed before triptorelin is prescribed.
Rarely, treatment with GnRH agonists may reveal the presence of previously unknown gonadotropic pituitary adenoma cells. These patients may present with pituitary apoplexy characterized by sudden headache, vomiting, visual disturbances and ophthalmoplegia.
There is an increased risk of episodes of depression (which can be serious) in patients treated with GnRH agonists, such as triptorelin. Patients should be informed and treated appropriately if symptoms appear.
Mood changes have been reported. Patients with known depression should be closely monitored during treatment.
Ovarian stimulation should only take place under strict medical supervision.
In patients with renal or hepatic impairment, triptorelin has a mean final half-life of 7-8 hours compared with 3-5 hours in healthy subjects. Despite this prolonged exposure, the presence of triptorelin in the circulation is not expected at the time of embryo transfer.
Pay particular attention to women with signs or symptoms of active allergies or with a history of predisposition to allergies. Treatment with Fertipeptil is not recommended in women with severe allergic reactions. Women of childbearing potential should be carefully monitored before treatment to rule out pregnancy.
Assisted reproductive techniques (ART) are associated with an increased risk of multiple pregnancies, miscarriage, ectopic pregnancies and congenital malformations. These risks also apply to treatment with Fertipeptil as additional therapy in controlled ovarian hyperstimulation. The use of Fertipeptil in controlled ovarian hyperstimulation may increase the risk of ovarian hyperstimulation syndrome (OHSS) and ovarian cysts.
The collection of follicles induced by the use of GnRH analogues and gonadotropins can be evidently increased in a minority of predisposed patients, particularly in the case of Polycystic Ovary Syndrome.
As with other GnRH analogues, there have been reports of ovarian hyperstimulation syndrome (OHSS) associated with the use of triptorelin in combination with gonadotropins.
Ovarian hyperstimulation syndrome (OHSS):
OHSS is a medical event distinct from uncomplicated ovarian enlargement. OHSS is a syndrome that can occur with varying degrees of severity. It includes marked ovarian enlargement, high serum levels of steroid sex hormones, and an increase in vascular permeability which can progress to an accumulation of fluid in the peritoneum, in the pleura and, rarely, in the pericardial cavity.
In severe cases of OHSS, the following symptoms may be observed: abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptoms such as nausea, vomiting and diarrhea. Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalance, ascites, haemoperitoneum, pleural effusions, hydrothorax, acute pulmonary insufficiency, and thromboembolic events.
Excessive ovarian response to gonadotropin treatment rarely results in OHSS if administration of hCG to induce ovulation is avoided. Therefore in cases of OHSS it is prudent not to administer hCG and to advise the patient to abstain from sexual intercourse or to use barrier methods of contraception for at least 4 days. OHSS can evolve rapidly (24 hours to several days) and become a serious medical event, therefore patients should be monitored for at least 2 weeks after hCG administration.
OHSS can be more severe and more prolonged if pregnancy occurs. Very often OHSS occurs after hormone treatment is stopped and reaches its maximum severity levels approximately seven to ten days after treatment. Generally, OHSS resolves spontaneously with the onset of menstruation.
If severe OHSS occurs, gonadotropin treatment should be discontinued, if still ongoing, the patient should be hospitalized and specific therapy for OHSS initiated, for example with absolute rest, intravenous infusion of electrolyte solutions or colloidal and heparin.
This syndrome occurs with a higher incidence in patients with polycystic ovary.
The risk of OHSS may be increased with the use of GnRH agonists in combination with gonadotropins compared to the use of gonadotropins alone.
Ovarian cysts:
Ovarian cysts may develop during the initial phase of GnRH agonist treatment. These cysts are usually asymptomatic and non-functional.
04.5 Interactions with other medicinal products and other forms of interaction -
Interactions of Fertipeptil with other medicinal products have not been studied for this indication.
Possible interactions with commonly used medicinal products, including histamine liberators, cannot be excluded.
When triptorelin is administered in combination with drugs that interfere with the pituitary secretion of gonadotropins, caution should be used and a monitoring of the patient's hormonal status is recommended.
04.6 Pregnancy and breastfeeding -
Pregnancy
Fertipeptil is not indicated during pregnancy. Pregnancy must be ruled out prior to initiation of infertility treatment. A non-hormonal method of contraception should be used during treatment until menstruation resumes. If the patient becomes pregnant during triptorelin therapy, the treatment should be discontinued.
When triptorelin is used for the treatment of "infertility, there is no evidence of a causal link between triptorelin and any subsequent abnormalities in the development of the oocytes, pregnancy or the newborn."
The limited data available on the use of triptorelin in pregnancy do not indicate an increased risk of congenital malformations. Studies in animals have shown reproductive toxicity (see section 5.3). Based on the pharmacological effects, a negative influence on pregnancy and the product of conception cannot be excluded.
Feeding time
Fertipeptil is not indicated during lactation.
04.7 Effects on ability to drive and use machines -
No studies on the ability to drive and use machines have been conducted. However, based on its pharmacological profile, Fertipeptil probably has no or negligible influence on the ability to drive and use machines.
04.8 Undesirable effects -
Frequently (≥ 2%) reported undesirable effects during treatment with Fertipeptil in clinical studies, both before and during co-treatment with gonadotropins, are shown in the table below. The most frequent adverse events are: headache (27%), vaginal bleeding / spotting (24%), abdominal pain (15%), injection site inflammation (12%) and nausea (10%).
Moderate to severe flushing and hyperhidrosis may occur and normally do not require discontinuation of treatment.
At the start of treatment with Fertipeptil, the combination with gonadotropins may cause ovarian hyperstimulation syndrome. Ovarian enlargement, dyspnoea, pelvic and / or abdominal pain may be observed (see section 4.4 "Special warnings and precautions for use"). Genital haemorrhage. , including menorrhagia and metrorrhagia, can occur at the start of treatment with Fertipeptil.
Ovarian cyst formation has been reported commonly (1%) during the initial phase of treatment with Fertipeptil.
During treatment with triptorelin some adverse reactions have shown a general pattern of hypo-estrogenic events related to a pituitary-ovarian block such as sleep disturbances, headache, mood changes, vulvovaginal dryness, dyspareunia and decreased libido.
Breast pain, muscle spasms, arthralgia, weight gain, nausea, abdominal pain, abdominal discomfort, asthenia and episodes of blurred vision and visual disturbances may be observed during treatment with Fertipeptil.
After injection of Fertipeptil, single cases of allergic reactions, localized or generalized, have been reported.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
In humans, overdose can be expressed as a prolongation of the duration of action. In the event of an overdose, treatment with Fertipeptil should be (temporarily) stopped.
No adverse reactions resulting from overdose have been reported.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Gonadotropin-releasing hormone analogs.
ATC code: L02AE04.
Triptorelin (acetate) is a synthetic decapeptide analogue of the natural hypothalamic hormone GnRH. Triptorelin has a duration of action longer than that of natural GnRH and has a biphasic action at the pituitary level. After a rapid and massive initial increase in LH levels. and FSH (flare-up), circulating levels of LH and FSH decrease due to desensitization of pituitary GnRH receptors, resulting in a marked decrease in gonadal production.
The exact duration of action of Fertipeptil has not been established, but pituitary suppression persists for at least 6 days after discontinuation of dosing. After discontinuation of Fertipeptil dosing, a further drop in levels of LH, which return to baseline in about two weeks.
The pituitary downregulation induced by Fertipeptil is able to prevent the LH surge and consequently premature ovulation and / or follicular luteinization. The use of downregulation with GnRH agonists reduces the cycle cancellation rate and improves the pregnancy rate in assisted reproductive cycles.
05.2 "Pharmacokinetic properties -
Pharmacokinetic data suggest that after subcutaneous administration of Fertipeptil the systemic bioavailability of triptorelin is close to 100%. The elimination half-life of triptorelin is approximately 3-5 hours, indicating that triptorelin is eliminated in 24 hours and therefore will not be in circulation at the time of embryo transfer. The molecule is metabolized into smaller peptides and amino acids mainly in the liver and kidneys. Triptorelin excretion occurs predominantly in the urine.
Clinical studies indicate that the risk of triptorelin accumulation in patients with hepatic impairment or severe renal impairment is low (observed half-life in these patients is approximately 8 hours).
05.3 Preclinical safety data -
In rats treated long-term with triptorelin, an increase in pituitary tumors was detected. The onset of pituitary tumors in rodents is known in relation to other similar LHRHs, due to the rodent-specific regulation of the endocrine system which is different from that of humans. The influence of triptorelin on pituitary changes in humans is not known and observations in the rat are not considered relevant to humans.
Triptorelin is not teratogenic but there are indications of delayed fetal development and delivery in the rat.
Non-clinical data indicate no special hazards for humans based on repeated dose toxicity and genotoxicity studies.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Sodium chloride
Glacial acetic acid (for pH adjustment)
Water for injections
06.2 Incompatibility "-
In the absence of compatibility studies, the product must not be mixed with other medicinal products.
06.3 Period of validity "-
3 years.
06.4 Special precautions for storage -
Store in a refrigerator (2 ° C - 8 ° C). Do not freeze.
Store in the original package to protect the medicine from light.
06.5 Nature of the immediate packaging and contents of the package -
1 ml of solution in pre-filled syringe (glass) with plunger stopper (chlorobutyl rubber), plunger (polystyrene), integrated needle and rigid needle cover, in packs of 7 or 28 syringes.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
Inject the entire contents of the single-use pre-filled syringe subcutaneously. For single use only.
There are no special precautions for disposal.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Ferring S.p.A.
Via Senigallia 18/2
20161 - MILAN (Italy)
08.0 MARKETING AUTHORIZATION NUMBER -
Fertipeptil 0.1 mg / 1ml Solution for Injection 7 Pre-filled Syringes AIC n. 039404013
Fertipeptil 0.1 mg / 1ml Injectable Solution 28 Pre-filled Syringes AIC n. 039404025
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Determination no. 1733/2010 of 07/06/2010
10.0 DATE OF REVISION OF THE TEXT -
16 August 2016
