Active ingredients: Leuprolide
ELIGARD 7.5 mg powder and solvent for solution for injection
Why is Eligard used? What is it for?
The active substance in ELIGARD belongs to the group of so-called gonadotropin releasing hormones. These medicines are used to reduce the production of some sex hormones (testosterone).
ELIGARD is used to treat advanced hormone-dependent prostate cancer in adult men.
Contraindications When Eligard should not be used
Do not use ELIGARD
- Whether she is a woman or a child
- If you are hypersensitive (allergic) to the active substance leuprorelin acetate, to medicines with activity comparable to the natural hormone gonadotropin or to any of the other ingredients of ELIGARD (listed in section 6).
- Following surgical removal of the testicles, since in this case ELIGARD does not cause a "further decrease in serum testosterone levels.
- As the only treatment if you have symptoms related to spinal cord compression or spinal tumors. In these cases, ELIGARD should only be used in combination with other medicines for the treatment of prostate cancer.
Precautions for use What you need to know before taking Eligard
Talk to your doctor, pharmacist or nurse before using ELIGARD
- If you are in any of the following situations: any heart or circulatory conditions, including heart rhythm problems (arrhythmia), or if you are being treated with medicines for these conditions. The risk of heart rhythm problems may increase when ELIGARD is used.
- If you have difficulty urinating. You must be monitored closely during the first few weeks of treatment.
- If you experience spinal cord compression or difficulty urinating. In analogy with other drugs characterized by a mechanism of action similar to that of ELIGARD, it has been reported that severe cases of spinal cord compression and narrowing of the ducts between the kidneys and the urinary bladder can contribute to the onset of paralysis. as a symptom. If these complications arise, standard therapy should be performed.
- If you experience sudden headache, vomiting, altered mental status and sometimes heart failure, within two weeks of taking ELIGARD, then tell your doctor or medical staff. There have been rare cases defined as pituitary apoplexy, which have been recorded WITH OTHER DRUGS with similar mechanism of action to ELIGARD.
- If you have diabetes mellitus (high blood sugar levels). You must be monitored regularly during treatment.
- Treatment with ELIGARD may increase the risk of fractures caused by osteoporosis (decreased bone density).
- There have been reports of depression in patients taking ELIGARD. If you are taking ELIGARD and feel depressed, please tell your doctor.
- In patients taking products similar to Eligard, there have been reports of cardiovascular events and it is not known whether these are related to taking these products. If you are taking ELIGARD and develop cardiovascular signs or symptoms, please tell your doctor.
- Convulsions have been reported in patients taking ELIGARD. If you are taking ELIGARD and have convulsions, please tell your doctor.
Complications that arise at the beginning of the treatment
During the first week of treatment, there is usually a transient increase in the levels of the male sex hormone testosterone in the blood. This can result in temporary worsening of disease-related symptoms and also the onset of new symptoms that the patient did not have. still had experience. These symptoms mainly include bone pain, urinary discomfort, spinal cord compression or blood in the urine. Usually these symptoms tend to subside with continued treatment. If symptoms persist, you should contact your doctor.
If ELIGARD does not make improvements
A group of patients have tumors that are not sensitive to the reduction in testosterone levels. If you have the impression that the effect of ELIGARD is too weak, talk to your doctor.
Interactions Which drugs or foods may change the effect of Eligard
ELIGARD may interfere with some medicines used to treat heart rhythm problems (e.g. quinidine, procainamide, amiodarone and sotalol) or may increase the risk of heart rhythm problems when used together with other medicines (e.g. methadone (used to reduce pain and substance abuse detox), moxifloxacin (an antibiotic), antipsychotics used for severe mental illness).
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
Warnings It is important to know that:
Pregnancy and breastfeeding
ELIGARD is not indicated for women.
Driving and using machines
Fatigue, dizziness or visual disturbances are possible side effects of treatment with ELIGARD or could be a consequence of the disease. If you experience these side effects, be careful while driving or using machines.
Dose, Method and Time of Administration How to use Eligard: Posology
Dosage
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
ELIGARD 7.5 mg is given once a month, unless otherwise directed by your doctor.
The injected solution forms a drug depot which allows the prolonged release of the active ingredient leuprorelin acetate for one month.
Additional tests
The response to therapy with ELIGARD should be verified by your doctor by following specific clinical parameters and by measuring the blood levels of the prostate specific antigen (PSA).
Method of administration
ELIGARD should only be administered by your doctor or nurse. They will also take care of the preparation of the ready-to-use solution (according to the instructions in Section 7. Information for healthcare professionals, at the end of this leaflet). After preparation, ELIGARD is administered by means of a subcutaneous injection (injection into the tissue under the skin). Intravenous (into an artery) or intravenous (into a vein) injection should be strictly avoided. As with other active substances injected subcutaneously, the injection site should be periodically changed.
If you forget to take ELIGARD
If you think you have forgotten the monthly administration of ELIGARD you should contact your doctor.
If you stop taking ELIGARD
As a general rule, prostate cancer therapy with ELIGARD requires long-term treatment. Therefore, therapy should not be discontinued, even if there is an improvement in symptoms or if they disappear completely.
If treatment with ELIGARD is stopped prematurely, worsening of the symptoms related to the disease may occur.
You must not stop therapy earlier than expected without first consulting your doctor.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
Overdose What to do if you have taken too much Eligard
Since the injection is usually given by your doctor or suitably trained personnel, no overdose is to be expected.
However, if more than expected is administered, your doctor will carry out specific monitoring and give you additional treatment as required.
Side Effects What are the side effects of Eligard
Like all medicines, ELIGARD can cause side effects, although not everybody gets them.
The undesirable effects observed during treatment with ELIGARD are mostly due to the specific effect of the active substance leuprorelin acetate, ie an increase and decrease in certain hormones. The most commonly described undesirable effects are hot flashes (in 58% of patients ), nausea, malaise and fatigue, as well as temporary local irritation at the injection site.
Initial side effects
During the first weeks of treatment with ELIGARD, the specific symptoms related to the disease may worsen, as in the first period there is usually a brief increase in the male sex hormone testosterone in the blood. Your doctor can then administer an adequate anti-androgen. (substance that inhibits the effects of testosterone) in the initial phase of treatment in order to mitigate these possible effects (see also Section 2. Before using ELIGARD, Complications that arise at the start of treatment).
Local side effects
The local side effects described following the injection of ELIGARD are typically those that are often associated with similar preparations injected subcutaneously (preparations that are injected into the tissue under the skin). A mild burning sensation immediately after injection is a very strong effect. common. Acute pain and pain after injection are common, as is bruising at the injection site. Cases of redness of the skin at the injection site have been reported as rare. Tissue hardening and ulceration are not These local side effects following subcutaneous injection are mild and described as short lasting effects. These side effects do not recur in the time interval between individual injections.
Very common side effects (may affect more than 1 in 10 people)
- Hot flashes
- Spontaneous bleeding of the skin or mucous membranes, redness of the skin
- Fatigue, injection-related side effects (see also Local side effects above)
Common side effects (may affect up to 1 in 10 people)
- Nasopharyngitis (cold symptoms)
- Nausea, malaise, diarrhea, inflammation of the stomach and intestines (gastroenteritis / colitis)
- Itching, night sweats
- Articolar pains
- Irregular urge to urinate (even at night), difficulty in starting to urinate, pain in urinating, decreased amount of urine passed
- Breast tenderness, breast swelling, testicular atrophy, testicular pain, infertility, erectile dysfunction, reduced penis size
- Chills (episodes of violent tremors with high fever), weakness
- Prolonged bleeding time, changes in blood parameters, decreased red blood cells / low red blood cell count.
Uncommon side effects (may affect up to 1 in 100 people)
- Urinary tract infections, local skin infections
- Worsening of diabetes mellitus
- Abnormal dreams, depression, decreased libido
- Dizziness, headache, changes in skin sensitivity, insomnia, taste disturbances, smell disturbances
- Hypertension (increase in blood pressure), hypotension (decrease in blood pressure)
- Wheezing
- Constipation, dry mouth, dyspepsia (digestive disturbances with symptoms such as a full stomach, stomach pains, belching, nausea, vomiting, heartburn sensation), vomiting
- Cold sweats, increased sweating
- Back pain, muscle cramps
- Hematuria (blood in the urine)
- Bladder spasms, increased urge to urinate, inability to urinate
- Male breast tissue enlargement, impotence
- Lethargy (sleepiness), pain, fever
- Weight gain
- Loss of balance, mental light-headedness
- Muscle wasting / loss of muscle tissue after prolonged use
Rare side effects (may affect up to 1 in 1,000 people)
- Abnormal involuntary movements
- Sudden loss of consciousness, fainting
- Flatulence, belching
- Hair loss, rash (boils on the skin)
- Breast pains
Very rare side effects (may affect up to 1 in 10,000 people)
- Injection site necrosis Not known (frequency cannot be estimated from the available data)
- EKG Changes (QT Prolongation)
Other undesirable effects Other undesirable effects that have been described in the literature in connection with treatment with leuprorelin, the active ingredient of ELIGARD, are edema (accumulation of fluid in the tissues, manifested as swelling of the hands and feet), pulmonary embolism ( manifested by symptoms such as shortness of breath, difficulty in breathing and chest pains), palpitations (awareness of one's heartbeat), muscle weakness, chills, rash, impaired memory and vision.
After long-term treatment with ELIGARD it is possible to predict the onset of symptoms attributable to bone reduction (osteoporosis). Due to the onset of osteoporosis, the risk of fractures increases. After administration of medicinal products belonging to the same class as ELIGARD, severe allergic reactions causing difficulty in breathing or dizziness have been reported rarely.
Convulsions have been reported following administration of medicinal products belonging to the same class as ELIGARD.
Reporting of side effects
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer carton. The expiry date refers to the last day of that month.
Instructions for storage
Store in a refrigerator (2 ° C-8 ° C).
Store in the original package to protect from moisture.
Before injection this medicine must be brought to room temperature. Remove from the refrigerator about 30 minutes before use.
Once out of the refrigerator this medicine can be stored in the original package, at room temperature (below 25 ° C), for up to four weeks. Once the tray is opened, the medicine must be prepared and used immediately. Disposable packaging.
Instructions for the disposal of unused or expired ELIGARD packs
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What ELIGARD contains
The active ingredient is leuprorelin acetate. One pre-filled syringe (Syringe B) contains 7.5 mg of leuprorelin acetate.
The other ingredients are copolymer of DL-lactic and glycolic acids (50:50) and N-methyl-2-pyrrolidone in a pre-filled syringe with solution for injection (Syringe A).
Description of what ELIGARD looks like and contents of the pack
ELIGARD contains a powder and a solvent for solution for injection.
ELIGARD 7.5 mg is available in the following pack sizes:
- Packaging in thermoformed tray containing two thermoformed trays in a cardboard box. One tray contains pre-filled syringe A, a longer plunger for syringe B and a desiccant sachet. The other tray contains the pre-filled syringe B, a sterile 20 diameter needle and a desiccant pouch.
- Multipack containing kits of 3 x 2 pre-filled syringes (1 for syringe A and 1 for syringe B).
Not all pack sizes may be marketed.
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
ELIGARD 7.5 MG POWDER AND SOLVENT FOR INJECTABLE SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One pre-filled syringe with powder for solution for injection contains 7.5 mg of leuprorelin acetate, equivalent to 6.96 mg of leuprorelin.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Powder and solvent for solution for injection.
Powder (Syringe B)
Pre-filled syringe with white to off-white powder.
Solvent (Syringe A)
Pre-filled syringe with clear, colorless to pale yellow solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
ELIGARD 7.5 mg is indicated for the treatment of advanced hormone-dependent prostate cancer.
04.2 Posology and method of administration
Dosage
Adult male patients
ELIGARD 7.5 mg should be administered under the supervision of healthcare professionals capable of controlling the response to treatment.
ELIGARD 7.5 mg should be administered as a single subcutaneous injection every month. The injected solution forms a drug deposit, ensuring the sustained release of leuprorelin acetate for one month.
Treatment of advanced prostate cancer with ELIGARD 7.5 mg normally requires long-term treatment and should not be discontinued when disease remission or improvement occurs.
The response to ELIGARD 7.5 mg should be monitored by clinical parameters and by detecting serum prostate specific antigen (PSA) levels. Clinical studies have shown that testosterone levels increase over the first 3 days of treatment in most cases. of patients who did not undergo orchiectomy and subsequently fall below medical castration levels over a 3-4 week period. Once achieved, the levels of castration are maintained for the entire duration of the treatment (episodes of testosterone elevation less than 1%). If a patient's response proves to be suboptimal, serum testosterone levels should be verified to have reached or are maintaining castration levels. As a lack of efficacy may occur following incorrect preparation, reconstitution or administration, testosterone levels should be evaluated in cases of suspected or confirmed handling errors (see section 4.4).
Pediatric population
Safety and efficacy have not been established in children 0 to 18 years of age (see also section 4.3).
Particular groups of patients
No clinical studies have been conducted in patients with hepatic or renal impairment.
Method of administration
ELIGARD 7.5 mg should only be prepared, reconstituted and administered by healthcare professionals familiar with these procedures. See section 6.6: Special precautions for disposal and handling.If the medicine is not prepared properly, it should not be administered.
The contents of the two pre-filled sterile syringes must be mixed immediately prior to administration of ELIGARD 7.5 mg by subcutaneous injection.
Based on animal data, intra-arterial or intravenous injections should be strictly avoided.
As with other drugs given by subcutaneous injection, the injection site should be changed periodically.
04.3 Contraindications
ELIGARD 7.5 mg is contraindicated in women and pediatric patients.
Hypersensitivity to leuprorelin acetate, to other GnRH agonists, or to any of the excipients listed in section 6.1.
Patients previously undergoing orchiectomy (as with other GnRH agonists, ELIGARD 7.5 mg does not cause a further drop in serum testosterone in case of surgical castration).
As the sole treatment in prostate cancer patients with spinal cord compression or evidence of spinal metastases (see also section 4.4).
04.4 Special warnings and appropriate precautions for use
Lack of clinical efficacy may occur due to incorrect reconstitution of the medicinal product. See section 4.2 and section 6.6 for instructions for preparation and administration of the medicinal product and for assessment of testosterone levels in cases of suspected or known handling errors.
Androgen deprivation therapy can prolong the QT interval.
In patients with a history of or with risk factors for QT interval prolongation and in patients receiving concomitant therapy with medicinal products that can prolong the QT interval (see section 4.5), physicians should ascertain the benefit risk profile , including the potential risk of Torsades de pointes, prior to initiating therapy with Eligard 7.5 mg.
Like other GnRH agonists, leuprorelin acetate causes a transient increase in serum concentrations of testosterone, dihydrotestosterone and acid phosphatase during the first week of treatment. Patients may notice worsening of symptoms or the onset of new symptoms - including bone pain, neuropathy, haematuria or ureteral or bladder outflow obstruction (see section 4.8). These symptoms usually subside with continued therapy.
Additional administration of an appropriate antiandrogen should be considered starting 3 days prior to leuprorelin therapy and continuing for the first two to three weeks of treatment. This procedure has been reported to prevent the consequences of an initial rise in serum testosterone.
Following surgical castration, ELIGARD 7.5 mg does not cause a further decrease in serum testosterone levels in male patients.
Cases of ureteral obstruction and spinal cord compression, which may contribute to paralysis with or without fatal complications, have been reported with GnRH agonists. If spinal cord compression or renal impairment occurs, the standard treatment for these complications should be performed.
Patients with spinal and / or brain metastases as well as patients with urinary tract obstruction should be monitored closely during the first few weeks of treatment.
A percentage of patients have tumors that are not sensitive to hormonal manipulation. Lack of clinical improvement despite adequate testosterone suppression is diagnostic of this condition, which would not improve with further treatment with ELIGARD 7.5 mg.
Cases of decreased bone density have been reported in the medical literature in men undergoing orchiectomy or treated with GnRH agonists (see section 4.8).
Antiandrogen therapy leads to a significant increase in the risk of fractures due to osteoporosis. In this respect, only limited data are available. Fractures due to osteoporosis were observed in 5% of patients at 22 months after initiation of androgen deprivation drug therapy and in 4% of patients at 5-10 years of treatment. The risk of fractures due to osteoporosis is generally higher than Risk of Pathological Fractures In addition to long-term testosterone deficiency, factors such as increasing age, smoking and alcohol consumption, obesity and insufficient exercise can also influence the development of osteoporosis.
In post-marketing studies, rare cases of pituitary apoplexy (clinical syndrome secondary to pituitary gland infarction) have been reported following administration of GnRH agonists. Most cases occurred in the first two weeks thereafter. at the first dose, and some in the first hour. In these cases, pituitary apoplexy presented as sudden headache, vomiting, disturbed vision, ophthalmoplegia, altered mental status and sometimes cardiovascular collapse. In such situations immediate medical intervention is required.
Hyperglycaemia and diabetes: Hyperglycaemia and an increased risk of developing diabetes have been reported in men treated with GnRH agonists. Hyperglycaemia may be a consequence of the onset of diabetes mellitus or worsening of glycemic control in diabetic patients. Check blood glucose and / or glycosylated hemoglobin (HbA1c) periodically in patients taking a GnRH agonist and treating hyperglycemia or diabetes according to current clinical practice.
Cardiovascular disease: An increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with the use of GnRH agonists in men. Based on the reported probabilities, the risk appears low and should be carefully assessed on the basis of cardiovascular risk factors at the time when treatment of patients with prostate cancer is set. Patients treated with GnRH agonists should be monitored for symptoms and signs that may suggest the development of cardiovascular disease and should be managed according to the current clinical practice.
04.5 Interactions with other medicinal products and other forms of interaction
No interaction pharmacokinetic studies have been performed between ELIGARD 7.5 mg and other drugs. There are no reports of interactions between leuprorelin acetate and other drugs.
Since androgen deprivation treatment can prolong the QT interval, concomitant use of Eligard 7.5 mg with medicinal products known to prolong the QT interval or with products capable of inducing Torsade de Pointes, such as Class IA antiarrhythmic medicinal products (e.g. quinidine, disopyramide) or III (e.g. amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin, antipsychotics, etc. should be carefully considered (see section 4.4).
04.6 Pregnancy and breastfeeding
Not relevant as ELIGARD 7.5 mg is contraindicated in women.
04.7 Effects on ability to drive and use machines
No studies on the effects of ELIGARD 7.5 mg on the ability to drive and use machines have been performed.
The ability to drive and use machines may be affected by fatigue, dizziness and visual disturbances which are among the possible side effects of the treatment or caused by the underlying disease.
04.8 Undesirable effects
The adverse reactions observed during treatment with ELIGARD 7.5 mg are mainly due to the specific pharmacological action of leuprorelin acetate, ie the increase and decrease of certain hormone levels. The most commonly reported adverse reactions are: flushing, nausea, malaise, fatigue and transient local irritation at the injection site. Mild or moderate hot flashes occur in approximately 58% of patients.
Tabular list of adverse reactions
In clinical trials, the adverse events below were observed in patients with advanced prostate cancer treated with ELIGARD and classified by frequency as very common (≥1 / 10), common (≥1 / 100,
Other adverse events generally reported following treatment with leuprorelin acetate include peripheral edema, pulmonary embolism, palpitations, myalgia, muscle weakness, impaired skin sensitivity, chills, peripheral dizziness, rash, amnesia, visual disturbances. Infarction of a pre-existing pituitary adenoma has been reported rarely after administration of both short- and long-acting GnRH agonists. There have been rare reports of thrombocytopenia and leukopenia. Changes in glucose tolerance have been reported.
Local adverse events observed after ELIGARD injection are typical of those frequently associated with subcutaneously injected drugs of a similar nature.
Generally, these localized adverse events reported following subcutaneous injection occur in a mild form and are described as effects of short duration.
Changes in bone density
A reduction in bone density has been reported in the medical literature in men who have undergone orchiectomy or treated with a GnRH agonist. Long periods of treatment with leuprorelin acetate can be expected to result in increasing signs of osteoporosis. Regarding the increased risk of fractures due to osteoporosis see section 4.4.
Exacerbation of the signs and symptoms of the pathology
Treatment with leuprorelin acetate may lead to "exacerbation of the signs and symptoms of the disease during the first few weeks of treatment. If conditions such as spinal metastases and / or" urinary tract obstruction or "haematuria worsen, this may occur. neurological disorders such as weakness and / or paraesthesia of the lower limbs or worsening of urinary symptoms.
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.it/it/responsabili.
04.9 Overdose
Intentional overdose of ELIGARD 7.5 mg is unlikely and there are no grounds for drug abuse. There have been no reports of abuse or overdose with leuprorelin acetate in clinical practice, but in case of excessive exposure. , patient monitoring and symptomatic supportive treatment are recommended.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Gonadotropin releasing hormone analogs.
ATC code: L02A E02.
Leuprorelin acetate is a synthetic nonapeptide, agonist of the physiologically present gonadotropin releasing hormone (GnRH) which, administered continuously, inhibits the secretion of pituitary gonadotropins and suppresses testicular steroidogenesis in males. This effect is reversible upon discontinuation of therapy with However, the agonist has a higher potency than the natural hormone and the recovery time of testosterone levels may vary from patient to patient.
Administration of leuprorelin acetate causes an initial increase in circulating levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), resulting in a transient increase in the levels of gonadal steroids, testosterone and dihydrotestosterone in males. Continuous administration of leuprorelin acetate causes a decrease in the levels of the hormones LH and FSH. In males, testosterone levels drop below the castration level (≤ £ 50 ng / dl). These decreases occur within 3-5 weeks of initiation of treatment. Mean testosterone levels at six months are 6.1 (± 0.4) ng / dl comparable to levels following bilateral orchiectomy. All patients enrolled in Pilot studies reached castration levels at 6 weeks; 94% had reached the goal by day 28, and 98% by day 35. In the vast majority of patients, the testosterone levels found were below 20 ng / dl, although the real benefit of such low values has not yet been established. PSA values decreased by 94% in six months.
Long-term studies have shown that continued therapy allows testosterone levels to be kept below castration levels for up to seven years, and presumably indefinitely.
Tumor size was not measured directly in clinical trials, but there was an indirect positive response demonstrated by a 94% reduction in mean PSA with ELIGARD 7.5 mg.
05.2 Pharmacokinetic properties
Absorption: In patients with advanced prostate cancer, mean serum concentrations of leuprorelin following the initial injection rise to 25.3 ng / ml at 4-8 hours (Cmax) after injection. Following the initial increase after each injection (the plateau phase between day 2 and day 28 after each dose), serum concentrations remain relatively constant (0.28-1.67 ng / mL). there is evidence of accumulation with repeated doses.
Distribution: The mean steady-state volume of distribution of leuprorelin following intravenous bolus administration to healthy male volunteers was 27 liters. In vitro human plasma protein binding ranged from 43% to 49%.
Elimination: Administration of 1 mg intravenous bolus leuprorelin acetate to healthy male volunteers resulted in a mean systemic clearance of 8.34 l / h, with a terminal elimination half-life of approximately 3 hours based on a two-compartment model.
No excretion studies have been conducted with ELIGARD.
Drug metabolism studies have not been conducted with ELIGARD.
05.3 Preclinical safety data
Preclinical studies with leuprorelin acetate have shown, in both sexes, effects on the reproductive system, which were expected on the basis of the known pharmacological properties. These effects have been shown to be reversible after discontinuation of treatment and an appropriate regeneration period.
Leuprorelin acetate showed no teratogenicity. In rabbits, embryotoxicity / lethality was observed, consistent with the pharmacological effects of leuprorelin acetate on the reproductive system.
Carcinogenicity studies were performed in rats and mice over a period of 24 months.
In rats, a dose-dependent increase in pituitary apoplexy was observed after subcutaneous administration at doses of 0.6 to 4 mg / kg / day. This effect was not observed in the mouse.
Leuprorelin acetate and related specialty ELIGARD 7.5 mg implant for one month did not show mutagenic effects in a series of tests. in vitro and in vivo.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Solvent (syringe A)
- Copolymer of DL-lactic and glycolic acids (50:50)
- N-methylpyrrolidone
Powder (syringe B)
- nobody
06.2 Incompatibility
The leuprorelin in syringe B must only be mixed with the solvent from syringe A and must not be mixed with other medicinal products.
06.3 Period of validity
2 years.
Once the medicine has been removed from the refrigerator, it can be stored in the original packaging at room temperature (below 25 ° C) for up to four weeks.
After first opening the tray, the powder and solvent for solution for injection must be immediately reconstituted and administered to the patient.
Once reconstituted: use immediately, as the viscosity of the solution increases over time.
06.4 Special precautions for storage
Store in the refrigerator (2 ° C - 8 ° C) in the original package to keep it away from moisture.
Before injection this medicine must be brought to room temperature. Remove from the refrigerator about 30 minutes before use. Once out of the refrigerator this medicine can be stored in the original package at room temperature (below 25 ° C) for up to four weeks.
06.5 Nature of the immediate packaging and contents of the package
Two pre-filled polypropylene / cyclic olefin copolymer syringes, one containing the powder (Syringe B) and the other containing the solvent (Syringe A). Together the two syringes form a mixing system.
Syringe A has a plunger with a sealing cap made of thermoplastic rubber and is protected at the end with a Luer-Lok cap made of polyethylene or polypropylene. The sealing cap and the two plungers of the syringe B are made of chlorobutyl rubber.
The following packs are available:
• package containing two thermoformed trays in a cardboard box. One tray contains pre-filled polypropylene syringe A, a longer plunger and a desiccant pouch. The other tray contains the pre-filled cyclic olefin copolymer syringe B, a sterile 20 diameter needle and a desiccant sachet.
• multipack containing kits of 3 x 2 pre-filled polypropylene / cyclic olefin copolymer syringes (1 for Syringe A; 1 for Syringe B).
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Bring the medicine to room temperature by removing it from the refrigerator about 30 minutes before use.
First prepare the patient for the injection, then prepare the medicine according to the instructions below. If the medicine is not prepared using the proper technique, it should not be administered as due to incorrect reconstitution of the medicine, a lack of clinical efficacy.
Step 1: Open both trays (peel off the sheet starting from the corner recognizable for a small swelling) and empty the contents onto a clean work surface (two trays containing Syringe A and Syringe B). Discard the desiccant bags .
Phase 2: Remove and do not unscrew the shorter blue plunger together with the attached gray cap of Syringe B and discard them. Do not try to mix the product with the two caps in place.
Step 3: Gently screw the white plunger into the remaining gray cap in Syringe B.
Step 4: Remove the gray rubber cap from Syringe B and put the Syringe away.
Step 5: Hold Syringe A upright to avoid liquid spillage and unscrew the clear cap from Syringe A.
Step 6: Join the two syringes together by pressing and rotating Syringe B into Syringe A until they are secure. Don't force it.
Step 7: Invert the joint units and continue to hold the syringes upright, with Syringe B in the lower position while injecting the contents of Syringe A into Syringe B containing the powder (leuprorelin acetate).
Step 8: Mix the product together by gently pushing the contents of both syringes back and forth between the syringes (approximately 60 times in total, which takes approximately 60 seconds) in a horizontal position, to obtain a viscous and homogeneous solution. Do not bend the system consisting of the joined syringes (be aware that this could cause leakage, as well as the partial unscrewing of the syringes).
When mixed well, the viscous solution will appear with a color described in the range of colorless to white to light yellow (may have shades of white to light yellow).
Important: After mixing, proceed immediately with the next steps as the product becomes more viscous over time. Do not refrigerate the product after it has been mixed.
Attention: the product must be mixed as described; agitation will NOT lead to adequate mixing of the product.
Step 9: Hold the syringes upright, with Syringe B at the bottom. The syringes must stay together firmly. Transfer all of the mixed product into Syringe B (short, wide syringe) by pressing the plunger of Syringe A and pulling out the plunger of Syringe B slightly.
Step 10: Detach Syringe A by continuing to push on the plunger of Syringe A. Make sure that the product does not come out, as in this case the needle will not be able to be inserted tightly.
Caution: Small air bubbles or one large bubble may remain in the formulation - this is acceptable.
Avoid removing air bubbles from Syringe B at this stage, as the product may be lost!
Step 11: Hold Syringe B upright. Open the safety needle package by lifting the paper back and take the safety needle. Secure the safety needle on Syringe B by holding the syringe steady and turning the needle clockwise to fully secure the needle. Do not force.
Step 12: Remove needle shield before administration.
Important: Do not manipulate the safety needle mechanism prior to administration.
Step 13: Before administration, remove large air bubbles from Syringe B. Administer the product subcutaneously. Make sure that the full amount of product contained in Syringe B is injected.
Step 14: After injection, lock the safety guard with one of the activation methods described below.
1. Closing on a flat surface
Press the safety guard, prying down, on a flat surface to cover the needle and lock the guard.
Check the locked position by paying attention to a signal ("click") that can be both heard and felt with the fingers. The guard, when locked, will completely cover the needle tip.
2. Thumb closure
Place your thumb on the lever, slide the guard towards the tip of the needle to cover the needle and lock the guard.
Check that the position of the guard is locked by paying attention to a signal ("click") that can be both heard and felt with the fingers. The guard, when locked, will completely cover the tip of the needle.
Step 15: Once the needle guard is locked, immediately dispose of the needle and syringe in the appropriate sharps container.
07.0 MARKETING AUTHORIZATION HOLDER
Astellas Pharma S.p.A.
Via del Bosco Rinnovato, 6 - U7 (Floor IV)
20090 Assago (Milan)
08.0 MARKETING AUTHORIZATION NUMBER
Tray packaging: 036967038
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization - Packaging in trays: October 26, 2007
Date of most recent renewal: 11 December 2012
10.0 DATE OF REVISION OF THE TEXT
13/10/2015
