ELIGARD 22,5 mg Pwdr/solv for sol inj Syr pwdr+Syr solv

Powder and solvent for solution for injection.
Powder (syringe B): pre-filled syringe with a white to off-white powder.
Solvent (syringe A): pre-filled syringe with a clear, colourless to pale yellow solution.

Kit containing 1 thermoformed tray and 1 sterile needle (20 gauge).
The tray contains a system of pre-connected syringes:

• one pre-filled syringe containing the powder + plunger (syringe B)
• one pre-filled syringe containing the solvent + plunger (syringe A)
• one connector with a locking button for syringes A and B.

Box of 1 kit + 1 desiccant sachet.

One pre-filled syringe of powder for solution for injection contains 22,5 mg of leuprorelin acetate, corresponding to 20,87 mg of leuprorelin.

Excipients:

ELIGARD 22,5 mg is indicated for the treatment of advanced stage hormone-dependent prostate cancer and in association with radiotherapy in the treatment of high-risk localised and locally advanced hormone-dependent prostate cancer.

Dosage

Adult male

ELIGARD 22,5 mg must be administered under the responsibility of a healthcare professional with the necessary skills to monitor the response to treatment.

ELIGARD 22,5 mg is administered once every three months, as a single subcutaneous injection. The injected solution forms a solid drug depot and ensures continuous release of leuprorelin acetate for three months.

As a general rule, treatment of advanced prostate cancer with ELIGARD 22,5 mg must be continued long-term and must not be interrupted in case of remission or improvement.

ELIGARD 22,5 mg may be used in neoadjuvant or adjuvant treatment in association with radiotherapy in high-risk localised and locally advanced prostate cancer.

The response to treatment with ELIGARD 22,5 mg must be monitored by performing clinical examinations and analysis of serum levels of prostate-specific antigen (PSA). Clinical studies have shown that testosterone levels increased during the 3 first days of treatment in most non-orchidectomised patients and then decreased in 3 to 4 weeks to reach values below those of medical castration. Once achieved, these levels are maintained as long as treatment is continued (transient testosterone rises < 1 %). In the case where a patient's response appears to be sub-optimal, it must be ensured that testosterone levels have reached castration levels or are maintained at these levels. A lack of efficacy that may occur due to poor preparation, reconstitution or administration, a testosterone assay must be performed in case of suspected or confirmed handling error (see section Warnings and precautions).

In patients with metastatic castration-resistant prostate cancer who have not undergone surgical castration, receiving treatment with a GnRH agonist, such as leuprorelin, and eligible for treatment with androgen synthesis inhibitors or androgen receptor inhibitors, treatment with a GnRH agonist may be continued.

Paediatric population

The safety and efficacy of ELIGARD 22,5 mg in children aged 0 to 18 years have not been established (see section Contraindications).

Special populations of patients

No clinical study has been conducted in patients with hepatic or renal impairment.

Method of administration

ELIGARD 22,5 mg must be prepared, reconstituted and administered only by a healthcare professional who has read the instructions relating to the reconstitution and administration steps. The reconstitution and administration instructions must be strictly followed (see sections Warnings and precautions and Disposal and handling). In the event of inadequate preparation of the product, the latter must not be administered.

The contents of the two sterile pre-filled syringes must be mixed just prior to administration of ELIGARD 22,5 mg by subcutaneous injection.

In view of the data in animals, intra-arterial or intravenous injection must absolutely be avoided.

As with other medicinal products administered by subcutaneous injection, it is recommended to regularly change the injection site.

ELIGARD 22,5 mg is contraindicated in women and children.

Hypersensitivity to leuprorelin acetate, to other GnRH agonists or to any of the excipients listed in section Composition.

In patients who have already undergone orchidectomy (as with other GnRH agonists, ELIGARD 22,5 mg does not lead to an additional decrease in serum testosterone levels in the case of surgical castration).

ELIGARD 22,5 mg must not be used as monotherapy in patients with prostate cancer with spinal cord compression or vertebral metastases (see section Warnings and precautions).

Correct reconstitution of the medicinal product: Cases of handling errors that may occur at any stage of the preparation process and that may lead to a lack of efficacy have been reported. The reconstitution and administration instructions must be strictly followed (see section Disposal and handling). In the event of a suspected or proven handling error, the patient must be adequately monitored (see section Dosage and administration).

Treatment with androgen suppression may prolong the QT interval : In patients with a history or risk factors for QT interval prolongation, and in patients receiving concomitantly medicinal products likely to prolong the QT interval (see section Interactions), physicians must assess the benefit/risk ratio taking into account the potential risk of torsades de pointes before initiating treatment with Eligard 22,5 mg.

Cardiovascular diseases : an increased risk of myocardial infarction, sudden cardiac death and stroke have been reported during the use of GnRH agonists in certain patients. The risk appears low based on published reports and must be carefully assessed according to the cardiovascular risk factors of patients with prostate cancer when choosing treatment. The onset of symptoms and signs suggestive of cardiovascular diseases must be monitored in patients treated with a GnRH agonist and managed in accordance with current recommendations.

Transient elevation of testosterone levels: Leuprorelin acetate, like other GnRH agonists, causes a transient elevation of serum concentrations of testosterone, dihydrotestosterone and acid phosphatases during the first week of treatment. Patients may experience worsening of symptoms or the appearance of new symptoms such as bone pain, neuropathy, haematuria, ureteral or bladder obstruction (see section Adverse effects). These symptoms usually disappear with continued treatment.

The concomitant administration of an appropriate anti-androgen must be considered starting 3 days before treatment with leuprorelin and continuing for the first two to three weeks of treatment. It has been observed that these modalities make it possible to prevent the consequences of an initial increase in serum testosterone.

After surgical castration, ELIGARD 22,5 mg does not lead to an additional decrease in serum testosterone in male subjects.

Bone density: A decrease in bone density has been reported in the medical literature in men who have undergone orchidectomy or who have been treated with a GnRH agonist (see section Adverse effects).

Anti-androgen treatment significantly increases the risk of fractures secondary to osteoporosis. There are only limited data on this subject. Fractures secondary to osteoporosis have been observed in 5% of patients after 22 months of pharmacological androgen deprivation treatment and in 4% of patients after 5 to 10 years of treatment. The risk of osteoporotic fractures is generally higher than the risk of pathological fractures. Apart from prolonged testosterone deficiency, advanced age, smoking and consumption of alcoholic beverages, obesity and lack of physical exercise may also promote the development of osteoporosis.

Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after administration of GnRH agonists, the majority occurring within 2 weeks following the first administration, and some within the first hour. In these cases, pituitary apoplexy manifested as sudden headache, vomiting, visual disturbances, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical management is required.

Metabolic changes : Hyperglycaemia and an increased risk of onset of diabetes have been reported in men receiving GnRH agonists. Hyperglycaemia may be linked to the onset of diabetes mellitus or to the deterioration of glycaemic control in diabetic patients. Blood glucose and/or glycosylated haemoglobin (HbA1c) levels must be monitored periodically in patients receiving a GnRH agonist, and these patients must be managed according to current practices regarding the treatment of hyperglycaemia or diabetes. The metabolic changes related to GnRH agonists may also include hepatic steatosis.

Convulsions: Cases of convulsions have been reported after marketing in patients treated with leuprorelin acetate with or without a history of predisposing factors. These convulsions must be managed according to current clinical practice.

Idiopathic intracranial hypertension : Cases of idiopathic intracranial hypertension (serous meningitis) have been reported in patients receiving leuprorelin. Patients should be warned of the possibility of signs and symptoms of idiopathic intracranial hypertension, including severe or recurrent headaches, visual disturbances and tinnitus. In the presence of idiopathic intracranial hypertension, discontinuation of treatment with leuprorelin should be considered.

Severe cutaneous adverse reactions: Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN, or Lyell's syndrome), which may be life-threatening or fatal, have been reported in association with leuprorelin treatment. At the time of prescription, patients should be informed of the signs and symptoms, and closely monitored in case of severe cutaneous reactions. In case of appearance of signs and symptoms suggestive of these reactions, treatment with leuprorelin must be stopped immediately and another treatment should be considered (where appropriate).

Other events: Cases of ureteral obstruction and spinal cord compression that may lead to paralysis with or without fatal complications have been reported with GnRH agonists. The occurrence of spinal cord compression or renal failure requires the initiation of standard treatment for these complications.

Patients with vertebral and/or cerebral metastases as well as patients with urinary tract obstruction should be closely monitored during the first weeks of treatment.

No pharmacokinetic drug interaction study has been conducted with ELIGARD 22,5 mg. There is no description of possible interactions of leuprorelin acetate with other medicinal products.

Androgen suppression treatment being likely to prolong the QT interval, the concomitant use of Eligard 22,5 mg with medicinal products known to prolong the QT interval, or medicinal products capable of inducing torsades de pointes such as class IA antiarrhythmics (for example quinidine, disopyramide) or class III (for example amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin, antipsychotics, etc. must be evaluated with caution (see section Warnings and precautions).

Not applicable as ELIGARD 22,5 mg is contraindicated in women.

The effects of ELIGARD 22,5 mg on the ability to drive and use machines have not been studied.

Fatigue, dizziness and visual disturbances being possible adverse effects of the treatment or the consequence of the underlying disease, the ability to drive and use machines may be impaired.

The adverse reactions observed with ELIGARD 22.5 mg are mainly due to the specific pharmacological action of leuprorelin acetate, namely increases and decreases in the levels of certain circulating hormones. The most frequently reported adverse reactions are hot flushes, nausea, malaise and fatigue as well as transient local irritation at the injection site. Mild to moderate hot flushes occur in approximately 58 % of patients.

Tabulated list of adverse reactions

The following adverse reactions have been reported during clinical trials conducted in patients with advanced prostate carcinoma treated with ELIGARD 22,5 mg. The adverse reactions are classified by frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1 000, < 1/100), rare (≥ 1/10 000, < 1/1 000), very rare (< 1/10 000) and frequency not known (cannot be estimated from the available data).

Table 1: Adverse reactions in clinical studies with Eligard
Infections and infestations
Common		nasopharyngitis.
Uncommon		urinary tract infection, local skin infection.
Metabolism and nutrition disorders
Uncommon		Aggravated diabetes mellitus.
Psychiatric disorders
Uncommon		abnormal dreams, depression, decreased libido.
Nervous system disorders
Uncommon		dizziness, headaches, hypoesthesia, insomnia, smell and taste disorders, vertigo.
Rare		abnormal and involuntary movements.
Frequency not known		idiopathic intracranial hypertension (serous meningitis) (see section Warnings and precautions).
Cardiac disorders
Frequency not known		QT interval prolongation (see sections Warnings and precautions and Interactions)
Vascular disorders
Very common		hot flushes.
Uncommon		hypertension, hypotension.
Rare		syncope, collapse.
Respiratory, thoracic and mediastinal disorders
Uncommon		rhinorrhoea, dyspnoea.
Frequency not known		interstitial lung disease.
Gastrointestinal disorders
Common		nausea, diarrhoea, gastroenteritis/colitis.
Uncommon		constipation, dry mouth, dyspepsia, vomiting.
Rare		flatulence, eructation.
Skin and subcutaneous tissue disorders
Very common		ecchymoses, erythema.
Common		pruritus, night sweats.
Uncommon		cold sweat, hyperhidrosis.
Rare		alopecia, rash.
Frequency not known		Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN or Lyell syndrome) (see section Warnings and precautions), toxic rash, erythema multiforme.
Musculoskeletal and connective tissue disorders
Common		arthralgia, limb pain, myalgia, stiffness, asthenia.
Uncommon		back pain, muscle cramps.
Renal and urinary disorders
Common		decreased urinary frequency, difficulty urinating, dysuria, nocturia, oliguria.
Uncommon		bladder spasms, haematuria, increased urinary frequency, urinary retention.
Reproductive system and breast disorders
Common		breast tenderness, testicular atrophy, testicular pain, infertility, breast hypertrophy, erectile dysfunction, decreased penis size.
Uncommon		gynaecomastia, impotence, testicular disorders.
Rare		breast pain.
General disorders and administration site abnormalities
Very common		fatigue, injection site burning, injection site paresthesia.
Common		malaise, injection site pain, injection site hematoma, painful tingling at the injection site.
Uncommon		injection site pruritus, injection site induration, lethargy, pain, fever.
Rare		injection site ulceration.
Very rare		injection site necrosis.
Blood and lymphatic system disorders
Common		hematological disturbances, anemia.
Investigations
Common		increased blood creatine phosphokinase, prolonged coagulation time.
Uncommon		increased alanine aminotransferase, increased blood triglycerides, increased prothrombin time, weight gain.

Other adverse effects have been reported generally in the case of treatment with leuprorelin acetate, including peripheral edema, pulmonary embolism, palpitations, myalgia, muscular weakness, altered cutaneous sensation, chills, rash, amnesia and visual disturbances. Muscular atrophy has been observed with prolonged use of medicines belonging to this pharmacological class. An infarction of a pre-existing pituitary apoplexy has been rarely described after administration of treatment with a GnRH agonist whether immediate-acting or prolonged-acting. Rare cases of leukopenia and thrombocytopenia have been reported. Changes in glucose tolerance have been reported.

Convulsions have been reported following administration of a GnRH agonist/analogue (see section Warnings and precautions).

The local adverse events reported after injection of ELIGARD 22,5 mg are similar to those associated with similar products injected subcutaneously.

Generally, these adverse events localized after a subcutaneous injection are mild and described as being of short duration.

Rare cases of anaphylactic/anaphylactoid reactions have been reported after administration of a GnRH agonist/analogue.

Variations in bone density

A decrease in bone density has been reported in the medical literature in men who have undergone orchiectomy or those treated with a GnRH analogue. It is likely that long-term treatment with leuprorelin reveals signs of worsening osteoporosis, with regard to the increased risk of osteoporotic fracture (see section Warnings and precautions).

Exacerbation of signs and symptoms of the disease

Treatment with leuprorelin acetate may lead to an exacerbation of the signs and symptoms of the disease during the first weeks of treatment. Worsening of conditions such as vertebral metastases and/or urinary obstruction or hematuria may give rise to neurological problems such as weakness and/or paresthesias of the lower limbs or a worsening of urinary symptoms.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse reaction via the national reporting system: Agence nationale de sécurité du médicament et des produits de santé (ANSM) and network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr.

Abusive use and voluntary overdose with ELIGARD 22,5 mg are unlikely. No cases of abusive use or overdose have been reported in clinical practice with leuprorelin acetate, but if excessive exposure occurs, patient monitoring and administration of adjuvant symptomatic treatment are recommended.

Pharmacotherapeutic group: Gonadotropin-releasing hormone analogues, ATC code: L02A E02.

Leuprorelin acetate is a synthetic nonapeptide, agonist of the natural gonadotropin-releasing hormone (GnRH) which, in the case of prolonged administration, leads to inhibition of pituitary gonadotropin secretion and suppression of testicular steroid synthesis in men. This effect is reversible upon discontinuation of drug treatment. However, the agonist has a more potent action than the natural hormone and the time required to restore testosterone levels may vary between patients.

Administration of leuprorelin acetate leads to an initial elevation of circulating levels of luteinizing hormones (LH) and follicle-stimulating hormones (FSH), responsible for a transient elevation in men of concentrations of gonadal steroids, testosterone and dihydrotestosterone. Continuous administration of leuprorelin acetate leads to a decrease in LH and FSH levels. In men, testosterone decreases below the castration threshold (≤ 50 ng/dL). These decreases appear three to five weeks after initiation of treatment. Mean testosterone levels at six months are 10,1 (±0,7) ng/dL, comparable to levels observed after bilateral orchiectomy. All patients who received the full dose of 22,5 mg of leuprorelin in the pivotal clinical study achieved castration levels at 5 weeks; 99 % achieved it at D28. In the great majority of patients, testosterone levels were below 20 ng/dL: the clinical benefit of these low levels has not yet been established. PSA levels decreased by 98 % at six months.

Long-term studies have shown that continuation of treatment maintained testosterone levels below the castration threshold for a period of up to seven years, and probably indefinitely.

Tumor size was not measured directly during the clinical study program, but a beneficial indirect tumor response was observed as indicated by a reduction of 98 % in the mean PSA level with ELIGARD 22,5 mg.

A phase III randomized clinical trial was conducted in 970 patients with locally advanced prostate cancer (mainly stages T2c to T4, and with some patients with stage T1c to T2b presenting regional lymphadenopathy), of whom 483 received short-term androgen suppression therapy (6 months) in combination with radiotherapy and 487 long-term androgen suppression therapy (3 years) in combination with radiotherapy. A non-inferiority analysis was performed to compare short-term and long-term concomitant and adjuvant hormonal treatment with a GnRH agonist (triptorelin or goserelin). The overall mortality rate at 5 years was 19,0 % and 15,2 % respectively in the short-term and long-term treatment groups. The observed Hazard Ratio of 1,42 with an upper limit of 1,79 of the one-sided 95,71 % CI or of 1,09 of the two-sided 95,71 % CI ; 1,85 (p = 0,65 for non-inferiority) shows that the combination of radiotherapy and 6 months of androgen suppression therapy induces inferior survival compared to radiotherapy combined with 3 years of androgen suppression therapy. Overall survival at 5 years is 84,8 % and 81,0 % respectively with long-term treatment and short-term treatment. Global quality of life assessed using the QLQ-C30 questionnaire was not significantly different between the two groups (p = 0,37). The results are mainly due to the population of patients with locally advanced tumors.

The arguments supporting the indication in high-risk localized prostate cancer are based on published studies relating to the combination of radiotherapy and GnRH analogues, including leuprolide acetate. The clinical data from five published studies were analyzed (EORTC 22863, RTOG 85-31, RTOG 92-02, RTOG 8610 and D'Amico et al., JAMA, 2004); they all demonstrate a benefit of combining a GnRH analogue with radiotherapy. It was not possible to clearly distinguish in the published studies the respective study populations for the indications in locally advanced prostate cancer and in high-risk localized prostate cancer.

Clinical data showed that radiotherapy followed by 3 years of androgen suppression therapy is preferable to radiotherapy followed by 6 months of androgen suppression therapy.

In patients with stage T3 to T4 cancer who receive radiotherapy, the duration of androgen suppression therapy recommended in medical guidelines is 2 to 3 years.

Absorption

In patients with advanced prostate cancer, mean serum leuprolide concentrations increase after the initial injection and reach 127 ng/mL after 4,6 hours (C_max). After the initial increase occurring after each injection (plateau phase observed after each injection from the 3^th to the 84^th day), serum concentrations remain relatively constant (0,2-2 ng/mL). There is no evidence of accumulation with repeated dose administration.

Distribution

The mean volume of distribution of leuprolide at steady state after intravenous bolus administration to healthy male volunteers was 27 liters. In vitro, binding to human plasma proteins varies between 43 % and 49 %.

Elimination

In healthy male volunteers, intravenous bolus administration of 1 mg leuprolide acetate resulted in a mean systemic clearance of 8,34 L/h, with a terminal elimination half-life of approximately 3 hours according to a two-compartment model.

No drug excretion study has been conducted with ELIGARD 22,5 mg.

No metabolism study of ELIGARD 22,5 mg has been conducted.

Preclinical studies with leuprolide acetate have shown effects on the reproductive system of both sexes, effects expected given the known pharmacological profile. These effects were shown to be reversible after treatment discontinuation and an appropriate period of regeneration. Leuprolide acetate did not reveal teratogenic activity. Embryotoxicity/ lethality was observed in the rabbit, related to the pharmacological effects of leuprolide acetate on the reproductive system.

Carcinogenicity studies were conducted in the rat and mouse for 24 months. In the rat, a dose-dependent increase in pituitary apoplexies was observed after subcutaneous administration at doses of 0,6 to 4 mg/kg/day. No such effect was observed in the mouse.

Leuprolide acetate and the 1-month ELIGARD 7,5 mg formulation were not shown to be mutagenic in tests conducted in vitro and in vivo.

The leuprolide contained in syringe B must be mixed only with the solvent in syringe A and must not be mixed with other medicinal products.

Before reconstitution:

2 years.

Once the product has been removed from the refrigerator, it may be stored in the original packaging at room temperature (not exceeding 25 °C) for a maximum of 4 weeks.

After first opening the tray, the powder and solvent for solution for injection must be used immediately to reconstitute the medicinal product and administer it to the patient.

Once reconstituted : administer the product immediately, the viscosity of the solution increasing with time.

Store in the refrigerator (between 2 °C and 8 °C).

Store in the original outer packaging, protected from moisture.

The product must be at room temperature before injection. Remove from the refrigerator approximately 30 minutes before use. Once removed from the refrigerator, the product may be stored in its original packaging at room temperature (not exceeding 25 °C) for a maximum of 4 weeks.

Allow the product to warm to room temperature by removing it from the refrigerator approximately 30 minutes before use.

Please prepare the patient for the injection first, then the preparation of the product, following the instructions below. In case of inadequate preparation of the product, the latter must not be administered, since a lack of clinical efficacy may occur due to incorrect reconstitution of the product.

Step 1:

On a clean work surface, open the tray by removing the aluminium foil by the corner to remove the contents. Discard the desiccant sachet.

Remove the pre-connected syringe system (Figure 1.1) from the tray. Open the packaging of the safety needle (Figure 1.2) by peeling off the paper tab.

Note: Syringe A and syringe B must not yet be aligned.

Step 2:

Take the connector lock button with the finger and thumb and press (Figure 2) until a click is heard. The two syringes will then be aligned. No particular orientation of the syringe system is necessary to activate the connector. Do not bend the syringe system (this may cause leaks as you risk partially unscrewing the syringes).

Step 3:

Holding the syringes in a horizontal position, transfer the liquid content of syringe A into syringe B containing the leuprorelin acetate powder.

Mix the product thoroughly for 60 cycles by gently pushing the contents of both syringes back and forth between the two syringes (one cycle corresponds to one push of the plunger for syringe A and one push of the plunger for syringe B) in a horizontal position, to obtain a homogeneous and viscous solution (Figure 3). Do not bend the syringe system (this may cause leaks as you risk partially unscrewing the syringes).

When perfectly mixed, the product will appear viscous with a colour range from colourless, to white, to pale yellow (which includes all shades from white to pale yellow).

Important: After mixing, proceed to the next step immediately, the product becoming increasingly viscous with time. Do not refrigerate the mixed product.

Please note that the product must be mixed as described; SHAKING WILL NOT MIX THE PRODUCT CORRECTLY.

Step 4:

After mixing, hold the syringes in a vertical position, with syringe B at the bottom. The syringes must remain well assembled. Transfer all the mixed product into syringe B (the large syringe) by pushing the plunger of syringe A and gently pulling the plunger of syringe B at the same time (Figure 4).

Step 5:

While ensuring that the plunger of syringe A is fully depressed, hold the connector and unscrew it from syringe B. Syringe A will remain attached to the connector (Figure 5).

Ensure that the product is not leaking as otherwise the needle will not be correctly attached.

Please note: Small air bubbles or a large air bubble may remain in the preparation. This is not a problem.

During this step, please do not try to purge the air bubbles from syringe B as product could be lost!

Step 6:

• Hold syringe B vertically and hold the white plunger to avoid any loss of product.
• Assemble the safety needle to syringe B by holding the syringe upright and gently turning the needle approximately three-quarters of a turn clockwise until it is securely attached (Figure 6).

Do not overtighten as this may crack the needle hub, causing leakage of the product during injection. The safety device may also be damaged if the needle is screwed on with too much force.

If the needle hub cracks, appears damaged or shows any leakage, the product must not be used. The damaged needle must not be substituted/replaced and the product must not be injected. The entire product must be disposed of safely.

If the needle hub is damaged, a new product must be used as a replacement.

Step 7 :

Move the needle safety device aside and remove the needle protective cap only before administration of the product (Figure 7).

Important: Do not engage the needle safety device before administration.

If the needle tip appears damaged or shows leakage, the product must NOT be used. The damaged needle must NOT be replaced and the product must NOT be injected. In this case, use another ELIGARD box.

Step 8 :

Before administration, purge the large air bubbles from syringe B. Administer the product by the subcutaneous route while keeping the safety device moved aside from the needle.

Administration procedure: Select an injection site on the abdomen, the upper part of the buttocks or another area with a sufficient amount of subcutaneous tissue, without excessive pigmentation, nodules, lesions or hair and that has not been used recently. Clean the injection site area with an alcohol swab (not supplied). Using the thumb and index finger, grasp and pinch the skin area around the injection site. With your dominant hand, quickly insert the needle at an angle of 90 ° relative to the skin surface. The depth of penetration will depend on the amount and condition of the subcutaneous tissue and the length of the needle. Once the needle is inserted, release the skin. Inject the medication by applying slow and steady pressure and push the plunger until the syringe is empty. Ensure that the entire amount of product contained in syringe B is injected before removing the needle. Quickly remove the needle at the same 90 ° angle used for insertion while maintaining pressure on the plunger.

Step 9 :

After injection, lock the safety device by following the instructions listed below:

1. Closure on a flat surface

Press the safety device, lever down, on a flat surface (Figure 9a) to cover the needle and lock the safety device.

A “Click” confirms, audibly and tactilely, that the device is locked. In the locked position, the needle tip is completely covered.

2. Closure with your thumb

Place your thumb on the safety device (Figure 9b), cover the needle tip and lock the safety device.

A “Click” confirms, audibly and tactilely, that the device is locked. In the locked position, the needle tip is completely covered.

Once the safety device is locked, discard the needle and syringe immediately in an appropriate container.

List I
Medicinal product requiring special monitoring during treatment:

MA	CIP 3400936690929 (Ser pdr+Ser solv).

Price:

258,98 euros (Ser pdr+Ser solv).

Social Security reimbursement at 100 %. Collect.

 

 

Marketing Authorisation Holder: Recordati Industria Chimica E Farmaceutica S.p.A., Via Matteo Civitali 1, 20148 Milan, Italy.