ELIGARD 45 mg Pdre/solv p sol inj Ser pdr+Ser 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 (18 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)
• a 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 45 mg of leuprorelin acetate, corresponding to 41,7 mg of leuprorelin.

Excipients:

ELIGARD 45 mg is indicated for the treatment of advanced hormone-dependent prostate cancer and in combination with radiotherapy in the treatment of high-risk localised and locally advanced hormone-dependent prostate cancer.

Dosage

Adult male

ELIGARD 45 mg must be administered under the responsibility of a healthcare professional with the necessary skills to monitor the response to treatment.

ELIGARD 45 mg is administered once every six months, as a single subcutaneous injection. The injected solution forms a solid drug depot and ensures continuous release of leuprorelin acetate for six months.

As a general rule, treatment of advanced prostate cancer with ELIGARD 45 mg must be continued long-term and must not be interrupted in case of remission or improvement.

ELIGARD 45 mg may be used as neoadjuvant or adjuvant treatment in combination with radiotherapy in high-risk localised and locally advanced prostate cancer.

The response to treatment with ELIGARD 45 mg must be monitored by 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 within 3 to 4 weeks to reach values below medical castration levels. Once achieved, these levels are maintained for as long as treatment is continued (transient testosterone surges < 1 %). In the event that 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 improper 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 the GnRH agonist may be continued.

Paediatric population

The safety and efficacy of ELIGARD 45 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 45 mg must be prepared, reconstituted and administered only by a healthcare professional who has read the instructions relating to the steps of reconstitution and administration. The instructions for reconstitution and administration must be strictly followed (see sections Warnings and precautions and Disposal and handling). In case 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 before administration of ELIGARD 45 mg by subcutaneous injection.

In view of the data in animals, an 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 45 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 orchiectomy (as with other GnRH agonists, ELIGARD 45 mg does not lead to an additional decrease in serum testosterone levels in case of surgical castration).

ELIGARD 45 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 step of the preparation process and that may lead to lack of efficacy have been reported. The instructions for reconstitution and administration must be strictly followed (see section Disposal and handling). In case of suspected or proven handling error, the patient must be adequately monitored (see section Dosage and administration).

Androgen suppression treatment may prolong the QT interval: In patients with a history or risk factors for QT interval prolongation, and in patients concomitantly receiving medicinal products that may 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 45 mg.

Cardiovascular diseases : An increased risk of myocardial infarction, sudden cardiac death and stroke has been reported during the use of GnRH agonists in some patients. The risk appears low based on published reports and must be carefully evaluated 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 new symptoms such as bone pain, neuropathy, haematuria, ureteral or bladder obstruction (see section Adverse effects). These symptoms usually disappear with continued treatment.

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 45 mg does not lead to any further 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 orchiectomy 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 can 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 after 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 related to the onset of diabetes mellitus or to 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 in accordance with current practices regarding the treatment of hyperglycaemia or diabetes. Metabolic changes related to GnRH agonists may also include hepatic steatosis.

Convulsions: Cases of convulsions have been reported after marketing in patients treated with leuprolide acetate with or without 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 leuprolide. 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 leuprolide treatment should be considered.

Severe cutaneous adverse reactions: Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN, or Lyell syndrome), which may be life-threatening or fatal, have been reported in association with leuprolide treatment. At the time of prescription, patients should be informed of the signs and symptoms, and monitored closely in case of severe cutaneous reactions. In case of appearance of signs and symptoms suggestive of these reactions, leuprolide treatment must be discontinued immediately and an alternative treatment should be considered (if 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 onset of spinal cord compression or renal failure requires initiation of standard treatment for these complications.

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

No drug interaction pharmacokinetic study has been performed with ELIGARD 45 mg. There is no description of possible interactions of leuprolide acetate with other medicinal products.

Androgen suppression treatment being likely to prolong the QT interval, the concomitant use of Eligard 45 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 due to the fact that ELIGARD 45 mg is contraindicated in women.

The effects of ELIGARD 45 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 45 mg are mainly due to the specific pharmacological action of leuprolide acetate, namely elevations and decreases in levels of certain circulating hormones. The most frequently reported adverse reactions are hot flushes, malaise, nausea and fatigue as well as transient local irritation at the injection site. Mild to moderate hot flushes appear 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 stage prostate carcinoma treated with ELIGARD 45 mg. 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, headache, 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 pneumonitis.
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 frequency of urination, difficult urination, 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	gynecomastia, impotence, testicular disorders.
	Rare	breast pain.
General disorders and administration site conditions
	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, pyrexia.
	Rare	injection site ulceration.
	Very rare	injection site necrosis.
Blood and lymphatic system disorders
	Common	hematologic 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 in general in the case of treatment with leuprolide acetate, including peripheral edema, pulmonary embolism, palpitations, myalgia, muscle weakness, altered cutaneous sensation, chills, rash, amnesia and visual disturbances. Muscle atrophy has been observed with prolonged use of drugs belonging to this pharmacological class. Infarction of a pre-existing pituitary apoplexy has been rarely described after administration of treatment with a GnRH agonist whether immediate-acting or prolonged-release. 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/analog (see section Warnings and precautions).

The local adverse events reported after injection of ELIGARD 45 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/analog.

Bone density variations

A decrease in bone density has been reported in the medical literature in men who have undergone orchiectomy or those treated with a GnRH analog. It is likely that long-term treatment with leuprolide 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 leuprolide 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 intentional overdose with ELIGARD 45 mg are unlikely. No case of abusive use or overdose has been reported in clinical practice with leuprolide acetate, but if excessive exposure were to occur, patient monitoring and administration of supportive symptomatic treatment are recommended.

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

Leuprolide acetate is a synthetic nonapeptide, agonist of the natural gonadotropin-releasing hormone (GnRH) which, in 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 leuprolide acetate leads to an initial elevation of circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), responsible for a transient elevation in men of concentrations of gonadal steroids, testosterone and dihydrotestosterone. Continuous administration of leuprolide 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 four weeks after initiation of treatment. Mean testosterone levels at six months are 10,4 (±0,53) ng/dL, comparable to levels observed after bilateral orchiectomy. All patients who received the full dose of 45 mg of leuprolide in the pivotal clinical study achieved castration levels at 4 weeks. In the vast 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 97% at six months.

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

The tumor size was not measured directly during the clinical study program, but an indirect beneficial tumor response was observed as indicated by a reduction of 97 % of the mean PSA level with ELIGARD 45 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 at stage T1c to T2b with regional adenopathy), of whom 483 received short-term androgen suppression treatment (6 months) in combination with radiotherapy and 487 long-term androgen suppression treatment (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 respectively 19,0 % and 15,2 % 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 unilateral IC at 95,71 % or of 1,09 of the bilateral IC at 95,71 % ; 1,85 (p = 0,65 for non-inferiority) shows that the combination of radiotherapy and androgen suppression treatment of 6 months induces inferior survival compared to radiotherapy associated with androgen suppression treatment of 3 years. The overall survival at 5 years is respectively 84,8 % and 81,0 % with long-term treatment and short-term treatment. The overall 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 the combination of 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 have shown that radiotherapy followed by androgen suppression treatment of 3 years is preferable to radiotherapy followed by androgen suppression treatment of 6 months.

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

Absorption

In patients with advanced prostate cancer, the mean serum concentrations of leuprolide increase after the initial injection and reach 82 ng/mL after 4,4 hours (C_maxAfter the initial increase occurring after each injection (plateau phase observed after each injection from the 3^th to the 168^th day), the serum concentrations remain relatively constant (0,2-2 ng/mL). There is no sign of accumulation during the administration of repeated doses.

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 of 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 performed with ELIGARD 45 mg.

No metabolism study of ELIGARD 45 mg has been performed.

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 discontinuation of treatment 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 performed 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 performed 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 of 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.

This product must be at room temperature before injection. Remove it 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 injection first, then prepare the product, following the instructions below. In the event 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 contents 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 pushing the plunger for syringe A and pushing 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 does not leak as otherwise the needle will not be properly attached.

Please note: There may remain small air bubbles or a large air bubble 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 back the white plunger to prevent 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 administering the product (Figure 7).

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

If the needle tip appears damaged or is leaking, 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 box of ELIGARD.

Step 8 :

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

Administration procedure:

Figure 8

Choose 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 penetration depth 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 angle of 90 ° as that 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
Medication requiring special monitoring during treatment:

MA	CIP 3400938263381 (Ser pdr+Ser solv).

Price:

516,14 euros (Ser pdr+Ser solv).

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