Epoetin alfa HEXAL 10,000 IU/1 ml solution for injection in apre-filled syringe

Epoetin alfa HEXAL contains a hormone called epoetin alfa, which stimulates the production of red blood cells. Epoetin alfa is produced by a specialised genetic technology and works in exactly the same way as the natural hormone erythropoietin.

Epoetin alfa HEXAL is used:

• for treating the condition of having less than the normal number of red blood cells or less than the normal quantity of hemoglobin in the blood (symptomatic anaemia) associated with kidney disease:
• in children and adults who need regular dialysis (treatment to clean and filter their blood)
• in adults on peritoneal dialysis, which is another procedure that replaces the work of your kidneys using the lining of your abdomen to filter your blood.
• for treating severe symptomatic anaemia caused by kidney disease in adults not yet undergoing dialysis (given by injection into a vein)
• for treating anaemia and reducing the need for a blood transfusion in adults receiving chemotherapy for solid tumours, malignant lymphoma or multiple myeloma, and at risk of transfusion as assessed by the doctor
• in moderately anaemic patients who are going to have surgery and prior to it, donate blood so that their own blood can be given to them during or after surgery (autologous predonation)
• as an alternative to a blood transfusion in adult patients about to undergo major orthopaedic (bone) surgery where there is a potentially high risk from blood transfusion complications.

Do not use Epoetin alfa HEXAL:

• if you are allergic (hypersensitive) to epoetin alfa or any of the other ingredients of Epoetin alfa HEXAL
• if you have developed Pure Red Cell Aplasia (reduced or stopped production of red blood cells) following treatment with any erythropoietin
• if you have high blood pressure which is not properly controlled
• if you are donating your own blood before surgery, and:
• you had a heart attack or stroke in the month before your treatment
• you have unstable angina pectoris (new or increasing chest pain)
• you are at risk of blood clots in the veins (deep venous thrombosis) ? for example, if you have had clots before
• if you cannot receive adequate treatment for the prevention of blood clots (antithrombotic prophylaxis)
• if you are due to have major orthopaedic surgery, and:
• you have severe disorders of blood circulation of the heart (coronary heart disease), arteries of the legs or arms (peripheral arterial occlusive disease), neck vessels (vascular disease of the carotids) or the brain (cerebrovascular disease)
• you had a recent heart attack or stroke

If any of these applies to you, or might apply, tell your doctor at once.

Take special care with Epoetin alfa HEXAL:

General

When you receive Epoetin alfa HEXAL therapy your blood pressure should be closely monitored. If you have high blood pressure (hypertension) it may be necessary to start antiyhypertensive therapy, or if your blood pressure is still high although you already take blood pressure medication, it may be necessary to initiate or increase treatment against high blood pressure. If your blood pressure cannot be controlled, Epoetin alfa HEXAL treatment should be stopped.

If you receive epoetin alfa you should have your haemoglobin levels measured on a regular basis until a stable level is achieved, and periodically thereafter. There is a potential increased risk of rare thromboembolic events (e.g. heart attacks, strokes, and pulmonary embolism) when haemoglobin levels increase above the target range.

All other potential causes of anaemia, e.g. iron deficiency, damage of red blood cells (haemolysis), blood loss, vitamin B 12 or folate deficiency, need to be taken into account and treated prior to initiating therapy with Epoetin alfa HEXAL. Your doctor may do blood tests to decide, if you need iron supplements in order to ensure optimum response to Epoetin alfa HEXAL.

In addition, your doctor may do regular blood tests to check your blood platelet count during the first 8 weeks of therapy. There may be a moderate dose-dependent increase in the platelet count within the normal range during treatment with Epoetin alfa HEXAL, which gradually regresses during the course of continued therapy.

Take special care with Epoetin alfa HEXAL if you have epilepsy or chronic liver disease.

There have been rare reports of patients developing antibodies against epoetin alfa resulting in a failure of red blood cell development, a condition called antibody-mediated Pure Red Cell Aplasia (PRCA). PRCA can result in sudden and severe anaemia, the symptoms of which are unusual tiredness, feeling dizzy or breathlessness. If you experience these symptoms you should talk to your doctor at once. If you develop PRCA your Epoetin alfa HEXAL therapy will be discontinued and your doctor will decide how best to treat your anaemia.

If you are a patient with hepatitis C and you receive interferon and ribavirin, you should discuss this with your doctor because a combination of erythropoiesis stimulating agents (ESAs) with interferon and ribavirin has lead to a loss of effect and development of a condition called pure red cell aplasia (PRCA), a severe form of anemia, in rare cases. ESAs are not approved in the management of anaemia associated with hepatitis C.

Kidney patients

There is not much experience with subcutaneous use (injection into the skin) of Epoetin alfa HEXAL in kidney patients. Therefore, if you are being treated for anaemia associated with kidney disease, Epoetin alfa HEXAL has to be given by injection into a vein (intravenously).

The correction of your anaemia may lead to increased appetite, and thus increased potassium and protein intake. If an elevated or increasing serum potassium level is detected, your doctor may consider to discontinue the treatment with Epoetin alfa HEXAL until the potassium level has returned to the normal range.

An increase in dose of a particular blood-thinning medicine (heparin) during haemodialysis is frequently required during the course of therapy with Epoetin alfa HEXAL. Inadequate thinning of the blood by heparin (heparinisation) may lead to occlusion of the dialysis system.

Cancer patients

Cancer patients receiving treatment with erythropoietin have an increased risk of blood clots/blood clotting disorders (thrombotic vascular events), particularly if they are obese or have a history of thrombotic vascular events (e.g. deep vein thrombosis or pulmonary embolism). This risk should be carefully weighed against the potenital benefit derived from treatment with epoetin alfa.

If you are a cancer patient you should be aware that Epoetin alfa HEXAL may act as a blood cell growth factor and in some circumstances may have a negative impact on your cancer. Depending on your individual situation a blood transfusion may be preferable. Please discuss this with your doctor.

Patients donating their own blood before surgery

Your doctor will consider warnings and precautions associated with autologous blood predonation, especially volume replacement.

Patients scheduled for orthopaedic surgery

If you are due to have major orthopaedic surgery, the cause of anaemia should be established and treated, if possible, before the start of Epoetin alfa HEXAL treatment. Your doctor will weight this risk carefully against the benefits to be derived from treatment with epoetin alfa.You should receive adequate measures in order to prevent blood clots (thrombotic prophylaxis), particularly if you have cardiovascular disorders.

If your levels of the red blood pigment (haemoglobin) are too high you should not receive Epoetin alfa HEXAL, since you have an increased risk of blood clotting after the surgery.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
If you are taking ciclosporin (medicine to suppress your immune system) during therapy with Epoetin alfa HEXAL, your doctor may order special blood tests to measure ciclosporin levels.

Take special care with other products that stimulate red blood cell production

Epoetin alfa HEXAL is one of a group of products that stimulate the production of red blood cells like the human protein erythropoietin does. Your healthcare professional will always record the exact product you are using.

Pregnancy and breast-feeding

There is not much experience with epoetin alfa in pregnant women or women who are breast-feeding.

Therefore, in kidney patients, Epoetin alfa HEXAL should be used in pregnancy only if the potential benefit outweighs the potential risk to the baby. In pregnant or breast-feeding patients donating their own blood before surgery, the use of epoetin alfa is not recommended.

Ask your doctor or pharmacist for advice before taking any medicine during pregnancy or when you are breast-feeding.

Driving and using machines

No effects on ability to drive or use machines have been observed.

Important information about some of the ingredients of Epoetin alfa HEXAL

This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled syringe i.e. essentially ?sodium-free?.

General

Your doctor will work out the correct dose of Epoetin alfa HEXAL for you to use and how long the treatment should continue. The dose you receive is based on your body weight in kilograms. The Epoetin alfa HEXAL pre-filled syringe is ready for use. Only solutions which are clear, colourless and free of visible particles may be injected. Epoetin alfa HEXAL is a sterile but unpreserved product and is for single use only.
This medicinal product must not be administered by intravenous infusion, or mixed with other medicinal products.
At the start of your therapy, Epoetin alfa HEXAL may be injected under the supervision of experienced medical staff.

Dosage

Adults receiving haemodialysis

The usual starting dose is 50 International Units (IU) per kilogram bodyweight. This is given three times a week by injection into a vein (intravenously). Do not give by injection under the skin (subcutaneously).
Depending on how your anaemia responds to treatment, the dose may be adjusted approximately every four weeks until your condition is controlled. Your doctor may order regular blood tests to see that this is being achieved and to ensure that your medicine is continuing to work properly and your haemoglobin does not exceed a certain level.

When your condition has been brought under control, you will receive regular doses of Epoetin alfa HEXAL. The recommended weekly dose is between 75 and 300 IU per kilogram.

Adults receiving peritoneal dialysis

The usual starting dose is 50 International Units (IU) per kilogram bodyweight. This is given twice a week by injection into a vein. Depending on how your anaemia responds, the dose may be adjusted until your condition is controlled. Your doctor may order regular blood tests to see that this is being achieved and to ensure that your medicine is continuing to work properly and your haemoglobin does not exceed a certain level. When your condition has been brought under control, you will receive regular doses of Epoetin alfa HEXAL between 25 and 50 IU/kg twice a week in two equal injections.

Adults with kidney disease not yet receiving dialysis

The usual starting dose is 50 International Units (IU) per kilogram bodyweight. This is given three times a week by injection into a vein. The starting dose may be adjusted by your doctor approximately every 4 weeks until your condition is controlled. Your doctor may order regular blood tests to see that control is being achieved and to ensure that your haemoglobin does not exceed a certain level. After your condition has been brought under control, you will receive regular doses of Epoetin alfa HEXAL between 17 and 33 IU/kg, three times a week. The dosage should not normally exceed 200 IU per kilogram, three times a week. Your doctor will order regular blood tests to ensure that your medicine is continuing to work properly.

Children receiving haemodialysis

The usual starting dose is 50 International Units (IU) per kilogram bodyweight. This is given three times a week, injected into a vein. Depending on how the anaemia responds, the dose may be adjusted approximately every 4 weeks until the condition is controlled. The doctor will order regular blood tests to see that this is being achieved and to ensure that the haemoglobin value does not exceed a certain level.

Cancer patients

The usual starting dose is 150 International Units (IU) per kilogram bodyweight. This is given 3 times a week by injection under the skin (subcutaneously). Alternatively, Epoetin alfa HEXAL can be administered as an initial dose of 450 IU/kg once a week by injection under the skin. The dose may be adjusted by your doctor depending on how your anaemia responds to treatment. Your doctor will check that your haemoglobin does not exceed a certain level. Treatment with Epoetin alfa HEXAL should be continued until one month after the end of chemotherapy.

Adult patients donating their own blood

The usual starting dose is 600 International Units (IU) per kilogram bodyweight. This is given 2 times a week by injection into a vein. You will receive Epoetin alfa HEXAL during the 3 weeks before your surgery. You will also take iron supplements before and during Epoetin alfa HEXAL treatment to increase the effectiveness of Epoetin alfa HEXAL.

Adult patients scheduled for orthopaedic surgery

The recommended dose of 600 International Units (IU) per kilogram bodyweight is given weekly for three weeks before surgery and on the day of surgery. This is given by injection under the skin (subcutaneously).

In cases where there is a need to shorten the time for treatment before the operation is carried out, a dose of 300 IU/kg is given on each of the next ten days before surgery, on the day of surgery and for four days immediately afterwards.
If blood tests in the period before the operation show your haemoglobin level to be too high, the treatment will be stopped.

It is important that levels of iron in your blood are normal throughout Epoetin alfa HEXAL treatment. Where appropriate you will receive oral doses of iron, ideally starting before the Epoetin alfa HEXAL treatment begins.

Instructions for injecting Epoetin alfa HEXAL under the skin

Please note: If you are a kidney patient Epoetin alfa HEXAL has to be given by injection into a vein. Do not give by injection under the skin (subcutaneously).

Epoetin alfa HEXAL should not be shaken.

The amount injected in any one place should not normally exceed one mililitre (1 ml). The injections are given preferably in the thigh or the front part of the abdominal wall. At the start of your therapy, Epoetin alfa HEXAL may be injected by medical staff. However, your doctor may decide that it is right for you to learn how to inject Epoetin alfa HEXAL under the skin yourself. You will receive appropriate training for you to do this. Under no circumstances should you attempt to inject yourself unless you have been trained to do so.

Instructions on how to inject yourself with Epoetin alfa HEXAL can be found at the end of this leaflet.

If you inject more Epoetin alfa HEXAL than you should

You should inform the doctor immediately if you think too much Epoetin alfa HEXAL has been injected.

If you forget to use Epoetin alfa HEXAL

If you have missed an injection, or injected too little, talk to your doctor.
Do not inject a double dose to make up for a forgotten dose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Epoetin alfa HEXAL can cause side effects, although not everybody gets them.

Tell your doctor or nurse immediately if you notice any of the effects in this list.

The frequency of possible side effects listed below is defined using the following convention: very common (affects more than 1 user in 10); common (affects 1 to 10 users in 100); uncommon (affects 1 to 10 users in 1,000); rare (affects 1 to 10 users in 10,000); very rare (affects less than 1 user in 10,000).

Very common side effects

• Flu-like symptoms, such as headache, aches and pains in the joints, fever, feeling of weakness, tiredness and dizziness. These may be more common at the start of treatment. If you have these symptoms during intravenous injection, a slower delivery of the injection may help to avoid them in future.

Common side effects

• Increased blood pressure in people with cancer and in people with symptomatic anaemia caused by kidney disease. Headaches, particularly sudden, stabbing migraine-like headaches, feeling confused or having fits may be signs of a sudden increase in blood pressure. This requires urgent treatment . Raised blood pressure may require treatment with some other medicines (or adjustment to any medicines you already take for high blood pressure).
• Chest pain, breathlessness, painful swelling in the leg which may be symptoms of blood clots (thrombosis), diarrhoea, seizures.
• Skin rashes and swelling around the eyes (oedema), which may result from an allergic reaction.

If you are receiving haemodialysis:

• Blood clots (thrombosis) may form in your dialysis shunt. This is more likely if you have low blood pressure or if your fistula has complications.
• Blood clots may also form in your haemodialysis system. Your doctor may decide to increase your heparin dose during dialysis.

Very rare side effects

• Pure red cell aplasia (PRCA)

PRCA means the inability to produce enough red blood cells in the bone marrow. PRCA can result in sudden and severe anaemia. The symptoms are:

• unusual tiredness,
• feeling dizzy,
• breathlessness.

PRCA has been very rarely reported after months to years of treatment with epoetin alfa and other products that stimulate red blood cell production in patients with chronic renal failure.

If you are receiving haemodialysis an increase in levels of small blood cells (called platelets), which are normally involved in the formation of a blood clot may occur, particularly when starting treatment. Your doctor will check on this. Thrombotic events (blood clotting) in vessels, such as disturbed blood perfusion of the heart, heart attack, cerebral haemorrhages, stroke, temporary disturbance of blood perfusion in the brain, deep vein thrombosis, arterial thrombosis, and blood clot in an artificial kidney have been reported in patients receiving erythropoietin treatment.

You may experience redness, burning and pain at the site of injection.

In rare cases, shock-like allergic reactions with symptoms of tingling, reddening, itching, hot flush and accelerated pulse have been reported.

Tell your doctor or nurse immediately if you are aware of any of these effects, or if you notice any other effects while you are receiving treatment with Epoetin alfa HEXAL.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

• Keep out of the reach and sight of children.
• Do not use Epoetin alfa HEXAL after the expiry date which is stated on the label and carton after ?EXP?. The expiry date refers to the last day of that month.
• Store and transport refrigerated (2°C -8°C).
• Do not freeze.
• Keep the pre-filled syringe in the outer carton in order to protect from light.
• You may take Epoetin alfa HEXAL out of the refrigerator and keep it at room temperature (up to 25°C) for no longer than 3 days. Once a syringe has been removed from the refrigerator and has reached room temperature (up to 25°C) it must either be used within 3 days or disposed of.

Do not use Epoetin alfa HEXAL

• if the solution is cloudy or there are particles in it.
• if the seal is broken.
• if the solution has been accidently frozen.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Epoetin alfa HEXAL contains

• The active substance is epoetin alfa. Epoetin alfa HEXAL 1,000 IU/0.5 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.5 ml solution for injection contains 1,000 international units (IU) corresponding to 8.4 micrograms epoetin alfa Epoetin alfa HEXAL 2,000 IU/1 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 1 ml solution for injection contains 2,000 international units (IU) corresponding to 16.8 micrograms epoetin alfa Epoetin alfa HEXAL 3,000 IU/0.3 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.3 ml solution for injection contains 3,000 international units (IU) corresponding to 25.2 micrograms epoetin alfa Epoetin alfa HEXAL 4,000 IU/0.4 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.4 ml solution for injection contains 4,000 international units (IU) corresponding to 33.6 micrograms epoetin alfa Epoetin alfa HEXAL 5,000 IU/0.5 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.5 ml solution for injection contains 5,000 international units (IU) corresponding to 42.0 micrograms epoetin alfa Epoetin alfa HEXAL 6,000 IU/0.6 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.6 ml solution for injection contains 6,000 international units (IU) corresponding to 50.4 micrograms epoetin alfa Epoetin alfa HEXAL 7,000 IU/0.7 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.7 ml solution for injection contains 7,000 international units (IU) corresponding to 58.8 micrograms epoetin alfa Epoetin alfa HEXAL 8,000 IU/0.8 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.8 ml solution for injection contains 8,000 international units (IU) corresponding to 67.2 micrograms epoetin alfa Epoetin alfa HEXAL 9,000 IU/0.9 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.9 ml solution for injection contains 9,000 international units (IU) corresponding to 75.6 micrograms epoetin alfa Epoetin alfa HEXAL 10,000 IU/1 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 1 ml solution for injection contains 10,000 international units (IU) corresponding to 84.0 micrograms epoetin alfa Epoetin alfa HEXAL 20,000 IU/0.5 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.5 ml solution for injection contains 20,000 international units (IU) corresponding to 168.0 micrograms epoetin alfa Epoetin alfa HEXAL 30,000 IU/0.75 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 0.75 ml solution for injection contains 30,000 international units (IU) corresponding to 252.0 micrograms epoetin alfa Epoetin alfa HEXAL 40,000 IU/1 ml solution for injection in a pre-filled syringe: one pre-filled syringe of 1 ml solution for injection contains 40,000 international units (IU) corresponding to 336.0 micrograms epoetin alfa
• The other ingredients are sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for pH-adjustment), and water for injections.

What Epoetin alfa HEXAL looks like and contents of the pack

Epoetin alfa HEXAL is presented as a clear, colourless solution for injection in a pre-filled syringe. The syringes are sealed in a blister.

Epoetin alfa HEXAL 1,000 IU/0.5 ml solution for injection in a pre-filled syringe The syringes contain 0.5 ml (1000 IU) of solution.

Epoetin alfa HEXAL 2,000 IU/1 ml solution for injection in a pre-filled syringe The syringes contain 1 ml (2,000 IU) of solution.

Epoetin alfa HEXAL 3,000 IU/0.3 ml solution for injection in a pre-filled syringe The syringes contain 0.3 ml (3,000 IU) of solution.

Epoetin alfa HEXAL 4,000 IU/0.4 ml solution for injection in a pre-filled syringe The syringes contain 0.4 ml (4,000 IU) of solution.

Epoetin alfa HEXAL 5,000 IU/0.5 ml solution for injection in a pre-filled syringe The syringes contain 0.5 ml (5,000 IU) of solution.

Epoetin alfa HEXAL 6,000 IU/0.6 ml solution for injection in a pre-filled syringe The syringes contain 0.6 ml (6,000 IU) of solution.

Epoetin alfa HEXAL 7,000 IU/0.7 ml solution for injection in a pre-filled syringe The syringes contain 0.7 ml (7,000 IU) of solution.

Epoetin alfa HEXAL 8,000 IU/0.8 ml solution for injection in a pre-filled syringe The syringes contain 0.8 ml (8,000 IU) of solution.

Epoetin alfa HEXAL 9,000 IU/0.9 ml solution for injection in a pre-filled syringe The syringes contain 0.9 ml (9,000 IU) of solution.

Epoetin alfa HEXAL 10,000 IU/1 ml solution for injection in a pre-filled syringe The syringes contain 1 ml (10,000 IU) of solution.

Epoetin alfa HEXAL 20,000 IU/0.5 ml solution for injection in a pre-filled syringe The syringes contain 0.5 ml (20,000 IU) of solution.

Epoetin alfa HEXAL 30,000 IU/0.75 ml solution for injection in a pre-filled syringe The syringes contain 0.75 ml (30,000 IU) of solution.

Epoetin alfa HEXAL 40,000 IU/1 ml solution for injection in a pre-filled syringe The syringes contain 1 ml (40,000 IU) of solution.

Pack size of 1 or 6 pre-filled syringe(s) with or without a needle safety guard.
Not all pack sizes may be marketed.

Marketing Authorisation Holder

Hexal AG
Industriestrasse 25
D-83607 Holzkirchen
Germany

Manufacturer

Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Hexal AG
Industriestrasse 25
D-83607 Holzkirchen
Germany
Tel: + 49 8024 908-0
Fax: + 49 8024 908-1290
e-mail: service@hexal.com

This leaflet was last approved in {MM/YYYY}.

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Instructions on how to inject yourself (for patients receiving chemotherapy, adult patients donating their own blood before surgery or adult patients scheduled for orthopaedic surgery only)

This section contains information on how to give yourself an injection of Epoetin alfa HEXAL. It is important that you do not try to give yourself the injection unless you have received special training from your doctor or nurse. Epoetin alfa HEXAL is provided with or without a needle safety guard and you will be shown how to use this by your doctor or nurse. If you are not sure about giving the injection or you have any questions, please ask your doctor or nurse for help.

1. Wash your hands.

2. Remove one syringe from the pack and remove the protective cap from the injection needle. Syringes are embossed with graduation rings in order to enable partial use if required. Each graduation ring corresponds to a volume of 0.1 ml. If partial use of a syringe is required, remove unwanted solution before injection.

3. Clean the skin at the injection site using an alcohol wipe.

4. Form a skin fold by pinching the skin between thumb and forefinger.

5. Insert the needle into the skin fold with a quick, firm action. Inject the Epoetin alfa HEXAL solution as you have been shown by your doctor. You should check with your doctor or pharmacist if you are not sure.

Pre-filled syringe without needle safety guard 6. Always keeping your skin pinched, depress the plunger slowly and evenly. 7. After injecting the liquid, remove the needle and let go of your skin. Apply pressure over the injection site with a dry, sterile pad. 8. Discard any unused product or waste material. Only use each syringe for one injection.

Pre-filled syringe with needle safety guard

6. Always keeping your skin pinched, depress the plunger slowly and evenly until the entire dose has been given and the plunger cannot be depressed any further. Do not release the pressure on the plunger 7. After injecting the liquid, remove the needle while maintaining pressure on the plunger and then let go of your skin. Apply pressure over the injection site with a dry, sterile pad. 8. Let go of the plunger. The needle safety guard will rapidly move to cover the needle. 9. Discard any unused product or waste material. Only use each syringe for one injection.