Innohep

Package leaflet: Information for the user

Innohep 8,000 IU anti-Xa/0.4 mL solution for injection, pre-filled syringe; 10,000 IU anti-Xa/0.5 mL solution for injection, pre-filled syringe; 12,000 IU anti-Xa/0.6 mL solution for injection, pre-filled syringe; 14,000 IU anti-Xa/0.7 mL solution for injection, pre-filled syringe; 16,000 IU anti-Xa/0.8 mL solution for injection, pre-filled syringe; 18,000 IU anti-Xa/0.9 mL solution for injection, pre-filled syringe

(20,000 IU anti-Xa/mL)
tinzaparin sodium
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse.
• Within this package leaflet, the pre-filled syringe presentations of Innohep listed above with a concentration of 20,000 IU anti-Xa/mL will be referred to as Innohep.

Contents of this leaflet

1. What Innohep is and what it is used for
2. What you need to know before using Innohep
3. How to use Innohep
4. Possible side effects
5. How to store Innohep
6. Contents of the pack and other information

1. What Innohep is and what it is used for

Innohep is a blood-thinning (anticoagulant) medicine that inhibits the blood's natural ability to clot.

• Innohep 20,000 IU anti-Xa/mL is used to treat blood clots and to prevent the formation of further clots in adults.

Contact your doctor if you do not feel better or if you feel worse.

2. What you need to know before using Innohep

Do not use Innohep:

• if you are allergic to tinzaparin sodium or to any of the other ingredients of this medicine (listed in section 6).
• if you have or have had heparin-induced thrombocytopenia (HIT).
• if you have major bleeding (for example, in the brain, spinal cord, eyes, or stomach).
• if you have an infection of the heart lining (infective endocarditis).
• if you are scheduled to receive spinal or epidural anaesthesia or lumbar puncture.

Warnings and precautions
Talk to your doctor or nurse before using Innohep:

• if you know you have a tendency to bleed.
• if you are being treated with other medicines administered by intramuscular injection.
• if you have a low platelet count in your blood.
• if you have high potassium levels in your blood (hyperkalaemia).
• if you have an artificial heart valve.
• if you have kidney problems.

Children and adolescents
Innohep is not intended for use in children and adolescents.
Other medicines and Innohep
Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.
Some medicines can interact with Innohep.
Talk to your doctor if you are taking any of the following medicines, as you may be more likely to bleed:

• Anti-inflammatory and pain-relieving medicines, particularly non-steroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid
• Medicines used to dissolve blood clots (thrombolytic agents)
• Medicines that block the action of vitamin K (vitamin K antagonists)
• Activated protein C
• Direct inhibitors of factors Xa and IIa

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Innohep in pre-filled syringes can be used during all trimesters of pregnancy.
If you are scheduled to receive epidural anaesthesia, inform your doctor that you are using Innohep.
Talk to your doctor or nurse if you have an artificial heart valve.
Driving and using machines
Innohep does not affect the ability to drive or operate machinery.
Innohep contains sodium metabisulphite

• Sodium metabisulphite may, in rare cases, cause severe hypersensitivity reactions and bronchospasm.
• This medicine contains 40 mg of sodium (a main component of table salt) per mL. This is equivalent to 2% of the maximum recommended daily dietary intake for an adult.

3. How to use Innohep

Always use this medicine exactly as instructed by your doctor or nurse. If you have any doubts, consult your doctor or nurse.
Your doctor may prescribe periodic blood tests to monitor the effects of Innohep.
Innohep must be injected under the skin (subcutaneous injection). During treatment with Innohep, intramuscular injection of other medicines should be avoided due to the risk of hematoma.

Recommended dose:
175 anti-Xa IU per kg of body weight injected once daily. Your doctor will prescribe the correct dose for you.
Treatment will be administered once daily for at least 6 days and may continue for up to 6 months. Whether treatment needs to continue beyond 6 months will be assessed by your doctor. Your doctor will inform you how long your treatment with Innohep will last.

How to inject Innohep – instructions:

1. Wash your hands thoroughly before injecting the medicine. Clean the skin around the injection site with an alcohol-soaked gauze pad and allow it to dry without rubbing.

2. Open the tube by fully bending the colored cap backwards and remove the syringe. Check the syringe contents before use. If the medicine appears cloudy or contains a precipitate, do not use it and take another syringe. The medicine may develop a yellow tint during storage; it may still be used if the solution is clear and the expiry date has not been exceeded. Each syringe is for single use only.

3. Bend the safety device downwards, away from the needle protective cap.

4. Remove the needle protective cap without bending the needle. Do not pull back the plunger and do not expel the air bubble. If the air bubble is not correctly positioned near the plunger, gently tap the syringe until the air bubble is in the correct position.

5. Gently lift a skin fold between the thumb and index finger of one hand, and with the other hand, slowly insert the needle vertically into the skin fold, i.e., at a right angle to the skin.

6. Slowly inject the required dose into the fatty tissue, for example, into the abdominal skin, the anterolateral surface of the thigh, the lower back area, or the arm. Wait a few seconds to allow the solution to disperse before removing the needle and releasing the skin fold.

7. Wipe away any blood with a tissue. For the next injection, choose a different injection site (for example, moving from the left to the right side of the abdomen).

8. Bend the safety device backwards to return it to its original position so that it lies beneath the needle. Then, place the safety device flat on a hard surface and press down until the needle locks into the device.

9. The used syringe may be placed into the tube with the needle pointing downwards, or into a sharps container. Once the syringe has been safely secured, the tube or sharps container can be handed over to the hospital or pharmacist for disposal.

If you use more Innohep than you should
If you use more Innohep than prescribed, bleeding may occur. Inform your doctor or nurse immediately if you feel unwell or think you have used too much Innohep.

If you forget to use Innohep
Do not inject a double dose to make up for a missed dose. If you have missed more than one dose, contact your doctor as soon as possible.

If you stop using Innohep
The blood-thinning effect will cease if you stop using Innohep. Do not stop treatment with Innohep without consulting your doctor or nurse.

If you have any questions about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Serious side effects:
Serious side effects requiring immediate medical attention are rarely observed during treatment with Innohep. If you experience any of the following symptoms, seek immediate medical help from your doctor or the nearest hospital for emergency medical treatment.

• Severe allergic reaction. Symptoms include sudden onset of severe rash, swelling of the throat, face, lips or mouth, and breathing difficulties.
• Severe bleeding. Symptoms include red or brown urine, black tarry stools, development of unusual bruising (bruises that are very painful, large or dark), and any bleeding that does not stop on its own.

The following side effects have been observed during treatment with Innohep:
Common: may affect up to 1 in 10 people

• Bleeding. Bleeding may lead to complications such as anaemia (low red blood cell count) or haematomas (bruising)
• Reaction at the injection site (including bruising, bleeding, pain, itching, redness, swelling and formation of a hard nodule at the injection site)

Uncommon: may affect up to 1 in 100 people

• Thrombocytopenia (reduced number of platelets in the blood)
• Hypersensitivity (allergic reaction)
• Bruising and skin discoloration
• Increased levels of liver enzymes
• Dermatitis (inflammation of the skin)
• Skin rash and itching

Rare: may affect up to 1 in 1,000 people

• Heparin-induced thrombocytopenia (reduced number of platelets in the blood due to heparin treatment)
• Thrombocytosis (increased number of platelets in the blood)
• Angioedema (swelling of the face, lips and tongue)
• Anaphylactic reaction (see "Severe allergic reaction" above)
• Hyperkalaemia (increased potassium levels in the blood)
• Toxic skin rash
• Skin necrosis (tissue death)
• Urticaria
• Osteoporosis, observed during long-term treatment
• Priapism (prolonged, usually painful erection without sexual desire)

Paediatric population
Limited information from one study and post-marketing data indicate that the pattern of adverse reactions in children and adolescents is comparable to that observed in adults.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Innohep

• Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions.
• Do not use this medicine if you notice cloudiness or precipitate in the syringe.
• The liquid may turn yellow during storage, but this does not affect the quality of the product, which remains safe to use.
• Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Innohep contains

• The active substance is tinzaparin sodium. Each mL of injectable solution contains 20,000 IU anti-Xa of tinzaparin sodium.
• The other components are sodium metabisulfite (E223), sodium hydroxide and water for injections.

Description of the appearance of Innohep and contents of the pack
Injectable solution.
Clear glass syringes containing a colourless or straw-coloured liquid, free from turbidity and any deposit at the bottom.
Pack sizes:

• 0.4 mL (8,000 IU anti-Xa), packs of 2, 6, 10, 30, 50 and 100 syringes
• 0.5 mL (10,000 IU anti-Xa), packs of 2, 6, 10, 30, 50 and 100 syringes
• 0.6 mL (12,000 IU anti-Xa), packs of 2, 6, 10, 30, 50 and 100 syringes
• 0.7 mL (14,000 IU anti-Xa), packs of 2, 6, 10, 30, 50 and 100 syringes
• 0.8 mL (16,000 IU anti-Xa), packs of 2, 6, 10, 30, 50 and 100 syringes
• 0.9 mL (18,000 IU anti-Xa), packs of 2, 6, 10, 30, 50 and 100 syringes

Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
LEO Pharma A/S
Industriparken 55
DK-2750 Ballerup
Denmark
Manufacturer:
Laboratoires LEO S.A.
39 Route de Chartres
FR - 28500 Vernouillet Cedex
France

Package leaflet: Information for the user

Innohep 2,500 IU anti-Xa/0.25 mL solution for injection, pre-filled syringe, 3,500 IU anti-Xa/0.35 mL solution for injection, pre-filled syringe, 4,500 IU anti-Xa/0.45 mL solution for injection, pre-filled syringe

(10,000 IU anti-Xa/mL)
tinzaparin sodium
Please read this entire leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse.
• Within this patient information leaflet, the Innohep pre-filled syringe presentations containing 10,000 IU anti-Xa/mL listed above will be referred to as Innohep.

Contents of this leaflet

1. What Innohep is and what it is used for
2. What you need to know before using Innohep
3. How to use Innohep
4. Possible side effects
5. How to store Innohep
6. Contents of the pack and other information

1. What Innohep is and what it is used for

Innohep is a blood-thinning (anticoagulant) medicine that inhibits the blood's natural ability to clot. Innohep 10,000 IU anti-Xa/mL is used for:

• preventing the formation of blood clots in adults before and after surgery.
• preventing the formation of blood clots in adults at increased risk of clot formation, for example due to an acute illness that limits mobility.
• preventing the formation of blood clots in dialysis equipment in patients undergoing haemodialysis or haemofiltration. During haemodialysis, blood is purified from waste products and excess fluids by means of a dialysis machine and a dialysis filter, which act as an artificial kidney.

2. What you need to know before using Innohep

Do not use Innohep:

• if you are allergic to tinzaparin sodium or to any of the other ingredients of this medicine (listed in section 6).
• if you have or have had heparin-induced thrombocytopenia (HIT).
• if you have significant bleeding (for example, in the brain, spinal cord, eyes, or stomach).
• if you have an infection of the heart lining (infective endocarditis).

Warnings and precautions
Talk to your doctor or nurse before using Innohep:

• if you are scheduled to receive spinal or epidural anaesthesia or a lumbar puncture.
• if you know you have a tendency to bleed.
• if you are being treated with other medicines administered by intramuscular injection.
• if you have a low platelet count in your blood.
• if you have increased potassium levels in your blood (hyperkalaemia).
• if you have an artificial heart valve.
• if you have kidney problems.

Children and adolescents
Innohep is not intended for use in children and adolescents.
Other medicines and Innohep
Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.
Some medicines may interact with Innohep.
Talk to your doctor if you are taking any of the following medicines, as you may be more likely to bleed:

• Anti-inflammatory and pain medicines, particularly non-steroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid
• Medicines used to dissolve blood clots (thrombolytic agents)
• Medicines that block the action of vitamin K (vitamin K antagonists)
• Activated protein C
• Direct inhibitors of factors Xa and IIa

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Innohep in pre-filled syringes may be used during all trimesters of pregnancy.
If you are scheduled to receive epidural anaesthesia, inform your doctor that you are using Innohep.
Talk to your doctor or nurse if you have an artificial heart valve.
Driving and using machines
Innohep does not affect the ability to drive or operate machinery.
Innohep contains sodium

• This medicine contains less than 1 mmol of sodium (23 mg) per mL, i.e. it is essentially ‘sodium-free’.

3. How to use Innohep

Always use this medicine exactly as instructed by your doctor or nurse. If you have any doubts, consult your doctor or nurse.
Your doctor may prescribe periodic blood tests to monitor the effects of Innohep.

To prevent the formation of blood clots in the veins
Innohep must be injected under the skin (subcutaneous injection). The dose and duration of treatment will depend on the type of surgery or illness you have. Your doctor will prescribe the correct dose and inform you how long your treatment with Innohep will last.

To prevent the formation of blood clots associated with haemodialysis or haemofiltration
Innohep will be administered into the tubing of the dialysis machine or into a vein. The dose will depend on the duration of dialysis.

How to inject Innohep – instructions:

1. Wash your hands thoroughly before injecting the medicine. Clean the skin around the injection site with an alcohol swab and allow it to dry without rubbing.

2. Open the tube by fully bending back the coloured cap and remove the syringe. Check the contents of the syringe before use. If the solution is cloudy or contains a precipitate, do not use it and take another syringe. The medicine may turn yellow during storage; it may still be used if the solution is clear and the expiry date has not been exceeded. Each syringe is for single use only.

3. Bend the safety device downwards, away from the needle protection cap.

4. Remove the needle protection cap without bending the needle. Do not pull back the plunger and do not expel the air bubble. If the air bubble is not correctly positioned near the plunger, gently tap the syringe until the air bubble reaches the correct position.

5. Gently lift a skin fold between the thumb and index finger of one hand and, with the other hand, slowly insert the needle vertically into the skin fold, at a right angle to the skin.

6. Slowly inject the required dose into the fatty tissue, for example, into the abdominal skin, the anterior-lateral surface of the thigh, the lower back area, or the arm. Wait a few seconds to allow the solution to disperse before removing the needle and releasing the skin fold.

7. Wipe away any blood with a tissue. For the next injection, choose a different injection site (for example, switch from the left to the right side of the abdomen).

8. Bend the safety device backwards to return it to its original position so that it lies beneath the needle. Then, place the safety device flat on a hard surface and press down until the needle locks into the device.

9. The used syringe may be placed in the tube with the needle pointing downwards, or into a sharps container. Once the syringe has been secured, the tube or sharps container can be returned to the hospital or pharmacist for disposal.

If you use more Innohep than you should
If you use more Innohep than prescribed, bleeding may occur. Inform your doctor or nurse immediately if you feel unwell or think you have used too much Innohep.

If you forget to use Innohep
Do not inject a double dose to make up for the dose you missed. If you have missed more than one dose, contact your doctor as soon as possible.

If you stop using Innohep
The blood-thinning effect will cease if you stop using Innohep. Do not stop treatment with Innohep without consulting your doctor or nurse.

If you have any questions about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

Serious side effects:

Serious side effects requiring immediate medical attention are rarely observed during treatment with Innohep. If you experience any of the following symptoms, seek immediate medical help from your doctor or the nearest hospital for emergency medical treatment.

• Severe allergic reaction. Symptoms include sudden onset of severe rash, swelling of the throat, face, lips or mouth, and breathing difficulties.
• Severe bleeding. Symptoms include red or brown urine, black tarry stools, unusual bruising (bruises that are very painful, large or dark), and any bleeding that does not stop spontaneously.

The following side effects have been observed during treatment with Innohep:

Common: may affect up to 1 in 10 people

• Bleeding. Bleeding may lead to complications such as anaemia (low number of red blood cells in the blood) or haematomas (bruising)
• Reaction at the injection site (including bruising, bleeding, pain, itching, redness, swelling, and formation of a hard nodule at the injection site)

Uncommon: may affect up to 1 in 100 people

• Thrombocytopenia (reduced number of platelets in the blood)
• Hypersensitivity (allergic reaction)
• Bruising and skin discoloration
• Increased levels of liver enzymes
• Dermatitis (inflammation of the skin)
• Skin rash and itching

Rare: may affect up to 1 in 1,000 people

• Heparin-induced thrombocytopenia (reduced number of platelets in the blood due to heparin treatment)
• Thrombocytosis (increased number of platelets in the blood)
• Angioedema (swelling of the face, lips and tongue)
• Anaphylactic reaction (see “Severe allergic reaction” above)
• Hyperkalaemia (increased levels of potassium in the blood)
• Toxic skin rash
• Skin necrosis (death of tissue)
• Urticaria
• Osteoporosis, observed with long-term treatment
• Priapism (persistent, usually painful erection, without sexual desire)

Paediatric population

Limited information from one study and post-marketing data indicate that the pattern of adverse reactions in children and adolescents is comparable to that observed in adults.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Innohep

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions.
• Do not use this medicine if you notice cloudiness or precipitate in the syringe.
• The liquid may turn yellow during storage, but this does not affect the quality of the product, and its use remains safe.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Innohep contains

• The active substance is tinzaparin sodium. Each mL of injectable solution contains 10,000 IU anti-Xa of tinzaparin sodium.
• The other components are sodium acetate trihydrate, sodium hydroxide and water for injections.

Description of the appearance of Innohep and contents of the pack
Injectable solution.
Clear glass syringes containing a colourless or straw-coloured liquid, free from turbidity and any
particulate matter settling at the bottom.
Pack sizes:

• 0.25 mL (2,500 IU anti-Xa), packs of 10 syringes
• 0.35 mL (3,500 IU anti-Xa), packs of 10 syringes
• 0.45 mL (4,500 IU anti-Xa), packs of 10 syringes

Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
LEO Pharma A/S
Industriparken 55
DK-2750 Ballerup
Denmark
Manufacturer:
Laboratoires LEO S.A.
39 Route de Chartres
FR - 28500 Vernouillet Cedex
France