Rovinadil

Patient Information Leaflet

ROVINADIL 2,000 IU (20 mg) in 0.2 mL injectable solution in pre-filled syringe, 4,000 IU (40 mg) in 0.4 mL injectable solution in pre-filled syringe, 6,000 IU (60 mg) in 0.6 mL injectable solution in pre-filled syringe, 8,000 IU (80 mg) in 0.8 mL injectable solution in pre-filled syringe, 10,000 IU (100 mg) in 1 mL injectable solution in pre-filled syringe

enoxaparin sodium
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this 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, ask 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 effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What ROVINADIL is and what it is used for

ROVINADIL contains the active substance called enoxaparin sodium, which is a low molecular weight heparin (LMWH).
ROVINADIL works in two ways.

1. It blocks the growth of existing blood clots. This helps the body to break them down and prevents them from causing harm.
2. It prevents the formation of new blood clots.
   ROVINADIL can be used to:

• Treat existing blood clots.
• Prevent the formation of blood clots in the following situations:
  • before and after surgery
  • in case of acute illness involving a period of reduced mobility
  • if you have had a blood clot due to cancer, to prevent further clots
  • in cases of unstable angina (a condition in which insufficient blood reaches the heart)
  • after a heart attack
• Prevent the formation of blood clots in the tubing of dialysis machines (used by people with severe kidney problems).

2. What you need to know before using ROVINADIL

Do not use ROVINADIL

• If you are allergic to enoxaparin sodium or to any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction include: rash, difficulty swallowing or breathing, swelling of the lips, face, throat, or tongue.
• If you are allergic to heparin or to other low molecular weight heparins such as nadroparin, tinzaparin, or dalteparin.
• If you have previously had a reaction to heparin that caused a severe drop in the number of blood cells responsible for clotting (platelets) (this reaction is called heparin-induced thrombocytopenia), within the last 100 days, or if you have antibodies against enoxaparin in your blood.
• If you are actively bleeding or have a condition with a high risk of bleeding (such as a stomach ulcer, recent brain or eye surgery), including recent hemorrhagic stroke.
• If you are using ROVINADIL to treat blood clots in the body and you are scheduled to receive spinal or epidural anaesthesia or a lumbar puncture within 24 hours.

Warnings and precautions
ROVINADIL must not be used interchangeably with other medicines belonging to the group of
low molecular weight heparins. These medicines are not identical and do not have the
same activity or usage instructions.
Consult your doctor before using ROVINADIL if:

• you have ever had a reaction to heparin causing a significant drop in platelet count
• you need to undergo spinal or epidural anaesthesia or lumbar puncture (see Surgery and anaesthesia): observe the recommended time interval between ROVINADIL use and this procedure
• you have had a heart valve implanted
• you suffer from endocarditis (an infection of the inner lining of the heart)
• you suffer from a stomach ulcer
• you have recently had a stroke
• you have high blood pressure
• you have diabetes or diabetic eye vessel problems (so-called diabetic retinopathy)
• you have recently undergone eye or brain surgery
• you are elderly (over 65 years of age), particularly if over 75
• you have kidney problems
• you have liver problems
• you are underweight or overweight
• you have high levels of potassium in your blood (levels can be checked with a blood test)
• you are currently taking medicines that may affect bleeding (see the following section – Other medicines).

You may need to have a blood test before starting this medicine and regularly during treatment to monitor your platelet count (blood cells responsible for clotting) and blood potassium levels.
Children and adolescents
The safety and efficacy of enoxaparin have not been established in children or adolescents.
Other medicines and ROVINADIL
Inform your doctor or pharmacist if you are taking or might take any other medicines.

• Warfarin – used to thin the blood.
• Aspirin (also known as acetylsalicylic acid or ASA), clopidogrel, or other medicines used to prevent blood clots (see also section 3, Switching anticoagulant medicines).
• Dextran injection – used as a blood substitute.
• Ibuprofen, diclofenac, ketorolac, or other medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) – used to treat pain and swelling in arthritis and other conditions.
• Prednisolone, dexamethasone, or other medicines used to treat asthma, rheumatoid arthritis, and other conditions.
• Medicines that increase potassium levels in the blood, such as potassium salts, diuretics, and some medicines for heart conditions. Surgery and anaesthesia If you are scheduled for a spinal puncture or a surgical procedure involving epidural or spinal anaesthesia, inform your doctor that you are using ROVINADIL. See the section "Do not use ROVINADIL". Also inform your doctor if you have any spinal problems or have previously undergone spinal surgery.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medicine.
If you are pregnant and have a mechanical heart valve, you may be at increased risk of developing blood clots. Your doctor will discuss this with you.
If you are breastfeeding or planning to breastfeed, consult your doctor before taking this medicine.
Driving and using machines
ROVINADIL does not affect the ability to drive or operate machinery.
Healthcare professionals are advised to record the brand name and batch number of the product you are using.
ROVINADIL contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially 'sodium-free'.

3. How to use ROVINADIL

Use this medicine exactly as your doctor has instructed. If you have any doubts, consult your doctor or pharmacist.

Administration of the medicine

• ROVINADIL is usually administered by a doctor or nurse, as it must be given by injection.
• When discharged from hospital, you may need to continue using ROVINADIL and therefore may have to self-administer it (see instructions below on how to do so).
• ROVINADIL is usually administered by subcutaneous (under the skin) injection.
• ROVINADIL may be administered by intravenous (into a vein) injection following certain types of heart attack or surgical procedures.
• ROVINADIL may be added to the arterial line (the tube draining blood from the body) at the beginning of each dialysis session. Do not administer ROVINADIL into a muscle.

How much medicine will be administered

• Your doctor will decide how much ROVINADIL you should receive. The amount depends on why it is being administered.

1. Treatment of blood clots present in the bloodstream.

   • The usual dose is 150 IU (1.5 mg) per kilogram of body weight per day or 100 IU (1 mg) per kilogram of body weight twice daily.
   • Your doctor will decide how long you should receive ROVINADIL.

2. Prevention of blood clot formation in the following situations:

   • Surgical procedures or periods of reduced mobility due to illness

     • The dose depends on how likely a clot is to develop. You will receive 2,000 IU (20 mg) or 4,000 IU (40 mg) of ROVINADIL daily.
     • If surgery is planned, the first injection is usually given 2 hours or 12 hours before the operation.
     • In cases of reduced mobility due to illness, 4,000 IU (40 mg) of ROVINADIL is usually administered daily.
     • Your doctor will decide how long you should receive ROVINADIL.

   • After a heart attack
     ROVINADIL may be used for two different types of heart attack called STEMI (ST-segment elevation myocardial infarction) or Non-STEMI (NSTEMI). The amount of ROVINADIL administered depends on your age and the type of heart attack experienced.

     • NSTEMI heart attack:

       • The recommended dose is 100 IU (1 mg) per kilogram of body weight every 12 hours.
       • Your doctor will usually also ask you to take aspirin (acetylsalicylic acid).
       • Your doctor will decide how long you should take ROVINADIL.

     • STEMI heart attack if you are under 75 years of age:

       • An initial dose of 3,000 IU (30 mg) of ROVINADIL will be administered as an intravenous injection.
       • At the same time, you will also receive ROVINADIL as a subcutaneous (under the skin) injection. The usual dose is 100 IU (1 mg) per kilogram of body weight every 12 hours.
       • Your doctor will usually also ask you to take aspirin (acetylsalicylic acid).
       • Your doctor will decide how long you should take ROVINADIL.

     • STEMI heart attack if you are 75 years of age or older:

       • The recommended dose is 75 IU (0.75 mg) per kilogram of body weight every 12 hours.
       • The maximum amount of ROVINADIL administered for the first two injections is 7,500 IU (75 mg).
       • Your doctor will decide how long you should receive ROVINADIL.

   • For patients undergoing a procedure called percutaneous coronary intervention (PCI):
     Depending on when ROVINADIL was last administered, your doctor may decide to administer an additional dose of ROVINADIL before a percutaneous coronary intervention. The medicine will be injected into a vein.

3. Prevention of clot formation in dialysis machine tubing.

   • The recommended dose is 100 IU (1 mg) per kilogram of body weight.
   • ROVINADIL is added to the arterial line (the tube draining blood from the body) at the beginning of the dialysis session. This amount is usually sufficient for a 4-hour session. However, your doctor may administer an additional dose of 50–100 IU (0.5–1 mg) per kilogram of body weight if necessary.

Instructions for using the syringe
How to administer your ROVINADIL injection

If you are able to self-administer ROVINADIL, your doctor or nurse will show you how to do it. Do not attempt to administer the dose with the syringe unless you have been properly trained. If you have any doubts, consult your doctor or nurse immediately. Administering the injection correctly under the skin (called "subcutaneous injection") will help reduce pain and bruising at the injection site.

Before injecting ROVINADIL

• Gather the items you need: syringe, alcohol swab or soap and water, and a sharps container.
• Check the expiry date on the medicine. Do not use it if the date has passed.
• Check that the syringe is undamaged and that the medicine inside is a clear, transparent solution. If not, use another syringe.
• Make sure you know how much medicine you are to inject.
• Check your abdomen to see if the last injection caused redness, skin discoloration, swelling, oozing, or if it is still painful. If so, consult your doctor or nurse.

Instructions for self-injection of ROVINADIL:
(Instructions for syringes without safety device)
Injection site preparation

1. Choose an area on the right or left side of your abdomen. It should be at least 5 centimeters away from the navel and on the outer side towards the hips.

• Do not administer the injection within 5 cm of the navel or near scars or bruises.
• Change the injection site between the right and left sides of the abdomen, depending on the location of the last injection.

2. Wash your hands. Clean (without rubbing) the injection site with an alcohol swab or with soap and water.
3. Sit or lie down in a comfortable position so that you are relaxed. Make sure you can clearly see the injection site. A padded chair, armchair, or bed supported with pillows is ideal.

Dose selection

1. Carefully remove the needle cap from the syringe. Discard the cap.

• Do not press the plunger before injection to remove air bubbles. This may result in loss of medicine.
• Once the cap is removed, avoid letting the needle touch any other objects to ensure it remains clean (sterile).

2. When the amount of medicine in the syringe matches the prescribed dose, no dose adjustment is needed. The syringe is ready for injection.
3. If the dose depends on body weight, you may need to adjust the dose in the syringe to match the prescribed amount. In that case, you can remove excess medicine by holding the syringe downward (to keep the air bubble in the syringe) and expelling the excess into a container.
4. A drop may appear at the tip of the needle. If so, remove the drop before injection by gently tapping the syringe with the needle pointing downward. The syringe is now ready for injection.

Injection

1. Hold the syringe in your writing hand (like a pencil). With the other hand, gently pinch the cleaned area of your abdomen between your index finger and thumb to create a skin fold.

• Make sure to keep the skin fold throughout the injection.

2. Hold the syringe so that the needle points straight down (vertically at a 90° angle). Insert the full length of the needle into the skin fold.

3. Press the plunger with your thumb to deliver the medicine into the fatty tissue of the abdomen. Complete the injection by using all the medicine in the syringe.
4. Remove the needle from the injection site by pulling it straight out. Point the needle away from yourself and anyone else present. Release the skin fold.

When finished

1. To avoid bruising, do not rub the injection site after administering the injection.
2. Dispose of the used syringe in a sharps container. Close the container lid tightly and place it out of reach of children. When the container is full, dispose of it according to your doctor’s or pharmacist’s instructions.

Unused medicine and waste material from this medicine must be disposed of in accordance with local regulations.

If you feel the dose is too strong (e.g., if you experience unexpected bleeding) or too weak (e.g., the dose does not seem effective), speak with your doctor or pharmacist.

Instructions for syringes with safety device:
Injection site preparation

1. Choose an area on the right or left side of your abdomen. It should be at least 5 centimeters away from the navel and on the outer side towards the hips.

• Do not administer the injection within 5 cm of the navel or near scars or bruises.
• Change the injection site between the right and left sides of the abdomen, depending on the location of the last injection.

2. Wash your hands. Clean (without rubbing) the injection site with an alcohol swab or with soap and water.
3. Sit or lie down in a comfortable position so that you are relaxed. Make sure you can clearly see the injection site. A padded chair, armchair, or bed supported with pillows is ideal.

Dose selection

1. Carefully remove the needle cap from the syringe. Discard the cap.

• Do not press the plunger before injection to remove air bubbles. This may result in loss of medicine.
• Once the cap is removed, avoid letting the needle touch any other objects to ensure it remains clean (sterile).

2. When the amount of medicine in the syringe matches the prescribed dose, no dose adjustment is needed. The syringe is ready for injection.
3. If the dose depends on body weight, you may need to adjust the dose in the syringe to match the prescribed amount. In that case, you can remove excess medicine by holding the syringe downward (to keep the air bubble in the syringe) and expelling the excess into a container.
4. A drop may appear at the tip of the needle. If so, remove the drop before injection by gently tapping the syringe with the needle pointing downward. The syringe is now ready for injection.

Injection

1. Hold the syringe in your writing hand (like a pencil). With the other hand, gently pinch the cleaned area of your abdomen between your index finger and thumb to create a skin fold.

• Make sure to keep the skin fold throughout the injection.

2. Hold the syringe so that the needle points straight down (vertically at a 90° angle). Insert the full length of the needle into the skin fold.

3. Press the plunger with your thumb to deliver the medicine into the fatty tissue of the abdomen. Complete the injection by using all the medicine in the syringe.
4. Remove the needle from the injection site by pulling it straight out. Point the needle away from yourself and anyone else present. The safety mechanism is activated by firmly pressing the plunger rod. The protective shield will automatically cover the needle and produce an audible "click" confirming activation of the device. Release the skin fold.

When finished

1. To avoid bruising, do not rub the injection site after administering the injection.
2. Dispose of the used syringe in a sharps container. Close the container lid tightly and place it out of reach of children. When the container is full, dispose of it according to your doctor’s or pharmacist’s instructions.

Changing anticoagulant treatment

• Switching from ROVINADIL to anticoagulants known as vitamin K antagonists (e.g. Warfarin)
  Your doctor will prescribe blood tests called INR and will instruct you when to stop taking ROVINADIL.
• Switching from anticoagulants known as vitamin K antagonists (e.g. Warfarin) to ROVINADIL
  Stop taking vitamin K antagonists. Your doctor will prescribe blood tests called INR and will tell you when to start taking ROVINADIL.
• Switching from ROVINADIL to treatment with a direct oral anticoagulant
  Stop taking ROVINADIL. Start taking the direct oral anticoagulant 0–2 hours before the time the next injection was due, then continue as usual.
• Switching from treatment with a direct oral anticoagulant to ROVINADIL
  Stop taking the direct oral anticoagulant. Do not start treatment with ROVINADIL until 12 hours after taking the final dose of the direct oral anticoagulant.

If you use more ROVINADIL than you should
If you think you have used too much or too little ROVINADIL, inform your doctor, nurse or pharmacist immediately, even if you do not notice any signs of problems. If a child accidentally injects or swallows ROVINADIL, take them immediately to the emergency room.

If you forget to use ROVINADIL
If you forget to take a dose, take it as soon as you remember. Do not take a double dose on the same day to make up for the missed dose. Keeping a diary will help you avoid missing doses.

If you stop using ROVINADIL
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.
It is important that you continue your ROVINADIL injections for as long as your doctor has prescribed them. If you stop, a blood clot may form, which could be very dangerous.

4. Possible side effects

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

As with other similar medicines (medicines used to reduce blood clotting), ROVINADIL may cause bleeding, which could potentially be life-threatening. In some cases, bleeding may not be obvious.

If you experience any type of bleeding that does not stop on its own, or if you notice signs of excessive bleeding (severe weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), consult your doctor immediately.

Your doctor may decide to monitor you closely or switch your medication.

Stop using enoxaparin and consult a doctor immediately if you notice any of the following symptoms:

• Any sign of a severe allergic reaction (such as difficulty breathing, swelling of the lips, mouth, throat, or eyes)
• A widespread red, scaly rash with bumps under the skin and blisters accompanied by fever. Symptoms usually appear early in treatment (acute generalized exanthematous pustulosis). You must inform your doctor immediately.
• Signs of a blood vessel blockage caused by a blood clot, such as:
  • Cramping pain, redness, warmth, or swelling in one of the legs – signs of deep vein thrombosis
  • Shortness of breath, chest pain, fainting, or coughing up blood – signs of pulmonary embolism.
• If you develop a painful rash with dark red spots under the skin that do not fade when pressed. Your doctor may ask you to have a blood test to check your platelet count.

General list of possible side effects:

Very common (may affect more than 1 in 10 people)

• Bleeding
• Increased liver enzymes

Common (may affect up to 1 in 10 people)

• Bruising more easily than usual. This may be due to a blood disorder with low platelet count
• Pink spots on the skin. These are more likely to appear in the area where ROVINADIL was injected
• Skin rash (bumps, hives)
• Itchy, red skin
• Bruising or pain at the injection site
• Decrease in red blood cells
• High number of platelets in the blood
• Headache

Uncommon (may affect up to 1 in 100 people)

• Sudden, severe headache, which may be a sign of bleeding in the brain
• Pain and swelling in the stomach. You may have bleeding in the stomach
• Large, irregular red skin lesions with or without blisters
• Skin irritation (local irritation)
• Yellowing of the skin or eyes and darker urine. This may indicate a liver problem

Rare (may affect up to 1 in 1,000 people)

• Severe allergic reaction. Signs may include rash, difficulty swallowing or breathing, swelling of the lips, face, throat, or tongue
• Increased potassium levels in the blood. This is more likely in people with kidney problems or diabetes. Your doctor may monitor this with a blood test
• Increased number of eosinophils in the blood. Your doctor may monitor this with a blood test
• Hair loss
• Osteoporosis (a condition that makes bones more fragile) after prolonged use
• Tingling, numbness, and muscle weakness (particularly in the lower part of the body) if you undergo spinal puncture or receive spinal anaesthesia
• Loss of bladder or bowel control (i.e. inability to control when you need to go to the toilet)
• Hard mass or nodule at the injection site

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at: www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ROVINADIL

Store below 25 °C. Do not freeze.
Pre-filled syringes are for single use only. Dispose of any unused medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of that month.
Do not use this medicine if you notice that the syringe is damaged or if the solution is not clear.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What ROVINADIL contains

• The active substance is enoxaparin sodium.

Each pre-filled syringe contains enoxaparin sodium with 2,000 IU anti-Xa activity (equivalent to 20 mg)
in 0.2 mL of water for injections.
Each pre-filled syringe contains enoxaparin sodium with 4,000 IU anti-Xa activity (equivalent to 40 mg)
in 0.4 mL of water for injections.
Each pre-filled syringe contains enoxaparin sodium with 6,000 IU anti-Xa activity (equivalent to 60 mg)
in 0.6 mL of water for injections.
Each pre-filled syringe contains enoxaparin sodium with 8,000 IU anti-Xa activity (equivalent to 80 mg)
in 0.8 mL of water for injections.
Each pre-filled syringe contains enoxaparin sodium with 10,000 IU anti-Xa activity (equivalent to 100 mg)
in 1 mL of water for injections.

• The other ingredient is water for injections.

Description of the appearance of ROVINADIL and contents of the pack
ROVINADIL is a clear, colourless to pale yellow solution for injection in a pre-filled syringe made of
Type I glass with an injection needle and with or without an automatic safety device. It is supplied as follows:
ROVINADIL 2,000 IU (20 mg) in 0.2 mL solution for injection in a 0.5 mL non-graduated pre-filled syringe.
Packs of 2, 6, 10, 20 and 50 syringes.
ROVINADIL 4,000 IU (40 mg) in 0.4 mL solution for injection in a 0.5 mL non-graduated pre-filled syringe.
Packs of 2, 6, 10, 20, 30 and 50 syringes.
ROVINADIL 6,000 IU (60 mg) in 0.6 mL solution for injection in a 1 mL graduated pre-filled syringe.
Packs of 2, 6, 10, 12, 24, 30 and 50 syringes.
ROVINADIL 8,000 IU (80 mg) in 0.8 mL solution for injection in a 1 mL graduated pre-filled syringe.
Packs of 2, 6, 10, 12, 24, 30 and 50 syringes.
ROVINADIL 10,000 IU (100 mg) in 1 mL solution for injection in a 1 mL graduated pre-filled syringe.
Packs of 2, 6, 10, 12, 24, 30 and 50 syringes.
Not all pack sizes may be marketed.
In some packs, the pre-filled syringes may be supplied with a safety device.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder
Laboratorios Farmacéuticos ROVI, S.A.
Julián Camarillo, 35
28037 - Madrid (Spain)
Manufacturer
ROVI Pharma Industrial Services S.A.
Julián Camarillo, 35
28037 - Madrid (Spain)

This medicinal product is authorised in the European Economic Area (EEA) Member States and in the United Kingdom (Northern Ireland) under the following names:
Austria, Bulgaria, Czech Republic, Denmark, Estonia, Greece, Spain, Finland, Germany, Croatia, Hungary, Latvia, Netherlands, Norway, Poland, Portugal, Romania, Sweden, Slovakia, United Kingdom (Northern Ireland): Crusia
France: Enoxaparine Crusia
Italy: Rovinadil
Belgium, Ireland, Slovenia, Luxembourg: Teuro