HEPARIN SODIUM ROVI 5000 IU/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Sodium Heparin ROVI 5,000 IU/ml Solution for Injection

Sodium Heparin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Sodium Heparin ROVI 5,000 IU/ml Solution for Injection and what is it used for
2. What you need to know before you use Sodium Heparin ROVI 5,000 IU/ml Solution for Injection
3. How to use Sodium Heparin ROVI 5,000 IU/ml Solution for Injection
4. Possible side effects
5. Storage of Sodium Heparin ROVI 5,000 IU/ml Solution for Injection
6. Contents of the pack and other information

1. What is Sodium Heparin ROVI 5,000 IU/ml Solution for Injection and what is it used for

Sodium Heparin belongs to a group of medicines called antithrombotics, i.e., those used to prevent and treat the formation of blood clots (thrombi).

This medicine is presented as a solution for injection, with a concentration of sodium heparin of 5,000 IU/ml, in 5 ml vials.

This medicine is indicated for:

• Treatment and prevention of venous thromboembolic disease: deep vein thrombosis, pulmonary thromboembolism.
• Treatment and prevention of peripheral arterial thromboembolism.
• Treatment of coronary artery disease: unstable angina and acute myocardial infarction.
• Prevention of thrombosis in the extracorporeal circuit during cardiac and vascular surgery and hemodialysis.

Sodium Heparin ROVI is indicated in pediatric population from 28 days of birth and in adults (see section 2).

2. What you need to know before you use Sodium Heparin ROVI 5,000 IU/ml Solution for Injection

Do not use Sodium Heparin ROVI 5,000 IU/ml Solution for Injection

• If you are allergic to sodium heparin, substances of porcine origin, or any of the other components of this medicine (listed in section 6).
• If you have a history of or suspected decrease in platelet count (thrombocytopenia).
• If you have a disease or condition that involves a risk of bleeding, such as a significant disorder of blood coagulation, vascular fragility, or injuries that may bleed, such as active gastroduodenal ulcer, cerebral hemorrhage, aneurysms, or brain tumors.
• If you have a severe liver or pancreatic disorder.
• If you are going to undergo surgery or have suffered damage to the central nervous system, eyes, or ears.
• If you have an infection in the heart called acute bacterial endocarditis.
• If you have a disease called Disseminated Intravascular Coagulation (DIC) due to a decrease in platelet count caused by heparin.
• If you have received heparin for treatment purposes, it is contraindicated to use regional anesthesia in scheduled surgical interventions.
• In premature and newborn infants, due to the content of benzyl alcohol in this medicine.
• If you are bleeding or have a high risk of bleeding due to problems with blood coagulation.

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Sodium Heparin ROVI 5,000 IU/ml Solution for Injection

• If you have a disease or injury that may bleed, such as uncontrolled hypertension, history of gastroduodenal ulcer, in case of vascular eye disease (choroid or retina), kidney or urethra stones, or if you have recently undergone surgery.
• If you have liver or kidney disease.
• If you have high potassium levels in the blood, as may occur if you have diabetes, chronic kidney disease, acidosis in the blood, or if you are taking medications that alter these levels, such as some diuretics. Your doctor may recommend monitoring your potassium levels.
• If you have or have had low platelet count (thrombocytopenia). Your doctor may recommend monitoring your platelet count.
• If you are going to undergo a procedure with spinal or epidural anesthesia, or if you are going to undergo a lumbar puncture.
• If skin degeneration occurs at the injection site when administered subcutaneously.
• If administered to the elderly, special caution should be exercised due to the risk of increased bleeding.
• If administered to low-birth-weight neonates, special caution should be exercised due to the risk of cerebral bleeding.
• If administered to women during breastfeeding, special caution should be exercised due to the risk of bone alterations.
• If you are going to receive other agents by intramuscular route, due to the risk of hematomas during heparin administration.

Other Medicines and Sodium Heparin ROVI 5,000 IU/ml Solution for Injection

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

It is especially important that you inform your doctor if you are taking any of the following medicines:

• Anticoagulants, antiplatelet agents (ticlopidine), fibrinolytics, non-steroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, paracetamol, or ibuprofen, glucocorticoids, dextran, high doses of penicillin, and some cephalosporins (cefamandole, cefoperazone), some contrast media, asparaginase, and epoprostenol, as these medications increase the effect of heparin with a consequent increase in the risk of bleeding.

• Alprostadil, as it may potentiate the anticoagulant effect of heparin and increase the risk of hemorrhage, in addition to altering the results of analytical tests that are performed.

• Oral antidiabetics (sulfonylureas), medications containing benzodiazepines (chlordiazepoxide, diazepam, oxazepam), or propranolol, as their effect may be increased in the presence of heparin.

• Epoetin or intravenous nitroglycerin, as they may decrease the anticoagulant effect of heparin and may require dose adjustment.

• Drugs that increase potassium levels in the blood.

Pregnancy and Breastfeeding

Pregnancy:

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Heparin will be administered with caution and under continuous monitoring, especially during the last trimester of pregnancy, interrupting it one or two days before the expected delivery date, due to the risk of fetal-maternal hemorrhage.

Breastfeeding:

Before starting treatment with Sodium Heparin ROVI 5,000 IU/ml Solution for Injection, inform your doctor if you are breastfeeding. Sodium Heparin ROVI 5,000 IU/ml Solution for Injection is not excreted in breast milk.

Use in Elderly

If this medicine is administered to the elderly, there is a greater risk of bleeding (especially in women), particularly if the patient also suffers from liver and/or kidney failure.

Driving and Using Machines

Sodium Heparin ROVI 5,000 IU/ml Solution for Injection does not affect the ability to drive or use machines.

Sodium Heparin ROVI 5,000 IU/ml Solution for Injection contains Benzyl Alcohol

This medicine should not be administered to premature or newborn infants because it contains 10 mg/ml of benzyl alcohol. It can cause toxic reactions and allergic reactions in children under 3 years of age.

3. How to use Sodium Heparin 5,000 IU/ml Solution for Injection

Follow the instructions for administration of this medicine exactly as indicated by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

The vials containing Sodium Heparin ROVI 5,000 IU/ml Solution for Injection are ready for immediate use by intravenous route (in continuous infusion with perfusion pump or in bolus form), intra-arterial, or subcutaneous route. It should not be administered by intramuscular route, and the intramuscular injection of other agents should be avoided due to the risk of hematoma during treatment with sodium heparin.

Your doctor will perform regular checks to monitor the doses. Follow the instructions unless your doctor has given you different instructions.

Your doctor will indicate the duration of your treatment with Sodium Heparin ROVI 5,000 IU/ml Solution for Injection. Do not stop treatment without consulting your doctor.

The dose of sodium heparin must be individualized according to the patient's weight and clinical situation. It must also be adjusted according to the coagulation time or the activated partial thromboplastin time (APTT).

In the section "Information intended for healthcare professionals only" at the end of this leaflet, the doses to be used for the different populations are detailed.

Adults:

Your doctor will adjust the dose according to the coagulation times.

Pediatric population:

Children from 28 days of birth

The doctor will adjust the dose according to the weight and the required APTT levels.

Elderly patients:

Your doctor will adjust the dose according to the weight and the required APTT levels.

Patients with renal and hepatic impairment:

A lower dose may be necessary. Your doctor will adjust the dose according to the weight and the required APTT levels.

Pregnant women:

Your doctor will adjust the dose according to the required APTT levels.

Instructions for the correct administration of the specialty:

Deep subcutaneous route:

Take a skin fold, without pressing, between the thumb and index finger of one hand. Maintaining this fold, insert the needle perpendicularly to the skin fold with the other hand, i.e., at a right angle to the skin. Carefully introduce the needle and slowly inject the necessary dose into the fatty tissue of the skin. Remove the needle after injection, pressing the application site for a few minutes. It is recommended to rotate the area to avoid the formation of edema.

If you use more Sodium Heparin ROVI 5,000 IU/ml Solution for Injection than you should

You may experience some type of bleeding. In this case, consult your doctor or go to the emergency department of the nearest hospital, accompanied by this leaflet. The bleeding can be reversed with 1% protamine sulfate.

In case of overdose or accidental administration, consult the Toxicology Information Service. Phone 91 562 04 20.

If you forget to use Sodium Heparin ROVI 5,000 IU/ml Solution for Injection

Do not administer a double dose to make up for the forgotten dose, and consult your doctor as soon as possible to indicate what to do in these cases.

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

4. Possible Side Effects

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

The following side effects have been observed:

Frequent side effects (affect 1 to 10 users in 100):

• Hemorrhagic complications, especially when high doses are administered. If you notice nasal bleeding, bleeding in the urine, stools, or any other type of bleeding, consult your doctor or go to the emergency department of the nearest hospital, with this leaflet. The bleeding can be reversed with 1% protamine sulfate.
• Alterations in liver function test results (increased serum levels of hepatic transaminases).

Uncommon side effects (affect 1 to 10 users in 1,000):

• Allergic skin manifestations (redness, itching).
• Hair loss (alopecia) in long-term treatments.
• Osteoporosis.
• Decrease in blood platelet count (thrombocytopenia).
• Increased serum potassium levels in case of kidney disease or diabetes.
• Suppression of aldosterone synthesis (hyperkalemia).

Rare side effects (affect 1 to 10 users in 10,000):

• Skin degeneration at the injection site, if administered subcutaneously.
• Severe general allergic reactions (nausea, vomiting, fever, difficulty breathing, bronchospasm, throat swelling, decreased blood pressure).
• Persistent erection of the penis (priapism).
• Severe decrease in blood platelet count of immunological origin (type II thrombocytopenia).

Very rare side effects (affect less than 1 user in 10,000):

• In very rare cases, if you have been treated with anticoagulant medications and undergo epidural or spinal anesthesia, bleeding may occur in the spinal canal. This can damage the nerves, causing loss of strength or sensation in the legs or lower half of the body.

If this occurs, stop treatment immediately and consult your doctor or go to the emergency department of the nearest hospital, with this leaflet.

If you experience side effects, consult your doctor or pharmacist, even if it is a side effect not listed in this leaflet.

Reporting of Side Effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Sodium Heparin ROVI 5,000 IU/ml Solution for Injection

Keep this medicine out of the sight and reach of children.

Do not store above 30°C.

Once the vial is opened, administer the product immediately.

Do not use this medicine after the expiry date which is stated on the packaging after EXP. The expiry date is the last day of the month indicated.

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

6. Container Contents and Additional Information

Composition of Heparin Sodium ROVI 5,000 IU/ml Injectable Solution

• The active ingredient is heparin sodium.
• The other components are sodium chloride, benzyl alcohol (10 mg/ml), sodium hydroxide, and water for injectable preparations.

Appearance of the Product and Container Contents

Colorless, transparent solution, free from visible particles.

Containers with 1 or 50 vials of 5 ml of injectable solution.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization 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

LABORATORIOS FARMACÉUTICOS ROVI, S.A.

Julián Camarillo, 35

28037-Madrid

Spain

Date of the Last Revision of this Prospectus:October 2023

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended only for healthcare professionals:

The recommended dose varies depending on the different indications, being in each case the following:

Adults:

Treatment of thromboembolic disease: deep vein thrombosis, pulmonary thromboembolism, and peripheral arterial thromboembolism:

An initial intravenous bolus of 80 IU/kg of heparin sodium will be administered, which may be increased to 120 IU/kg in cases of severe pulmonary embolism. This initial dose should be followed by a maintenance dose, administered by continuous intravenous infusion, of 18 IU/kg. Subsequently, the dose must be individualized and adjusted according to the activated partial thromboplastin time (APTT), which should be maintained between 1.5 and 2.5 times the control value. Control should be performed 4-6 hours after starting the infusion and at similar intervals whenever it is necessary to vary the administered dose. A treatment duration of 5-10 days is recommended.

In the prevention of venous thromboembolic disease, 5,000 IU will be administered subcutaneously every 8-10 hours for 7 days or until the patient is ambulatory.

In surgical patients, the first injection will be administered 1-2 hours before the intervention.

In non-surgical patients, the duration of treatment will coincide with the duration of the thromboembolic risk.

Unstable angina or acute myocardial infarction without thrombolytic therapy:

An initial intravenous bolus of 5,000 IU of heparin sodium is recommended, followed by 32,000 IU/24h in continuous intravenous infusion adjusted according to APTT.

Acute myocardial infarction after thrombolytic therapy:

An initial intravenous bolus of 5,000 IU of heparin sodium is recommended, followed by 24,000 IU/24h in continuous intravenous infusion adjusted according to APTT.

Prevention of thrombosis in the extracorporeal circulation circuit during cardiac surgery and hemodialysis:

Cardiac surgery:It is recommended to heparinize the patient with 150-300 IU/kg, varying the dose based on the coagulation tests performed to control anticoagulation levels.

Hemodialysis:Before starting dialysis, a bolus injection of 25-30 IU/kg is administered, followed by a continuous infusion of 1,500-2,000 IU per hour throughout the hemodialysis session. The heparin infusion is stopped approximately 30 minutes before the end of the dialysis process to allow for recovery of hemostasis before removing the catheter.

Pediatric population:

Children from 28 days of age:It is recommended to adjust the dose according to weight and required APTT levels. In general, for anticoagulation, 80 IU/kg will be administered in a bolus, followed by 18 IU/kg/h, adjusting the dose to maintain an APTT between 1.5 and 2.5 times the control value.

Due to the presence of benzyl alcohol in the composition, the maximum daily amount of Heparin Sodium ROVI in children under 3 years of age must be less than 9 ml of injectable solution/kg/day.

Elderly patients:

It is recommended to adjust the dose according to weight and required APTT levels.

Renal and hepatic impairment:

A lower dose may be necessary. It is recommended to adjust the dose according to weight and required APTT levels.

Pregnant women:

Prevention of venous thromboembolic disease:The administration of 5,000 IU subcutaneously every 8-12 hours is usually adequate in the first months of pregnancy, and doses of up to 10,000 IU every 12 hours may be necessary during the third trimester of pregnancy.

Careful monitoring according to APTT is advised.

Treatment of venous thromboembolic disease:It is recommended to administer heparin in an intravenous bolus followed by continuous infusion to maintain APTT levels in the therapeutic range for at least 5 days, and subsequently subcutaneous doses every 12 hours adjusted to therapeutic APTT values, throughout the remainder of pregnancy.

Prophylaxis in pregnant women with heart valves:It is recommended to administer subcutaneous heparin every 12 hours at doses adjusted to maintain APTT values in the therapeutic range.