VAZOSTENON 20 micrograms/ml concentrate for infusion solution

Introduction

Package Leaflet:information for the patient

Vazostenon 20 micrograms/ml concentrate for solution for infusion

Alprostadil

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 pack and other information

1. What is Vazostenon and what is it used for
2. What you need to know before you use Vazostenon
3. How to use Vazostenon
4. Possible side effects

5 Conservation of Vazostenon

1. Contents of the pack and further information

1. What is Vazostenon and what is it used for

Vazostenon contains the active substance alprostadil. Alprostadil dilates blood vessels and improves blood circulation.

Vazostenon is used for the treatment of critical peripheral ischemia (peripheral arterial occlusive disease in Fontaine stages III and IV) in adult patients in whom revascularization is not indicated or has not been successfully performed.

2. What you need to know before you use Vazostenon

Do not useVazostenon

• If you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• If you have impaired cardiac function, such as heart failure with dyspnea during normal movement and breathing difficulties at rest, arrhythmia, uncontrolled coronary artery disease, high-level cardiac valve defects. History of myocardial infarction in the last six months.
• If you have severe hypotension (low blood pressure)
• If you have heart failure, and there is suspicion of pulmonary edema (fluid accumulation in the lungs) or history of pulmonary edema.
• If you have severe chronic obstructive pulmonary disease (COPD) (chronic airflow limitation) or pulmonary veno-occlusive disease (PVOD) (obstruction of the pulmonary veins)
• If you have disseminated pulmonary infiltration (due to pneumonia or sarcoidosis).
• If you have liver failure, including signs of acute liver failure (elevated transaminases or gamma GT) or severe known liver failure (including history of the first)
• If you have renal dysfunction (oliguria)
• If you have a tendency to suffer from bleeding, for example in case of multiple injuries.
• If you have active or potential bleeding such as patients with stomach inflammation with superficial lesions (acute erosive gastritis) or active gastric and/or duodenal bleeding.
• If you have cerebral hemorrhage (intracerebral bleeding).
• If you have a history of stroke in the last six months.
• If you are pregnant, breastfeeding, or planning to become pregnant or have recently given birth (postpartum period).
• Before, during, and after an operation.
• Children and adolescents
• If you have a general contraindication for perfusion treatment (such as congestive heart failure, pulmonary edema, or cerebral edema and hyperhydration)

Warnings and precautions

Consult your doctor before starting to use Vazostenon.

This medicine should only be administered under the strict supervision of a specialized doctor, in centers with adequate equipment that allows for cardiovascular monitoring of the patient.

Patients receiving alprostadil should be closely monitored during each dose. Frequent checks of cardiovascular function, including blood pressure monitoring, heart rate, and fluid balance, should be performed. Weight monitoring, central venous pressure, or echocardiography may be required. Before discharge, the patient should have a stable cardiovascular condition.

Patient who, due to age, may be prone to developing heart failure, cardiac ischemic disease, peripheral edema, or renal failure, should remain hospitalized under medical supervision during and up to one day after treatment with this medicine.

Patient with renal failureshould be closely monitored (e.g., fluid balance and renal function tests).

Alprostadil should only be administered by doctors with experience in the treatment of peripheral arterial occlusive disease and who are familiar with the monitoring of cardiovascular functions, in suitable facilities. Alprostadil should not be administered by bolus injection.

If you have heart failure, take medication that reduces blood pressure, and have coronary artery disease, your cardiac parameters will be closely monitored during treatment with alprostadil (see section "Other medicines and Vazostenon").

Alprostadil should be used with caution in patients with a history of gastrointestinal disease, including erosive gastritis, gastrointestinal bleeding, and gastric and/or duodenal ulcers or with a history of intracerebral hemorrhage or other bleeding.

Caution should be exercised if you are taking medicinesthat may increase the risk of bleeding, such as anticoagulants or platelet aggregation inhibitors. You will be closely monitored for signs and symptoms of bleeding (see section "Other medicines and Vazostenon"). Women who may become pregnantshould use adequate contraceptive measures during treatment.

Children and adolescents

Alprostadil is not recommended for use in children and adolescents.

Other medicines and Vazostenon

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

The effects of the following medicines may be increased if taken at the same time as Vazostenon: medicines that reduce blood pressure (such as antihypertensives, vasodilators) and medicines used to treat coronary heart disease.

As alprostadil has vasodilatory properties (widening of blood vessels), precautions should be taken in patients receiving other vasodilators concomitantly.

Taking this medicine at the same time as other medicines that inhibit coagulation (anticoagulants, antiplatelet agents) may increase bleeding. Since alprostadil is a weak antiplatelet agent, caution should be exercised if anticoagulants are taken at the same time.

As alprostadil may increase the effect of blood pressure-reducing drugs (such as antihypertensives, vasodilators), thorough blood pressure monitoring should be performed in patients receiving these drugs.

Pregnancy, breastfeeding, and fertility

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

Alprostadil should not be administered to women who may become pregnant, are pregnant, or are breastfeeding. Women of childbearing age treated with alprostadil should use effective contraceptive methods during treatment. Preclinical fertility studies have been performed, and at the recommended clinical dose of alprostadil, no effects on fertility are expected.

Driving and using machines

Alprostadil may cause a decrease in systolic blood pressure and may therefore have a moderate influence on the ability to drive and use machines. You should be cautious when driving a vehicle or operating machinery.

Vazostenon contains ethanol

This medicine contains 785 mg of alcohol (ethanol) in each dose unit, which is equivalent to 785 mg/ml (99.55% v/v). The amount in 1 ml of this medicine is equivalent to 20 ml of beer or 8 ml of wine.

It is unlikely that the amount of alcohol in this medicine will have a noticeable effect on adults.

The amount of alcohol in this medicine may alter the effect of other medicines. Consult your doctor if you are taking other medicines.

If you have an alcohol addiction, consult your doctor or pharmacist before taking this medicine.

3. How to use Vazostenon

Vazostenon should only be administered under the strict supervision of a specialized doctor, in centers with adequate equipment that allows for cardiovascular monitoring of the patient.

Alprostadil is dissolved in a 0.9% sodium chloride solution and administered by infusion into a vein or artery.

Intravenous administration

The recommended dose is 40 micrograms/12 hours or 60 micrograms/24 hours by intravenous infusion.

Initial dose: Treatments will start at a dose of 40 micrograms/12 hours by IV infusion.

When the response to treatment allows for hospital discharge, the dose will be 60 micrograms/24 hours by IV infusion.

Unless otherwise specified, the following dosage regimen is recommended:

Dissolve the contents of 2 ampoules of Vazostenon (40 micrograms of alprostadil) in 50-250 ml of 0.9% sodium chloride solution and administer by intravenous infusion over 2 hours. This dose should be administered twice a day.

Alternatively, the contents of 3 ampoules of Vazostenon (60 micrograms of alprostadil) can be dissolved in 50-250 ml of 0.9% sodium chloride solution and administered by intravenous infusion over 3 hours, once a day.

Patient with renal failure:

In patients with renal failure (TFG ≤ 89 ml/min/1.73 m2) treatment should start with one ampoule of Vazostenon by intravenous infusion over 2-3 hours, twice a day (2 x 20 micrograms of alprostadil). After 2-3 days, depending on the overall clinical condition, the dose may be increased to the normal dose.

In patients with renal failure as well as in patients with heart failure, the total infusion volume should not exceed 50-100 ml/day and a perfusion pump should be used for administration (see "Warnings and precautions").

Elderly patients:

The usual dose is recommended for the treatment of patients over 65 years of age.

Intra-arterial administration:

Unless otherwise specified, the following dosage regimen is recommended:

Dissolve the contents of one ampoule of Vazostenon (20 micrograms of alprostadil) in 50 ml of 0.9% sodium chloride solution.

As an initial dose, administer half an ampoule of Vazostenon (10 micrograms of alprostadil) by intra-arterial infusion over a period of 1-2 hours using a perfusion pump. If necessary and if tolerated by the patient, the dose may be increased to one ampoule of Vazostenon (20 micrograms of alprostadil). In general, administer this dose once a day.

If intra-arterial administration is performed through an insertion catheter, depending on tolerability and disease severity, administration of 0.1 to 0.6 nanograms/kg/min is recommended, administered by infusion pump over 12 hours (corresponding to a quarter of an ampoule or one and a half ampoules of Vazostenon, respectively).

Duration of treatment

After 3 weeks of treatment with alprostadil, it should be decided whether it is clinically indicated to continue treatment. If no therapeutic effect has been achieved in this time, treatment should be discontinued. The duration of treatment should not exceed 4 weeks.

Special populations

Patient with renal failure:

Patient with mild renal failure (TFG ≤ 89 ml/min/1.73 m2) or moderate renal failure (TFG ≤ 59 ml/min/1.73 m2) should be closely monitored (e.g., fluid balance and renal function tests).

Patient with renal failure

Treatment with Vazostenon is contraindicated in patients with signs of acute renal failure or severe known liver failure.

Method of administration

See: Information for healthcare professionalsat the end of this leaflet.

Use in children and adolescents

Alprostadil should not be used in children and adolescents under 18 years of age.

If you use more Vazostenon than you should

Symptoms

Due to the vasodilatory effects, overdose with alprostadil may cause a decrease in blood pressure and reflex tachycardia (rapid heart rate).

In addition, the following systemic symptoms may occur: vasovagal reactions (stimuli from the vagus nerve in blood vessels) with pallor, sweating, nausea, and vomiting, myocardial ischemia, and heart failure.

Locally at the infusion site, pain, swelling, and redness may occur.

Treatment

If overdose or symptoms of overdose occur, the infusion should be reduced or discontinued immediately. In case of hypotension, the patient's legs should be elevated. If symptoms persist, further cardiac diagnostic tests should be performed and the use of sympathomimetics should be considered.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, telephone: 91 562 04 20, indicating the medicine and the amount ingested.

4. Possible side effects

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

Very common:may affect more than 1 in 10 people

• Pain at the injection site, redness of the skin (erythema) or edema of the infused limb after administration in the artery.

Common:may affect up to 1 in 10 people

• Symptoms similar to those with intravenous administration, additional redness of the vein.
• Headache, sensory disorders in the affected limb.
• Temporary inability to breathe (apnea)
• Redness of the skin, swelling, and feeling of heat.
• After intra-arterial administration: feeling of heat, feeling of swelling, localized edema, abnormal sensation.

Uncommon:may affect up to 1 in 100 people

• Dizziness, weakness, fatigue
• Decrease in blood pressure (hypotension), rapid heart rate (tachycardia), feeling of oppression in the chest (angina pectoris), palpitations.
• Gastrointestinal reactions including diarrhea, nausea, and vomiting, and properties of accelerated alprostadil (diarrhea, nausea, vomiting).
• Increased activity of liver enzymes (transaminases), changes in the concentration of C-reactive protein in blood.
• Sweating, chills, fever
• Allergic reactions (rash, itching, joint discomfort, fever, sweating, chills).
• Pain in the joints
• After intravenous administration: feeling of heat, feeling of swelling, localized edema, redness of the vein, abnormal sensation.

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

• Changes in blood composition (thrombocytopenia, leucopenia, leucocytosis).
• Confusional states, convulsions
• Arrhythmias, heart failure.
• Pulmonary edema, abnormally slow breathing (bradypnea), excessive carbon dioxide in the blood (hypercapnia)
• Swelling of the stomach lining (hyperplasia of the antral mucosa), possible pyloric obstruction
• Changes in liver enzymes.

Very rare:may affect up to 1 in 10,000 people

• Hypersensitivity reactions (anaphylactic or anaphylactoid reactions)
• Reversible hyperostosis of long bones

Not known:frequency cannot be estimated from the available data

• Stroke
• Heart attack (myocardial infarction), bleeding
• Difficulty breathing
• Bleeding from the stomach and/or intestine.
• Phlebitis, thrombosis at the injection site (coagulation disorder at the catheter insertion site), localized bleeding.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Agency's online platform: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Vazostenon

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

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

This medicine should be stored and disposed of in a medical environment. Vazostenon should not be stored at home. The hospital pharmacist will keep the medicine in the refrigerator (2-8°C), in the original packaging, to protect it from light.

Physical and chemical stability has been demonstrated for 12 hours at temperatures up to 20°C, protected from light. From a microbiological point of view, unless the method of dilution prevents the risk of microbial contamination, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user.

6. Container Content and Additional Information

Vazostenon Composition

• The active ingredient is alprostadil. Each 1 ml ampoule contains 20 micrograms of alprostadil.
• The other components are anhydrous ethanol

Product Appearance and Container Content

Transparent and colorless solution in a 1 ml ampoule.

Packaging with 5, 10, or 20 ampoules.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

AS Kevelt

Teaduspargi 3/1

12618 Tallinn

Estonia

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Portugal: Vazostenon

Spain: Vazostenon 20 micrograms/ml concentrate for solution for infusion

Date of the Last Revision of thisleaflet:September 2023

Detailed and updated information on this medicinal product is available on the website of the {Spanish Agency for Medicines and Health Products (AEMPS)} (http://www.aemps.gob.es/)

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This information is intended exclusively for healthcare professionals:

Treatment Duration

After 3 weeks of treatment with alprostadil, it should be decided whether it is clinically indicated to continue treatment. If no therapeutic effect has been achieved during this time, treatment should be discontinued. The treatment duration should not exceed 4 weeks.

Method of Administration

Vazostenon should be dissolved in a 0.9% sodium chloride solution and administered by venous or arterial infusion. This medicinal product should not be administered by bolus injection.

Precautions for Use

In the event of adverse effects, reduce the infusion rate or discontinue administration quickly.

When using an infusion pump, take maximum care to prevent air bubbles from entering the bag or syringe.

Handling and Disposal

The solution should be prepared immediately before infusion.

The suitable solution for dilution of Vazostenon is 0.9% sodium chloride solution. The concentrate dissolves after addition of the physiological serum, immediately obtaining a transparent and colorless solution. Compatibility with other solvents has not been determined.