Vazosteon 20 micrograms/ml concentrate for solution for infusion

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

Vazostenon 20 micrograms/ml concentrate for solution for infusion

Alprostadil

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.

• If you have any questions, consult your doctor.

• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.

  • If you experience any adverse effects, consult your doctor, even if these adverse effects are not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Vazostenon is and what it is used for

2. What you need to know before using Vazostenon

3. How to use Vazostenon

4. Possible side effects

5. Storage of Vazostenon

6. Contents of the pack and other information

1. What Vazostenon is and what it is used for

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

Vazostenon is used for the treatment of critical limb ischaemia (occlusive peripheral arterial disease at 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 using Vazostenon

Do not use Vazostenon

• If you are allergic to the active substance or to any of the other components of this medicine (listed in section 6).
• If you have impaired cardiac function, such as heart failure with dyspnea during normal activity and breathing difficulty at rest, arrhythmia, poorly controlled coronary artery disease, severe valve defects, or a history of myocardial infarction within 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 a history of pulmonary edema.
• If you suffer from 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 known severe liver failure (including prior history).
• If you have renal dysfunction (oliguria).
• If you have a tendency to bleed, for example in cases of multiple injuries.
• If you have active or potential bleeding, such as patients with stomach inflammation and superficial lesions (acute erosive gastritis) or active gastric and/or duodenal hemorrhage.
• If you have brain hemorrhage (intracerebral bleeding).
• If you have a history of stroke within the last six months.
• If you are pregnant, breastfeeding, planning to become pregnant, or have recently given birth (postpartum period).
• Before, during, and after surgery.
• Children and adolescents.
• If you have general contraindications for infusion therapy (such as congestive heart failure, pulmonary or cerebral edema, or hyperhydration).

Warnings and precautions

Talk to your doctor before starting to use Vazostenon.

This medicine must be administered only under medical prescription and strict specialized medical supervision, in centers equipped to provide cardiovascular monitoring of the patient.

Patients receiving alprostadil must be closely monitored during each dose. Frequent monitoring of cardiovascular function should be performed, including blood pressure, heart rate, and fluid-electrolyte balance. Monitoring of body weight, central venous pressure, or echocardiography may be required. A patient should not be discharged until cardiovascular stability has been achieved.

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

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

Alprostadil should only be administered by physicians experienced in the treatment of peripheral arterial occlusive disease and familiar with cardiovascular monitoring, and only in appropriate medical facilities. Alprostadil must not be administered as a bolus injection.

If you have heart failure, are taking medications that lower blood pressure, or 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, or gastric and/or duodenal ulcer, or with a history of intracerebral hemorrhage or other bleeding.

Caution is advised if you are taking medicines that 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 could become pregnant should use adequate contraceptive measures during treatment.

Children and adolescents

The use of alprostadil is not recommended in children and adolescents.

Other medicines and Vazostenon

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

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

Since alprostadil has vasodilatory properties (widening of blood vessels), caution should be exercised in patients receiving other vasodilators concomitantly.

Taking this medicine together with other medicines that inhibit coagulation (anticoagulants, antiplatelets) may increase bleeding. Because alprostadil is a weak antiplatelet agent, caution should be exercised when it is administered together with anticoagulants.

Since alprostadil may enhance the effect of blood pressure-lowering drugs (such as antihypertensives, vasodilators), careful monitoring of blood pressure is required in patients receiving these drugs.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Alprostadil must not be administered to women who are or could become pregnant, are pregnant, or are breastfeeding. Women of childbearing potential receiving alprostadil should use effective contraceptive methods during treatment. Preclinical fertility studies have been conducted, and at the recommended clinical dose of alprostadil, effects on fertility are not expected.

Driving and using machines

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

Vazostenon contains ethanol

This medicine contains 785 mg of alcohol (ethanol) per dose unit, 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 any noticeable effect in adults.

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

If you are addicted to alcohol, consult your doctor or pharmacist before taking this medicine.

3. How to use Vazostenon

Vazostenon must be administered only under a physician's direction and under strict supervision by specialized medical personnel in centers equipped with appropriate facilities. This allows adequate monitoring of the patient during administration of this medicine.

Alprostadil is dissolved in 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: Treatment should be initiated at a dose of 40 micrograms/12 hours by IV infusion.

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

Unless otherwise specified, the following dosing regimen is recommended:

Dissolve the contents of 2 Vazostenon vials (40 micrograms of alprostadil) in 50–250 ml of 0.9% sodium chloride solution and administer intravenously over two hours. This dose should be given twice daily.

Alternatively, dissolve the contents of 3 Vazostenon vials (60 micrograms of alprostadil) in 50–250 ml of 0.9% sodium chloride solution and administer intravenously over three hours, once daily.

Patients with renal impairment:

In patients with renal impairment (eGFR ≤ 89 ml/min/1.73 m²), treatment should be initiated with one vial of Vazostenon administered intravenously over 2–3 hours, twice daily (2 × 20 micrograms of alprostadil). After 2–3 days, depending on the patient's general clinical condition, the dose may be increased to the normal dose.

In patients with renal impairment as well as in patients with cardiac insufficiency, the total infusion volume should not exceed 50–100 ml/day, and an infusion pump must 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.

Intraarterial administration:

Unless otherwise specified, the following dosing regimen is recommended:

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

As initial dose, administer half a vial of Vazostenon (10 micrograms of alprostadil) intraarterially over a period of 1–2 hours using an infusion pump. If necessary and if tolerated by the patient, the dose may be increased up to one full vial of Vazostenon (20 micrograms of alprostadil). In general, this dose should be administered once daily.

If intraarterial administration is performed via an indwelling catheter, depending on tolerability and severity of disease, administration of 0.1 to 0.6 nanograms/kg/min via infusion pump over 12 hours is recommended (corresponding to one-quarter of a vial or one and a half vials of Vazostenon, respectively).

Duration of treatment

After 3 weeks of treatment with alprostadil, a decision should be made whether continued treatment is clinically indicated. If no therapeutic effect has been achieved within this time, treatment should be discontinued. The duration of treatment should not exceed 4 weeks.

Special populations

Patients with renal impairment:

Patients with mild (eGFR ≤ 89 ml/min/1.73 m²) or moderate (eGFR ≤ 59 ml/min/1.73 m²) renal impairment should be closely monitored (e.g., electrolyte balance and renal function tests).

Patients with renal impairment

Vazostenon treatment is contraindicated in patients with signs of acute renal failure or known severe hepatic impairment.

Method of administration

See: Information for healthcare professionals at the end of this leaflet.

Use in children and adolescents

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

If you use more Vazostenon than you should

Symptoms

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

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

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

Treatment

If overdose occurs or symptoms of overdose appear, the infusion should be immediately reduced or stopped. 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 sympathomimetic agents should be considered.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medication and the amount ingested.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Very common: may affect more than 1 in 10 people

• Pain at the injection site, redness of the skin (erythema), or swelling (edema) of the infused limb following arterial administration.

Common: may affect up to 1 in 10 people

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

Uncommon: may affect up to 1 in 100 people

• Dizziness, weakness, fatigue.
• Decrease in blood pressure (hypotension), excessively rapid heartbeat (tachycardia), feeling of chest tightness (angina pectoris), palpitations.
• Gastrointestinal reactions including diarrhea, nausea, and vomiting, and prostaglandin E1-related properties (diarrhea, nausea, vomiting).
• Increase in liver enzyme activity (transaminases), changes in blood concentration of C-reactive protein.
• Sweating, chills, fever.
• Allergic reactions (rash, itching, joint discomfort, fever, sweating, chills).
• Joint pain.
• After intravenous administration: sensation of warmth, sensation of swelling, localized edema, redness of the vein, abnormal sensation of sensitivity.

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

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

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

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

Unknown frequency: cannot be estimated from the available data

• Stroke.
• Heart attack (myocardial infarction), hemorrhage.
• Difficulty breathing.
• Stomach and/or intestinal bleeding.
• Phlebitis, thrombosis at the injection site (coagulation disorder at the catheter insertion site), localized bleeding.

Reporting of adverse effects

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

5. Storage of Vazostenon

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

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the month indicated.

This medicine must be stored and disposed of in a medical setting. Vazostenon must not be stored at home. The hospital pharmacist will store the medicine in a refrigerator (2-8°C), in the original packaging, protected from light.

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

6. Contents of the pack and other information

Composition of Vazostenon

• The active substance is alprostadil. Each 1 ml ampoule contains 20 micrograms of alprostadil.
• The other component is anhydrous ethanol.

Nature of the product and pack contents

Clear, colourless solution in a 1 ml ampoule.

Pack sizes of 5, 10 or 20 ampoules.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

AS Kevelt
Teaduspargi 3/1
12618 Tallinn
Estonia

This medicinal product is authorized in the European Economic Area member states under the following names:

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

Date of the most recent review of this leaflet: September 2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

This information is intended for healthcare professionals only:

Duration of treatment

After 3 weeks of treatment with alprostadil, a decision should be made as to whether continued treatment is clinically indicated. If no therapeutic effect has been achieved within this time, treatment should be discontinued. The duration of treatment must not exceed 4 weeks.

Method of administration

Vazostenon must be diluted in 0.9% sodium chloride solution and administered by intravenous or intra-arterial infusion. This medicinal product must not be administered by bolus injection.

Precautions for use

If adverse effects occur, reduce the infusion rate or discontinue administration promptly.

When using an infusion pump, take maximum care to ensure that air bubbles do not enter the bag or syringe.

Handling and disposal

The solution must be prepared immediately before infusion.

The appropriate solution for diluting Vazostenon is 0.9% sodium chloride solution. The concentrate dissolves upon addition of physiological saline, immediately yielding a clear, colourless solution. Compatibility with other solvents has not been established.