Prospecto:Information for the Patient

Vazostenon 20 micrograms/ml Concentrate for Solution for Infusion

Alprostadil

Read this prospectus carefully before starting to use this medication,because it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor.

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

• If you experience any adverse effects, consult your doctor, even if they do not appear in this prospectus. See section 4.

1.What is Vazostenon and what is it used for

2.What you need to know before starting to use Vazostenon

3.How to use Vazostenon

4.Possible adverse effects

5Storage of Vazostenon

6.Contents of the package and additional information

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

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

No useVazostenon

• If you are allergic to the active ingredient or any of the other components of this medication (listed in section 6).
• If you have heart function deterioration, such as heart failure with shortness of breath during normal movement and difficulty breathing at rest, arrhythmia, uncontrolled coronary disease, high-level heart 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 limitation of airflow) or pulmonary veno-occlusive disease (PVOD) (obstruction of pulmonary veins)
• If you have disseminated pulmonary infiltration (due to pneumonia or sarcoidosis).
• If you have liver insufficiency, including signs of acute liver insufficiency (elevated transaminases or gamma GT) or with severe liver insufficiency known (including history of the first)
• If you have renal dysfunction (oliguria)
• If you have a tendency to suffer from hemorrhages, for example in case of multiple injuries.
• If you have active or potential bleeding, such as patients with gastric inflammation with superficial lesions (acute erosive gastritis) or active gastric and/or duodenal hemorrhage.
• If you have cerebral hemorrhage (intracerebral hemorrhage).
• If you have a history of stroke in the last six months.
• If you are pregnant, breastfeeding, or planning to become pregnant or have just given birth (postpartum period).
• Before, during, and after surgery.
• Children and adolescents
• If you have a general contraindication for treatment with perfusion (such as congestive heart failure, pulmonary or cerebral edema, and hyperhydration)

Warnings and precautions

Consult your doctor before starting to use Vazostenon.

This medication should only be administered under the doctor's indication, under strict specialized medical control, in centers with adequate equipment that allows cardiovascular monitoring of the patient.

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

Patients who, due to age, may have a tendency to develop heart failure, ischemic heart disease, peripheral edema, or renal insufficiency, should remain hospitalized under medical supervision during and until one day after treatment with this medication.

Patients withrenal insufficiencyshould be strictly monitored (e.g., fluid balance and renal function tests).

Alprostadil should only be administered by doctors experienced in the treatment of peripheral arterial occlusive disease and familiar with cardiovascular function monitoring, in suitable facilities. Alprostadilshould not be administered by bolus injection.

If you have heart failure, take medications that reduce blood pressure and have coronary artery disease, your cardiac parameters will be strictly monitored during treatment with alprostadil (see section “Other medications and Vazostenon”).

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

Care should be taken if takingmedicationsthatmay increase the risk of bleeding, such as anticoagulants or antiplatelet inhibitors. You will be strictly monitored for signs and symptoms of bleeding (see section “Other medications and Vazostenon”).

Women who may become pregnantshould use adequate contraceptive measures during treatment.

Children and adolescents

This medication is not recommended for use in children and adolescents.

Other medications and Vazostenon

Inform your doctor if you are using, have used recentlyor may need to use any other medication.

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

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

The taking of this medication at the same time as other medications that inhibit coagulation (anticoagulants, antiplatelet inhibitors) may increase bleeding. Since alprostadil is a weak antiplatelet agent, caution should be exercised if receiving anticoagulants at the same time.

Since alprostadil may increase the effect of blood pressure-lowering medications (such as antihypertensives, vasodilators), a thorough control of blood pressure should be performed in patients receiving these medications.

Pregnancy,breastfeedingand fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consultyour doctor before using this medication.

Alprostadil should not be administered to women who may become pregnant, are pregnant, or breastfeeding. Women of childbearing age treated withalprostadil should use effective contraceptive methods during treatment. Preclinical fertility studies and the recommended clinical dose of alprostadil do not predict effects on fertility.

Driving and operating machinery

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

Vazostenon contains ethanol

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

It is unlikely that the amount of alcohol contained in this medication will have a perceptible effect on adults.

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

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

Vazostenon should be administered only on the doctor's indication, under strict specialized medical supervision, in centers with adequate equipment. In this way, adequate monitoring of the patient during administration of this medication is allowed.

Alprostadil is dissolved in sodium chloride solution at 0.9% and administered through perfusion in the vein or artery.

Intravenous administration

The recommended dose is 40 micrograms/12 hours or 60 micrograms/24 hours through intravenous perfusion.

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

When the treatment response allows hospital discharge, the dose will pass to 60 micrograms/24 hours by IV perfusion.

Unless otherwise specified, the following dose regimen is recommended:

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

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

Patients with renal insufficiency:

In patients with renal insufficiency (GFR ≤ 89 ml/min/1.73 m2) treatment should start with one Vazostenon vial administered intravenously over 2-3 hours, twice a day (2 x 20 micrograms of alprostadil). After 2-3 days, depending on the general clinical condition, the dose can be increased to the normal dose.

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

Patients of advanced age:

It is recommended to use the usual dose for the treatment of patients over 65 years old.

Intraarterial administration

Unless otherwise specified, the following dose regimen is recommended:

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

As an initial dose, administer half a Vazostenon vial (10 micrograms of alprostadil) through intraarterial administration over a period of 1-2 hours using a perfusion pump. If necessary and if it is tolerable for the patient, the dose can be increased to one Vazostenon vial (20 micrograms of alprostadil). Generally, administer this dose once a day.

If intraarterial administration is performed through a catheter insertion, depending on tolerance and the severity of the disease, it is recommended to administer 0.1 to 0.6 nanograms/kg/min, administered through infusion pump over 12 hours (corresponding to a quarter of a vial or one and a half vials of Vazostenon, respectively).

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 in this time, treatment should be interrupted. The duration of treatment should not exceed 4 weeks.

Special populations

Patients with renal insufficiency:

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

Patients with renal insufficiency

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

Method of administration

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

Use in children and adolescents

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

If you use more Vazostenon than you should

Symptoms

Due to the vasodilatory effects, overdose with alprostadil can 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, reduce or immediately interrupt the perfusion. In case of hypotension, elevate the patient's legs. If symptoms persist, perform other cardiac diagnostic tests and consider the use of sympathomimetics.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Very common:may affect more than 1 in 10 people

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

Common:may affect up to 1 in 10 people

• Similar symptoms 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 heat.
• After an intraarterial administration: sensation of heat, sensation of swelling, localized edema, abnormal sensation of sensitivity.

Uncommon:may affect up to 1 in 100 people

• Dizziness, weakness, fatigue
• Decreased blood pressure (hypotension) irregular heartbeatofheartbeatschestpressure,palpitations.
• Gastrointestinal reactions including diarrhea, nausea, and vomiting and properties of alprostadil (diarrhea, nausea, vomiting).
• Increased activity of liver enzymes (transaminases), changes in the concentration of C-reactive protein in the blood.
• Sweating, chills, fever
• Allergic reactions (itchy rash, joint pain, fever, sweating, chills).
• Joint pain
• After an intravenous administration: sensation of heat, sensation of swelling, localized edema, redness of the vein, abnormal sensation of sensitivity.

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

• Variations in blood composition (thrombocytopenia, leukopenia, leukocytosis).
• Confusional states, convulsions
• Arrhythmias, heart failure.
• Pulmonary edema, abnormally slow breathing (bradypnea), excessive amounts of carbon dioxide in the blood (hypercapnia)
• Swelling of the gastric lining (hyperplasia of the antral mucosa), possible pyloric obstruction
• Liver enzyme alterations.

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

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

Unknown: the 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 (alteration of coagulation at the catheter insertion site), localized hemorrhage.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is about possible adverse effects that do not appear in this prospectus. You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting adverse effects, you can contribute to providing more information about the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears onthe boxafter CAD.The expiration date is the last day of the month indicated.

This medication must be stored and disposed of in a medical environment. Vazostenon should not be stored at home. The hospital pharmacist will store the medication 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 standpoint, unless the dilution method prevents microbial contamination risk, the product should be used immediately. If not used immediately, storage times and conditions before use are the responsibility of the user.

Composition of Vazostenon

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

Appearance of the product and contents of the container

Transparent and colourless solution in a 1 ml ampoule.

Containers with 5, 10 or 20 ampoules.

Only some sizes of containers may be marketed.

Holder of the marketing authorization and responsible for manufacturing

AS Kevelt

Teaduspargi 3/1

12618 Tallinn

Estonia

This medicine is authorized in the member states of the European Economic Area with the following names:

Portugal:Vazostenon

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

Last review date of thisleaflet:September 2023

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

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This information is intended solely 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 in this time, treatment should be discontinued. The duration of treatment should not exceed 4 weeks.

Method of administration

Vazostenon should be dissolved in a 0.9% sodium chloride solution and administered via intravenous or arterial infusion. This medicine should not be administered via bolus injection.

Precautions for use

In the event of the appearance of side effects, reduce the infusion rate or discontinue administration rapidly.

When using a perfusion pump, take great care to prevent air bubbles from entering the bag or syringe.

Handling and disposal

The solution should be prepared immediately before infusion.

The appropriate solution for diluting Vazostenon is a 0.9% sodium chloride solution. The concentrate dissolves after the addition of physiological serum, resulting in an immediately transparent and colourless solution. Compatibility with other solvents has not been determined.