Leaflet: information for the user

Alprostadil Altan 20 micrograms powder for solution for infusionEFG

Read this leaflet carefully before you start using this medicine, because 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, pharmacist or nurse.
• This medicine has been prescribed for you only, and you must not give it to otherseven if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet.Seesection4.

The active ingredient of this medication is prostaglandin E1 (alprostadil) whose hemodynamic properties and antiplatelet aggregation action justify its use in the treatment of severe peripheral vascular disease.

This medication is indicated for the treatment of lower limb arteriosclerotic occlusive arteriopathy in stages III and IV of Leriche-Fontaine, excluding patients who are candidates for amputation.

No use Alprostadil Altan

• If you are allergic to alprostadil or any of the other components of this medication (listed in section 6)
• Patients with heart function deterioration, such as patients with a New York Heart Association (NYHA) classification of III and IV heart failure, hemodynamically relevant arrhythmia, uncontrolled coronary disease, mitral and/or aortic valve stenosis and/or insufficiency. History of myocardial infarction in the last six months.
• Severe hypotension (low blood pressure)
• Acute pulmonary edema (fluid accumulation in the lungs) or history of pulmonary edema in patients with heart failure.
• Severe chronic obstructive pulmonary disease (COPD) (chronic limitation of airflow) or pulmonary veno-occlusive disease (PVOD) (obstruction of pulmonary veins)
• Disseminated pulmonary infiltration.
• Tendency to bleed, such as patients with acute erosive ulcers or gastric and/or duodenal hemorrhage.
• History of stroke in the last six months.
• Patients with renal dysfunction (oliguria)
• Patients with signs of acute liver failure (elevated transaminases or gamma GT) or known severe liver insufficiency (including history of the first)
• General contraindication for treatment with infusion (such as congestive heart failure, pulmonary or cerebral edema, and hyperhydration)
• Patients in whom bleeding complications may be expected (e.g. recent gastrointestinal ulcer, polytrauma)
• Aortic or mitral valve stenosis and/or insufficiency
• Postpartum period
• Pre-intra and post-operative
• Pregnant women, lactating women, or women who may become pregnant
• Children and adolescents

Caution should be taken when administering the product to high-risk patients (see section "Warnings and precautions").

Warnings and precautions:

Consult your doctor, pharmacist, or nurse before starting to use Alprostadil Altan.

General precautions

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.

Administration with precautions

Patients receiving alprostadil should be closely monitored during each dose. Frequent controls of cardiovascular function should be performed, including monitoring of blood pressure, heart rate, and fluid balance. Before discharging a patient, they must have a stable cardiovascular condition.

Patients with renal insufficiency should be closely monitored (e.g. fluid balance and renal function tests).

Patients who, due to age, may have a tendency to develop heart failure, or those with peripheral edema or renal insufficiency (creatinine > 1.5 mg/dL), should remain hospitalized under medical supervision during and until one day after treatment with this medication.

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. Alprostadil should not be administered by bolus injection.

Alprostadil should not be administered to women who may become pregnant.

The use of Alprostadil Altan in pediatric patients is not recommended.

The use of Alprostadil Altan in patients with severe liver insufficiency is contraindicated.

Children and adolescents

Alprostadil Altan is contraindicated in children and adolescents.

Use of Alprostadil Altan with other medications

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

Since alprostadil has vasodilatory properties and is, in vitro, a weak inhibitor of platelet aggregation, precautions should be taken in patients receiving other vasodilators or anticoagulants concomitantly. 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.

The treatment with Alprostadil Altan may potentiate the effect of hypotensive medications (antihypertensives), vasodilators, and medications used to treat ischemic heart disease.

Patients receiving these treatments and Alprostadil Altan concomitantly require strict cardiovascular monitoring.

The concomitant administration of Alprostadil Altan and anticoagulants and antiplatelet agents may increase the risk of bleeding.

In most clinical trials, the administration of antiplatelet agents was suspended during treatment with Alprostadil Altan to facilitate a more accurate assessment of its efficacy. Consequently, there is insufficient data on the concomitant use of both medications, and their joint administration should be excluded.

Pregnancy and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Alprostadil Altan should not be administered to women who may become pregnant, are pregnant, or breastfeeding.

Women of childbearing age treated with Alprostadil 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 Altan may cause a decrease in systolic blood pressure and may therefore have a moderate influence on the ability to drive and operate machinery. Patients should be warned of this possibility and informed of the need to be cautious when driving a vehicle or operating machinery.

Follow exactly the administration instructions of the medication contained in this leaflet or those indicated by your doctor, pharmacist, or nurse.In case of doubt, ask your doctor, pharmacist, or nurse.

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

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

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

40 micrograms/12 hours: Dissolve the contents of 2 vials of Alprostadil Altan (equivalent to 40micrograms ofalprostadil) in 50-250 ml of physiological saline solution and infuse the resulting solution intravenously for a period of at least 2 hours.

60 micrograms/24 hours: Dissolve the contents of 3 vials of Alprostadil Altan (equivalent to 60micrograms ofalprostadil) in 50-250 ml of physiological saline solution and infuse the resulting solution intravenously for a period of 3 hours.

Renal insufficiency:

In patients with renal insufficiency (creatinine > 1.5 mg/dL) treatment should start with a vial of Alprostadil Altan (equivalent to 20microgramsof alprostadil) by intravenous infusion for 2-3 hours, twice a day. After 2-3 days, depending on the general clinical condition, the dose may be increased to the normal dose. In patients with renal insufficiency as well as in patients with heart failure, the total infusion volume should not exceed 50-100 ml/day.

Liver insufficiency:

The use of Alprostadil Altan in patients with severe liver insufficiency is contraindicated.

Older patients:

It is recommended to use the usual dose.

Use in children and adolescents

Alprostadil Altan is contraindicated in children and adolescents.

Administration guidelines

See NORMAS DE ADMINISTRACIÓN PARA EL PROFESIONAL SANITARIO section.

If you use more Alprostadil Altan than you should

Given its administration method, it is unlikely that poisoning will occur. However, in case of accidental overdose, consult the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount administered.

Symptoms of overdose

In case of overdose, due to vasodilatory effects, hypotension (low blood pressure) and reflex tachycardia (rapid heart rate) may occur. In addition, the following systemic symptoms may occur: vasovagal reactions (stimuli from the vagus nerve in blood vessels) with pallor, sweating, nausea, and vomiting, heart failure, and myocardial ischemia (insufficient blood supply to the heart muscle). Locally at the infusion site, pain, swelling, and redness may occur.

Treatment of overdose

At the onset of symptoms of overdose (severe pain, low blood pressure) the dose of Alprostadil Altan should be reduced or the infusion should be stopped 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.

If you forgot to use Alprostadil Altan

Do not take a double dose to compensate for the missed doses.

If you have any other questions about the use of thismedication, ask your doctor,pharmacistor nurse.

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

The frequency of the possible side effects listed below is defined using the following classification:

Very common: can affect more than 1 in 10 people

Common: can affect up to 1 in 10 people

Uncommon: can affect up to 1 in 100 people

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

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

Unknown: the frequency cannot be estimated with the available data.

• Blood and lymphatic system disorders

-Uncommon: increase in C-reactive protein (CRP) that is normally present in trace amounts in the blood but increases during episodes of acute inflammation

-Rare: variations in white blood cell count (leucopenia or leucocytosis), thrombocytopenia (decreased platelet count).

• Nervous system disorders

-Common: headache.

-Uncommon: dizziness, weakness, fatigue.

-Rare: confusional states, seizures of cerebral origin

-Unknown: stroke

• Cardiac and vascular disorders

-Uncommon: decreased systolic blood pressure, tachycardia (rapid heartbeat), angina pectoris, palpitations.

-Rare: arrhythmias, biventricular heart failure.

-Unknown: myocardial infarction.

• Respiratory, thoracic and mediastinal disorders

-Common: apnea (temporary inability to breathe)

-Rare: pulmonary edema, bradypnea (abnormally slow breathing), hypercapnia (excessive carbon dioxide in the blood)

-Unknown: dyspnea (difficulty breathing or slow breathing)

• Gastrointestinal disorders

-Uncommon: gastrointestinal reactions (nausea, vomiting, diarrhea, abdominal pain); prostaglandin E1 properties (diarrhea, nausea, and vomiting).

-Rare: gastric mucosa hyperplasia, possible pyloric obstruction

-Unknown: gastrointestinal bleeding

• General disorders

-Very common: pain, headache, erythema or edema of the infused limb

-Common: pain, after intra-arterial administration: sensation of heat, sensation of swelling, localized edema, paresthesia (abnormal sensation of general sensitivity that translates into a sensation of tingling, numbness, aching, etc.).

-Uncommon: after intravenous administration: sensation of heat, sensation of swelling, localized edema, paresthesia; fever, sweating, intermittent fever.

-Very rare: anaphylactic/anaphylactoid reactions (generalized allergic reactions),

-Unknown: phlebitis at the injection site (inflammation of the vein wall at the injection site), thrombosis at the catheter insertion site, localized hemorrhage.

• Hepatobiliary disorders

-Rare: liver enzyme alterations.

• Musculoskeletal and connective tissue disorders

-Uncommon: joint pain

-Very rare: reversible hyperostosis of long bones in a small number of patients treated for a period exceeding 4 weeks.

• Skin and subcutaneous tissue disorders

-Common: erythema, edema, flushing, and rubor.

-Uncommon: skin allergic reactions such as rash (skin eruption), joint discomfort, febrile reactions, sweating, and chills).

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly to theSpanish System for the Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

Store the vials in the outer packaging to protect it from light. Do not store at a temperature above 25°C.

The reconstituted solution must be prepared immediately before use.

In sodium chloride 0.9% solution, Alprostadil Altan is stable at 2-8°C for 24 hours.

Composition of Alprostadil Altan

• The active ingredient is alprostadil 20 micrograms
• The other components are alpha-cyclodextrin and lactose monohydrate

Aspect of the product and content of the packaging

White or almost white powder

Alprostadil Altan 20 micrograms, powder for solution for infusion is packaged in boxes containing 1, 28 or 50 (clinical pack) vials of transparent type I glass of 8 ml capacity, bromobutyl rubber stopper.

Only some sizes of packaging may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Altan Pharmaceuticals S.A.

C/Colquide, Nº 6, Portal 2, 1st floor, Office F. Prisma Building

28230Las Rozas (Madrid)

Spain

Responsible for manufacturing

Altan Pharmaceuticals S.A.

Constitution Avenue 198-199, Monte Boyal Industrial Estate,

45950 Casarrubios del Monte (Toledo), Spain

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

Austria:Alprostadil Altan 20μg, Powder for the preparation of an infusion solution

Revision date of this leaflet: March 2018.

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This information is intended solely for healthcare professionals:

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

After 3 weeks of treatment, it should be decided whether the continuation of treatment is beneficial for the patient. If there has been no therapeutic response, treatment should be discontinued.

The treatment period should not exceed 4 weeks in total.

The solution should be prepared immediately before infusion. The reconstituted solution is stable for 24 hours at 2-8°C.

Precautions for use

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

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

The 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/.