ALPROSTADIL ALTAN 20 micrograms powder for solution for infusion

2. What you need to know before you use Alprostadil Altan

Do not use Alprostadil Altan

• If you are allergic to alprostadil or any of the other ingredients of this medicine (listed in section 6)
• Patient with impaired cardiac function, such as patients with grade III and IV heart failure according to the New York Heart Association (NYHA) classification, hemodynamically relevant arrhythmia, uncontrolled coronary artery disease, mitral and/or aortic 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 the pulmonary veins)
• Diffuse pulmonary infiltration
• Tendency to bleed, such as patients with acute erosive or gastric and/or duodenal bleeding
• History of stroke in the last six months
• Patient with renal dysfunction (oliguria)
• Patient with signs of acute liver failure (elevated transaminases or gamma GT) or with known severe liver failure (including history of the first)
• General contraindication for infusion treatment (such as congestive heart failure, pulmonary edema, or cerebral edema and hyperhydration)
• Patient in whom bleeding complications can be expected (e.g. recent gastrointestinal ulcer, polytrauma)
• Mitral and/or aortic stenosis and/or insufficiency
• Postpartum period
• Pre-, intra-, and postoperative
• Pregnant, breastfeeding, or potentially pregnant women
• Children and adolescents

Precautions should be taken when the product is administered to patients at risk (see "Warnings and precautions" section)

Warnings and precautions:

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

General precautions

This medicine should only be administered under strict medical supervision, in centers with adequate equipment to allow for cardiovascular monitoring of the patient

Administration with precautions

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

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

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

Alprostadil should only be administered by doctors with experience in the treatment of peripheral arterial occlusive disease and who are 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

It is not recommended to use Alprostadil in the pediatric population

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 medicines

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

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

Treatment with Alprostadil Altan may potentiate the effect of hypotensive (antihypertensive) medications, vasodilators, and medications used to treat ischemic heart disease

Patient receiving these treatments and Alprostadil Altan concomitantly require strict cardiovascular monitoring

The concomitant administration of Alprostadil Altan and anticoagulant and antiplatelet medications may increase the risk of bleeding

In most clinical trials, the administration of antiplatelet agents was suspended during treatment with Alprostadil Altan in order to facilitate a more accurate assessment of its efficacy. Consequently, there is not enough data on the concomitant use of both medications, and their combined administration should therefore be excluded

Pregnancy and fertility

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

Alprostadil Altan 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 Altan may cause a decrease in systolic blood pressure and may therefore have a moderate influence on the ability to drive and use machines. Patient should be warned of this possibility and advised to be cautious when driving a vehicle or operating machinery

3. How to use Alprostadil Altan

Follow exactly the administration instructions of the medicine contained in this leaflet or as indicated by your doctor, pharmacist, or nurse. If you are unsure, ask your doctor, pharmacist, or nurse

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

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

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

Renal insufficiency:

In patients with renal insufficiency (creatinine > 1.5 mg/dL), treatment should start with one vial of Alprostadil Altan (equivalent to 20 micrograms of alprostadil) intravenously over 2-3 hours, twice a day. After 2-3 days, depending on the overall 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

Hepatic insufficiency:

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

Elderly patients:

The usual dose is recommended

Use in children and adolescents

Alprostadil Altan is contraindicated in children and adolescents

Administration guidelines

See section ADMINISTRATION GUIDELINES FOR HEALTHCARE PROFESSIONALS

If you use more Alprostadil Altan than you should

Given its form of administration, it is unlikely that an overdose will occur. But in case of accidental overdose, consult the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount administered

Overdose symptoms

In case of overdose, due to the vasodilatory effects, hypotension (low blood pressure) and reflex tachycardia (rapid heart rate) may occur. Additionally, the following systemic symptoms may occur: vasovagal reactions (stimuli from the vagus nerve in the 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 overdose symptoms (severe pain, low blood pressure), the dose of Alprostadil Altan should be reduced or the infusion should be interrupted immediately. In case of hypotension, the patient's legs should be elevated. If symptoms persist, other cardiac diagnostic tests should be performed, and the use of sympathomimetics should be considered

If you forget to use Alprostadil Altan

Do not take a double dose to make up for forgotten doses

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

4. Possible side effects

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

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

Very common: may affect more than 1 in 10 people

Common: may affect up to 1 in 10 people

Uncommon: may affect up to 1 in 100 people

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

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

Not known: frequency cannot be estimated from the available data

• Blood and lymphatic system disorders

• Uncommon: increased C-reactive protein (CRP), which is normally present in traces in the blood serum but increases during episodes of acute inflammation
• Rare: variations in the white blood cell count (leukopenia or leukocytosis), thrombocytopenia (decrease in the number of circulating platelets)

• Nervous system disorders

• Common: headache
• Uncommon: dizziness, weakness, fatigue
• Rare: confusional states, convulsions of cerebral origin
• Not known: stroke

• Cardiac and vascular disorders

• Uncommon: decrease in systolic blood pressure, tachycardia (rapid heart rate), angina pectoris, palpitations
• Rare: arrhythmias, biventricular heart failure
• Not known: myocardial infarction

• Respiratory, thoracic, and mediastinal disorders

• Common: apnea (temporary inability to breathe)
• Rare: pulmonary edema, bradypnea (abnormally slow breathing), hypercapnia (excessive amounts of carbon dioxide in the blood)
• Not known: dyspnea (difficulty breathing or slow breathing)

• Gastrointestinal disorders

• Uncommon: gastrointestinal reactions (nausea, vomiting, diarrhea, abdominal pain); properties of acceleration of alprostadil (diarrhea, nausea, and vomiting)
• Rare: hyperplasia of the antral mucosa, possible pyloric obstruction
• Not known: stomach and/or intestinal bleeding

• General disorders

• Very common: pain, headache, erythema, or edema of the infused limb
• Common: pain, after intraarterial administration: sensation of heat, sensation of swelling, localized edema, paresthesia (abnormal sensation of general sensitivity that translates into a sensation of tingling, numbness, 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)
• Frequency not known: phlebitis at the injection site (inflammation of the vein wall at the injection site), thrombosis at the catheter insertion point, localized bleeding

• Hepatobiliary disorders

• Rare: alterations in liver enzymes

• Musculoskeletal and connective tissue disorders

• Uncommon: joint pain
• Very rare: in a very small number of patients treated for more than 4 weeks, reversible hyperostosis of long bones has been observed

• Skin and subcutaneous tissue disorders

• Common: erythema, edema, redness, and flushing
• Uncommon: allergic skin reactions such as rash (skin eruption), joint discomfort, febrile reactions, sweating, and chills

Reporting of side effects

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

5. Storage of Alprostadil Altan

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. The expiry date refers to the last day of the month stated

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

The reconstituted solution should be prepared immediately before use

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

6. Container Contents and Additional Information

Composition of Alprostadil Altan

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

Appearance of the Product and Container Contents

White or almost white powder

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

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Altan Pharmaceuticals S.A.

C/Colquide, Nº 6, Portal 2, 1ª planta, Oficina F. Edificio Prisma

28230 Las Rozas (Madrid)

Spain

Manufacturer

Altan Pharmaceuticals S.A.

Avda. de la Constitución 198-199, P.I. Monte Boyal,

45950 Casarrubios del Monte (Toledo), Spain

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

Austria: Alprostadil Altan 20μg, Pulver zur Herstellung einer Infusionslösung

Date of the last revision of this leaflet: March 2018.

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This information is intended exclusively for healthcare professionals:

INFORMATION FOR THE HEALTHCARE PROFESSIONAL

After 3 weeks of treatment, it should be decided whether continuation of the treatment is beneficial for the patient. If there has been no therapeutic response, the 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 adverse effects, reduce the infusion rate or suspend administration quickly.

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

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/.