TREPROSTINIL FERRER 1 mg/ml SOLUTION FOR INFUSION

2. What you need to know before starting to use Treprostinil Ferrer

Do not use Treprostinil Ferrer:

• if you are allergic to treprostinil or any of the other ingredients of this medicine (listed in section 6);
• if you have been diagnosed with a disease called "pulmonary veno-occlusive disease". In this disease, the blood vessels that carry blood through the lungs become swollen and blocked, increasing pressure in the blood vessels between the heart and lungs;
• if you have severe liver failure;
• if you have a heart problem, such as:
  • a heart attack in the last six months
  • severe changes in heart rate
  • severe coronary heart disease or unstable angina
  • a diagnosed heart defect, such as a faulty heart valve that causes the heart to malfunction
  • any untreated or closely monitored heart disease;

• if you have a high specific risk of bleeding, such as active stomach ulcers, injuries, or other bleeding disorders;
• if you have had a stroke in the last three months or any interruption of blood supply to the brain.

Warnings and precautions

Consult your doctor before starting to use Treprostinil Ferrer:

• if you have any liver disease
• if you have been told you are clinically obese (BMI over 30 kg/m2)
• if you have HIV infection
• if you have high blood pressure in the liver veins (portal hypertension)
• if you have a congenital heart defect that affects the way blood flows through it
• if you are on a low-salt diet

During treatment with this medicine, inform your doctor:

• if your blood pressure drops (hypotension)
• if you experience a rapid increase in breathing difficulties or persistent cough (may be related to pulmonary congestion, asthma, or other disease), consult your doctor immediately.
• if you experience excessive bleeding, as treprostinil may increase the risk by preventing blood clotting.
• if you have a fever while receiving treprostinil intravenously, or if the infusion site becomes red, swollen, or painful to the touch, as it may be a sign of infection

Using Treprostinil Ferrer with other medicines

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

Tell your doctor if you are taking:

• medicines to treat high blood pressure (antihypertensive medicines or other vasodilators)
• medicines used to increase the amount of urine excreted (diuretics), including furosemide
• medicines that prevent blood clotting (anticoagulants), such as products containing warfarin, heparin, or nitric oxide
• any non-steroidal anti-inflammatory drug (NSAID) (such as acetylsalicylic acid or ibuprofen)
• medicines that may increase or decrease the effect of treprostinil (such as gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St. John's Wort), as your doctor may need to adjust the dose of treprostinil.

Pregnancy and breastfeeding

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

Treprostinil is not recommended during pregnancy, unless your doctor considers it essential. The safety of this medicine for use during pregnancy has not been established.

Treprostinil is not recommended during breastfeeding, unless your doctor considers it essential. You are advised to stop breastfeeding if you are prescribed treprostinil, as it is unknown whether this medicine is excreted in breast milk.

It is highly recommended to use contraceptive methods during treatment with treprostinil.

Driving and using machines

Treprostinil Ferrer may cause low blood pressure, with dizziness and fainting. In this case, do not drive or operate machinery, and consult your doctor.

Treprostinil Ferrer contains sodium

This medicine contains up to 78.4 mg (3.41 mmol) of sodium (the main component of table salt/cooking salt) per 20 ml. This is equivalent to 4% of the maximum recommended daily intake of sodium for an adult.

3. How to use Treprostinil Ferrer

Follow the administration instructions of this medicine exactly as indicated by your doctor. If in doubt, consult your doctor again.

Treprostinil Ferrer is administered as a continuous infusion:

• Subcutaneously (under the skin) through a small tube (cannula) inserted in the abdomen or thigh; or
• Intravenously through a tube (catheter) usually inserted in the neck, chest, or groin.

In both cases, a portable pump pumps treprostinil through the tube.

Before leaving the hospital or clinic, your doctor will tell you how to prepare Treprostinil Ferrer and at what speed the pump should administer Treprostinil Ferrer. You will also be provided with information on how to use the pump correctly and what to do if it stops working. The information should also include contact persons in case of an emergency.

Flushing the infusion tube while connected can cause an accidental overdose.

Treprostinil Ferrer is diluted only when administered intravenously:

For intravenous infusion only:The Treprostinil Ferrer solution should only be diluted with sterile water for injection or a 0.9% sodium chloride solution for infusion if it is to be administered by continuous intravenous infusion.

Adult patients

Treprostinil Ferrer is available as a solution for infusion of 1 mg/ml, 2.5 mg/ml, 5 mg/ml, or 10 mg/ml. Your doctor will determine the infusion rate and suitable dose for your disease.

Overweight patients

If you are overweight (weigh 30% or more of your ideal body weight), your doctor will determine the initial and subsequent doses based on your ideal body weight. See section 2, "Warnings and precautions".

Elderly patients

Your doctor will determine the infusion rate and suitable dose for your disease.

Dose adjustment

The infusion rate in each individual patient may be reduced or increased only under medical supervision.

The goal of adjusting the infusion rate is to establish an effective maintenance rate that improves PAH symptoms while minimizing side effects.

If your symptoms worsen or if you need absolute rest, or are confined to bed or a chair, or if any physical activity causes discomfort and your symptoms appear at rest, do not increase the dose without consulting your doctor. It may be that treprostinil is no longer sufficient to treat your disease, and you may need another treatment.

How can bloodstream infections be avoided during intravenous administration of treprostinil?

As with all long-term intravenous treatments, there is a risk of contracting a bloodstream infection. Your doctor will tell you how to avoid them.

Use in children and adolescents

There is limited data available in children and adolescents.

If you use more Treprostinil Ferrer than you should

If treprostinil is accidentally administered in excess, you may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, fainting), flushing, or headache.

If any of these symptoms become severe, you should contact your doctor or hospital immediately. Your doctor may reduce the dose or interrupt administration until the symptoms disappear. Then, the administration of treprostinil will be resumed with the dose recommended by your doctor.

In case of overdose, consult your doctor or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount used.

If you stop treatment with Treprostinil Ferrer

Always use treprostinil as indicated by your doctor or hospital specialist. Do not stop using treprostinil unless your doctor tells you to.

Abrupt interruption or sudden reduction of the treprostinil dose can cause PAH to recur, with possible rapid and severe deterioration of your condition.

If you have any other questions about the use of this medicine, ask your doctor.

4. Possible side effects

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

Very common side effects (may affect more than 1 in 10 people)

• vasodilation with flushing
• pain or pain on palpation around the infusion site
• skin discoloration or bruising around the infusion site
• headaches
• skin rash
• nausea
• diarrhea
• jaw pain

Common side effects (may affect up to 1 in 10 people)

• dizziness
• vomiting
• dizziness or fainting due to low blood pressure
• itching or redness of the skin
• swelling of feet, ankles, legs, or fluid retention
• bleeding episodes such as nosebleeds, coughing up blood, blood in urine, bleeding gums, blood in stool
• joint pain
• muscle pain
• pain in a limb

Other possible side effects (Frequency not known (cannot be estimated from the available data))

• infection at the infusion site
• abscess at the infusion site

• reduction of blood clotting cells (platelets) in the blood (thrombocytopenia)

• bleeding at the infusion site
• bone pain
• skin rash with color change or bumps
• infection of the tissue under the skin (cellulitis)

• excessive blood flow from the heart, causing difficulty breathing, fatigue, swelling of legs and abdomen due to fluid accumulation, persistent cough.

Other side effects associated with intravenous administration

• vein inflammation (thrombophlebitis)
• bacterial infection in the bloodstream (bacteremia)*. See section 3.
• septicemia (severe bacterial infection of the blood)

• There have been reports of fatal and potentially fatal cases of bacterial infection in the bloodstream.

Reporting side effects

If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Treprostinil Ferrer

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

This medicine does not require special storage conditions.

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

Do not use this medicine if you notice damage to the vial, color change, or other signs of deterioration.

Treprostinil Ferrer vials should be discarded 30 days after opening.

During continuous subcutaneous infusion, a single container (syringe) of undiluted Treprostinil Ferrer should be used within 72 hours.

During continuous intravenous infusion, a single container (syringe) of diluted Treprostinil Ferrer should be used within 24 hours.

The diluted solution that is not used should be discarded.

For instructions on use, see section 3 "How to use Treprostinil Ferrer".

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicines in the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package contents and additional information

Composition of Treprostinil Ferrer

• The active ingredient is treprostinil 1 mg/ml, 2.5 mg/ml, 5 mg/ml, 10 mg/ml.

• The other ingredients are: sodium citrate (E-331iii), sodium chloride, sodium hydroxide (E-524), hydrochloric acid (E-507), metacresol, and water for injection.

Appearance and package contents

Treprostinil Ferrer is a clear, colorless to slightly yellowish solution, available in a 20 ml transparent glass vial closed with a rubber stopper and a colored cap:

• Treprostinil Ferrer 1 mg/ml solution for infusion has a yellow rubber cap.
• Treprostinil Ferrer 2.5 mg/ml solution for infusion has a blue rubber cap.
• Treprostinil Ferrer 5 mg/ml solution for infusion has a green rubber cap.
• Treprostinil Ferrer 10 mg/ml solution for infusion has a red rubber cap.

Each carton contains one vial.

Marketing authorization holder and manufacturer:

Marketing authorization holder:

Ferrer Internacional, S.A.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer:

Ferrer Internacional, S.A.

Joan Buscallà, 1-9

08173 - Sant Cugat del Vallès (Barcelona)

Spain

or

Kwizda Pharmadistribution GmbH

Achauerstrasse 2

2333 Leopoldsdorf

Austria

You can request more information about this medicine from the local representative of the marketing authorization holder:

Ferrer Farma, S.A.

Av. Diagonal nº 549 5ª planta

08029 Barcelona

Spain

Date of last approval of this leaflet: April 2021

Other sources of information

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).