Remodulin

1. What is Remodulin and what is it used for

What is Remodulin

The active substance of Remodulin is treprostinil.
Treprostinil belongs to a group of medicines that work in a similar way to naturally occurring prostacyclins. Prostacyclins are hormone-like substances. They lower blood pressure by relaxing blood vessels, causing them to widen and making it easier for blood to flow. Additionally, prostacyclins may also help prevent blood clotting.

What diseases is Remodulin used to treat

Remodulin is used to treat pulmonary arterial hypertension (PAH) in patients with moderate symptoms. Pulmonary arterial hypertension is a condition where the blood pressure is too high in the blood vessels between the heart and lungs, causing shortness of breath, dizziness, fatigue, fainting, palpitations or irregular heartbeat, dry cough, chest pain, and swelling of the ankles or legs.
Remodulin is initially administered as a continuous subcutaneous infusion. Some patients may not be able to tolerate such an infusion due to local pain and swelling. The doctor will decide whether Remodulin can be administered as a continuous intravenous infusion through a central venous catheter connected to an external pump or, depending on the patient's condition, an implantable pump surgically implanted under the abdominal skin. The doctor will decide which option is best for the patient.

How does Remodulin work

Remodulin lowers blood pressure in the pulmonary artery, improving blood flow and reducing the heart's workload. Improved blood flow leads to better oxygen supply to the body and reduces the strain on the heart muscle, improving the efficiency of the heart's work. Remodulin alleviates symptoms associated with PAH and improves exercise tolerance in patients who need to limit physical activity.

2. Important information before using Remodulin

When not to use Remodulin

• 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 pulmonary veno-occlusive disease. This is a disease where the blood vessels in the lungs become swollen and blocked, causing increased blood pressure in the vessels between the heart and lungs.
• If you have severe liver disease.
• If you have heart disease, such as a heart attack in the last six months, severe changes in heart rate, severe coronary artery disease, or unstable angina, a heart valve defect that impairs heart function, or heart disease that is not being treated or is not under close medical supervision.
• If you are at risk of significant bleeding - such as active stomach ulcers, injuries, or other types of bleeding.
• If you have had a stroke in the last three months or other blood flow disorders.

Warnings and precautions

Before starting treatment with Remodulin, you should tell your doctor:

• if you have liver disease,
• if you have been medically diagnosed with obesity (BMI over 30 kg/m),
• if you have an HIV infection,
• if you have high blood pressure in the liver veins (portal hypertension),
• if you have a congenital heart defect that affects blood flow through the heart.

During treatment with Remodulin, you should inform your doctor if:

• you experience low blood pressure (hypotension),
• you experience sudden difficulty breathing or persistent cough (may be related to pulmonary edema, asthma, or other disease), you should contact your doctor immediately,
• you experience excessive bleeding, as treprostinil may increase this risk due to its anti-clotting effect,
• you develop fever or redness, swelling, and (or) tenderness when touching the infusion site during intravenous administration, as this may be a sign of infection.

Remodulin and other medicines

You should tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
You should inform your doctor if you are taking:

• medicines used to treat high blood pressure(antihypertensive or other vasodilating medicines),
• medicines used to increase urine production(diuretics), including furosemide,
• medicines that prevent blood clotting(anticoagulants) such as warfarin, heparin, or nitric oxide,
• any non-steroidal anti-inflammatory drugs ( NSAIDs) (e.g., acetylsalicylic acid, ibuprofen),
• medicines that may increase or decrease the effect of Remodulin (e.g., gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St. John's Wort), as the dose of Remodulin may need to be adjusted by your doctor.

Pregnancy and breastfeeding

Remodulin is not recommended for women who are pregnant, planning to become pregnant, or suspect they are pregnant, unless the doctor considers it necessary. The safety of Remodulin in pregnant women has not been established.
Remodulin is not recommended for women who are breastfeeding, unless the doctor considers it necessary. If Remodulin is prescribed to a breastfeeding woman, it is recommended to stop breastfeeding, as it is not known whether the medicine passes into breast milk.
It is strongly recommended to use contraceptive measures during treatment with Remodulin.
If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor before using this medicine.

Driving and using machines

Remodulin may cause low blood pressure with dizziness and fainting. In such cases, you should not drive or operate machinery and should consult your doctor for advice.

Remodulin contains sodium

The medicine contains up to 78.4 mg of sodium (the main component of common salt) in each 20 ml. This corresponds to 4% of the maximum recommended daily intake of sodium in the diet of adults

3. How to use Remodulin

You should always use this medicine as directed by your doctor. If you have any doubts, you should consult your doctor.
Remodulin is administered as a continuous infusion:

• subcutaneously using a small tube (cannula) inserted under the skin of the abdomen or thigh of the patient or
• intravenously using a venous catheter in the neck, chest, or groin.

In both cases, Remodulin is pumped through a drain using a portable pump located outside the body (externally).
Before leaving the hospital, the doctor will inform the patient how to prepare Remodulin and at what rate the pump should deliver it.
Flushing the connected infusion line may cause accidental overdose.
Remodulin can also be administered intravenously using an implanted infusion pump, usually surgically implanted under the abdominal skin. In this case, the pump and tubes are completely inside (inside the body) and periodic hospital visits will be required (e.g., every 4 weeks) to refill the internal reservoir.
Additionally, the patient will receive information on how to properly use the pump and what to do in case of pump failure. The information provided should also include instructions on who to contact in case of an emergency.
Remodulin is diluted only in the case of intravenous administration in continuous infusion:
In the case of intravenous administration using a portable external infusion pump:The patient must dilute the Remodulin solution with sterile water for injections or 0.9% sodium chloride for injections (as directed by the doctor), only if the medicine is administered as a continuous intravenous infusion.
In the case of intravenous administration using an implanted infusion pump:The patient must periodically (e.g., every 4 weeks) visit the hospital, where a healthcare professional will dilute the Remodulin solution with 0.9% sodium chloride for injections and refill the internal reservoir.
Adult patients
Remodulin is available as a 1 mg/ml, 2.5 mg/ml, 5 mg/ml, or 10 mg/ml solution for infusion. The doctor will determine the infusion rate and dose suitable for the patient's clinical condition.
Patients with obesity
If the patient has obesity (body weight exceeds ideal body weight by 30% or more), the doctor will determine the initial dose and subsequent doses based on the target body weight. See also section 2 "Warnings and precautions".
Elderly patients
The doctor will determine the infusion rate and dose suitable for the patient's clinical condition.
Children and adolescents
There are limited data available on the use of Remodulin in children and adolescents.
Dose adjustments
The infusion rate can be decreased or increased individually only under medical supervision.
The goal of adjusting the infusion rate is to establish an effective maintenance dose that alleviates PAH symptoms while minimizing side effects.
If symptoms worsen or the patient requires complete rest or is limited to bed or chair rest, or if any physical exertion causes discomfort, and symptoms occur at rest, the dose should not be increased without consulting a doctor.
Remodulin may not be sufficient to treat the condition, and other medicines may be indicated.

How can blood infections be prevented during intravenous treatment with Remodulin?

As with any long-term intravenous treatment, there is a risk of blood infection.
The doctor will train the patient in preventing such infections.

Using a higher dose of Remodulin than recommended

If the patient accidentally overdoses on Remodulin, they may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, feeling of emptiness in the head, or fainting), flushing of the skin, and (or) headaches.
If any of these symptoms are severe, you should contact your doctor or hospital. The doctor may reduce the dose or stop the infusion until the symptoms subside. Then, the Remodulin solution for infusion will be administered again at the dose prescribed by the doctor.

Stopping treatment with Remodulin

You should always use Remodulin as directed by your doctor or a hospital specialist. You should not stop using Remodulin without your doctor's advice.
Sudden withdrawal or reduction of the Remodulin dose may cause a recurrence of pulmonary hypertension, with possible severe worsening of the patient's condition.
If you have any doubts about using the medicine, you should consult 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 of the skin,
• pain or tenderness at the infusion site,
• discoloration of the skin 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,
• feeling of emptiness in the head or fainting due to low blood pressure,
• tingling or flushing of the skin,
• swelling of the feet, ankles, legs, or fluid retention,
• bleeding, e.g., nosebleeds, coughing up blood, blood in urine, bleeding from the gums, blood in stool,
• joint pain,
• muscle pain,
• pain in the legs and (or) arms.

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

• infection at the infusion site,
• abscess at the infusion site,
• decreased platelet count (thrombocytopenia),
• bleeding at the infusion site,
• bone pain,
• skin rashes with discoloration or nodules,
• infection of the tissue under the skin (cellulitis),
• excessive blood pumped by the heart, leading to shortness of breath, fatigue, swelling of the legs and abdomen, caused by fluid accumulation, persistent cough.

Additional side effects related to intravenous administration

• phlebitis (thrombophlebitis),
• bacterial infection of the blood (bacteremia)* (see section 3),
• sepsis (severe blood infection).

* life-threatening or fatal bacterial blood infections have been reported.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: + 48 22 49 21 301; Fax: + 48 22 49 21 309;
Website: https://smz.ezdrowie.gov.pl
By reporting side effects, you can help provide more information on the safety of this medicine.
Side effects can also be reported to the marketing authorization holder.

5. How to store Remodulin

Store in a place inaccessible and invisible to children.

There are no special precautions for storing the medicinal product.
Do not use this medicine after the expiry date stated on the carton and on the vial.
The expiry date refers to the last day of the month stated.
Do not use Remodulin if you notice damage to the vial, discoloration, or other signs of deterioration.
The vial of Remodulin should be used or discarded within 30 days of first opening.
During continuous subcutaneous infusion, one container (syringe) of undiluted Remodulin must be used within 72 hours.
During continuous intravenous infusion using an external portable infusion pump, one container (syringe) of diluted Remodulin must be used within 24 hours.
During continuous intravenous infusion using an implanted infusion pump, the diluted Remodulin solution introduced into the reservoir must be used within 35 days. A healthcare professional in the hospital will each time provide the patient with the return date to the hospital for the next filling of the reservoir.
Unused diluted solution should be discarded.
Information on use is provided in section 3 "How to use Remodulin".
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.
6.

Contents of the pack and other information

What Remodulin contains

The active substance of Remodulin is treprostinil 1 mg/ml; 2.5 mg/ml; 5 mg/ml; 10 mg/ml.
Remodulin also contains:
sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid (concentrated), metacresol, and water for injections.

What Remodulin looks like and contents of the pack

Remodulin is a clear, colorless or slightly yellow solution, available in a 20 ml glass vial of type I, closed with a bromobutyl rubber stopper and an aluminum seal and a colored-coded cap.

• Remodulin 1 mg/ml solution for infusion with a yellow rubber cap.
• Remodulin 2.5 mg/ml solution for infusion with a blue rubber cap.
• Remodulin 5 mg/ml solution for infusion with a green rubber cap.
• Remodulin 10 mg/ml solution for infusion with 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

Kwizda Pharmadistribution GmbH
Achauerstrasse 2
Leopoldsdorf 2333 bei Wien
Austria

Date of last revision of the leaflet: 10/2024.