Remodulin

REMODULIN, 1 mg/ml, solution for infusion
REMODULIN, 2.5 mg/ml, solution for infusion
REMODULIN, 5 mg/ml, solution for infusion
REMODULIN, 10 mg/ml, solution for infusion
Treprostinilum
Please read the following information carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor.
• This medicine has been prescribed for a specific individual only. Do not share it with others. This medicine may harm another person, even if their symptoms are similar.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

1. What Remodulin is and what it is used for
2. Important information before using Remodulin
3. How to use Remodulin
4. Possible side effects
5. How to store Remodulin
6. Contents of the pack and other information

1. What Remodulin is and what it is used for

What Remodulin is
The active substance in Remodulin is treprostinil.
Treprostinil belongs to a group of medicines that act similarly to naturally occurring prostacyclins in the body. Prostacyclins are hormone-like substances. They lower blood pressure by relaxing blood vessels, causing them to widen, thereby improving blood flow. In addition, prostacyclins may also help prevent blood clotting.

For what conditions is Remodulin used
Remodulin is used in the treatment of idiopathic or hereditary pulmonary arterial hypertension (PAH) in patients with moderate symptoms. Pulmonary arterial hypertension is a condition in which blood pressure is too high in the blood vessels between the heart and the 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 tolerate this infusion due to local pain and swelling. Your doctor will decide whether Remodulin can be administered as a continuous intravenous infusion via a central venous catheter connected to an external pump, or, depending on the patient's condition, via an implantable pump surgically placed under the abdominal skin (in the abdominal cavity). Your doctor will determine which option is best for you.

How Remodulin works
Remodulin lowers blood pressure in the pulmonary artery, improving blood flow and reducing the workload of the heart. Improved blood flow leads to better oxygen delivery to the body and reduces strain on the heart muscle, thereby enhancing cardiac efficiency. Remodulin alleviates symptoms associated with PAH and improves exercise tolerance in patients who must limit their physical activity.

2. Important information before using Remodulin

When not to use Remodulin

• If the patient is allergic to treprostinil or any of the other ingredients of this medicine (listed in section 6).
• If the patient has been diagnosed with pulmonary veno-occlusive disease. This is a condition in which blood vessels in the lungs become swollen and blocked, leading to increased blood pressure in the vessels between the heart and lungs.
• If the patient has severe liver disease.
• If the patient has heart diseases, e.g. myocardial infarction (heart attack) within the last six months, serious disturbances in heart rate, severe coronary artery disease or unstable angina pectoris, diagnosed heart defect such as valvular heart disease causing impaired heart function, or heart disease that is untreated or not under close medical supervision.
• If the patient is at significant risk of bleeding – for example, active peptic ulcer, wounds, or other types of bleeding.
• If the patient has had a stroke within the last 3 months or other cerebral circulation disorders.

Warnings and precautions
Before starting treatment with Remodulin, inform your doctor:

• if the patient has liver disease,
• if the patient has been medically diagnosed with obesity (BMI over 30 kg/m²),
• if the patient is infected with human immunodeficiency virus (HIV),
• if the patient has high blood pressure in the liver veins (portal hypertension),
• if the patient has a congenital heart defect affecting blood flow direction through the heart.

During treatment with Remodulin, inform your doctor if:

• low blood pressure (hypotension) occurs,
• sudden worsening of breathing difficulties or persistent cough develops (this may be related to pulmonary congestion, asthma, or another condition) – contact your doctor immediately,
• excessive bleeding occurs, as treprostinil may increase this risk due to its anticoagulant effect,
• fever, redness, swelling, and/or tenderness at the infusion site occurs during intravenous administration of Remodulin, as this may indicate infection.

Remodulin with other medicines
Inform your doctor about all medicines currently used, recently taken, or planned for use.
Inform your doctor if the patient is taking:

• medicines used to treat high blood pressure (antihypertensives or other vasodilators),
• medicines used to increase urine output (diuretics), including furosemide,
• medicines that prevent blood clotting (anticoagulants), such as warfarin, heparin, or nitric oxide-containing drugs,
• any non-steroidal anti-inflammatory drugs ( NSAIDs ) (e.g. acetylsalicylic acid, ibuprofen),
• any medicines that may increase or decrease the effect of Remodulin (e.g. gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St John’s wort), as dose adjustment of Remodulin may be necessary.

Pregnancy and breastfeeding
Remodulin is not recommended for women who are pregnant, planning pregnancy, or suspect they may be pregnant, unless the doctor considers its use necessary. The safety of Remodulin during pregnancy has not been established.
Remodulin is not recommended for women who are breastfeeding, unless the doctor considers its use necessary. If Remodulin is prescribed, breastfeeding should be discontinued, as it is unknown whether the drug passes into breast milk.
Effective contraception is strongly recommended during treatment with Remodulin.
If the patient is pregnant or breastfeeding, suspects pregnancy, or plans to become pregnant, she should consult her doctor before using this medicine.

Driving and operating machinery
Remodulin may cause low blood pressure with dizziness and fainting. In such cases, driving or operating machinery should be avoided, and medical advice should be sought.

Remodulin contains sodium
This medicine contains up to 78.4 mg of sodium (the main component of table salt) in each 20 ml. This corresponds to 4% of the maximum daily dietary sodium intake recommended by WHO for adults.

3. J R
Always use this medicine exactly as prescribed by your doctor. In case of doubt, consult your doctor.
Remodulin is administered as a continuous infusion:

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

In both cases, Remodulin is delivered through a line by an external portable pump placed outside the body.
Before discharge from hospital, the doctor will inform the patient how to prepare Remodulin and at what rate the pump should deliver it.
Filling of the connected infusion line may lead to accidental overdose.
Remodulin may also be administered intravenously using an implanted infusion pump, usually surgically placed under the skin of the abdomen (peritoneal cavity). In this case, the pump and tubing are entirely internal, and periodic hospital visits (e.g. every 4 weeks) will be required to refill the internal reservoir.
Additionally, the patient will receive instructions on how to properly use the pump and what to do in case of pump malfunction. These instructions should also include information on whom to contact in an emergency.
Remodulin is diluted only when administered intravenously in continuous infusion:
For intravenous administration using an external portable pump: The patient must dilute the Remodulin solution with sterile water for injection or 0.9% sodium chloride for injection (as directed by the doctor), but only when administered as a continuous intravenous infusion.
For intravenous administration using an implanted infusion pump: The patient must visit the hospital periodically (e.g. every 4 weeks), where a healthcare professional will dilute the Remodulin solution with 0.9% sodium chloride for injection and refill the internal reservoir.

Adults
Remodulin is available as a 1 mg/ml, 2.5 mg/ml, 5 mg/ml, or 10 mg/ml infusion solution. The doctor will determine the infusion rate and dose appropriate for the patient’s clinical condition.

Patients with obesity
If the patient has obesity (body weight exceeding ideal body weight by 30% or more), the doctor will determine the initial and subsequent doses based on target body weight. See also section 2 "Warnings and precautions".

Elderly patients
The doctor will determine the infusion rate and dose appropriate for the patient’s clinical condition.

Children and adolescents
Limited data are available on the use of this medicine in children and adolescents.

Dose modifications
The infusion rate may be individually increased or decreased only under medical supervision.
The aim of adjusting the infusion rate is to establish an effective maintenance dose that relieves symptoms of PAH while minimizing adverse effects.
Do not increase the dose without contacting your doctor if symptoms worsen, if the patient requires complete rest, is confined to bed or chair, or if any physical exertion causes discomfort and symptoms occur at rest.

Remodulin alone may be insufficient for treating the condition, and additional medicines may be required.

How to prevent bloodstream infections during intravenous treatment with Remodulin?
As with any long-term intravenous therapy, there is a risk of bloodstream infection. Your doctor will train you in preventing such infections.

Accidental overdose of Remodulin
If the patient accidentally receives more Remodulin than prescribed, symptoms such as nausea, vomiting, diarrhoea, low blood pressure (with dizziness, lightheadedness, or fainting), skin flushing, and/or headache may occur.
If any of these symptoms are severe, contact your doctor or hospital immediately. The doctor may reduce the dose or temporarily stop the infusion until symptoms resolve. The Remodulin infusion will then be restarted at the dose prescribed by the doctor.

Stopping treatment with Remodulin
Always use Remodulin exactly as directed by your doctor or hospital specialist. Do not stop using Remodulin without medical advice.
Sudden discontinuation or dose reduction of Remodulin may lead to recurrence of pulmonary arterial hypertension, possibly with rapid and severe clinical deterioration.
If you have any doubts about using this medicine, consult your doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.

Very common adverse reactions (may occur in more than 1 in 10 people):

• Vasodilation with skin flushing,
• Pain or tenderness at the infusion site,
• Skin discoloration or phlebitis around the infusion site,
• Headache,
• Skin rash,
• Nausea,
• Diarrhea,
• Jaw pain.

Common adverse reactions (may occur in up to 1 in 10 people):

• Dizziness,
• Vomiting,
• Lightheadedness or fainting due to low blood pressure,
• Tingling or redness of the skin,
• Swelling of the feet, ankles, legs, or fluid retention,
• Bleeding, e.g. nosebleeds, coughing up blood, blood in urine, bleeding from gums, blood in stool,
• Joint pain,
• Muscle pain,
• Pain in legs and (or) arms.

Other possible adverse reactions (frequency unknown – frequency cannot be estimated from 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 subcutaneous tissue (cellulitis),
• Excessive blood volume pumped by the heart leading to shortness of breath, fatigue, swelling of legs and abdomen due to fluid accumulation, persistent cough.

Additional adverse reactions associated with intravenous administration:

• Vein inflammation (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 of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the 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
Reporting adverse reactions helps to provide more information on the safety of the medicine.
Adverse reactions may also be reported to the marketing authorization holder.

5. How to store Remodulin

Keep this medicine out of the sight and reach of children.
No special precautions for storage of the medicinal product are required.
Do not use this medicine after the expiry date stated on the cardboard box and on the vial.
The expiry date refers to the last day of the specified month.
Do not use Remodulin if the vial is damaged, discoloured, or shows any other signs of deterioration.
The Remodulin vial should be used or discarded within 30 days of first opening.
During continuous subcutaneous infusion, one reservoir (syringe) of undiluted Remodulin must be used within 14 days.
During continuous intravenous infusion using an external portable infusion pump, one reservoir (syringe) of diluted Remodulin must be used within 24 hours.
During continuous intravenous infusion using an implanted infusion pump, diluted Remodulin placed in the reservoir must be used within 35 days. A healthcare professional at the hospital will inform the patient of the date to return to the hospital for the next reservoir refill.
Any unused portion of diluted solution must 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. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Remodulin contains

The active substance is treprostinil 1 mg/mL; 2.5 mg/mL; 5 mg/mL; 10 mg/mL.

Other ingredients include:
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, colourless or slightly yellow solution for infusion, supplied in a 20 mL vial made of colourless type I glass, closed with a bromobutyl rubber stopper, aluminium seal, and colour-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 cardboard box contains one vial.

Marketing Authorisation Holder and Manufacturer:

Marketing Authorisation 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