Tresuvi - Treprostinil uses, dose and side effects

Treprostinil belongs to a group of drugs that work in almost the same way as naturally occurring prostacyclins. Prostacyclins are hormone-like substances that lower blood pressure by causing the blood vessels to relax so that they widen, which makes blood flow easier. Prostacyclin er may also have an effect by preventing the blood from clotting.

What Tresuvi is used to treat

Tresuvi is used to treat idiopathic or hereditary pulmonary arterial hypertension (PAH) in patients with moderately severe symptoms. Pulmonary arterial hypertension is a condition where the blood pressure is too high in the blood vessels between the heart and the lungs, causing shortness of breath, dizziness, fatigue, fainting, palpitations or abnormal heartbeats, dry cough, chest pain, and swollen ankles or legs.

Tresuvi is initially given as a continuous subcutaneous infusion ( infusion under the skin). Some patients may not tolerate this due to pain and swelling at the administration site. Your doctor will decide whether Tresuvi can instead be given as a continuous intravenous infusion ( infusion into a vein). This requires the insertion of a central venous catheter, which is usually done in the neck, chest, or groin area.

How Tresuvi works

Tresuvi lowers blood pressure et in the pulmonary artery by improving blood flow and reducing the work of the heart. Improved blood flow leads to improved oxygen supply to the body and reduced strain on the heart, making it work more efficiently. Tresuvi improves the symptoms associated with PAH and the ability to exercise in patients who are limited in terms of activity.

The treprostinil contained in Tresuvi may also be approved to treat other conditions not mentioned in this product information. Ask your doctor, pharmacist, or another healthcare professional if you have any further questions, and always follow their instructions.

What you need to know before you use Tresuvi

Do not use Tresuvi

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”. This is a disease where the blood vessels that transport blood through the lungs become swollen and clogged, which causes increased pressure in the blood vessels between the heart and the lungs.
if you have severe liver disease
if you have heart problems, for example:
- myocardial infarction (heart attack) within the last six months
- severe changes in heart rate
- severe coronary artery disease or unstable angina
- heart defect has been diagnosed, for example, a valve that causes the heart to work poorly
- heart disease that is not treated or not closely monitored by doctors
if you have a particularly high risk of bleeding – for example, active peptic ulcers, injuries, or other bleeding conditions
if you have had a stroke within the last 3 months or any other interruption of the blood supply to the brain.

Warnings and precautions

Talk to your doctor before using Tresuvi if you:

have any liver disease
have any kidney disease
have been told that you are medically obese ( BMI of more than 30 kg/m ² )
have HIV (human immunodeficiency virus) infection
have high blood pressure in the hepatic veins (portal hypertension)
have a congenital heart defect that affects blood flow through the heart
follows a low-sodium diet.

During treatment with Tresuvi, tell your doctor:

if your blood pressure drops ( hypotension )
if you experience rapidly increasing difficulty breathing or persistent cough (this may be related to congestion in the lungs or asthma or another condition), consult your doctor immediately
if you have heavy bleeding, treprostinil may increase the risk by preventing the blood from clotting
if you develop a fever while receiving treprostinil intravenously or if the site of the intravenous catheter becomes red, swollen, and/or painful to the touch, these may be signs of infection.

Children and young people

There are limited data for children and adolescents.

Other medicines and Tresuvi

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

Tell your doctor if you are taking:

medicines used to treat high blood pressure (antihypertensives or other vasodilators)
medicines used to increase urine output ( diuretics ), including furosemide
medicines that prevent the blood from clottings (blood thinners), such as warfarin, heparin, or nitric oxide-based agents
non-steroidal anti-inflammatory drugs ( NSAIDs ) (eg aspirin, ibuprofen )
medicines that can increase or decrease the effect of treprostinil (eg gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St. John’s wort ) because your doctor may need to adjust the dose of Tresuvi.

Pregnancy and breastfeeding

Tresuvi is not recommended if you are pregnant, planning to become pregnant, or think you may be pregnant unless your doctor considers it necessary. The safety of this medicine, when used during pregnancy, has not been established.

The use of contraception is strongly recommended during treatment with Tresuvi.

Use of Tresuvi is not recommended during breastfeeding unless your doctor considers it necessary. You should stop breastfeeding if you have been prescribed Tresuvi, as it is not known whether this medicine is excreted in breast milk.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.

Driving ability and use of machinery

Tresuvi may cause low blood pressure with dizziness or fainting. In such conditions, you should not drive or use machines and you should ask your doctor for advice.

You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires increased vigilance. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. A description of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. Discuss with your doctor or pharmacist if you are unsure.

Tresuvi contains sodium

Tell your doctor if you are on a low-salt diet. He/she will take into account that a vial of Tresuvi contains the following amount of sodium:

Tresuvi 1 mg/ml solution for infusion :

This medicine contains 36.8 mg of sodium (the main ingredient in common/table salt) per 10 ml vial. This corresponds to 1.8% of the maximum recommended daily intake of sodium for adults.

Tresuvi 2.5 mg/ml solution for infusion :

This medicine contains 37.3 mg of sodium (the main ingredient in common/table salt) per 10 ml vial. This corresponds to 1.9% of the maximum recommended daily intake of sodium for adults.

Tresuvi 5 mg/ml solution for infusion :

This medicine contains 39.1 mg of sodium (the main ingredient in common/table salt) per 10 ml vial. This corresponds to 2.0% of the maximum recommended daily intake of sodium for adults.

Tresuvi 10 mg/ml solution for infusion :

This medicine contains 37.4 mg of sodium (the main ingredient in common/table salt) per 10 ml vial. This corresponds to 1.9% of the maximum recommended daily intake of sodium for adults.

How to use Tresuvi

Always use this medicine as directed by your doctor. Consult a doctor if you are unsure.

Mode of administration

Tresuvi is given as a continuous infusion either:

subcutaneously (under the skin) through a narrow tube (cannula) placed in the abdomen or thigh
intravenously via a tube ( catheter ) which is usually placed in the neck, chest, or groin area.

In both cases, Tresuvi is pushed through the pipe using a portable pump.

Before you leave the hospital or clinic, the doctor will tell you how to prepare Tresuvi and at what speed the pump should give you Tresuvi. You also get information on how to use the pump correctly and what to do if it stops working. You also get information about who to contact in an emergency.

Flushing the infusion line while connected may cause an accidental overdose.

Tresuvi is diluted only when given intravenously:

For intravenous infusion only: If Tresuvi is given as a continuous intravenous infusion, dilute the treprostinil solution only with sterile water for injections or with 9 mg/ml (0.9%) sodium chloride solution for injections (provided by your doctor).

Adult patients

Tresuvi is available as 1 mg/ml, 2.5 mg/ml, 5 mg/ml or 10 mg/ml solution for infusion . Your doctor will determine the infusion rate and infusion dose that is appropriate for your condition.

Obese patients

If you are overweight (weighing 30% or more than your ideal body weight), your doctor will determine the first and subsequent doses based on your ideal body weight. See also section 2, “Warnings and precautions”.

Elderly

Your doctor will determine the infusion rate and infusion dose that is appropriate for your condition.

Use for children and adolescents

There are limited data for children and adolescents.

Dose adjustment

The infusion rate can be lowered or increased individually only under medical supervision.

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

If your symptoms increase you need complete rest or are confined to a bed or chair, or if any physical activity causes discomfort and your symptoms occur at rest, do not increase the dose without a doctor’s prescription. This medicine may no longer be enough to treat your illness and other treatment may be needed.

How can infection in the bloodstream be prevented during treatment with Tresuvi given intravenously?

As with any long-term intravenous treatment, there is a risk of infection in the bloodstream. Your doctor will instruct you on how to avoid this.

If you use too much Tresuvi

If you accidentally overdose on this medicine, you may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, feeling of intoxication or fainting), flushing, and/or headache.

If any of these effects become severe, contact a doctor or hospital immediately. Your doctor may reduce the dose or stop the infusion until the symptoms have disappeared. Treatment with Tresuvi solution for infusion is restarted at a dose recommended by your doctor.

If you have ingested too much medicine or if, for example, a child has ingested the medicine by mistake, contact a doctor or hospital for an assessment of the risk and advice.

If you stop using Tresuvi

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

On the contrary, discontinuation or sudden dose reductions of treprostinil may cause pulmonary arterial hypertension to return, with the risk of rapid and serious deterioration of your condition.

If you have any further questions about this medicine, ask your doctor.

Possible side effects

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

Very common (may affect more than 1 in 10 users)

dilated blood vessels with skin redness
pain or redness at the infusion site
skin discoloration or bruising at the infusion site
headache
rash
nausea
diarrhea
pain in the jaws.

Common (may affect up to 1 in 10 users)

dizziness
vomiting
feeling intoxicated or fainting due to low blood pressure
itching or redness of the skin
swelling of the feet, ankles, and legs or fluid retention
bleeding such as epistaxis, coughing up blood, blood in the urine, bleeding in the gums, blood in the stool
joint pain
muscle pain
pain in the legs and/or arms.

Has been reported (occurring in an unknown number of users)

infusion site infection
wart formation at the infusion site
reduced number of blood cells ( platelets ) that cause the blood to clot ( thrombocytopenia )
bleeding at the infusion site
tissue infection under the skin ( cellulitis )
bone pain
skin rash with discoloration or raised nodules
too much blood pumped from the heart leads to shortness of breath, fatigue, swelling of the legs and abdomen due to fluid retention, and persistent cough.

Has been reported (occurring in an unknown number of users)

Side effects associated with intravenous administration

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

*life-threatening or fatal cases of bacterial infection in the bloodstream have been reported

How to store Tresuvi

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

Use before the expiry date which is stated on the carton and vial after EXP. The expiration date is the last day of the specified month.

Do not use this medicine if you notice any damage to the vial, discoloration, or other signs of deterioration. A vial of Tresuvi must be used or discarded within 30 days of the first opening.

No special storage instructions.

Durability under continuous subcutaneous infusion

A reservoir ( syringe ) of undiluted treprostinil administered subcutaneously is chemically, physically, and microbiologically stable for up to 72 hours at 37°C. Other storage times and conditions of use are at the user’s own risk.

Durability under continuous intravenous infusion

A reservoir ( syringe ) of diluted treprostinil solution administered intravenously is chemically, physically, and microbiologically stable for up to 48 hours at 37°C in polyvinyl chloride, polypropylene, and glass (at concentrations of at least 0.004 mg/ml). However, to minimize the risk of infection in the bloodstream, the maximum time of use of diluted treprostinil must not exceed 24 hours. Other storage times and conditions of use are at the user’s own risk.

Any diluted solution left over must be discarded.

Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.

Contents of the packaging and other information

Contents declaration

The active substance is treprostinil.

Tresuvi 1 mg/ml solution for infusion :

Each ml contains 1 mg treprostinil, as treprostinil sodium.

Tresuvi 2.5 mg/ml solution for infusion :

Each ml contains 2.5 mg treprostinil, as treprostinil sodium.

Tresuvi 5 mg/ml solution for infusion :

Each ml contains 5 mg of treprostinil, as treprostinil sodium.

Tresuvi 10 mg/ml solution for infusion :

Each ml contains 10 mg of treprostinil, as treprostinil sodium

Other ingredients are:

sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid (for pH adjustment ), meta cresol, and water for injections.

Appearance and package sizes of the medicine

Tresuvi is a clear, colorless to a slightly yellow solution without visible particles, contained in a 10 ml clear glass vial sealed with a rubber stopper and color-coded cap:

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

Each carton contains one vial.

Marketing Authorisation Holder

Orpha-Devel Handels und Vertriebs GmbH

Wintergasse 85/1B

3002 Purkersdorf

Austria

Manufacturer

AOP Orphan Pharmaceuticals GmbH

Leopold-Ungar-Platz 2

1190 Vienna