Patient Information Leaflet

Revestive 5 mg powder and solvent for solution for injection

teduglutida

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read the entire patient information leaflet carefully before starting to use this medicine, as it contains important information for you.

- Keep this leaflet, as you may need to refer to it again.

- If you have any questions, consult your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.

- If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1. What Revestive is and for what it is used

2. What you need to know before starting to use Revestive

3. How to use Revestive

4. Possible adverse effects

5. Storage of Revestive

6. Contents of the pack and additional information

Revestive contains the active ingredient teduglutida. It improves the intestinal absorption of nutrients and liquids from your gastrointestinal tract (intestine).

Revestive is used for the treatment of short bowel syndrome in adults, children, and adolescents (4 months and older). Short bowel syndrome is a disorder that occurs due to an inability to absorb nutrients from food and water in the intestine. It is generally caused by partial or total surgical removal of the small intestine.

Do not use Revestive

• If you are allergic to teduglutida or any of the other components of this medicine (listed in section 6) or to traces of tetracycline residues;
• • If you have or think you may have cancer;
  • If you have had cancer in any part of the gastrointestinal tract, such as the liver, gallbladderor the bile ducts and pancreas, in the last five years.

Warnings and precautions

Consult your doctor before starting to use Revestive:

-If you have severe liver failure. Your doctor will take this into account when prescribing this medicine;

-If you have any cardiovascular disease (affecting the heart and/or blood vessels), such as high blood pressure (hypertension) or heart failure. Symptoms and signs include sudden weight gain, facial swelling, swelling in the ankles and/or difficulty breathing;

-If you have other severe diseases that are not well controlled. Your doctor will take this into account when prescribing this medicine;

-If you have kidney failure. Your doctor may need to give you a lower dose of this medicine.

Your doctor may adjust the amount of fluids or intravenous nutrition you receive while starting or while receiving treatment with Revestive.

Medical reviews before and during treatment with Revestive

Before starting treatment with this medicine, your doctor will need to perform a colonoscopy (a procedure to observe the inside of the colon and rectum) to detect the presence of polyps (small abnormal growths) and remove them. It is recommended that your doctor perform these examinations once a year for the first two years after starting treatment and then, at least, once every five years. If polyps are found before or during treatment with Revestive, your doctor will decide whether you should continue using this medicine. If cancer is diagnosed during the colonoscopy, do not use Revestive. Your doctor will monitor your electrolytes and body fluids as an imbalance could cause fluid overload or dehydration.

Your doctor will pay special attention and monitor the function of your small intestine and signs and symptoms indicating problems in your gallbladder, bile ducts, and pancreas.

Children and adolescents

Medical reviews before and during treatment with Revestive

Before starting treatment with this medicine, a test will be performed to see if there is blood in the stool. A colonoscopy (a procedure to observe the inside of the colon and rectum to detect the presence of polyps [small abnormal growths] and remove them) will also be performed if there is unexplained blood in the stool. If polyps are found before treatment with Revestive, your doctor will decide whether you should use this medicine. If cancer is diagnosed during the colonoscopy, do not use Revestive. Your doctor will perform more colonoscopies while you continue receiving treatment with Revestive. Your doctor will monitor your electrolytes and body fluids as an imbalance could cause fluid overload or dehydration.

Children under 4 months of age

This medicine should not be used in children under 4 months of age. There are no data available for Revestive in this age group.

Other medicines and Revestive

Inform your doctor, pharmacist, or nurse if you are using, have used recently, or may need to use any other medicine.

Revestive may affect how other medicines are absorbed in the intestine and, therefore, reduce their effectiveness. Your doctor may need to change the dose of other medicines.

Pregnancy and breastfeeding

Revestive is not recommended for use if you are pregnant or breastfeeding.

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

Driving and operating machines

This medicine may cause dizziness. If this happens, do not drive or operate machines until you feel better.

Important information about some components of Revestive

This medicine contains less than 23 mg of sodium (1 mmol) per dose; this is essentially “sodium-free”.

Be cautious if you are hypersensitive to tetracyclines (see the “Do not use Revestive” section).

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor, pharmacist, or nurse again.

Dose

The recommended daily dose is 0.05 mg per kilogram of body weight. The dose will be given in milliliters (ml) of solution.

Your doctor will decide on the most suitable dose for you based on your body weight. Your doctor will instruct you on the dose to inject. If in doubt, consult your doctor, pharmacist, or nurse again.

Use in children and adolescents

Revestive can be used in children and adolescents (4 months or older). Follow exactly the administration instructions for this medication as indicated by your doctor.

How to Use Revestive

Revestive is injected under the skin (subcutaneously) once a day. The injection can be administered by the patient themselves or another person, for example, your doctor, caregiver, or home nurse. If you are injecting the medication yourself, or having it injected by your caregiver, both you and your caregiver must receive proper training from your doctor or nurse. You will find detailed injection instructions at the end of this leaflet.

We strongly recommend that each time you or your child receive a dose of Revestive, you record the name and batch number of the medication in order to maintain a record of the batches used.

If you use more Revestive than you should

If, by accident, you inject more Revestive than indicated by your doctor, you must contact your doctor, pharmacist, or nurse.

If you forget to use Revestive

If you forget to use this medication (or cannot use it at your usual time), use it as soon as possible that same day. Never use more than one injection on the same day. Do not use a double dose to compensate for missed doses.

If you interrupt treatment with Revestive

Continue using this medication for the time indicated by your doctor. Do not stop using this medication without consulting your doctor, as sudden interruption may cause changes in fluid balance.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Seek immediate medical attention if any of the following side effects occur:

Common(may affect up to 1 in 10 people):

-Heart failure. Contact your doctor if you experience fatigue, difficulty breathing, or swelling of the ankles, legs, or face.

-Pancreatitis (inflammation of the pancreas). Contact your doctor or emergency services if you experience severe stomach pain and fever.

-Intestinal obstruction (intestinal blockage). Contact your doctor or emergency services if you experience severe stomach pain, vomiting, and constipation.

- Reduced bile flow from the gallbladder and/or inflammation of the gallbladder.

Contact your doctor or emergency services if you experience yellowing of the skin and the white part of the eyes, itching, dark urine, and light-colored stools, or if you experience pain in the upper right side or the middle of the stomach area.

Uncommon(may affect up to 1 in 100 people):

-Fainting. If your heart rate and breathing are normal and you wake up quickly, inform your doctor. In other cases, seek assistance as soon as possible.

Other side effects included:

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

• Respiratory tract infection (any infection in the nasal passages, throat, airways, or lungs).
• Headache.
• Stomach pain, stomach swelling, feeling of dizziness (nausea), inflammation of the stoma (artificial opening for waste elimination), vomiting.
• Redness, pain, or inflammation at the injection site.

Common(may affect up to 1 in 10 people):

• Flu or flu-like symptoms.
• Loss of appetite.
• Swelling of hands and/or feet.
• Difficulty sleeping, anxiety.
• Cough, difficulty breathing.
• Polyps (growth of small abnormal masses) in the large intestine.
• Gas (flatulence).
• Narrowing or blockage of the pancreatic duct, which may cause pancreatitis.
• Inflammation of the gallbladder.

Uncommon(may affect up to 1 in 100 people):

• Polyps (growth of small abnormal masses) in the small intestine.

Frequency not known(cannot be estimated from available data):

• Allergic reaction (hypersensitivity).
• Fluid retention.
• Polyps (growth of small abnormal masses) in the stomach.

Use in children and adolescents

In general, side effects in children and adolescents are similar to those observed in adults.

No data are available for children under 4 months of age.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in the Appendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box, vial, and pre-filled syringe after CAD. The expiration date is the last day of the month indicated.

Store below 25°C.

Do not freeze.

After reconstitution, from a microbiological point of view, the solution must be used immediately. Nevertheless, chemical and physical stability has been demonstrated for 3 hours at 25°C.

Do not use this medication if you observe that the solution is cloudy or contains particles.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment. All needles and syringes must be disposed of in sharp object containers.

Composition of Revestive

• The active ingredient is teduglutide. A vial of powder contains 5 mg of teduglutide. After reconstitution, each vial contains 5 mg of teduglutide in 0.5 ml of solution, corresponding to a concentration of 10 mg/ml.
• The other components are L-histidine, mannitol, sodium phosphate monohydrate, and disodium phosphate heptahydrate, sodium hydroxide (pH adjustment), and hydrochloric acid (pH adjustment).
• The solvent contains water for injection.

Appearance of the product and contents of the package

Revestive is a powder and a solvent for injectable solution (5 mg of teduglutide in vial, 0.5 ml of solvent in pre-loaded syringe).

The powder is white and the solvent is transparent and colorless.

Revestive is available in package sizes of 1 vial of powder with 1 pre-loaded syringe or 28 vials of powder with 28 pre-loaded syringes.

Only some package sizes may be commercially available.

Marketing authorization holder and manufacturer

Takeda Pharmaceuticals International AG Ireland Branch

Block 2 Miesian Plaza

50 – 58 Baggot Street Lower

Dublin 2, D02 HW68

Ireland

Last revision date of this leaflet: 06/2023

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.There are also links to other websites on rare diseases and orphan medicines.

Instructions for preparation and injection of Revestive

Important information:

• Read the leaflet before using Revestive.
• Revestive is injected subcutaneously.
• Do not inject Revestive intravenously or intramuscularly.
• Keep Revestive out of the sight and reach of children.
• Do not use Revestive after the expiry date that appears on the box, vial, and pre-loaded syringe. The expiry date is the last day of the month indicated.
• Store below 25°C.
• Do not freeze.
• After reconstitution, the solution should be used immediately. However, chemical and physical stability has been demonstrated for up to 3 hours at 25°C.
• Do not use Revestive if the solution is cloudy or contains particles.
• Medicines should not be disposed of by flushing down the toilet or throwing them away. Ask your pharmacist how to dispose of the packaging and unused medicines. This will help protect the environment.
• Dispose of all needles and syringes in a puncture-proof container.

Materials included in the package:

- 1 or 28 vials with 5 mg of teduglutide in powder form.

- 1 or 28 pre-loaded syringes with solvent.

Materials necessary but not included in the package:

• Needles for reconstitution (22G, 1½" [0.7 x 40 mm] long).
• Syringes for injection of 0.5 ml or 1 ml (with scale intervals of 0.02 ml or less). For children, a syringe for injection of 0.5 ml (or smaller) may be used.
• Thin needles for subcutaneous injection (e.g., 26G, 5/8" [0.45 x 16 mm] long or smaller needles for children, if necessary).
• Alcohol-soaked cotton balls.
• Alcohol-soaked cotton swabs.
• Puncture-proof container for disposing of used syringes and needles.

NOTE:Before starting, wash your hands and ensure you have a clean surface to handle the materials before proceeding.

1. Mount the pre-loaded syringe

Once you have prepared all the materials, you must mount the pre-loaded syringe. The following procedure should be followed:

2. Dissolve the powder

You can now dissolve the powder with the solvent.

NOTE:Do not shake the vial. Shaking the vial may produce foam, making it difficult to extract the solution from the vial.

2.7 Check if the vial contains undissolved powder. If there is still undissolved powder, repeat steps 2.5 and 2.6. Do not shake the vial. If there is still undissolved powder, discard the vial and repeat the procedure from the beginning with a new vial.

NOTE:The final solution must be transparent. If the solution is cloudy or contains particles, it should not be injected.

NOTE:Once prepared, the solution should be used immediately. It should be stored below 25°C for a maximum of 3 hours.

3. Prepare the injection syringe

NOTE:If your doctor has told you that you need two vials, prepare a second pre-loaded syringe with solvent and a second powder vial, just like steps 1 and 2. With the same syringe that you just used, extract the solution from the second vial by repeating step 3.

4. Inject the solution

NOTE:Do not always inject in the same area, change the area (use the upper, lower, left, or right part of your abdomen) to avoid discomfort. Avoid inflamed, swollen, scarred, or covered areas by a mole, birthmark, or any type of injury.

4.4 Gently pull the plunger. If you see blood in the syringe, remove the needle and replace it with a new and clean one of the same size. You can still use the medicine that is in the syringe. Try to choose another injection site on the same area of clean skin.

4.5 Inject the medicine slowly, pressing the plunger continuously, until you have injected all the medicine and the syringe is empty.

4.6 Quickly remove the needle from the skin and dispose of the needle and syringe in a puncture-proof container. It may bleed a little. If necessary, press the injection site gently with an alcohol-soaked cotton swab or a 2x2 gauze until the bleeding stops.

4.7 Dispose of all needles and syringes in a puncture-proof container or a container with thick walls (e.g., a detergent bottle with a lid). You must use a puncture-proof container or a container with thick walls (including the lid and the sides). If you need a puncture-proof container, please consult your doctor.