Package leaflet: Information for the patient

Revestive 1.25 mg powder and solvent for solution for injection

Teduglutide

For children and adolescents

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.

• If you have any further questions, ask your child’s doctor, pharmacist or nurse.

• This medicine has been prescribed for your child only. Do not pass it on to others. It may harm them, even if their signs of illness are the same.

• If the child gets any side effects, talk to your child’s doctor, pharmacist or nurse. This includes

  any possible side effects not listed in this leaflet. See section 4.

  
  

  What is in this leaflet

  
  

  1. What Revestive is and what it is used for

  2. What you need to know before you use Revestive

  3. How to use Revestive

  4. Possible side effects

  5 How to store Revestive

  6. Contents of the pack and other information

  
  

  1. What Revestive is and what it is used for

     
     

     Revestive contains the active substance teduglutide. It improves the absorption of nutrients and fluid from your child’s remaining gastrointestinal tract (gut).

     Revestive is used to treat children and adolescents (aged 1 year and above) with Short Bowel Syndrome. Short Bowel Syndrome is a disorder arising from an inability to absorb food nutrients and fluid across the gut. It is often caused by surgical removal of all or part of the small intestine.

     
     

  2. What you need to know before you use Revestive Do not use Revestive

• if your child is allergic to teduglutide or any of the other ingredients of this medicine (listed in section 6) or trace residues of tetracycline.

• if your child has or is suspected to have cancer.

• if your child has had cancer in the gastrointestinal tract, including liver, gallbladder or bile ducts, and pancreas within the last five years.

  
  

  Warnings and precautions

  
  

  Talk to your child’s doctor before using Revestive:

• if your child has severely decreased liver function. The doctor will consider this when prescribing this medicine.

• if your child suffers from certain cardiovascular diseases (affecting the heart and/or blood vessels) such as high blood pressure (hypertension) or has a weak heart (cardiac insufficiency).

  The signs and symptoms include sudden weight gain, face swelling, swollen ankles and/or shortness of breath.

• if your child has other severe diseases that are not well controlled. The doctor will consider this

  when prescribing this medicine.

• if your child has decreased kidney function. The doctor may need to give your child a lower dose of this medicine.

  
  

  When starting and while getting treated with Revestive, the doctor may adjust the amount of intravenous fluids or nutrition your child receives.

  Medicalcheck-upsbeforeandduringtreatmentwithRevestive

  Before starting treatment with this medicine, your child will have a test done to see if there is blood in the stool. Your child will also have a colonoscopy done (a procedure to see inside their colon and rectum to check for the presence of polyps (small abnormal growths) and have them removed) if they have unexplained blood in their bowel movements (stools). If polyps are found before treatment with Revestive, the doctor will decide whether your child should use this medicine. Revestive should not be used if a cancer is detected during colonoscopy. The doctor will perform further colonoscopies if your child continues treatment with Revestive. The doctor will monitor your child’s body fluids and electrolytes as an imbalance may cause fluid overload or dehydration.

  
  

  The doctor will take special care and monitor your child’s small bowel function and monitor for signs and symptoms indicating problems with the gallbladder, bile ducts and pancreas.

  
  

  Children and adolescents

  
  

  Childrenbelow1yearofage

  This medicine should not be used in children under 1 year of age. This is because there is limited experience with Revestive in this age group.

  
  

  Other medicines and Revestive

  
  

  Tell the doctor, pharmacist or nurse if your child is using, has recently used or might use any other medicines.

  
  

  Revestive may affect how other medicines are absorbed from the gut and therefore how well they work. The doctor may have to change your child’s dose of other medicines.

  
  

  Pregnancy and breast-feeding

  
  

  If your child is pregnant or breast-feeding, the use of Revestive is not recommended.

  If your child is pregnant or breast-feeding, may be pregnant or is planning to have a baby, ask the doctor, pharmacist or nurse for advice before using this medicine.

  
  

  Driving, cycling and using machines

  
  

  This medicine may cause your child to feel dizzy. If this happens to your child, they should not drive, ride a bicycle or use machines until they feel better.

  
  

  Important information about some of the ingredients in Revestive

  
  

  This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that it is essentially ‘sodium-free’.

  Caution is needed if your child is hypersensitive to tetracycline (see “Do not use Revestive” section).

  1. How to use Revestive

     
     

     Always use this medicine exactly as the doctor has told you. Check with your child’s doctor, pharmacist or nurse if you are not sure.

     
     

     Dose

     The recommended daily dose for your child is 0.05 mg per kg body weight. The dose will be given in millilitres (ml) of solution.

     
     

     The doctor will choose the dose that is right for your child, depending on their body weight. The doctor will tell you which dose to inject. If you are not sure, ask the doctor, pharmacist or nurse.

     
     

     HowtouseRevestive

     Revestive is injected under the skin (subcutaneously) once daily. The injection can be

     self-administered or given by another person, for example your child’s doctor, his/her assistant or your child’s home nurse. If you, or the carer, are injecting the medicine, you or the carer must receive

     adequate training by the doctor or nurse. You will find detailed instructions for injections at the end of

     this leaflet.

     
     

     It is strongly recommended that every time your child receives a dose of Revestive, the name and lot number of the product are recorded in order to maintain a record of the lots used.

     
     

     If you use more Revestive than you should

     
     

     If you inject more Revestive than you are told to by your child’s doctor, you should contact the doctor, pharmacist or nurse.

     
     

     If you forget to use Revestive

     
     

     If you forget to inject this medicine (or cannot inject it at the usual time), use it as soon as possible on that day. Never use more than one injection in the same day. Do not inject a double dose to make up for a forgotten dose.

     
     

     If you stop using Revestive

     
     

     Keep using this medicine for as long as your child’s doctor prescribes it for them. Do not stop using this medicine without consulting the doctor, as a sudden stop can cause changes in your child’s fluid balance.

     
     

     If you have any further questions on the use of this medicine, ask your child’s doctor, pharmacist or nurse.

     
     

  2. Possible side effects

     
     

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

     Seek immediate medical attention if any of the following side effects occur: Common (may affect up to 1 in 10 people):

• Congestive heart failure. Contact the doctor if your child experiences tiredness, shortness of breath or swelling of ankles or legs or face swelling.

• Inflammation of the pancreas (pancreatitis). Contact the doctor or the emergency unit if your child experiences severe stomach ache and fever

• Intestinal obstruction (blockage of the bowel). Contact the doctor or the emergency unit if your child experiences severe stomach ache, vomiting and constipation

• Reduced flow of bile from the gallbladder and/or inflammation of the gallbladder. Contact the doctor or the emergency unit if your child experiences yellowing of the skin and the whites in the eyes, itching, dark urine and light-coloured stools or pain in the upper right side or middle of the stomach area

  
  

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

• Fainting. If heart rate and breathing is normal and your child awakens fast, speak to the doctor.

  In other cases, seek help as soon as possible

  
  

  Other side effects include:

  
  

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

• Respiratory tract infection (any infection of the sinuses, throat, airways or lungs)

• Headache

• Stomach pain, bloated stomach, feeling sick (nausea), swelling of stoma (an artificial opening for waste removal), vomiting

• Reddening, pain or swelling at the site of the injection

  
  

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

• Flu (influenza) or flu-like symptoms

• Decreased appetite

• Swelling of hands and/or feet

• Problems sleeping, anxiety

• Cough, shortness of breath

• Polyps (small abnormal growths) in your child’s large bowel

• Passing gas (flatulence)

• Narrowing or blockage of your child’s pancreatic duct, which may cause inflammation of the pancreas

• Inflammation of the gallbladder

  
  

  Uncommon (may affect up to 1 in 100 people)

• Polyps (small abnormal growths) in your child’s small bowel

  
  

  Not known (frequency cannot be estimated from the available data):

• Allergic reaction (hypersensitivity)

• Fluid retention

• Polyps (small abnormal growths) in your child’s stomach

  
  

  Use in children and adolescents

  
  

  In general, the side effects in children and adolescents are similar to those seen in adults. There is limited experience in children under 1 year of age.

  Reporting of side effects

  
  

  If your child gets any side effects, talk to your child’s doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via thenationalreporting systemlistedinAppendixV.

  
  

  By reporting side effects you can help provide more information on the safety of this medicine.

  
  

  1. How to store Revestive

     
     

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

     Do not use this medicine after the expiry date which is stated on the carton, the vial and the pre-filled syringe after EXP. The expiry date refers to the last day of that month.

     
     

     Store in a refrigerator (2°C – 8°C). Do not freeze.

     
     

     After reconstitution, from a microbiological point of view, the solution should be used immediately. However, chemical and physical stability has been demonstrated for 24 hours at 25°C.

     
     

     Do not use this medicine if you notice that the solution is cloudy or contains particulate matter.

     
     

     Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. Dispose of all needles and syringes in a sharps disposal container.

     
     

  2. Contents of the pack and other information What Revestive contains

• The active substance is teduglutide. One vial of powder contains 1.25 mg of teduglutide. After reconstitution, each vial contains 1.25 mg teduglutide in 0.5 ml of solution, corresponding to a concentration of 2.5 mg/ml.

• The other ingredients are L-histidine, mannitol, sodium phosphate monohydrate, disodium phosphate heptahydrate.

• The solvent contains water for injections.

  
  

  What Revestive looks like and contents of the pack

  
  

  Revestive is a powder and solvent for solution for injection (1.25 mg teduglutide in vial, 0.5 ml solvent in pre-filled syringe).

  
  

  The powder is white and the solvent is clear and colourless.

  
  

  Revestive comes in pack sizes of 28 vials of powder with 28 pre-filled syringes.

  
  

  Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder

  Takeda Pharmaceuticals International AG Ireland Branch Block 3 Miesian Plaza

  50 – 58 Baggot Street Lower

  Dublin 2, D02 Y754 Ireland

  Tel: +800 66838470

  E-mail: medinfoEMEA@takeda.com

  
  

  Manufacturer

  
  

  Shire Pharmaceuticals Ireland Limited Block 2 & 3 Miesian Plaza

  50 – 58 Baggot Street Lower

  Dublin 2 Ireland

  
  

  This leaflet was last revised in

  . There are also links to other websites about rare diseases and treatments.

  InstructionsforpreparingandinjectingRevestive

  
  

  Important information:

  
  

• Read the Package Leaflet before using Revestive.

• Revestive is for injection under the skin (subcutaneous injection).

• Do not inject Revestive into a vein (intravenously) or muscle (intramuscularly).

• Keep Revestive out of the sight and reach of children.

• Do not use Revestive after the expiry date which is stated on the carton, the vial and the pre-filled syringe. The expiry date refers to the last day of that month.

• Store in a refrigerator (2°C – 8°C).

• Do not freeze.

• After reconstitution, from a microbiological point of view, the solution should be used immediately. However, chemical and physical stability has been demonstrated for 24 hours at

  25ºC.

• Do not use Revestive if you notice that the solution is cloudy or contains particulate matter.

• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the

  environment.

• Dispose of all needles and syringes in a sharps disposal container.

  
  

  

  Materialsprovidedinthepack:

  • 28 vials with 1.25 mg teduglutide as a powder

  • 28 pre-filled syringes with solvent

    
    

    Materialsneededbutnotincludedinthepack:

• Reconstitution needles (size 22G, length 1½" (0.7 x 40 mm))

• 0.5 or 1 ml injection syringes (with scale intervals of 0.02 ml or smaller). For children, a 0.5 ml (or smaller) injection syringe may be used

• Thin injection needles for subcutaneous injection (e.g., size 26G, length 5/8" (0.45 x 16 mm), or

  smaller needles for children, as appropriate)

• Alcohol wipes

• Alcohol swabs

• A puncture-proof container for safe disposal of the used syringes and needles

NOTE: Before you start, make sure you have a clean work surface and that you have washed your hands before proceeding.

1. Assemble the pre-filled syringe

   
   

   Once you have all the materials ready, you need to assemble the pre-filled syringe. The following procedure shows how you do this.

   
   

   

   1.1 Take the pre-filled syringe with solvent and flip off the top part of the white plastic cap so that it is ready for the reconstitution needle to be attached.

   
   

   

   
   

2. Dissolve the powder

   1.2 Attach the reconstitution needle (22G, 1½" (0.7 x 40 mm)) to the assembled pre-filled syringe by screwing it on in a clockwise direction.

   
   

   Now you are ready to dissolve the powder with the solvent.

   
   

   

   1. Remove the blue flip-off button from the powder vial, wipe the top with an alcohol wipe and allow to dry. Do not touch the top of the vial.

      
      

      

   2. Uncap the reconstitution needle on the assembled pre-filled syringe with solvent without touching the tip of the needle.

      
      

      

   3. Taking the powder vial, insert the reconstitution needle

      attached to the assembled pre-filled syringe into the centre of the rubber stopper and gently push the plunger all the way down to inject all the solvent into the vial.

      
      

      

   4. Leave the reconstitution needle and empty syringe in the vial. Let the vial rest for approximately 30 seconds.

      
      

      

   5. Gently roll the vial between your palms for about 15 seconds. Then gently turn the vial upside-down once with the reconstitution needle and empty syringe still in the vial.

      
      

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

      

   6. Let the vial rest for about two minutes.

      
      

   7. Observe the vial for any undissolved powder. If any powder remains, repeat steps 2.5 and 2.6. Do not shake the vial. If there is still some undissolved powder, discard the vial and start the preparation again from the beginning with a new vial.

   
   

   NOTE: The final solution should be clear. If the solution is cloudy or contains particulate matter, do not inject it.

   
   

   NOTE: Once prepared, the solution should be used immediately. It should be kept below 25°C and maximum storage time is twenty-four hours.

   
   

3. Prepare the injection syringe

   
   

   

   1. Remove the reconstitution syringe from the reconstitution needle which is still in the vial and discard the reconstitution syringe.

      
      

      

   2. Take the injection syringe and attach it to the reconstitution needle which is still in the vial.

      
      

      

   3. Turn the vial upside down, slide the tip of the reconstitution needle close to the stopper and allow all the medicine to fill the syringe by pulling the plunger back gently.

      
      

      NOTE: If your child’s doctor has told you that you need two vials, prepare a second pre-filled syringe with solvent and a second powder vial as shown in the main steps 1 and 2. Withdraw the solution from the second vial into the same injection syringe by repeating step 3.

      
      

      

   4. Remove the injection syringe from reconstitution needle leaving the needle in the vial. Discard the vial and reconstitution needle together into the sharps disposal container.

      
      

      

      
      

      

      
      

      

      
      

4. Inject the solution

1. Take the injection needle, but do not remove the plastic needle cap. Attach the needle to the injection syringe containing the medicine.

   
   

2. Check for air bubbles. If air bubbles are present, gently tap the syringe until they rise to the top. Then gently push up the plunger to expel the air.

   
   

3. Your child’s dose in ml has been calculated by the doctor. Expel any excessive volume from the syringe with the needle cap still on until your dose is reached.

1. Find an area on your child’s belly, or if they have pain or hardening of the tissue on

   their belly, on your child’s thigh where it is easy

   for you to give the injection (see the diagram).

   
   

   NOTE: Do not use the same area each day for each injection - rotate sites (use upper, lower, and left and right side of your child’s belly) to avoid discomfort. Avoid areas that are inflamed, swollen, scarred or covered by a mole, birthmark or other lesion.

   
   

   

2. Clean the intended site of injection on your child’s skin with an alcohol swab, using a circular motion, working outwards. Allow the area to air-dry.

   
   

   

3. Remove the plastic cap from the needle of the prepared injection syringe. Gently grasp the cleaned skin at the injection site

   with one hand. With the other hand, hold the syringe as you would with

   a pencil. Bend your wrist back and quickly insert the needle at a 45° angle.

   
   

4. Pull back the plunger slightly. If you see any blood in the syringe, withdraw the needle and replace the needle on the injection syringe with a clean one of the same size. You can still use the medicine that is already in the syringe. Try to inject in another place in the cleaned skin area.

5. Inject the medicine slowly by pushing steadily on the plunger until all the medicine is injected and the syringe is empty.

   
   

6. Pull the needle straight out of the skin and discard the needle and syringe together into the sharps disposal container. A small amount of bleeding may occur. If necessary, press gently on the injection site with an alcohol swab or 2x2 gauze until any bleeding has stopped.

   
   

7. Dispose all needles and syringes in a sharps disposal container or hard-walled container (for example, a detergent bottle with a lid). This container must be puncture proof (top and sides). If you need a sharps disposal container, please contact your child’s doctor.