Pombiliti

Patient Information Leaflet

Pombiliti 105 mg powder for concentrate for solution for infusion

cipaglucosidase alfa

This medicinal product is under additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before you are given this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effect, including those not listed in this leaflet, inform your doctor. See section 4.

Contents of this leaflet

1. What Pombiliti is and what it is used for
2. What you need to know before you are given Pombiliti
3. How Pombiliti is administered
4. Possible side effects
5. How to store Pombiliti
6. Contents of the pack and other information

1. What Pombiliti is and what it is used for

What Pombiliti is
Pombiliti is a type of "enzyme replacement therapy" used to treat late-onset Pompe disease in adults. It contains the active substance "cipaglucosidase alfa".
What it is used for
Pombiliti is always used in combination with another medicine called miglustat 65 mg hard capsules. It is very important to also read the package leaflet for miglustat 65 mg hard capsules.
If you have any questions about medicines, speak to your doctor or pharmacist.
How Pombiliti works
People affected by Pompe disease have low levels of the enzyme acid alpha-glucosidase (GAA). This enzyme helps regulate levels of glycogen (a type of carbohydrate) in the body. In Pompe disease, high amounts of glycogen accumulate in the body's muscles. This prevents muscles from working properly, such as the leg muscles needed for walking, the muscles below the lungs that help with breathing, and the heart.
Pombiliti reaches the cells of the muscles affected by Pompe disease. Once inside the cells, cipaglucosidase alfa acts like the natural acid alpha-glucosidase enzyme, helping to break down glycogen and control its levels.

2. What you should know before being given Pombiliti

Do not take Pombiliti

• If you have experienced potentially life-threatening hypersensitivity reactions to:
• cipaglucosidase alfa
• miglustat
• any of the other components of this medicine (listed in section 6).
• If you had to discontinue a previous infusion and were unable to resume treatment due to potentially life-threatening hypersensitivity reactions.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Pombiliti.

Contact your doctor or nurse immediately if you experience, think you are experiencing, or have previously experienced any of the following reactions with another enzyme replacement therapy:

• allergic reactions including anaphylaxis (a severe allergic reaction) – for symptoms of life-threatening reactions, see section 4 “Possible side effects”
• infusion-associated reactions during or immediately after administration of the medicine – for symptoms of life-threatening reactions, see section 4 under “Possible side effects”.

Inform your doctor if you have previously had heart or lung disease. These conditions may worsen during or immediately after infusion with Pombiliti. Immediately inform your doctor or nurse if you experience shortness of breath, cough, rapid or irregular heartbeat, or any other symptoms related to these conditions. Also inform your doctor if you experience swelling in the legs, generalized body swelling, severe skin rashes, or foamy urine during urination. Your doctor will decide whether the Pombiliti infusion should be stopped and will provide appropriate medical treatment. Your doctor will also determine whether you can continue receiving Pombiliti.

Pre-treatment medication
Your doctor may administer other medicines before Pombiliti, including:

• antihistamines and corticosteroids to prevent or reduce infusion-related reactions
• antipyretics to reduce fever.

Children and adolescents
This medicine must not be administered to patients under 18 years of age. This is because the effects of Pombiliti in combination with miglustat in this age group are unknown.

Other medicines and Pombiliti
Inform your doctor or pharmacist if you are taking, have recently taken, or plan to take any other medicines. This includes medicines purchased without a prescription, including herbal products.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, immediately seek advice from your doctor or pharmacist before using this medicine. There are no data available on the use of Pombiliti in combination with miglustat during pregnancy.

• You must not receive Pombiliti and/or miglustat 65 mg hard capsules if you are pregnant. Be sure to inform your doctor immediately if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. There may be risks to the fetus.
• Pombiliti in combination with miglustat must not be administered to women who are breastfeeding. A decision must be made whether to discontinue treatment or to discontinue breastfeeding.

Contraception and fertility
Female patients of childbearing potential must use reliable contraceptive methods during treatment with these medicines and for 4 weeks after discontinuation of both medicines.

Driving and using machines
You may experience dizziness, drowsiness, or low blood pressure (hypotension) after receiving Pombiliti or pre-treatment medication. If this occurs, do not drive or operate tools or machinery.

Pombiliti contains sodium
This medicine contains 10.5 mg of sodium (a main component of table salt) per vial. This corresponds to 0.52% of the maximum recommended daily dietary intake of sodium for an adult.

3. How Pombiliti is administered

Pombiliti is administered by a doctor or nurse through an intravenous infusion (IV infusion) into a vein.
Inform your doctor if you wish to receive treatment at home. After an assessment, your doctor will decide whether you can safely receive Pombiliti infusions at home. If you experience any adverse reaction during a home infusion of Pombiliti, the healthcare provider can stop the infusion and initiate appropriate medical treatment.

Pombiliti must be used in combination with miglustat. Use only the 65 mg miglustat capsules in combination with cipaglucosidase alfa. DO NOT use the 100 mg miglustat capsules (this is a different medicine).
Follow your doctor's instructions and read the miglustat 65 mg hard capsules package leaflet for the recommended dosage.

How much Pombiliti is administered
The amount of medicine you will receive is based on your body weight. The recommended initial dose is 20 mg per kilogram of body weight.

When and for how long Pombiliti is administered

• Treatment with Pombiliti occurs once every two weeks. The 65 mg miglustat capsules are taken on the same day as Pombiliti. Read the package leaflet for miglustat 65 mg hard capsules for information on how to take miglustat.
• The cipaglucosidase alfa infusion should begin 1 hour after taking the 65 mg miglustat hard capsules.
• If there is a delay, the infusion must not start more than 3 hours after taking miglustat.
• The cipaglucosidase alfa infusion lasts approximately 4 hours.

Figure 1. Dosing schedule

*
Switching from another enzyme replacement therapy
If you are currently receiving another enzyme replacement therapy:

• your doctor will advise you when to stop the other enzyme replacement therapy before starting Pombiliti
• inform your doctor when you have completed your last dose.

If you receive more Pombiliti than you should
If you have difficulty breathing, feel bloated, or have a rapid heartbeat, you may have received too much Pombiliti. Inform your doctor immediately. Infusing Pombiliti too quickly may cause symptoms related to fluid accumulation in the body, including shortness of breath, rapid heartbeat, or widespread swelling.

If you miss a dose of Pombiliti
If you miss an infusion, contact your doctor or nurse as soon as possible to schedule a new appointment to receive Pombiliti treatment in combination with miglustat, 24 hours after your last dose of miglustat.

If you stop Pombiliti treatment
Talk to your doctor if you wish to stop treatment with Pombiliti. Your disease symptoms may worsen if you stop treatment.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Pombiliti is used together with miglustat, and side effects may occur with either of the two medicines. Side effects have mainly been observed during or shortly after Pombiliti infusion (infusion-related reactions). Inform your doctor immediately if you experience an infusion-related reaction or an allergic reaction. Some of these reactions may become severe and potentially fatal. To prevent such reactions, your doctor may administer certain medicines before the infusion.

Infusion-related reactions
Most infusion-related reactions are mild or moderate in severity. Symptoms of infusion-related reactions may include difficulty breathing, swelling, fever, chills, dizziness, skin redness, itching, and rash.

Allergic reactions
Allergic reactions may include symptoms such as skin rash anywhere on the body, swollen eyes, prolonged difficulty breathing, cough, swelling of the lips, tongue, or throat, skin itching, and hives.

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

• headache

Common (may affect up to 1 in 10 people)

• severe, potentially fatal allergic reaction (anaphylactic reaction)
• dizziness
• tremor
• somnolence
• taste disturbances
• sensation of numbness, tingling (paraesthesia)
• rapid heartbeat
• skin redness
• low blood pressure
• laboured breathing
• cough
• diarrhoea
• feeling unwell (nausea)
• stomach ache
• flatulence
• swelling
• vomiting
• hives
• itching
• rash
• excessive sweating
• painful muscle contractions
• muscle pain
• muscle weakness
• joint pain
• fatigue
• fever
• chills
• chest discomfort
• swelling at the site where the needle was inserted
• pain
• swelling of the hands, feet, ankles, legs
• increased blood pressure

Uncommon (may affect up to 1 in 100 people)

• allergic reaction
• inability to maintain balance
• burning sensation
• migraine
• feeling faint
• unusual paleness of the skin
• asthma
• wheezing
• discomfort in mouth and throat
• throat swelling
• indigestion
• painful spasms or pain in the oesophagus
• pain or discomfort in the mouth
• tongue swelling
• skin colour changes
• skin swelling
• pain in the area between the ribs and hip
• muscle fatigue
• muscle stiffness
• weakness
• pain in cheeks, gums, lips, chin
• pain at the infusion site
• general feeling of discomfort
• chest pain
• facial swelling
• changes in body temperature
• scratches or skin damage

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pombiliti

The doctor, pharmacist or nurse is responsible for the storage of this medicinal product and the proper disposal of opened vials. The following information is intended exclusively for healthcare professionals.
Keep this medicine out of the sight and reach of children.
Do not use this medicinal product after the expiry date which is stated on the vial and outer carton after "Exp.". The expiry date refers to the last day of that month.
Unopened vials: store in a refrigerator (2 °C – 8 °C). Keep the vial in the outer packaging to protect from light.
After dilution, immediate use is recommended. However, it has been demonstrated that the intravenous infusion bag containing Pombiliti can be stored for up to 6 hours at 20 °C - 25 °C and for up to 24 hours at 2 °C - 8 °C.
Do not dispose of any medicinal product via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Pombiliti contains
The active substance is cipaglucosidase alfa. One vial contains 105 mg of cipaglucosidase alfa. After
reconstitution, the solution in the vial contains 15 mg of cipaglucosidase alfa per mL. The final
concentration of cipaglucosidase alfa diluted in the intravenous infusion bag ranges from 0.5 mg/mL to 4 mg/mL.
The other components are:

• disodium citrate dihydrate (E331)
• citric acid monohydrate (E330)
• mannitol (E421)
• polysorbate 80 (E433)

Description of the appearance of Pombiliti and contents of the pack
Pombiliti is a powder ranging in colour from white to slightly yellowish. After reconstitution, it appears as a solution ranging from clear to opalescent, colourless to slightly yellow, free from foreign particles and practically free of particulate matter in the form of white to translucent particles. The reconstituted solution must be further diluted in an infusion bag. Pombiliti is a powder for concentrate for solution for infusion contained in a vial. Packs containing 1 vial, 10 vials or 25 vials are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Amicus Therapeutics Europe Limited
Block 1, Blanchardstown Corporate Park
Ballycoolin Road
Blanchardstown, Dublin
D15 AKK1
Ireland
Tel: +353 (0) 1 588 0836
Fax: +353 (0) 1 588 6851
e-mail: [email protected]

Manufacturer
Manufacturing Packaging Farmaca (MPF) B.V.
Neptunus 12, Heerenveen, 8448CN, The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Tél/Tel: (+32) 0800 89172 Tel: (+370) 8800 33167
e-mail: [email protected] El. paštas: [email protected]

България Luxembourg/Luxemburg
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Teл.: (+359) 00800 111 3214 Tél/Tel: (+352) 800 27003
имейл: [email protected] e-mail: [email protected]

Česká republika Magyarország
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Tel.: (+420) 800 142 207 Tel.: (+36) 06 800 21202
e-mail: [email protected] e-mail: [email protected]

Danmark Malta
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Tlf.: (+45) 80 253 262 Tel: (+356) 800 62674
e-mail: [email protected] e-mail: [email protected]

Deutschland Nederland
Amicus Therapeutics GmbH Amicus Therapeutics BV
Tel: (+49) 0800 000 2038 Tel: (+31) 20 235 8510 / (+31) 0800 022 8399
E-mail: [email protected] e-mail: [email protected]

Eesti Norge
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Tel: (+372) 800 0111 911 Tlf: (+47) 800 13837
e-post: [email protected] e-post: [email protected]

Ελλάδα Österreich
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Τηλ: (+30) 00800 126 169 Tel: (+43) 0800 909 639
e-mail: [email protected] E-Mail: [email protected]

España Polska
Amicus Therapeutics S.L.U. Amicus Therapeutics Europe Limited
Tel: (+34) 900 941 616 Tel.: (+48) 0080 012 15475
e-mail: [email protected] e-mail: [email protected]

France Portugal
Amicus Therapeutics SAS Amicus Therapeutics Europe Limited
Tél: (+33) 0 800 906 788 Tel: (+351) 800 812 531
e-mail: [email protected] e-mail: [email protected]

Hrvatska România
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Tel: (+358) 0800 222 452 Tel.: (+40) 0808 034 288
e-pošta: [email protected] e-mail: [email protected]

Ireland Slovenija
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Tel: (+353) 1800 936 230 Tel.: (+386) 0800 81794
e-mail: [email protected] e-pošta: [email protected]

Ísland Slovenská republika
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Sími: (+354) 800 7634 Tel: (+421) 0800 002 437
Netfang: [email protected] e-mail: [email protected]

Italia Suomi/Finland
Amicus Therapeutics S.r.l. Amicus Therapeutics Europe Limited
Tel: (+39) 800 795 572 Puh/Tel: (+358) 0800 917 780
e-mail: [email protected] sähköposti/e-mail: [email protected]

Κύπρος Sverige
Amicus Therapeutics Europe Limited Amicus Therapeutics Europe Limited
Τηλ: (+357) 800 97595 Tfn: (+46) 020 795 493
e-mail: [email protected] e-post: [email protected]

Latvija United Kingdom (Northern Ireland)
Amicus Therapeutics Europe Limited Amicus Therapeutics, UK Limited
Tel: (+371) 800 05391 Tel: (+44) 08 0823 46864
e-pasts: [email protected] e-mail: [email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.
The following information is intended for healthcare professionals only.

Instructions for use: reconstitution, dilution and administration

Pombiliti must be reconstituted with water for injections, then diluted with a 9 mg/mL (0.9%) sodium chloride injectable solution, and finally administered by intravenous infusion. Reconstitution and dilution must be performed in accordance with good practice standards, particularly with regard to asepsis.
Since this medicinal product is a protein, particulate formation may occur in the reconstituted solution and in the final diluted solution in the infusion bag. Therefore, a low protein-binding in-line filter with a pore size of 0.2 micron must be used during administration. The use of a 0.2 micron in-line filter has been shown to remove visible particles without apparent loss of protein or activity.
Determine the number of vials to reconstitute based on the patient’s dosing regimen (mg/kg), and remove the required number of vials from the refrigerator to allow them to reach room temperature (approximately 30 minutes). Each vial of Pombiliti is for single use only.
Use aseptic technique.
Reconstitution
Reconstitute each 105 mg Pombiliti vial with 7.2 mL of water for injections using a syringe with a needle no larger than 18 gauge. Add the water for injections slowly, directing the stream down the side of the vial and not directly onto the lyophilized powder. Gently tilt and rotate each vial. Do not invert, shake, or agitate the vial. The resulting solution should appear as a clear to opalescent, colourless to slightly yellow solution, free from foreign particles and practically free from particulate matter in the form of white to translucent particles. Immediately inspect reconstituted vials for particulate matter and discoloration. Do not use if, upon immediate inspection, foreign particles other than those described above are observed or if the colour of the reconstituted solution is altered. The pH of the reconstituted solution is approximately 6.0.
After reconstitution, prompt dilution of the vials is recommended (see below).
Dilution
Once reconstituted as described above, the solution in the vial contains 15 mg of cipaglucosidase alfa per mL. The reconstituted volume allows accurate withdrawal of 7.0 mL (equivalent to 105 mg) from each vial. This solution must then be further diluted as follows: using a syringe with a needle no larger than 18 gauge, slowly withdraw the reconstituted solution from the vials, including any volume less than 7.0 mL from a partial vial, to obtain the patient’s required dose. The recommended final concentration of cipaglucosidase alfa in the infusion bags ranges from 0.5 mg/mL to 4 mg/mL. Remove air from the infusion bag.
Additionally, withdraw from the 9 mg/mL (0.9%) sodium chloride injectable solution an amount equal to the total volume (mL) of reconstituted cipaglucosidase alfa to be added. Slowly inject the reconstituted Pombiliti directly into the 9 mg/mL (0.9%) sodium chloride injectable solution. Invert or gently massage the infusion bag to mix the diluted solution. Do not shake or agitate the infusion bag excessively.
The final infusion solution should be administered as soon as possible after preparation.
Any unused medicinal product and waste materials arising from its use must be disposed of in accordance with local regulations.
Administration
Pombiliti infusion should begin 1 hour after the patient takes miglustat capsules. If the infusion is delayed, administration must not start more than 3 hours after miglustat intake.
The recommended dosage regimen for Pombiliti is 20 mg/kg body weight, administered once every two weeks via intravenous infusion.
Infusions should be administered using an incremental regimen. It is recommended to initiate the infusion at an initial rate of 1 mg/kg/hour, then gradually increase by 2 mg/kg/hour approximately every 30 minutes, provided no infusion-related reactions (IARs) occur, up to a maximum rate of 7 mg/kg/hour.