Prospect: information for the patient

Pombiliti 105 mg powder for concentrate for solution for infusion

cipaglucosidase alfa

This medicine is subject to additional monitoring, which will expedite 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 this prospect carefully before starting to receive this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

1. What is Pombiliti and what it is used for

2. What you need to know before starting to receive Pombiliti

3. How to administer Pombiliti

4. Possible adverse effects

5. Storage of Pombiliti

6. Contents of the package and additional information

Pombiliti is a type of "enzymatic substitution therapy" (EST) indicated for adults with late-onset Pompe disease. It contains the active ingredient called "alpha-glucosidase alfa".

What it is used for

Pombiliti is used always together with another medicine called miglustat 65 mg hard capsules. It is very important that you also read the prospectus of miglustat 65 mg hard capsules.

If you have any doubts about these medicines, consult your doctor or pharmacist.

How Pombiliti actsiti

People with Pompe disease have low levels of an enzyme called acid alpha-glucosidase (GAA). This enzyme helps regulate glycogen (a type of carbohydrate) levels in the body.

In Pompe disease, large amounts of glycogen accumulate in the muscles of the entire body. This prevents the proper functioning of the muscles, for example those that help walking, those that facilitate breathing in the lungs and the cardiac muscle.

Pombiliti enters the affected muscle cells. Once inside the cells, the medicine acts as GAA, promoting the breakdown of glycogen and regulating its levels.

Do not receive Pombiliti

• If you have ever had potentially fatal hypersensitivity reactions to the following:

• cipaglucosidase alfa
• miglustat
• any of the other components of this medication (listed in section 6).

• If a previous infusion had to be interrupted and could not be resumed due to potentially fatal hypersensitivity reactions.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Pombiliti

Consult your doctor or nurse immediatelyif any of the following situations apply to you, or if you think they might apply, or if you have ever had any of these reactions with another enzyme replacement therapy (ERT):

• allergic reactions, including anaphylaxis (a severe allergic reaction) - see section 4 of the "Possible side effects" section below for symptoms of potentially fatal reactions;
• reaction associated with infusion while receiving the medication or in the hours following, see section 4 of the "Possible side effects" section below for symptoms of potentially fatal reactions.

Inform your doctor if you have a history of any heart or lung disease. These diseases may worsen during or immediately after Pombiliti infusion. Inform your doctor or nurse immediately if you experience difficulty breathing, cough, rapid or irregular heartbeat, or any other effects of these diseases.

Also inform your doctor if you experience swelling in the legs or generalized body swelling, severe skin rash, or foamy urine when urinating. The doctor will decide if the Pombiliti infusion should be interrupted and will give you the appropriate medical treatment. The doctor will also decide if you can continue receiving Pombiliti.

Medications prior to treatment

Your doctor may administer other medications before starting treatment with Pombiliti, for example:

• antihistamines and corticosteroids to prevent or mitigate infusion-associated reactions;
• antipyretics to reduce fever.

Children and adolescents

This medication should not be administered to patients under 18 years of age, as the effects of Pombiliti combined with miglustat in this age group are unknown.

Other medications and Pombiliti

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication, including over-the-counter medications and herbal medications.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, do not receive this medication, but consult your doctor or pharmacist immediately before using it.

There are no data on the use of Pombiliti in combination with miglustat during pregnancy.

• If you are pregnant, do not receive Pombiliti and/or take miglustat 65 mg hard capsules. Inform your doctor immediately if you become pregnant, think you may be pregnant, or intend to become pregnant. There may be risks to the fetus.
• Pombiliti in combination with miglustat should not be administered to women who are breastfeeding. It will be decided whether to stop breastfeeding or stop treatment.

Contraception and fertility

Women of childbearing age should use effective contraceptive methods during and for 4 weeks after completing administration of both medications.

Driving and operating machinery

You may experience dizziness, drowsiness, or low blood pressure (hypotension) after receiving Pombiliti or the medications prior to treatment. In this case, do not drive or use tools or machinery.

Pombiliti contains sodium

This medication contains 10.5 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 0.52% of the recommended daily maximum sodium intake for an adult.

Pombiliti is administered by a doctor or nurse. It is administered in the form of an infusion into a vein. This form of administration is called intravenous perfusion.

Consult your doctor if you wish to be treated at home. They will decide, after evaluation, whether it is safe for you to receive the Pombiliti infusion at your home. If you experience any side effect during a Pombiliti infusion, it is possible that the member of staff administering it will stop the infusion and initiate the corresponding pharmacological treatment.

Pombiliti must be used in combination with miglustat. You can only use miglustat 65 mg capsules with cipaglucosidasa alfa. Do not use miglustat 100 mg capsules (different medication). Regarding the recommended dose, follow your doctor's instructions and read the miglustat 65 mg hard capsules prospectus.DO NOTuse miglustat 100 mg capsules (different medication). With regard to the recommended dose, follow your doctor's instructions and read the miglustat 65 mg hard capsules prospectus.

How much Pombiliti is administered

The amount of medication you will receive is based on your weight. The recommended dose is 20 mg per kilogram of body weight.

When Pombiliti is administered and for how long

• You will receive treatment with Pombiliti once every two weeks. Miglustat 65 mg capsules are taken on the same day as the administration of Pombiliti. Consult the miglustat 65 mg hard capsules prospectus for information on how to take miglustat.
• The cipaglucosidasa alfa infusion must start 1 hour after taking miglustat 65 mg hard capsules.

• In case of delay, the start of the infusion must not exceed 3 hours from the time of miglustat intake.

• The cipaglucosidasa alfa infusion lasts for 4 hours.

Figure 1. Chronological development of doses

*The cipaglucosidasa alfa infusion must start 1 hour after taking the miglustat capsules. In case of delay in the infusion, the start of this must not exceed 3 hours from the time of miglustat intake.

Change from another enzyme replacement therapy (ERT)

If you are currently receiving another ERT:

• Your doctor will indicate when you should stop the other ERT before starting Pombiliti.
• Inform your doctor of when you received the last dose.

If you receive more Pombiliti than you should

If you have difficulty breathing, feel swelling or inflammation, or notice an accelerated heart rate, it is possible that you have been administered too much Pombiliti;inform your doctor immediately. Excessive infusion rate of Pombiliti could cause symptoms due to excess fluid in the body, for example, difficulty breathing, high heart rate, or generalized swelling throughout the body.

If you forget your Pombiliti dose

If you have missed a perfusion, contact your doctor or nurse as soon as possible to schedule an appointment and have Pombiliti administered in combination with miglustat 24 hours after the last intake of miglustat.

If you interrupt treatment with Pombiliti

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

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

Pombiliti is used in combination with miglustat and any of these medicines may cause side effects. Side effects have been observed mainly in patients during the infusion of Pombiliti (reactions associated with infusion) or shortly after. Inform your doctor immediately if you experience a reaction associated with infusion or an allergic reaction. Some of these reactions can be severe and potentially life-threatening. Your doctor may administer medications before the infusion to prevent these reactions.

Reactions associated with infusion

Most reactions associated with infusion are mild or moderate. Symptoms of a reaction associated with infusion include, among others, difficulty breathing, swelling, fever, chills, dizziness, redness, and itching of the skin and hives.

Allergic reactions

Allergic reactions can cause symptoms such as hives anywhere on the body, swelling of the eyes, prolonged difficulty breathing, coughing, swelling of the lips, tongue, or throat, itching of the skin, and urticaria.

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

• Headache

Common(may affect up to 1 in 10 people)

• Coughing
• Sudden redness of the face, neck, or upper chest
• Chest pain
• Hives, itching
• Increased blood pressure
• Sweating
• Abdominal swelling
• Flatulence or gas
• Diarrhea, loose stools
• Vomiting
• Nausea
• Fever or chills
• Urticaria
• Swelling or pain at the site of the needle insertion
• Muscle cramps, pain, or weakness
• Trembling in one or more parts of the body
• Increased sweating
• Pain
• Alteration of taste
• Constant feeling of fatigue or sleepiness
• Difficulty breathing

Uncommon(may affect up to 1 in 100 people)

• Difficulty breathing that causes coughing, wheezing while breathing, and a feeling of lack of air (asthma)
• Allergic reaction
• Swelling of the hands, feet, ankles, legs
• Swelling of the face
• Indigestion
• Stomach pain
• Constant feeling of fatigue
• Pain or irritation of the throat
• Abnormal and painful contractions of the throat
• Irritation of the mouth
• Pain in the mouth or discomfort in the back of the mouth
• Pain in the cheeks, gums, lips, chin
• Loss of strength and energy, feeling of weakness
• General feeling of malaise, lethargy
• Burning sensation
• Rashes or skin lesions
• Alterations in body temperature
• Decrease in a type of white blood cell (detected in blood tests)
• Drowsiness
• Dizziness
• Pain in the joints
• Pain in the area between the hip and ribs
• Muscle fatigue
• Increased muscle stiffness
• Inability to maintain balance
• Low blood pressure
• Sensation of impending fainting
• Pain on one or both sides of the head, stabbing pain, aura, eye pain, sensitivity to light (migraine)
• Spots on the skin

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, 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 theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Your doctor, pharmacist, or nurse is responsible for conserving this medication and properly disposing of opened vials. This information is intended solely for healthcare professionals.

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the bottle and on the box after “CAD.” The expiration date is the last day of the month indicated.

Unopened vials: Store in refrigerator (between 2 °C and 8 °C). Store the vial in the outer packaging to protect it from light.

After dilution, immediate use is recommended. However, the conservation of the intravenous infusion bag with Pombiliti has been demonstrated for 6 hours at a temperature between 20 °C and 25 °C and for 24 hours at a temperature between 2 °C and 8 °C.

Medications should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Pombiliti

The active principle is cipaglucosidase alfa. A vial contains 105 mg of cipaglucosidase alfa. After reconstitution, the solution contained in the vial contains 15 mg of cipaglucosidase alfa per milliliter. A final concentration of cipaglucosidase alfa diluted in the intravenous infusion bag of 0.5 mg/ml to 4 mg/ml is recommended.

The other components are:

• Sodium citrate dihydrate (E331)
• Citric acid monohydrate (E330)
• Manitol (E421)
• Polysorbate 80 (E433)

Appearance of the product and contents of the package

Pombiliti is a white to slightly yellowish powder. After reconstitution, it is a transparent to opalescent solution, between colorless and slightly yellowish, without foreign particles and practically free of white to translucent particles. The reconstituted solution must be diluted further in an intravenous infusion bag.

Pombiliti is a powder for concentrate for solution for infusion in a vial.

Packages of 1, 10 or 25 vials

Only some package sizes may be commercially available.

Marketing Authorization Holder

Amicus Therapeutics Europe Limited

Block 1, Blanchardstown Corporate Park

Ballycoolin Road

Blanchardstown, Dublin

D15 AKK1

Ireland

Phone: +353 (0) 1 588 0836

Fax: +353 (0) 1 588 6851

Email:[email protected]

Responsible Person

Manufacturing Packaging Farmaca (MPF) B.V.

Neptunus 12, Heerenveen, 8448CN, Netherlands

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of the summary of product characteristics

Other sources of information

Detailed information on this medicinal product 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.

This information is intended for healthcare professionals only:

Instructions for use: reconstitution, dilution and administration

Pombiliti must be reconstituted with water for injections and then diluted in a sodium chloride 9 mg/ml (0.9%) solution for injections and administered by intravenous infusion. Reconstitution and dilution must be carried out in accordance with good clinical practice, especially with regard to asepsis.

Since this medicinal product is a protein, it is possible that particles may form in the reconstituted solution and in the final diluted infusion bag. Therefore, a low-protein binding 0.2 micrometer in-line filter must be used for administration. It has been demonstrated that the use of a 0.2 micrometer in-line filter eliminates visible particles and does not cause an apparent loss of protein or activity.

Determine the number of vials to be reconstituted according to the patient's posological regimen (mg/kg) and remove the necessary vials from the refrigerator to reach room temperature (about 30 minutes). Each vial of Pombiliti is for single use.

Use an aseptic technique.

Reconstitution

Reconstitute the 105 mg per vial of Pombiliti in 7.2 ml of water for injections using a syringe with a needle diameter not exceeding 18 G. Add water for injections drop by drop to the side of the vial and not directly onto the lyophilized powder. Incline and rotate each vial carefully. Do not invert, remove or shake the vial. The extraction volume is a transparent to opalescent solution, between colorless and slightly yellowish, without foreign particles and practically free of white to translucent particles. Immediately inspect the reconstituted vials to verify that there are no particles or color alteration. If particles other than those described are observed in the immediate inspection or the reconstituted solution presents a color alteration, do not use it. The pH of the reconstituted solution is approximately 6.0.

After reconstitution, it is recommended to dilute the vials immediately (see below).

Dilution

After the reconstitution described above, the reconstituted solution in the vial contains 15 mg of cipaglucosidase alfa per milliliter. The reconstituted volume allows for the exact extraction of 7.0 ml (equivalent to 105 mg) from each vial. The solution must be diluted further as follows: using a syringe with a needle diameter not exceeding 18 G, extract the reconstituted solution from each vial, including the volume below 7.0 ml from the vial, to obtain the patient's dose. The recommended final concentration of cipaglucosidase alfa in the infusion bags is between 0.5 mg/ml and 4 mg/ml. Extract the air from the interior of the infusion bag.

Similarly, extract an equivalent volume of sodium chloride 9 mg/ml (0.9%) solution for injections, which will be replaced by the volume of reconstituted Pombiliti. Inject the reconstituted Pombiliti solution slowly into the sodium chloride 9 mg/ml (0.9%) solution for injections. Invert or massage the infusion bag carefully to mix the diluted solution. Do not shake or agitate the infusion bag excessively.

The final infusion solution must be administered as soon as possible after preparation.

Elimination of unused medicinal product and all materials that have come into contact with it will be carried out in accordance with local regulations.

Administration

The infusion of Pombiliti must begin 1 hour after taking the miglustat capsules. In case of delay in infusion, its start must not exceed 3 hours from the intake of miglustat. The recommended posological regimen of Pombiliti is 20 mg/kg of body weight administered every 2 weeks by intravenous infusion.

Infusions must be administered gradually. It is recommended that the initial infusion rate be 1 mg/kg/h and be gradually increased by 2 mg/kg/h every 30 minutes, if no signs of RAP (reactions associated with infusion) appear, until a maximum rate of 7 mg/kg/h is reached.