Lamzede 10 mg powder for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Lamzede 10 mg powder for solution for infusion

velmanase alfa

This medicinal product is subject to additional monitoring, which will allow rapid identification of new information on its safety. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, talk to your doctor, nurse, or pharmacist, even if it is a side effect not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Lamzede is and what it is used for

Lamzede contains the active substance velmanase alfa, which belongs to a group of medicines called enzyme replacement therapies. It is used to treat patients with mild to moderate alpha-mannosidosis. It is used to treat the non-neurological symptoms of the disease.

Alpha-mannosidosis is a rare genetic disorder caused by a deficiency of an enzyme called alpha-mannosidase, which is needed to break down certain sugar-containing compounds (called "mannose-rich oligosaccharides") in the body. When this enzyme is missing or does not function properly, these sugar-containing compounds accumulate inside cells and cause the signs and symptoms of the disease. Typical manifestations of the disease include distinctive facial features, intellectual disability, difficulty controlling movements, hearing and speech difficulties, frequent infections, skeletal problems, muscle pain, and weakness.

Velmanase alfa is designed to replace the missing enzyme in patients with alpha-mannosidosis.

2. What you need to know before using Lamzede

Do not use Lamzede

• if you are allergic to velmanase alfa or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor before Lamzede treatment is started.

Hypersensitivity reactions may occur with the administration of Lamzede. These reactions usually occur during or shortly after the infusion and may present with various symptoms, such as localized or widespread skin reactions, gastrointestinal symptoms, or swelling of the throat, face, lips, or tongue (see section 4 “Possible side effects”). If the hypersensitivity reaction is severe, administration of Lamzede should be immediately discontinued and current medical emergency protocols should be followed. Less severe hypersensitivity reactions may be managed by temporarily interrupting the infusion or reducing the infusion rate; your doctor may consider administering medications used to treat allergies.

If you are receiving Lamzede, you may experience an adverse reaction during or immediately after the infusion used to administer the medicine (see section 4 “Possible side effects”). This is known as a infusion-related reaction, and it can sometimes be serious.

• Your doctor may decide to monitor you for one hour or longer after the infusion due to the risk of infusion-related reactions.
• Infusion-related reactions may include dizziness, headache, nausea, low blood pressure, fatigue, and fever. If you experience an infusion-related reaction, you must inform your doctor immediately.
• If you have an infusion-related reaction, you may be given additional medications to treat or help prevent future reactions. These may include medications used to treat allergies (antihistamines), medications used to treat fever (antipyretics), and medications to control inflammation (corticosteroids).
• If the infusion-related reaction is severe, your doctor will stop the infusion immediately and begin appropriate medical treatment.
• If infusion-related reactions are severe and/or a loss of effectiveness of this medicine occurs, your doctor may perform a blood test to check for antibodies that could affect treatment outcomes.
• In most cases, you can continue receiving Lamzede even if you experience an infusion-related reaction.

Antibodies may play a role in the hypersensitivity and infusion-related reactions observed with the use of Lamzede. Although 24% of patients developed antibodies against Lamzede during clinical development, no clear correlation was observed between antibody titers and reduced efficacy or the occurrence of hypersensitivity reactions.

Other medicines and Lamzede

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before this medicine is used.

You should not take this medicine during pregnancy unless your doctor clearly considers it necessary. Your doctor will discuss this with you.

It is unknown whether velmanase alfa passes into human milk. Lamzede may be used during breastfeeding, as the breastfed infant will not absorb velmanase alfa.

Driving and using machines

The influence of Lamzede on the ability to drive and use machines is negligible or none.

Lamzede contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose unit; i.e., essentially “sodium-free”.

3. How to use Lamzede

This medicine should only be used under the supervision of a physician experienced in the treatment of alpha-mannosidosis or similar disorders, and must be administered only by a healthcare professional.

Lamzede should only be used under the supervision of a physician experienced in the treatment of alpha-mannosidosis. Your doctor may advise you to receive treatment at home if you meet certain criteria. Contact your doctor if you wish to receive treatment at home.

Dosage

The recommended dose of Lamzede is 1 mg/kg body weight administered once weekly.

Use in children and adolescents

Lamzede may be administered to children and adolescents at the same dose and frequency as in adults.

Administration

Lamzede is supplied in a vial as a powder for infusion, which must be reconstituted with water for injections before administration.

Once reconstituted, the medicine will be administered via an infusion pump (infusion set) into a vein over a period of at least 50 minutes under the supervision of your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. Most adverse effects occur during or shortly after the infusion (“infusion-related reaction”, see section 2 “Warnings and precautions”).

While you are receiving treatment with Lamzede, you may experience one or more of the following reactions:

Serious adverse effects

Frequent adverse effects (may affect up to 1 in 10 people)

• loss of consciousness (fainting, which may be preceded by dizziness, lightheadedness, or confusion)
• acute kidney injury (kidney problems that may be recognized by fluid retention, swelling of the legs, ankles, or feet, drowsiness, shortness of breath, or fatigue)
• hypersensitivity and severe allergic reaction (symptoms include localized or widespread skin itching, dizziness, difficulty breathing, chest pain, chills, fever, gastrointestinal symptoms such as nausea, vomiting, diarrhea, or abdominal pain, swelling of the throat, face, lips, or tongue)

If you experience any adverse effects similar to those described, inform your doctor immediately.

Other adverse effects

Very frequent adverse effects (may affect more than 1 in 10 people)

• diarrhea
• weight gain
• fever/increased body temperature

Frequent adverse effects (may affect up to 1 in 10 people)

• slow heart rate (bradycardia)
• bluish discoloration of the skin and lips (cyanosis)
• psychotic behavior (mental illness with hallucinations, difficulty thinking clearly and understanding reality, anxiety), difficulty sleeping
• confusion, fainting, tremor, dizziness, headache
• abdominal pain, stomach irritation due to digestive acids (reflux gastritis), nausea, vomiting
• pain at the infusion site, chills, feeling of warmth, general malaise, fatigue
• skin rashes (urticaria), increased sweating (hyperhidrosis)
• nosebleed
• joint pain, back pain, joint stiffness, muscle pain, limb pain (hands, feet)
• eye irritation, eyelid swelling (periorbital edema), eye redness
• increased appetite

Adverse effects of unknown frequency (cannot be estimated from available data)

• infection of the inner lining of the sac surrounding the heart (endocarditis)
• boil
• infection caused by a bacterium called Staphylococcus
• decreased appetite
• agitation, fecal incontinence, restlessness
• inability to coordinate muscle movements
• drowsiness
• increased tear secretion
• deafness
• aortic valve incompetence (a disorder in which the aortic valve does not close tightly)
• fast heart rate
• low blood pressure
• vascular fragility
• oropharyngeal pain
• wheezing (“whistling” when breathing)
• pain when swallowing
• skin redness
• joint swelling, joint warmth
• weakness
• symptoms of mild infusion-related reaction such as pallor, lack of interest and energy, and decreased muscle strength or tone

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Lamzede

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

Do not use this medicine after the expiry date stated on the label and the carton after “EXP/CAD”. The expiry date refers to the last day of the month indicated.

Store and transport refrigerated (between 2 °C and 8 °C). Do not freeze.

Keep in the original packaging to protect from light.

After reconstitution, the medicine should be used immediately. If not used immediately, the reconstituted solution may be stored for up to 24 hours at between 2 °C and 8 °C.

This medicine should not be used if the reconstituted solution contains opaque particles or has changed colour.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Lamzede

• The active substance is velmanase alfa.

One vial contains 10 mg of velmanase alfa.

After reconstitution, 1 ml of solution contains 2 mg of velmanase alfa (10 mg / 5 ml).

• The other components are: disodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate dihydrate (see section 2 “Lamzede contains sodium”), mannitol (E 421), and glycine.

Appearance of the medicinal product and contents of the pack

Lamzede is a white to off-white powder for infusion solution, supplied in a glass vial.

Each carton contains 1, 5 or 10 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Chiesi Farmaceutici S.p.A.

Via Palermo 26/A

43122 Parma

Italy

Manufacturer

Chiesi Farmaceutici S.p.A.

Via San Leonardo, 96

43122 Parma

Italy

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary of product characteristics:

This medicinal product has been authorised under "exceptional circumstances". This type of approval means that, due to the rarity of the disease, it has not been possible to obtain complete information about this medicinal product.

The European Medicines Agency will review any new information about this medicinal product annually, and this summary of product characteristics will be updated as necessary.

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicinal products are also available.

This information is intended for healthcare professionals only.

Lamzede requires reconstitution and is for intravenous infusion only.

Each vial is for single use only.

Reconstitution and administration instructions

Reconstitution and administration of Lamzede must be performed by a healthcare professional.

Aseptic technique must be used during preparation. Filter needles must not be used during preparation.

• The number of vials required must be calculated based on the patient's individual body weight. The recommended dose of 1 mg/kg is determined using the following calculation:
  • Patient's weight (kg) × dose (mg/kg) = Patient dose (in mg).
  • Patient dose (in mg) divided by 10 mg/vial (content of one vial) = number of vials to be reconstituted. If the calculated number of vials includes a fraction, it must be rounded up to the next whole number.
  • Approximately 30 minutes before reconstitution, the required number of vials should be removed from the refrigerator. The vials must reach room temperature (between 15 °C and 25 °C) before reconstitution.

Each vial is reconstituted by slowly injecting 5 ml of water for injections against the inner wall of the vial. Each millilitre of reconstituted solution contains 2 mg of velmanase alfa. Only the volume corresponding to the recommended dose should be administered.

Example:

• Patient weight (44 kg) × dose (1 mg/kg) = Patient dose (44 mg).

• 44 mg divided by 10 mg/vial = 4.4 vials; therefore, 5 vials should be reconstituted.

• From the total reconstituted volume, only 22 ml (corresponding to 44 mg) should be administered.

• The powder must be reconstituted within the vial by slowly adding water for injections drop by drop against the inner wall of the vial, not directly onto the lyophilised powder. Forceful ejection of water for injections from the syringe onto the powder must be avoided to minimise foam formation. Reconstituted vials should stand upright on a flat surface for about 5–10 minutes. Then, each vial should be tilted and gently rolled for 15–20 seconds to enhance the dissolution process. The vial must not be inverted, shaken, or agitated.

• Immediately after reconstitution, the solution must be inspected visually for particulate matter and discoloration. The solution should be clear and must not be used if opaque particles are observed or if discoloration has occurred. Due to the nature of the medicinal product, the reconstituted solution may occasionally contain small protein particles in the form of fine white strands or translucent fibres, which will be removed by the integrated filter during infusion (see point e).

• The reconstituted solution must be slowly withdrawn from each vial, taking care to avoid foam formation in the syringe. If the volume of solution exceeds the capacity of a single syringe, the necessary number of syringes should be prepared to allow rapid replacement during infusion.

• The reconstituted solution must be administered using an infusion set equipped with an infusion pump and an integrated low protein-binding 0.22 µm filter.

The total infusion volume is determined according to the patient's body weight and must be administered over a minimum of 50 minutes. A dilution of 2 mg/ml should always be used. In patients weighing less than 18 kg who are to receive less than 9 ml of reconstituted solution, the infusion rate must be calculated so that the infusion time is ≥50 minutes. The maximum infusion rate is 25 ml/hour. The infusion time can be calculated using the following table:

• When the last syringe is empty, replace the dosing syringe with a 20 ml syringe filled with 9 mg/ml (0.9%) sodium chloride injectable solution. Administer a volume of 10 ml of sodium chloride solution through the infusion system to infuse the remaining fraction of Lamzede into the patient's line.

Elimination

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