Maapliv

Package leaflet: Information for the patient

Maapliv infusion solution

L-alanine, L-arginine, L-aspartic acid, L-cysteine hydrochloride monohydrate, L-glutamic acid,
glycine, L-histidine, L-lysine monohydrate, L-methionine, L-phenylalanine, L-proline, L-serine, taurine, L-
threonine, L-tryptophan, L-tyrosine
This medicinal product is subject to 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 using this medicine because it contains important information for you.

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

Contents of this leaflet

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

1. What Maapliv is and what it is used for

Maapliv contains amino acids, which belong to a group of medicines called amino acids for parenteral use. It contains the following amino acids:
L-alanine, L-arginine, L-aspartic acid, L-cysteine hydrochloride monohydrate, L-glutamic acid, glycine, L-histidine, L-lysine monohydrate, L-methionine, L-phenylalanine, L-proline, L-serine, taurine, L-threonine, L-tryptophan, L-tyrosine.
Maapliv is used to treat maple syrup urine disease (MSUD) in patients from birth onwards. It is used when patients experience an acute worsening of MSUD and cannot follow a special diet lacking certain amino acids. MSUD is a rare genetic disorder in which the body is unable to break down certain amino acids found in proteins. This leads to a buildup of harmful substances in the blood and urine, which in turn can cause serious health problems.

2. What you need to know before using Maapliv

Do not use Maapliv

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

Warnings and precautions
Inform your doctor if you have:

• heart failure
• reduced kidney function
• reduced liver function
• a tendency towards thromboembolism

Before starting treatment, your doctor will monitor you and carry out tests, particularly at the beginning of the infusion. These include:

• monitoring of fluid and electrolyte levels;
• serum osmolarity (a measure of water and dissolved substances, such as glucose, blood urea nitrogen, and sodium, in the blood);
• acid-base balance (presence of the correct amounts of acids and bases in the blood and other body fluids);
• blood glucose;
• blood ammonia (a normal waste product of the body);
• blood proteins;
• liver and kidney function.

If you have severe imbalances in fluids and electrolytes, excess fluid in the body, or a severe metabolic disorder, these will be corrected before the infusion is administered.
Severe, sudden anaphylactic reactions may occur with amino acid solutions, such as Maapliv, used for parenteral nutrition. If you experience any signs or symptoms of an allergic reaction during treatment, inform your doctor or nurse immediately. These include:

• hives
• skin rash
• itching
• dizziness
• wheezing
• difficulty breathing
• swelling of the tongue

Patients receiving parenteral nutrition may develop blood vessel blockages in the lungs. If you experience any signs or symptoms of a blockage during treatment, inform your doctor or nurse immediately. These include:

• shortness of breath
• difficulty breathing
• cough
• chest discomfort
• rapid heartbeat
• bluish discoloration around the mouth, lips, or nails due to low oxygen levels in the blood.

In patients with severe acute or critical decompensation and very high levels of leucine in the blood, Maapliv may need to be administered intravenously in combination with hemodialysis or hemofiltration.
Clinical studies have primarily focused on leucine levels. The impact on symptom improvement or other aspects of clinical status is unknown.
Limited information is available on repeated intravenous administration of the BCAA-free formulation.

Other medicines and Maapliv
Inform your doctor if you are taking, have recently taken, or might take any other medicines. Amino acid solutions may trigger acute folate deficiency, which requires daily administration of folic acid.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before this medicine is administered.
Adequate data on the use of Maapliv in pregnant or breastfeeding women are not available.
If you are pregnant, you will be given this medicine only if your doctor considers it absolutely necessary for your recovery. Maapliv should be administered to pregnant women only after careful evaluation.
At therapeutic doses of Maapliv, effects on breastfed infants are not expected. However, Maapliv should be administered to breastfeeding women only after careful evaluation.

Driving and using machines
Maapliv does not affect the ability to drive or operate machinery.

3. How to use Maapliv

Maapliv will be administered by intravenous infusion (drip).
The dose of Maapliv will be adjusted according to the ability to metabolize amino acids, age, body weight, and nutritional requirements.
The recommended dose ranges from 39 to 58 mL/kg/24 hours for newborns and infants up to 2 years of age, and from 19 to 39 mL/kg/24 hours for children, adolescents, and adults.
Keep the vial protected from light during administration.
If you are given more Maapliv than you should
It is highly unlikely that you will receive a dose higher than intended, as treatment will be administered under the supervision of a doctor or nurse.
Effects of an overdose may include symptoms of fluid overload/retention, electrolyte disturbances, and acute pulmonary edema; symptoms of amino acid overdose such as tremors, vomiting, headache, nausea, hyperammonaemia (excessive amount of ammonia in the blood), and increased loss of amino acids through the kidneys.
In case of overdose, the infusion must be stopped immediately and may be restarted at a reduced dose or at a slower infusion rate.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. The frequency of these adverse reactions is "uncommon" (may affect up to 1 in 100 people).

Serious side effects

• Allergic reactions (anaphylactic, anaphylactoid). Hypersensitivity. Symptoms may include fever or chills, tremors, excessive sweating, skin rashes, facial or eyelid swelling, breathing difficulties, abnormally high heart rate, abnormally low or high blood pressure.

If you experience any of these signs of an allergic reaction, the infusion must be stopped immediately.

• Metabolic/nutritional disorders leading to hyperammonaemia. In case of hyperammonaemia, the infusion must be stopped immediately and the doctor must initiate specific treatment.
• Renal and urinary disorders leading to azotaemia.
• Blood clots forming and blocking blood vessels in the lungs (pulmonary embolism) or veins (venous thromboembolism). This may cause chest pain, shortness of breath, and fainting. If these symptoms occur, the infusion must be stopped and immediate medical evaluation must be initiated.

Other side effects

• Abnormal blood test results due to impaired liver function. There may be increased bilirubin levels in the blood and elevated liver enzymes; cholecystitis and cholelithiasis may also occur.
• Inflammation of the gallbladder, gallstones, and problems with bile flow.
• Inflammation of the vein at the infusion site, venous irritation, pain, warmth, swelling, and hardening of the venous tract may occur.

If you notice any change in how you feel during or after treatment, inform your doctor or another member of the medical team immediately.

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via 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 Maapliv

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect the medicine from light.
Do not refrigerate or freeze.
Do not use this medicine after the expiry date stated on the carton and vial after
Exp. The expiry date refers to the last day of that month.
Do not use this medicine if the vial is leaking or if you notice particles in the
solution.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Maapliv contains

• The active substances are L-alanine, L-arginine, L-aspartic acid, L-cysteine hydrochloride monohydrate, L-glutamic acid, glycine, L-histidine, L-lysine monohydrate, L-methionine, L-phenylalanine, L-proline, L-serine, taurine, L-threonine, L-tryptophan, L-tyrosine.
• The other components are acetic acid or sodium hydroxide (for pH adjustment) and water for injections.

Description of the appearance of Maapliv and contents of the pack
Maapliv is an infusion solution available in 500 mL colourless glass bottles. Each bottle is packaged in a cardboard box.
Clear, particle-free solution.

Marketing Authorization Holder
RECORDATI RARE DISEASES
Tour Hekla
52 avenue du Général De Gaulle
92800 Puteaux
France

Manufacturer
RECORDATI RARE DISEASES
Eco River Parc
30 rue des Peupliers
92000 Nanterre
France
RECORDATI RARE DISEASES
Tour Hekla
52 avenue du Général De Gaulle
92800 Puteaux
France
Industria Farmaceutica Galenica Senese S.r.l.
Via Cassia Nord, 351
53014 Monteroni d’Arbia (SI)
Italy

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

Belgique/België/Belgien Lietuva
Recordati bv Recordati AB.
Tél/Tel: +32 2 46101 36 Tel: + 46 8 545 80 230
Švedija

България Luxembourg/Luxemburg
RECORDATI RARE DISEASES Recordati bv
Teл.: +33 (0)1 47 73 64 58 Tél/Tel: +32 2 46101 36
Франция Belgique/Belgien

Česká republika Magyarország
RECORDATI RARE DISEASES RECORDATI RARE DISEASES
Tel: +33 (0)1 47 73 64 58 Tel: +33 (0)1 47 73 64 58
Francie Franciaország

Danmark Malta
Recordati AB. RECORDATI RARE DISEASES
Tlf: +46 8 545 80 230 Tel: +33 1 47 73 64 58
Sverige Franza

Deutschland Nederland
RECORDATI RARE DISEASES Germany Recordati bv
GmbH Tel: +32 2 46101 36
Tel: +49 731 140 554 0 België

Eesti Norge
Recordati AB. Recordati AB.
Tel: + 46 8 545 80 230 Tlf: +46 8 545 80 230
Rootsi Sverige

Ελλάδα Österreich
Recordati Hellas RECORDATI RARE DISEASES Germany
Τηλ: +30 210 6773822 GmbH
Tel: +49 731 140 554 0
Deutschland

España Polska
RECORDATI RARE DISEASES Spain S.L.U. RECORDATI RARE DISEASES
Tel: + 34 91 659 28 90 Tel: +33 (0)1 47 73 64 58
Francja

France Portugal
RECORDATI RARE DISEASES Jaba Recordati S.A.
Tél: +33 (0)1 47 73 64 58 Tel: +351 21 432 95 00

Hrvatska România
Recordati Rare Diseases RECORDATI RARE DISEASES
Tél: +33 (0)1 47 73 64 58 Tel: +33 (0)1 47 73 64 58
Francuska Franţa

Ireland Slovenija
RECORDATI RARE DISEASES RECORDATI RARE DISEASES
Tel: +33 (0)1 47 73 64 58 Tel: +33 (0)1 47 73 64 58
Francia Francija

Ísland Slovenská republika
Recordati AB. RECORDATI RARE DISEASES
Simi: +46 8 545 80 230 Tel: +33 (0)1 47 73 64 58
Svíþjóð Francúzsko

Italia Suomi/Finland
RECORDATI RARE DISEASES Italy Srl Recordati AB.
Tel: +39 02 487 87 173 Puh/Tel: +46 8 545 80 230
Sverige

Κύπρος Sverige
RECORDATI RARE DISEASES Recordati AB.
Τηλ: +33 1 47 73 64 58 Tel: +46 8 545 80 230
Γαλλία

Latvija
Recordati AB.
Tel: + 46 8 545 80 230
Zviedrija

This medicinal product has been granted a marketing authorization under "exceptional circumstances".
This 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 on this medicinal product annually, and this package leaflet will be updated if necessary.

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu. In addition, links to other websites on rare diseases and their treatments are provided.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

ANNEX IV
CONCLUSIONS ON THE GRANTING OF THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
Conclusions presented by the European Medicines Agency on:

• Granting of the marketing authorisation under exceptional circumstances
  Following the evaluation of the marketing authorisation application, the Committee for Medicinal Products for Human Use (CHMP) concluded that the benefit-risk balance is favourable and recommended granting the marketing authorisation under exceptional circumstances, as further described in the European Public Assessment Report (EPAR).