Summary of Product Characteristics: Information for the User

Livmarli 9.5 mg/ml Oral Solution

maralixibat

This medicine is subject to additional monitoring, which will facilitate 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 leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you or your child experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

What is Livmarli

Livmarli contains the active ingredient maralixibat (in the form of chloride). It helps to eliminate certain substances called bile acids from the body.

Bile acids are found in the digestive fluid called bile produced by the liver. Bile acids pass from the liver to the intestine and help digest food. After helping with digestion, they return to the liver.

What is Livmarli used for

Livmarli is used to treat pruritus in patients aged 2 months and older with Alagille syndrome (SALG).Livmarli is also used to treat progressive familial intrahepatic cholestasis (PFIC) in patients aged 3 months and older.

SALG and PFIC are rare genetic diseases that can cause a buildup of bile acids in the liver, known as cholestasis. Cholestasis can worsen over time and typically produces intense itching, subcutaneous fat deposits (xanthomas), growth retardation, and fatigue.

How Livmarli (maralixibat) works

Maralixibat acts by reducing the accumulation of bile acids in the liver. It does this by preventing bile acids from being transported back to the liver once they have completed their function in the intestines. This allows bile acids to leave the body through feces.

No use Livmarli

• If you or your child are allergic to maralixibat or any of the other components of this medication (listed in section 6).
• If you or your child have severe kidney and/or liver failure.

Warnings and precautions

Consult your doctor if your diarrhea worsens while taking Livmarli. If you have diarrhea, drink plenty of liquids to avoid dehydration.

You may observe an increase in liver enzyme levels in liver function tests while taking Livmarli. Before starting Livmarli, your doctor will measure your liver function to check if your liver is working correctly. Your doctor will perform regular checks to monitor liver function.

Your doctor may perform blood tests before starting or during treatment with Livmarli to check your INR (international normalized ratio; a laboratory test to control the risk of bleeding) and levels of certain fat-stored vitamins (vitamins A, D, E, and K). If your vitamin levels are low, your doctor may recommend taking vitamins.

Some diseases, medications, or surgeries may affect the movement of food through the intestine. They may also affect the movement of bile acids between the liver and the intestine. This may affect the proper functioning of maralixibat.

Make sure your doctor knows about any diseases, medications, or surgeries you have had or taken.

The use of Livmarli with medications containing alcohol may produce adverse effects in children under 5 years of age or in patients with reduced liver and/or kidney function. If you or your child have reduced liver and/or kidney function or if your child is under 5 years of age, consult your doctor or pharmacist before starting to use this medication, especially if you or your child use other medications or dietary supplements containing propylene glycol or alcohol.

Children

Livmarli is not recommended for children with Alagille syndrome under 2 months of age. This is because it is still unknown if it is safe and effective in this age group.

Other medications and Livmarli

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including over-the-counter and herbal medications.

Inform your doctor if you are taking any of the following medications:

• Fluvastatin, rosuvastatin, or simvastatin (medications used to treat high cholesterol levels in the blood)
• Midazolam (a medication used for sedation or to induce sleep)
• Ursodeoxycholic acid (a medication used to treat liver diseases)

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication. If you are pregnant, it is best not to take Livmarli.

Livmarli does not enter the bloodstream, so it is not expected to pass into breast milk. However, always follow your doctor's recommendations.

Driving and operating machines

The influence of Livmarli on the ability to drive and operate machines is negligible or insignificant.

Livmarli contains propylene glycol and sodium

This medication contains 364.5 mg of propylene glycol per ml.When taken according to the recommended administration schedule for SALG, the exposure to propylene glycol will be a maximum of 17 mg/kg/day. When taken according to the recommended administration schedule for CIFP, the exposure to propylene glycol will be a maximum of 50 mg/kg/day.

If your child is under 5 years of age, consult your doctor or pharmacist before starting to administer this medication, especially if they use other medications containing propylene glycol or alcohol. If you are pregnant or breastfeeding, or if you have liver or kidney disease, do not take this medication unless your doctor recommends it. Your doctor may perform additional checks while you are taking this medication.

This medication contains less than 1 mmol of sodium (23 mg) per dose; this is, essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

How much to take

• The dose of Livmarli that will be administered to you depends on your body weight. Your doctor will calculate the dose and tell you how much to take and what size oral syringe to use.Your doctor will also note this information and other relevant data (e.g., your weight) in a special patient leaflet. Bring the patient leaflet with you every time you visit your doctor.Do not calculate the dose yourself and take only the dose that your doctor calculates for you. The doses of maralixibat administered to patients with Primary Alimentary Lymphatic Disease (SALG) and with Cholesteryl Ester Storage Disease (CIFP) are different. Your doctor will ensure that the correct dose is selected for you, depending on your disease and body weight.

• For SALG: the target dose is 380 micrograms of maralixibat per kilogram of body weight once a day.

-The initial dose is 190 micrograms per kilogram of body weight once a day.

-The dose will be increased to 380 micrograms per kilogram of body weight once a day after one week. Your doctor will tell you when you can increase the dose. They will also tell you how much to take and what size oral syringe to use for a higher dose.

• For CIFP: the initial dose is 285micrograms per kilogram of body weight once a day, in the morning.

-This dose can be increased to 285micrograms per kilogram of body weight twice a day and, subsequently, to 570micrograms per kilogram of body weight twice a day, as tolerated.

-Patients under 5years of age and patients with moderate reduction of liver or kidney function should not take doses greater than 285micrograms per kilogram of body weight twice a day. Your doctor will tell you if this dose restriction affects you or your child.

Medication intake

You can take Livmarli with food or on an empty stomach up to 30 minutes before eating, in the morning.

Administer the dose in the mouth with the help of the oral syringe and swallow (see Figure M). Do not mix the oral solution with food or drinks.

Use the table below to ensure that you use the correct size of oral syringe for the prescribed dose:

Make sure to measure carefully the volume to avoid an overdose.

How to take a dose of this medication

Step 1: Dose extraction

1.1To open the bottle, remove the child-resistant cap by pressing it firmly down and turning it to the left (counterclockwise) (see Figure A). Do not discard the child-resistant cap as you will need to put it back on after extracting the dose you need.

Figure A

1.2Make sure to use the correct size of oral syringe for the prescribed dose (see table above). Your doctor will tell you which size of oral syringe to use.

• If you are using a new oral syringe, take it out of the packaging (see Figure B). Throw the packaging away.
• If you are using a previously used oral syringe, make sure it is clean and dry (see 2.4 cleaning instructions).

Figure B

• If the oral syringe has a cap, remove it and discard it in the household trash (see Figure C).

Figure C

The syringe has dose markings on the barrel. One end of the syringe has a coupling cone that is inserted into the medication bottle. The other end of the syringe has a retaining clip and a plunger that is used to extract the medication from the syringe and administer it (see Figure D).

Figure D

1.3Push the plunger all the way down to remove the air from the syringe (see Figure E).

Figure E

1.4Make sure to remove the child-resistant cap from the bottle and insert the coupling cone of the syringe into the bottle in a vertical position. The coupling cone of the syringe should fit snugly into the bottle opening

Figure F

1.5Once the syringe is in place, turn the bottle clockwise (see Figure G).

Figure G

1.6To extract a dose from the bottle, pull the plunger back slowly until the plunger aligns with the dose marking on the syringe barrel that corresponds to the prescribed dose (see Figure H). There are two types of plungers that you may receive with the syringe: a plunger with a flat coupling cone or a plunger with a pointed coupling cone (see Figure I below Step 1.6). See Figure I to know how to align the plunger with the prescribed dose. In the case of the plunger with the flat coupling cone, the flat end of the plunger should be aligned with the dose marking on the barrel that corresponds to the prescribed dose (Figure I.a.). In the case of the plunger with the pointed coupling cone, make sure that the flat and wide area located below the coupling cone is aligned with the correct marking (Figure I.b.).

1.7Check the syringe for air bubbles. If you see air bubbles:

• Press the plunger to push the air bubbles back into the bottle (see Figure J).
• Then, re-extract the prescribed dose following the instructions in Step 1.6.

1.8Once the correct dose without air bubbles is extracted, leave the syringe in the bottle and turn the bottle clockwise (see Figure K).

Figure K

1.9Remove the syringe from the bottle carefully (see Figure L). To do this, hold the bottle firmly with one hand and the syringe by the barrel with the other.

• Do not press the plunger during this step.

Figure L

Step 2: Dose administration

Note:You or your child should stand up while taking the dose and for a few minutes afterwards.

2.1Insert the coupling cone of the oral syringe against the inner cheek (see Figure M).

Press the plunger slowly until the bottom and gently pour the oral solution into the mouth (see Figure N).

FigureMFigure N

2.2Make sure you or your child swallows the dose. If you are unsure whether you have swallowed the entire dose, do not administer another dose. Wait until the next scheduled dose.

2.3To close the bottle,put the child-resistant cap back on the bottle by turning it clockwise (in the direction of the clock hands) (see Figure O).

Figure O

2.4Remove the plunger from the syringe barrel (see Figure P) and wash it with water after each use. Let the plunger air dry before using it again.

Figure P

• Oral syringes can be rinsed with water, air dried, and reused for 130 days.

If you take more Livmarli than you should

Inform your doctor if you take more Livmarli than you should.

If you forget to take Livmarli

If you have forgotten to take a dose, take the next dose at the usual time.

If you interrupt treatment with Livmarli

Do not interrupt treatment with Livmarli without consulting your doctor first.

Like all medications, this medication may produce adverse effects, although not everyone will experience them. The following adverse effects may occur with this medication.

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

• Diarrhea
• Abdominal pain (SALG)

Common(may affect up to 1 in 10 people)

• Abdominal pain (CIFP)
• Increased liver enzymes (ALT, AST)

These adverse effects are usually mild or moderate and may improve during continued treatment with Livmarli.

If you experience any other adverse effect, call your doctor.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the national notification system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

This medication does not require any special storage temperature. Store in the original packaging to protect it from light.

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

Once the bottle is opened, it must be stored below 30 °C and administer the medication within 130 days after opening. After these 130 days have passed, the bottle must be discarded, even if it is not empty. Note the opening date on the Livmarli bottle.

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

Composition of Livmarli

• The active ingredient is maralixibat (in the form of chloride).
• Each ml of solution contains maralixibat chloride equivalent to 9.5 mg of maralixibat.
• The other components are propylene glycol (E1520) (see section 2 “Livmarli contains propylene glycol and sodium”), disodium edetate (see section 2 “Livmarli contains propylene glycol and sodium”), sucralose, grape aroma, and purified water.

Appearance of the product and contents of the container

Livmarli is a transparent and colorless to light yellow oral solution. It is preserved in amber-colored 30 ml plastic bottles with a pre-installed adapter and a child-resistant safety closure with a foam seal. The three oral syringe sizes (0.5 ml, 1 ml, and 3 ml) supplied in the container are compatible with the pre-installed adapter and the reusable bottle cap. To ensure the correct administration of Livmarli, consult the table in section 3 (“How to take Livmarli”) to select the correct size of the oral syringe.

Container size

1 bottle of 30 ml with 3 oral syringes (0.5 ml, 1 ml, and 3 ml).

Marketing Authorization Holder

Mirum Pharmaceuticals International B.V.

Kingsfordweg 151

1043 GR Amsterdam,

Netherlands

Responsible for manufacturing

Millmount Healthcare Limited

Block 7 City North Business Campus

Stamullen, Co. Meath, K32 YD60

Ireland

Last review date of this leaflet:

This medicine has been authorized under «exceptional circumstances». This type of authorization means that due to the rarity of this disease, it has not been possible to obtain complete information about this medicine.

Other sources of information

The detailed information about this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.There are also links to other websites about rare diseases and orphan medicines.