Livmarli 9.5 mg/ml oral solution
Spain
Table of Contents
Package leaflet: Information for the user
Introduction
Package leaflet: information for the user
Livmarli 9.5 mg/ml oral solution
maralixibat
This medicinal product is subject to additional monitoring, which will allow for faster detection of new safety information. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions is included at the end of section 4.
Read all of 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 questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
- If you or your child experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are possible adverse reactions not listed in this leaflet. See section 4.
Contents of this leaflet
- What Livmarli is and what it is used for
- What you need to know before you or your child start taking Livmarli
- How to take Livmarli
- Possible side effects
- How to store Livmarli
- Contents of the pack and other information
1. What Livmarli is and what it is used for
What Livmarli is
Livmarli contains the active substance maralixibat (as chloride). It helps remove substances called bile acids from the body.
Bile acids are found in a digestive fluid called bile, which is produced by the liver. Bile acids travel from the liver to the intestine and help digest food. After aiding digestion, they return to the liver.
What Livmarli is used for
Livmarli is used to treat cholestatic pruritus in patients aged 2 months and older with Alagille syndrome (ALGS). Livmarli is also used to treat progressive familial intrahepatic cholestasis (PFIC) in patients aged 3 months and older.
ALGS and PFIC are rare genetic diseases that can cause bile acids to accumulate in the liver. This is known as cholestasis. Cholestasis may worsen over time and often causes severe itching, fatty deposits under the skin (xanthomas), growth delay, and feelings of fatigue.
How Livmarli (maralixibat) works
Maralixibat works by reducing the accumulation of bile acids in the liver. It does this by preventing bile acids from being transported back to the liver after they have performed their function in the intestines. This allows bile acids to be eliminated from the body through the feces.
2. What you need to know before you or your child start taking Livmarli
Do not use Livmarli
- If you or your child are allergic to maralixibat or any of the other ingredients of this medicine (listed in section 6).
- If you or your child have severe renal and/or hepatic impairment.
Warnings and precautions
Consult your doctor if your diarrhea worsens while taking Livmarli. If you have diarrhea, drink plenty of fluids to avoid dehydration.
An increase in liver enzyme levels may be observed in liver function tests during treatment with Livmarli. Before starting Livmarli, your doctor will measure your liver function to check whether your liver is working properly. Your doctor will perform periodic checks to monitor liver function.
Your doctor may carry out blood tests before starting or during treatment with Livmarli to check your INR (international normalized ratio; a laboratory test to monitor bleeding risk) and levels of certain fat-soluble vitamins (vitamins A, D, E, and K). If your vitamin levels are low, your doctor may recommend vitamin supplementation.
Certain diseases, medications, or surgeries may affect the movement of food through the intestine. They may also affect the transport of bile acids between the liver and intestine. This could interfere with the proper functioning of maralixibat.
Ensure that your doctor is aware of any diseases, medications, or surgeries you have had or are taking.
Taking Livmarli with medications containing alcohol may cause adverse effects in children under 5 years of age or in patients with impaired 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 this medicine, especially if you or your child are taking other medications or dietary supplements containing propylene glycol or alcohol.
Children
Livmarli is not recommended in children with Alagille syndrome under 2 months of age, as safety and efficacy have not yet been established in this age group.
Other medicines and Livmarli
Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including over-the-counter and herbal medicines.
Inform your doctor if you are taking any of the following medicines:
- Fluvastatin, rosuvastatin, or simvastatin (medicines used to treat high cholesterol levels in the blood)
- Midazolam (a medicine used for sedation or to induce sleep)
- Ursodeoxycholic acid (a medicine used to treat liver diseases)
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. If you are pregnant, it is best not to take Livmarli.
Livmarli does not enter the bloodstream and therefore is not expected to pass into breast milk. However, always follow your doctor’s advice.
Driving and using machines
The effect of Livmarli on the ability to drive and use machines is negligible or none.
Livmarli contains propylene glycol and sodium
This medicine contains 364.5 mg of propylene glycol per ml. When taken according to the recommended dosing regimen for PFIC, exposure to propylene glycol will be up to a maximum of 17 mg/kg/day. When taken according to the recommended dosing regimen for ALGS, exposure to propylene glycol will be up to a maximum of 50 mg/kg/day.
If your child is under 5 years of age, consult your doctor or pharmacist before starting this medicine, especially if using 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 medicine unless your doctor recommends it. Your doctor may carry out additional monitoring while you are taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially “sodium-free.”
3. How to take Livmarli
Follow exactly the instructions for administering this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.
How much to take
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The dose of Livmarli you will be given depends on your body weight. Your doctor will calculate the dose and tell you how much to take and which size of oral syringe to use. Your doctor will also record this information and other relevant details (e.g., your weight) in a special patient booklet. Always carry this patient booklet with you whenever you visit your doctor. Do not calculate the dose yourself and take only the dose calculated for you by your doctor. The doses of maralixibat administered to patients with ALGS and PIBD are different. Your doctor will ensure the correct dose is selected for you, depending on your condition and body weight.
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For ALGS: the target dose is 380 micrograms of maralixibat per kilogram of body weight once daily.
- The starting dose is 190 micrograms per kilogram of body weight once daily.
- The dose will be increased to 380 micrograms per kilogram of body weight once daily after one week. Your doctor will tell you when to increase the dose. They will also inform you how much to take and which size of oral syringe to use for the higher dose.
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For PIBD: the starting dose is 285 micrograms per kilogram of body weight once daily in the morning.
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This dose may be increased to 285 micrograms per kilogram of body weight twice daily, and then to 570 micrograms per kilogram of body weight twice daily, depending on how well it is tolerated.
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Patients under 5 years of age and patients with moderate impairment of liver or kidney function must not take doses higher than 285 micrograms per kilogram of body weight twice daily. Your doctor will advise you whether this dose restriction applies to you or your child.
Taking the medicine
You may take Livmarli with food or on an empty stomach up to 30 minutes before a meal, in the morning.
Administer the dose into the mouth using the oral syringe and swallow it (see Figure M). Do not mix the oral solution with food or drinks.
Use the table below to ensure you are using the correct size of oral syringe for the dose prescribed to you:
Prescribed dose volume (ml) | Oral syringe size (ml) |
0.1 to 0.5 | 0.5 |
0.6 to 1 | 1 |
1.25 to 3 | 3 |
Make sure to measure the volume carefully to avoid an overdose.
How to take a dose of this medicine
Step 1: Extracting the dose
1.1 To open the bottle, remove the child-resistant safety cap by pressing it down firmly and turning it to the left (counterclockwise) (see Figure A). Do not discard the child-resistant safety cap, as you will need to replace it after withdrawing the required dose.
Figure A
1.2 Make sure you use the correct oral syringe size for the prescribed dose (see table above). Your doctor will advise you which syringe size to use.
- If you are using a new oral syringe, remove it from the packaging (see Figure B). Discard the packaging in household waste.
- If you are using a previously used oral syringe, ensure it is clean and dry (see section 2.4 for cleaning instructions).
Figure B
- If the oral syringe has a cap, remove and discard it in household waste (see Figure C).
Figure C
The syringe has dose markings on the barrel. One end of the syringe has a connecting cone that inserts into the medicine bottle. The other end of the syringe has a finger flange and a plunger used to draw up and administer the medicine (see Figure D).
Figure D
1.3 Push the plunger fully down to remove air from the syringe (see Figure E).
Figure E
1.4 Make sure to remove the safety cap from the bottle and insert the syringe’s connecting cone into the bottle in an upright position. The syringe’s connecting cone must fit snugly into the bottle opening.
Figure F
1.5 Once the syringe is in place, turn the bottle upside down (see Figure G).
Figure G
1.6 To withdraw a dose from the bottle, slowly pull the plunger back until the plunger aligns with the marking on the syringe barrel corresponding to the prescribed dose (see Figure H). There are two types of plungers that may come with the syringe: a plunger with a flat connecting cone or a plunger with a pointed connecting cone (see Figure I below step 1.6). See Figure I to learn how to align the plunger with the prescribed dose. For the plunger with a flat connecting cone, align the flat end of the plunger with the marking on the barrel corresponding to the prescribed dose (Figure I.a.). For the plunger with a pointed connecting cone, ensure the flat, wide part located below the connecting cone is aligned with the correct marking (Figure I.b.).
1.7 Check 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, withdraw the prescribed dose again following the instructions in step 1.6.
| |
Figure J.a. Check for air bubbles | Figure J.b. Push the plunger in the syringe to remove air bubbles. |
1.8 Once the correct dose has been drawn up without air bubbles, leave the syringe in the vial and turn the vial upwards (see Figure K).
Figure K
1.9 Carefully remove the syringe from the vial (see Figure L). To do this, hold the vial firmly with one hand and the syringe by the barrel with the other.
- Do not press the plunger of the syringe during this step.
Figure L
Step 2: Administration of the dose
Note: You or your child should be standing while taking the dose and for a few minutes afterwards.
2.1 Insert the oral syringe adapter cone against the inside of the cheek (see Figure M).
Slowly press the plunger fully down and gently dispense the oral solution into the mouth (see Figure N).
Figure M Figure N
2.2 Make sure that you/your child swallows the dose. If you are unsure whether the full dose was swallowed, do not administer another dose. Wait until the next scheduled dose.
2.3 To close the bottle, screw the child-resistant safety cap back onto the bottle by turning it to the right (clockwise) (see Figure O).
Figure O
2.4 Remove the plunger from the syringe barrel (see Figure P) and wash it with water after each use. Allow the plunger to air-dry before using it again.
Figure P
- Oral syringes may be rinsed with water, air-dried, and reused for up to 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 your usual time.
If you stop treatment with Livmarli
Do not stop treatment with Livmarli without first consulting your doctor.
4. Possible adverse effects
Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. The following adverse effects may occur with this medicine.
Very common (may affect more than 1 in 10 people)
- Diarrhoea
- Stomach (abdominal) pain (SALG)
Common (may affect up to 1 in 10 people)
- Stomach (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, contact your doctor.
Reporting of adverse effects
If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.
5. Storage of Livmarli
Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage temperature. Store in the original packaging to protect it from light.
Do not use this medicine after the expiry date stated on the carton and on the bottle after "EXP". The expiry date refers to the last day of the month indicated.
After opening the bottle, store it below 30 °C and use the medicine within 130 days of opening. After this 130-day period, the bottle must be discarded, even if it is not empty. Record the date of opening on the Livmarli bottle.
Medicines must 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 container and other information
Composition of Livmarli
- The active substance is maralixibat (as 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 flavour, and purified water.
Appearance of the product and contents of the container
Livmarli is a clear, colourless to pale yellow oral solution. It is supplied in 30 ml amber plastic bottles with a pre-installed adapter and a child-resistant closure with a foam seal. The three sizes of oral syringes (0.5 ml, 1 ml and 3 ml) provided in the package are compatible with the pre-installed adapter and the resealable bottle cap. To ensure correct administration of the Livmarli dose, refer to the table in section 3 (“How to take Livmarli”) to select the appropriate oral syringe size.
Package size
1 bottle of 30 ml with 3 oral syringes (0.5 ml, 1 ml and 3 ml).
Marketing Authorisation Holder
Mirum Pharmaceuticals International B.V.
Kingsfordweg 151
1043 GR Amsterdam,
The Netherlands
Manufacturer
Millmount Healthcare Limited
Block 7 City North Business Campus
Stamullen, Co. Meath, K32 YD60
Ireland
Date of the most recent review of this summary:
This medicine 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 medicine.
Other sources of information
Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicines are also provided.