LIVMARLI Oral solution Ref.[50565] Active ingredients: Maralixibat

Treatment with Livmarli should be initiated under the supervision of a physician experienced in the management of patients with cholestatic liver diseases.

Alagille syndrome (ALGS)

The recommended target dose is 380 mcg/kg once daily. The starting dose is 190 mcg/kg once daily and should be increased to 380 mcg/kg once daily after one week. Table 1 provides the dose in mL of solution to be given for each weight range. In case of poor tolerability, dose reduction from 380 mcg/kg/day to 190 mcg/kg/day, or treatment interruption should be considered. Renewed dose-escalation can be attempted as tolerated. The maximum recommended daily dose volume for patients above 70 kg is 3 mL (28.5 mg).

Table 1. Individual dose volume by patient weight: ALGS:

Progressive familial intrahepatic cholestasis (PFIC)

The starting dose is 285 mcg/kg once daily (QD) and may be increased after 1-2 weeks to 285 mcg/kg twice daily (BID, morning and evening). After 1-2 weeks, the dose can be increased to 570 mcg/kg twice daily if clinically indicated, as tolerated. Table 2 provides the dose in mL of solution to be given for each weight range. In case of poor tolerability, dose reduction or treatment interruption should be considered. Renewed dose-escalation can be attempted as tolerated. The maximum daily dose volume for patients above 50 kg is 6 mL (57 mg).

Table 2. Individual dose volume by patient weight: PFIC:

Alternative treatment should be considered in patients for whom no treatment benefit can be established following 3 months of continuous daily treatment with maralixibat.

Missed dose

If a dose is missed, the dose should be omitted, and the original dose schedule resumed with the next scheduled intake.

Special populations

Renal impairment

Maralixibat has not been studied in patients with renal impairment or end-stage renal disease (ESRD) requiring haemodialysis. Maralixibat has minimal plasma concentrations and negligible renal excretion (see section 5.2).

ALGS: No dose adjustment is required.

PFIC: The maximum recommended dose of Livmarli in patients with moderate renal impairment (creatinine clearance CrCl ≥30 and < 60 ml/min) is 285 mcg/kg BID, due to propylene glycol content. Livmarli should not be used in patients with PFIC and severe renal impairment (creatinine clearance CrCl <30 ml/min; see sections 4.3 and 4.4)

Hepatic impairment

Maralixibat has not been sufficiently studied in patients with liver impairment.

ALGS: Due to minimal absorption of maralixibat, no dose adjustment is required for patients with hepatic impairment. Close monitoring is, however, advised for patients with end-stage liver disease or progression to decompensation.

PFIC: The maximum recommended dose of Livmarli in patients with moderate hepatic impairment is 285 mcg/kg BID, due to propylene glycol content. Livmarli should not be used in patients with PFIC and severe hepatic impairment (see sections 4.3 and 4.4).

Paediatric population

The safety and efficacy of Livmarli in infants less than 2 months of age in ALGS, or less than 3 months of age in PFIC, have not been established. Currently available data are described in sections 4.8, 5.1, and 5.2, and no recommendation on a posology can be made in these age groups.

ALGS (≥2 months of age): No dose adjustment is required.

PFIC (≥3 months of age): The maximum recommended dose of Livmarli in PFIC patients below 5 years of age is 285 mcg/kg BID, due to propylene glycol content (see section 4.4).

Special attention should be paid to accurate calculation of the Livmarli dose and clear communication of dosing instructions to caregivers and patients to minimise the risk of erroneous dosing and overdose.

Method of administration

Livmarli is administered orally via an oral syringe by a caregiver or the patient, before (up to 30 minutes) or with a meal, in the morning for once daily dosing, or in the morning and evening for twice daily dosing.

Mixing Livmarli oral solution directly into food or drink prior to administration has not been studied and should be avoided.

Three sizes of oral syringe (0.5 mL, 1 mL and 3 mL) are provided with each bottle of Livmarli. Tables 1 and 2 provide the correct oral syringe size for each weight range.

Maralixibat is minimally absorbed from the gastrointestinal tract and overdose is not expected to result in high plasma levels of the active substance. Single doses of up to 500 mg, approximately 18-fold higher than the recommended dose, have been administered in healthy adults without any adverse consequences.

Livmarli contains propylene glycol; overdose could result in overdose of propylene glycol (see section 4.4).

In the event of an overdose, general supportive measures should be followed and the patient should be monitored for signs and symptoms of propylene glycol toxicity (see section 4.4). In the event of overdose, propylene glycol can be removed from the body through dialysis.

30 months.

After first opening:

After the first opening of the bottle, the medicinal product must be used within 130 days stored below 30°C. Then the bottle and its contents have to be discarded, even if not empty.

This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from light.

For storage conditions after first opening of the medicinal product, see section 6.3.

30 mL amber-coloured PET bottle with a preinstalled LDPE adapter and a HDPE child-resistant closure with a foam liner, containing 30 mL oral solution.

Pack size:

Each pack contains one 30 mL bottle and is co-packaged with three oral repeated-use syringes (0.5 mL, 1 mL and 3 mL) with the following graduations:

• 0.5 mL polypropylene syringe with a white plunger: numbers for each 0.1 mL, major hash marks for 0.05 mL increments, and minor hash marks for 0.01 mL increments.
• 1 mL polypropylene syringe with a white plunger: numbers for each 0.1 mL increment.
• 3 mL polypropylene syringe with a white plunger: numbers for each 0.5 mL increment, and hash marks for each 0.25 mL increment between 0.5 mL and 3 mL.

The oral syringes may be rinsed with water, air dried and reused for 130 days.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.