LIVMARLI- maralixibat chloride solution

Nchi: Marekani

Lugha: Kiingereza

Chanzo: NLM (National Library of Medicine)

Viambatanisho vya kazi:

maralixibat chloride (UNII: V78M04F0XC) (maralixibat - UNII:UYB6UOF69L)

Inapatikana kutoka:

Mirum Pharmaceuticals Inc.

Njia ya uendeshaji:

ORAL

Dawa ya aina:

PRESCRIPTION DRUG

Matibabu dalili:

LIVMARLI® is indicated for the treatment of cholestatic pruritus in patients 3 months of age and older with Alagille syndrome (ALGS). LIVMARLI is indicated for the treatment of cholestatic pruritus in patients 5 years of age and older with progressive familial intrahepatic cholestasis (PFIC). Limitations of Use: LIVMARLI is not recommended in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in non-functional or complete absence of bile salt export pump (BSEP) protein [see Clinical Studies (14.2)] . LIVMARLI is contraindicated in patients with prior or active hepatic decompensation events (e.g., variceal hemorrhage, ascites, hepatic encephalopathy) [see Warnings and Precautions (5.1)] . Risk Summary Maternal use at the recommended clinical dose of LIVMARLI is not expected to result in measurable fetal exposure because systemic absorption following oral administration is low [see Clinical Pharmacology (12.3)]. Maralixibat may inhibit the absorption of fat-soluble vitamins [see Warnings and Precautions (5.3) and Clinical Considerations] . In animal reproduction studies, no developmental effects were observed (see Data) . The estimated background risk of major birth defects for ALGS is higher than the general population because ALGS is an autosomal dominant condition. The background risk of miscarriage for ALGS is unknown. The background risk of birth defects and miscarriage for PFIC is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Maralixibat may inhibit the absorption of fat-soluble vitamins (FSV). Monitor for FSV deficiency and supplement as needed. Increased supplementation of FSVs may be needed during pregnancy [see Warnings and Precautions (5.3)] . Data Animal Data No effects on embryo-fetal development were observed in pregnant rats treated orally with up to 1000 mg/kg/day (approximately 3300 to 12000 times the maximum recommended dose based on AUC [area under the plasma concentration-time curve]) or in pregnant rabbits treated orally with up to 250 mg/kg/day (approximately 1200 to 4700 times the maximum recommended dose based on AUC) during the period of organogenesis. No effects on postnatal development were observed in a pre- and postnatal development study, in which female rats were treated orally with up to 750 mg/kg/day during organogenesis through lactation. Maternal systemic exposure to maralixibat at the maximum dose tested was approximately 2500 to 9400 times the maximum recommended dose based on AUC. Risk Summary LIVMARLI has low absorption following oral administration, and breastfeeding is not expected to result in exposure of the infant to LIVMARLI at the recommended dose [see Clinical Pharmacology (12.3)] . There are no data on the presence of LIVMARLI in human milk, the effects on the breastfed infant, or the effects on milk production. Patients with ALGS or PFIC can have FSV deficiency as part of their disease. Maralixibat may reduce absorption of fat-soluble vitamins [see Warnings and Precautions (5.3)] . Monitor FSV levels and supplement FSV intake, if FSV deficiency is observed during lactation. The developmental and health benefits of breastfeeding should be considered along with the mother's need for LIVMARLI and any potential adverse effects on the breastfed child from LIVMARLI or from the underlying maternal condition. ALGS The safety and effectiveness of LIVMARLI for the treatment of cholestatic pruritus in Alagille syndrome have been established in pediatric patients aged 3 months of age and older. Use of LIVMARLI in this population is supported by evidence from a study of patients 1 to 15 years of age (N=31) that included 18 weeks of open-label treatment followed by a 4 week placebo-controlled randomized withdrawal period and a subsequent 26-week open-label treatment period. Additional safety information was obtained from four studies in patients up to 21 years of age (N=55) [see Adverse Reactions (6) and Clinical Studies (14.1)] . Use of LIVMARLI in patients 3 to <12 months of age is supported by an open-label, multicenter study of LIVMARLI which showed a similar safety, tolerability and pharmacokinetic profile to patients with ALGS ≥12 months of age. The safety and effectiveness of LIVMARLI have not been established in patients with ALGS less than 3 months of age. PFIC The safety and effectiveness of LIVMARLI for the treatment of cholestatic pruritus in PFIC have been established in pediatric patients aged 5 years of age and older. Use of LIVMARLI in this population is supported by evidence from Trial 2 in patients 1 to <18 years of age that included 26 weeks of placebo-controlled safety and efficacy data [see Adverse Reactions (6) and Clinical Studies (14.2)] . The safety and effectiveness of LIVMARLI have not been established in patients with PFIC younger than 12 months of age. The safety and effectiveness of LIVMARLI for the treatment of pruritus in ALGS or PFIC in adult patients, 65 years of age and older, have not been established. Clinical studies of LIVMARLI included ALGS or PFIC patients with impaired hepatic function at baseline. The efficacy and safety in ALGS or PFIC patients with clinically significant portal hypertension and in patients with decompensated cirrhosis have not been established. LIVMARLI is contraindicated in patients with prior or active hepatic decompensation events [see Dosage and Administration (2.5), Contraindications (4), Warnings and Precautions (5.1), and Clinical Studies (14)] . - Before you give LIVMARLI for the first time, talk to your healthcare provider or pharmacist about how to correctly measure your prescribed dose. - You may be given 1 or more dosing dispensers of different sizes as shown in Table 1 below. Always use the correct dosing dispenser size provided with LIVMARLI based on your current prescribed dose. - Your prescribed dose may change over time. Use the table above to choose the correct dosing dispenser size for your prescribed dose. - If you do not have the correct dosing dispenser size for your prescribed dose, contact your healthcare provider or pharmacist. - The dosing dispenser may be used for 100 days if cleaned correctly (see Section C). After 100 days, replace the dosing dispenser with a new one. A new replacement dosing dispenser may be used within the 100 days if necessary. - Do not use a household teaspoon or any other dosing device to measure the dose. - Do not open more than 1 bottle at a time. - Do not give more than the prescribed dose. - Do not use LIVMARLI after 100 days of first opening the bottle or after the throw away (discard) date listed on the pharmacy label (see Section D). - When you start a new bottle of LIVMARLI, use a new dosing dispenser. - Store unopened LIVMARLI at room temperature, between 68°F and 77°F (20°C and 25°C). - After opening the LIVMARLI bottle, store below 86°F (30°C). - Store the dosing dispenser in a clean, dry place when not in use. LIVMARLI (9.5 mg/mL):                                          Figure A                                          Figure B                                                  Figure C Figure D Figure E - Make sure you use the correct dosing dispenser size for your prescribed dose (See Table 1). - After 100 days, replace with a new dosing dispenser provided. A new replacement dosing dispenser may be used within the 100 days if necessary. - Check the dosing dispenser for any damage to the barrel, plunger or tip (See Figure G). If you cannot see the dosage marking or if it becomes hard to move the plunger, replace with a new dosing dispenser. Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M Figure N Figure O Figure P Figure Q Figure R Section C: Cleaning instructions for the dosing dispenser Figure S Figure T Figure U Figure V Figure W Figure X Before you give the next dose, put the dosing dispenser back together by pushing the plunger into the barrel (See Figure Y). Figure Y Section D: Disposal - Throw away (dispose of) the bottle of LIVMARLI following the steps below 100 days after first opened or after the throw away (discard) date listed on the pharmacy label, even if there is still medicine in it. Mix medicine with a substance such as dirt, cat litter, or used coffee grounds. Place the mixture in a container such as a sealed plastic bag. Delete all personal information on the prescription label of the empty medicine bottle, then throw away (dispose of) in the household trash or recycle the empty bottle. - Mix medicine with a substance such as dirt, cat litter, or used coffee grounds. - Place the mixture in a container such as a sealed plastic bag. - Delete all personal information on the prescription label of the empty medicine bottle, then throw away (dispose of) in the household trash or recycle the empty bottle. - Throw away (dispose of) used dosing dispensers in the household trash.

Bidhaa muhtasari:

Oral Solution LIVMARLI is a clear, colorless to yellow oral solution. Each amber plastic bottle contains LIVMARLI oral solution at a concentration of 9.5 mg per mL. One 30 mL amber plastic bottle: NDC 79378-110-01 Storage and Handling Store unopened LIVMARLI between 20°C and 25°C (68°F and 77°F), excursion permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. After opening the LIVMARLI bottle, store below 30°C (86°F) [see Dosage and Administration (2.4)] .

Idhini hali ya:

New Drug Application

Tabia za bidhaa

LIVMARLI- MARALIXIBAT CHLORIDE SOLUTION
MIRUM PHARMACEUTICALS INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LIVMARLI SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR LIVMARLI.
LIVMARLI (MARALIXIBAT) ORAL SOLUTION
INITIAL U.S. APPROVAL: 2021
RECENT MAJOR CHANGES
Indications and Usage (1)
3/2024
Dosage and Administration (2)
3/2024
Contraindications (4)
3/2024
Warnings and Precautions (5.1)
3/2024
Warnings and Precautions (5.2)
3/2024
Warnings and Precautions (5.3)
3/2024
INDICATIONS AND USAGE
LIVMARLI is an ileal bile acid transporter (IBAT) inhibitor indicated
for:
the treatment of cholestatic pruritus in patients 3 months of age and
older with Alagille syndrome
(ALGS). (1.1)
the treatment of cholestatic pruritus in patients 5 years of age and
older with progressive familial
intrahepatic cholestasis (PFIC). (1.2)
Limitations of Use:
LIVMARLI is not recommended in a subgroup of PFIC type 2 patients with
specific ABCB11 variants
resulting in non-functional or complete absence of bile salt export
pump (BSEP) protein. (14.2)
DOSAGE AND ADMINISTRATION
ALGS: The recommended dosage is 380 mcg/kg once daily, taken 30
minutes before a meal in the
morning. (2.1)
Starting dose is 190 mcg/kg orally once daily, and should be increased
to 380 mcg/kg once daily
after one week, as tolerated and not to exceed a maximum daily dose of
28.5 mg. (2.1)
PFIC: The recommended dosage is 570 mcg/kg twice daily. (2.2)
Starting dose is 285 mcg/kg orally once daily in the morning and
should be increased to 285 mcg/kg
twice daily, 428 mcg/kg twice daily, and then to 570 mcg/kg twice
daily, as tolerated and not to
exceed a maximum daily dose of 38 mg. (2.2)
DOSAGE FORMS AND STRENGTHS
Oral solution: 9.5 mg of maralixibat per mL. (3)
CONTRAINDICATIONS
Patients with prior or active hepatic decompensation events (e.g.,
variceal hemorrhage, ascites, hepatic
encephalopathy). (4)
WARNINGS AND PRECAUTIONS
Hepatotoxicity: Obtain baseline liver tests and monitor patien