Maralixibat chloride

Monitor patients for signs of potential propylene glycol toxicity, including hemolysis, hyperosmolarity with anion gap metabolic acidosis, acute kidney injury, and CNS toxicity. Discontinue LIVMARLI oral solution if propylene glycol toxicity is suspected [see Overdosage ].

Recommended Dosage for Progressive Familial Intrahepatic Cholestasis Use LIVMARLI Oral Solution 19 mg/mL or LIVMARLI Tablets for the treatment of PFIC . The two strengths of LIVMARLI, 9.5 mg/mL and 19 mg/mL, should not be substituted for one another when treating PFIC patients. Special attention should be given to the accurate calculation of the dose volume of LIVMARLI.

This is especially important for pediatric patients less than 5 years old as LIVMARLI oral solution contains the excipient propylene glycol (364.5 mg/mL) [see Warnings and Precautions and Overdosage ]. The recommended dosage is 570 mcg/kg twice daily 30 minutes before a meal. The 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.

The maximum daily dose should not exceed 38 mg (2 mL) per day for LIVMARLI oral solution and 40 mg per day for LIVMARLI tablets. Refer to the dosing by weight guidelines presented in Table 3 for LIVMARLI oral solution and Table 4 for LIVMARLI tablets. [See table below.] 9 mg/mL LIVMARLI Oral Solution for Patients with PFIC: Volume per Dose (mL) by Weight Patient Weight (kg) 285 mcg/kg (once daily titrated to twice daily) 428 mcg/kg (twice daily) 570 mcg/kg (twice daily as tolerated) 19 mg/mL Solution (for PFIC) Volume per Dose (mL) 5 0.1 0.1 0.15 6 to 7 0.1 0.15 0.2 8 0.1 0.2 0.25 9 0.15 0.2 0.25 10 to 12 0.15 0.25 0.3 13 to 15 0.2 0.3 0.4 16 to 19 0.25 0.4 0.5 20 to 24 0.3 0.5 0.6 25 to 29 0.4 0.6 0.8 30 to 34 0.45 0.7 0.9 35 to 39 0.6 0.8 1 40 to 49 0.6 0.9 1 50 to 59 0.8 1 1 60 or higher 0.9 1 1 [See table below.] 44 or higher 15 mg 20 mg 20 mg

Dosage Modification for Management of Adverse Events Establish the baseline pattern of variability of liver tests prior to starting LIVMARLI, so that potential signs of liver injury can be identified. Monitor liver tests (e.g., ALT [alanine aminotransferase], AST [aspartate aminotransferase], TB [total bilirubin]), DB [direct bilirubin], and International Normalized Ratio [INR]) during treatment with LIVMARLI.

Reduce the dosage or interrupt LIVMARLI if new onset liver test abnormalities occur. Once the liver test abnormalities either return back to baseline values or stabilize at a new baseline value, consider restarting LIVMARLI at the last tolerated dose, and increase the dose as tolerated. Consider discontinuing LIVMARLI permanently if liver test abnormalities recur or symptoms consistent with clinical hepatitis are observed [see Warnings and Precautions ] .

LIVMARLI has not been studied in patients with hepatic decompensation. Discontinue LIVMARLI permanently if a patient experiences a hepatic decompensation event (e.g., variceal hemorrhage, ascites, hepatic encephalopathy).

Important Administration Information

Use LIVMARLI Oral Solution 9.5 mg/mL for treatment of ALGS.

Use LIVMARLI Oral Solution 19 mg/mL for treatment of PFIC.

The two strengths of LIVMARLI Oral Solution, 9.5 mg/mL and 19 mg/mL, should not be substituted for one another when treating PFIC patients [see Dosage and Administration ].

LIVMARLI tablets can be used for treatment of both ALGS and PFIC in patients weighing 25 kg and above who can swallow tablets. Select LIVMARLI Oral Solution or LIVMARLI Tablets based on the patient's weight and ability to swallow tablets [see Dosage and Administration (2.2 , 2.3 )].

Important Administration Instructions Administer LIVMARLI oral solution and tablets 30 minutes before a meal [see Clinical Pharmacology ] . A calibrated measuring device (0.5 mL, 1 mL or 3 mL oral dosing dispenser) for LIVMARLI oral solution will be provided by the pharmacy to measure and deliver the prescribed dose accurately.

After opening the LIVMARLI oral solution bottle, store below 30°C (86°F) and discard any remaining LIVMARLI oral solution after 100 days.

Administration Modification for Drug Interaction Bile Acid Binding Resins Administer LIVMARLI at least 4 hours before or 4 hours after administering the bile acid binding resins [see Drug Interactions ] when used concomitantly .