Posology : מינונים

5      DOSAGE AND ADMINISTRATION

5.1    Dosing
The recommended dosage is 380 mcg/kg once daily, taken 30 minutes before a meal in the morning.
Start dosing at 190 mcg/kg administered orally once daily; after one week, increase to 380 mcg/kg once daily, as tolerated. The maximum daily dose volume for patients above 70kg is 3 mL or 28.5 mg per day. Refer to the dosing by weight guidelines presented in Table 1.

Table 1: Individual Dose Volume by Patient Weight

Days 1-7                             Beginning Day 8
(190 mcg/kg once daily)                  (380 mcg/kg once daily)
Patient Weight
(kg)
Volume QD          Dosing dispenser     Volume QD         Dosing dispenser (mL)               size (mL)            (mL)              size (mL)
5 to 6               0.1                                        0.2
7 to 9              0.15                                        0.3                  0.5 10 to 12              0.2                                       0.45
13 to 15              0.3                  0.5                   0.6
16 to 19             0.35                                        0.7
1
20 to 24             0.45                                        0.9
25 to 29              0.5                                         1
30 to 34              0.6                                       1.25
35 to 39              0.7                                        1.5
1
40 to 49              0.9                                       1.75
3
50 to 59               1                                        2.25
60 to 69             1.25                                        2.5
3
70 or higher            1.5                                         3 
5.2     Missed Dose
If a dose is missed, it should be taken as soon as possible within 12 hours of the time it is usually taken, and the original dosing schedule should be resumed. If a dose is missed by more than 12 hours, the dose can be omitted and the original dosing schedule resumed.

5.3     Important Administration Instructions
Administer LIVMARLI 30 minutes before a meal in the morning [see Pharmacokinetics (13.3)].
For patients taking bile acid binding resins, take LIVMARLI at least 4 hours before or 4 hours after taking a bile acid binding resin [see Drug Interactions (9.1)].
A calibrated measuring device (0.5 mL, 1 mL or 3 mL oral dosing dispenser) shell be used by the patient to measure and deliver the prescribed dose accurately.

5.4     Dose 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. Interrupt LIVMARLI if new onset liver test abnormalities occur in the absence of other causes. Once the liver test abnormalities either return back to baseline values or stabilize at a new baseline value, consider restarting LIVMARLI at 190 mcg/kg, and increase to 380 mcg/kg as tolerated. Consider discontinuing LIVMARLI permanently if liver test abnormalities recur or symptoms consistent with clinical hepatitis are observed [see Warnings and Precautions (7.1)].

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).