Posology : מינונים

2      DOSAGE AND ADMINISTRATION

2.1    Recommended Dosage
Conduct baseline testing of thiamine (Vitamin B1) levels prior to initiation of INREBIC [see Dosage and Administration (2.2), Warnings and Precautions (5.1)].
The recommended dosage of INREBIC is 400 mg taken orally once daily for patients with a baseline platelet count of greater than or equal to 50 x 109/L.

INREBIC may be taken with or without food. Administration with a high fat meal may reduce the incidence of nausea and vomiting.

The capsules should not be opened, broken or chewed. They should be swallowed whole, preferably with water.

Modify the dose for patients using concomitant strong CYP3A4 inhibitors, and in patients with severe renal impairment (creatinine clearance (CLcr) 15 mL/min to 29 mL/min) [see Dosage and Administration (2.3, 2.4)].

If a dose of INREBIC is missed, the next scheduled dose should be taken the following day.

Patients that are on treatment with ruxolitinib before the initiation of INREBIC must taper and discontinue according to the ruxolitinib prescribing information.

2.2       Monitoring for Safety
Obtain the following blood tests prior to starting treatment with INREBIC, periodically during treatment, and as clinically indicated [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5)]: •   Thiamine (Vitamin B1) level
•   Complete blood count with platelets
•   Creatinine and BUN
•   Hepatic panel
•   Amylase and lipase

2.3       Dose Modifications with Concomitant Use of Strong CYP3A4 Inhibitors
Reduce INREBIC dose when administering with strong CYP3A4 inhibitors to 200 mg once daily.
In cases where coadministration with a strong CYP3A4 inhibitor is discontinued, INREBIC dosage should be increased to 300 mg once daily during the first two weeks after discontinuation of the CYP3A4 inhibitor, and then to 400 mg once daily thereafter as tolerated [see Drug Interactions (7.1)].
2.4       Dose Modifications for Severe Renal Impairment
Reduce INREBIC dose to 200 mg once daily in patients with severe renal impairment (creatinine clearance (CLcr) 15 mL/min to 29 mL/min as estimated by Cockcroft-Gault (C-G) equation).
2.5       Dose Modifications for Adverse Reactions
Modify dose for hematologic and nonhematologic adverse reactions per Table 1 and Table 2. Discontinue INREBIC in patients unable to tolerate a dose of 200 mg daily. See Warnings and Precautions for other mitigating strategies.
Table 1: Dose Modifications for Hematologic Adverse Reactions

Hematologic Adverse Reactions                                 Dose Reduction 
Grade 4 Thrombocytopenia or                           Interrupt dose until resolved to Grade 2 or lower or baseline. Restart dose at 100 mg daily below the last
Grade 3 Thrombocytopenia with active bleeding         given dose.
Interrupt dose until resolved to Grade 2 or lower or
Grade 4 Neutropenia                                   baseline. Restart dose at 100 mg daily below the last given dose.

Consider dose reductions for patients who become transfusion-dependent during treatment with INREBIC.

Table 2: Dose Reductions for Nonhematologic Adverse Reactions
Nonhematologic Adverse Reactions                                Dose Reduction Interrupt dose until resolved to Grade 1 or lower or
Grade 3 or higher Nausea, Vomiting, or Diarrhea not baseline. Restart dose at 100 mg daily below the last responding to supportive measures within 48 hours given dose.


Nonhematologic Adverse Reactions                                   Dose Reduction Interrupt dose until resolved to Grade 1 or lower or baseline. Restart dose at 100 mg daily below the last given dose.
Grade 3 or higher ALT, AST, or Bilirubin               Monitor ALT, AST, and bilirubin (total and direct) more frequently following the dose reduction. If reoccurrence of a Grade 3 or higher elevation, discontinue treatment with INREBIC.
Interrupt dose until resolved to Grade 1 or lower or
Grade 3 or higher Other Nonhematologic Toxicities      baseline. Restart dose at 100 mg daily below the last given dose.
2.6    Management of Thiamine Levels and Wernicke’s Encephalopathy (WE)
Assess thiamine levels and nutritional status prior to starting INREBIC and periodically during treatment and as clinically indicated. Do not start INREBIC in patients with thiamine deficiency; replete thiamine prior to treatment initiation and during treatment if thiamine levels are low. If Wernicke’s encephalopathy is suspected, immediately discontinue treatment with INREBIC and initiate parenteral thiamine treatment. Monitor until symptoms resolve or improve and thiamine levels normalize [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].