Source: FDA, National Drug Code (US) Revision Year: 2020
INREBIC is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).
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 × 109/L.
INREBIC may be taken with or without food. Administration with a high fat meal may reduce the incidence of nausea and vomiting.
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.
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)]:
Reduce INREBIC dose when administering with strong CYP3A4 inhibitors to 200 mg once daily.
In cases where co-administration 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)].
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).
Modify dose for hematologic and non-hematologic 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 Grade 3 Thrombocytopenia with active bleeding | Interrupt dose until resolved to Grade 2 or lower or baseline. Restart dose at 100 mg daily below the last given dose. |
| Grade 4 Neutropenia | Interrupt dose until resolved to Grade 2 or lower or 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 Non-hematologic Adverse Reactions:
| Non-hematologic Adverse Reactions | Dose Reduction |
|---|---|
| Grade 3 or higher Nausea, Vomiting, or Diarrhea not responding to supportive measures within 48 hours | 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 | Interrupt dose until resolved to Grade 1 or lower or baseline. Restart dose at 100 mg daily below the last given dose. Monitor ALT, AST, and bilirubin (total and direct) more frequently following the dose reduction. If re-occurrence of a Grade 3 or higher elevation, discontinue treatment with INREBIC. |
| Grade 3 or higher Other Non-hematologic Toxicities | Interrupt dose until resolved to Grade 1 or lower or baseline. Restart dose at 100 mg daily below the last given dose. |
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)].
Store below 86°F (30°C).
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
