Prescription Drug Information: TAVALISSE
TAVALISSE- fostamatinib tablet
Rigel Pharmaceuticals, Inc.
1 INDICATIONS AND USAGE
TAVALISSE is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
Initiate TAVALISSE at a dose of 100 mg taken orally twice daily. After a month, if platelet count has not increased to at least 50 × 109 /L, increase TAVALISSE dose to 150 mg twice daily.
Use the lowest dose of TAVALISSE to achieve and maintain a platelet count at least 50 × 109 /L as necessary to reduce the risk of bleeding.
TAVALISSE may be taken with or without food. In the case of a missed dose of TAVALISSE, instruct patients to take their next dose at its regularly scheduled time.
2.2 Monitoring
After obtaining baseline assessments:
- Monitor CBCs, including platelet counts, monthly until a stable platelet count (at least 50 × 109 /L) is achieved. Thereafter, continue to monitor CBCs, including neutrophils, regularly.
- Monitor liver function tests (LFTs) (e.g., ALT, AST, and bilirubin) monthly.
- Monitor blood pressure every 2 weeks until establishment of a stable dose, then monthly thereafter.
2.3 Dose Modification for Adverse Reactions
TAVALISSE dose modification is recommended based on individual safety and tolerability. Management of some adverse reactions may require dose-interruption, reduction, or discontinuation.
A dose reduction schedule is provided in Table 1, based on daily dose. For example, if a patient is on the maximum dose at the time of an adverse reaction, the first dose reduction would be from 300 mg/day to 200 mg/day.
Daily Dose | Administered as: | |
---|---|---|
AM | PM | |
300 mg/day | 150 mg | 150 mg |
200 mg/day | 100 mg | 100 mg |
150 mg/day | 150 mg * | — |
100 mg/day † | 100 mg * | — |
The recommended dose modifications for adverse reactions are provided in Table 2.
Adverse Reaction | Recommended Action |
---|---|
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BP = blood pressure; BL = bilirubin; ULN = upper limit of normal; LFT = liver function tests (AST, ALT, total BL with fractionation if elevated, alkaline phosphatase); AST/ALT = AST or ALT | |
Hypertension | |
Stage 1: systolic between 130-139 or diastolic between 80-89 mmHg |
|
Stage 2: systolic at least 140 or diastolic at least 90 mmHg |
|
Hypertensive crisis: systolic over 180 and/or diastolic over 120 mmHg |
|
Hepatotoxicity | |
AST/ALT is 3 × ULN or higher and less than 5 × ULN | If patient is symptomatic (e.g., nausea, vomiting, abdominal pain):
|
If patient is asymptomatic:
| |
AST/ALT is 5 × ULN or higher and total BL is less than 2 × ULN |
|
AST/ALT is 3 × ULN or higher and total BL is greater than 2 × ULN |
|
Elevated unconjugated (indirect) BL in absence of other LFT abnormalities |
|
Diarrhea | |
Diarrhea |
|
Neutropenia | |
Neutropenia |
|
2.4 Dose Modification for Drug Interactions
Concomitant use with a strong CYP3A4 inhibitor increases exposure to R406 (the major active metabolite). Monitor for toxicities of TAVALISSE that may require TAVALISSE dose modifications (see Table 1) when given concurrently with a strong CYP3A4 inhibitor [see Drug Interactions (7.1)].
2.5 Discontinuation
Discontinue TAVALISSE after 12 weeks of treatment if the platelet count does not increase to a level sufficient to avoid clinically important bleeding [see Clinical Studies (14)].
3 DOSAGE FORMS AND STRENGTHS
TAVALISSE is available as:
- 100 mg tablet: orange, film-coated, round, biconvex tablets debossed with “100” on one side and “R” on the reverse side.
- 150 mg tablet: orange, film-coated, oval, biconvex tablets debossed with “150” on one side and “R” on the reverse side.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Hypertension
Hypertension can occur with TAVALISSE treatment; hypertensive crisis occurred in 1% of patients. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects of TAVALISSE.
Monitor blood pressure every 2 weeks until stable, then monthly and adjust or initiate antihypertensive therapy to ensure maintenance of blood pressure control during TAVALISSE therapy. If increased blood pressure persists despite appropriate therapy, TAVALISSE interruption, reduction or discontinuation may be necessary [see Dosage and Administration (2.3)].
5.2 Hepatotoxicity
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE.
In the placebo-controlled studies, laboratory testing showed maximum ALT/AST levels more than 3 × the upper limit of normal (ULN) in 9% of patients receiving TAVALISSE [see Adverse Reactions (6.1)]. For most patients, transaminases recovered to baseline levels within 2 to 6 weeks of dose-modification.
Monitor liver function tests monthly during treatment. If ALT or AST increase more than 3 × ULN, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation [see Dosage and Administration (2.3)].
5.3 Diarrhea
Diarrhea occurred in 31% of patients treated with TAVALISSE. Severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea. Manage diarrhea using supportive care measures, including dietary changes, hydration and/or antidiarrheal medication, early after the onset of symptoms. Interrupt, dose reduce, or discontinue TAVALISSE if diarrhea becomes severe (Grade 3 or above) [see Dosage and Administration (2.3)].
RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.