Source: FDA, National Drug Code (US) Revision Year: 2020
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.
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.
After obtaining baseline assessments:
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.
Table 1. Dose Reduction Schedule:
| 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* | --- |
* Once daily TAVALISSE should be taken in the morning.
† If further dose reduction below 100 mg/day is required, discontinue TAVALISSE.
The recommended dose modifications for adverse reactions are provided in Table 2.
Table 2. Recommended Dose Modifications and Management for Specific Adverse Reactions:
| Adverse Reaction | Recommended Action |
|---|---|
| Hypertension | |
| Stage 1: systolic between 130-139 or diastolic between 80-89 mmHg | • Initiate or increase dosage of antihypertensive medication for patients with increased cardiovascular risk, and adjust as needed until BP is controlled. • If the BP target is not met after 8 weeks, reduce TAVALISSE to next lower daily dose (refer to Table 1). |
| Stage 2: systolic at least 140 or diastolic at least 90 mmHg | • Initiate or increase dosage of antihypertensive medication, and adjust as needed until BP is controlled. • If BP remains 140/90 mmHg or higher for more than 8 weeks, reduce TAVALISSE to next lower daily dose (refer to Table 1). • If BP remains 160/100 mmHg or higher for more than 4 weeks despite aggressive antihypertensive therapy, interrupt or discontinue TAVALISSE. |
| Hypertensive crisis: systolic over 180 and/or diastolic over 120 mmHg | • Interrupt or discontinue TAVALISSE. • Initiate or increase dosage of antihypertensive medication, and adjust as needed until BP is controlled. If BP returns to less than the target BP, resume TAVALISSE at same daily dose. • If repeat BP is 160/100 mmHg or higher for more than 4 weeks despite aggressive antihypertensive treatment, discontinue TAVALISSE. |
| Hepatotoxicity | |
| AST/ALT is 3 × ULN or higher and less than 5 × ULN | If patient is symptomatic (e.g., nausea, vomiting, abdominal pain):• Interrupt TAVALISSE. • Recheck LFTs every 72 hours until ALT/AST values are no longer elevated (below 1.5 × ULN) and total BL remains less than 2 × ULN. • Resume TAVALISSE at next lower daily dose (refer to Table 1). |
| If patient is asymptomatic:• Recheck LFTs every 72 hours until ALT/AST are below 1.5 × ULN) and total BL remains less than 2 × ULN. • Consider interruption or dose reduction of TAVALISSE if ALT/AST and TBL remain in this category (AST/ALT is 3 to 5 × ULN; and total BL remains less than 2 × ULN) • If interrupted, resume TAVALISSE at next lower daily dose (refer to Table 1) when ALT/AST are no longer elevated (below 1.5 × ULN) and total BL remains less than 2 × ULN. | |
| AST/ALT is 5 × ULN or higher and total BL is less than 2 × ULN | • Interrupt TAVALISSE. • Recheck LFTs every 72 hours:•• If AST and ALT decrease, recheck until ALT and AST are no longer elevated (below 1.5 × ULN) and total BL remains less than 2 × ULN; resume TAVALISSE at next lower daily dose (refer to Table 1). •• If AST/ALT persist at 5 × ULN or higher for 2 weeks or more, discontinue TAVALISSE. |
| AST/ALT is 3 × ULN or higher and total BL is greater than 2 × ULN | • Discontinue TAVALISSE. |
| Elevated unconjugated (indirect) BL in absence of other LFT abnormalities | • Continue TAVALISSE with frequent monitoring since isolated increase in unconjugated (indirect) BL may be due to UGT1A1 inhibition |
| Diarrhea | |
| Diarrhea | • Manage diarrhea using supportive measures (e.g., dietary changes, hydration and/or antidiarrheal medication) early after the onset until symptom(s) have resolved. • If symptom(s) become severe (Grade 3 or above), temporarily interrupt TAVALISSE. • If diarrhea improves to mild (Grade 1), resume TAVALISSE at the next lower daily dose (refer to Table 1). |
| Neutropenia | |
| Neutropenia | • If absolute neutrophil count decreases (ANC less than 1.0 × 109/L) and remains low after 72 hours, temporarily interrupt TAVALISSE until resolved (ANC greater than 1.5 × 109/L). • Resume TAVALISSE at the next lower daily dose (refer to Table 1). |
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
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)].
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)].
There is no specific antidote for overdose with TAVALISSE, and the amount of R406 (the pharmacologically active metabolite of fostamatinib) cleared by dialysis is negligible. In the event of an overdose, monitor patient closely for signs and symptoms of adverse reactions, and treat the reactions with supportive care [see Warnings and Precautions (5)].
Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not remove desiccants.
© 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.
