Bleeding disorders:

Indications for: TAVALISSE

Thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had insufficient response to previous treatment.

Clinical Trials:

Tavalisse was studied in two placebo-controlled efficacy and safety studies (referred to as FIT-1 [ Identifiers: NCT02076399] and FIT-2 [NCT02076412]), and in an open-label extension study referred to as FIT-3 ( Identifier: NCT 02077192).

Randomized, Placebo-Controlled Studies

  • A total of 150 patients with persistent or chronic ITP, who had an insufficient response to previous treatment were enrolled in two identical, double-blind, placebo-controlled studies that were conducted in different countries. 
  • Patients were randomized 2:1 to Tavalisse or placebo for 24 weeks; randomization was stratified with respect to prior splenectomy and severity of thrombocytopenia. 
  • Stable concurrent ITP therapy was allowed, and rescue therapy was permitted, if needed. 
  • All patients initially received the study drug at 100 mg twice daily (or matching placebo). 
  • Based on platelet count and tolerability, dose escalation to 150 mg twice daily (or matching placebo) was undertaken in 88% of patients at Week 4 or later. 
  • Patients who did not respond to treatment after 12 weeks, as well as patients who completed the 24-week double blind study, were eligible to enroll in open-label extension study (FIT-3).
  • At baseline, the median platelet count was 16×109/L (with almost half [45]% <15×109/L) and 47% were on stable ITP therapy.
  • In Study FIT-1 (n=76), 51 patients were randomized to the Tavalisse group and 25 to the placebo group.
  • In Study FIT-2 (n=74), 50 patients were randomized to the Tavalisse group and 24 to the placebo group.
  • The efficacy of Tavalisse was based on stable platelet response (at least 50×109/L on at least 4 of the 6 visits between Weeks 14 to 24). 
  • Results in FIT-1 showed 18% of the Tavalisse group achieved stable platelet response vs 0% in the placebo group (P =.03). While in FIT-2, 16% of the Tavalisse group achieved stable platelet response vs 4% in the placebo group (P-value not significant).

Extension Study

  • The FIT-3 trial is an open label extension study. 
  • Patients from FIT-1 and FIT-2 who completed 24 weeks of treatment, or who did not respond to treatment any time after 12 weeks, were eligible to enroll in this study.
  • Patients designated as responders (defined as achievement of platelet count of at least 50×109/L) at the time of roll over continued in the extension study at their current trial dose and regimen.
  • Patients who entered the extension study as non-responders (defined as platelet count <50×109/L) received Tavalisse 100 mg twice daily regardless of their dose and regimen in the prior study.
  • For the FIT-3 trial (n=123), 44 patients were previously randomized to placebo; 79 patients were previously randomized to Tavalisse.
  • Stable response was prospectively defined as no 2 visits (at least 4 weeks apart) with a platelet count <50×109/L, without an intervening visit with a platelet count of at least 50×109/L, within a period of 12 weeks following initial achievement of the target platelet count.
  • Sixty-one of the 123 subjects (50%) have discontinued from the study early.
  • In the prospective analysis, the 44 patients treated with placebo in the prior study were evaluated for stable response for Tavalisse. Ten of these subjects (23%) met the criteria for stable response.

Among the patients who achieved stable response in FIT-1, FIT-2 and FIT-3 trials, 18 patients maintained the platelet count of at least 50×109/L for 12 months or longer.

Adult Dosage:

≥18yrs: Initially 100mg twice daily. Increase to 150mg twice daily if platelet count not at ≥50x109/L after 4 weeks. Discontinue if insufficient increase in platelet count after 12 weeks. Dose modifications: see full labeling.

Children Dosage:

<18yrs: not recommended.

TAVALISSE Warnings/Precautions:

Monitor CBCs, including platelets, monthly until stable count (≥50x109/L) achieved, then periodically thereafter. Monitor LFTs monthly. Discontinue if AST/ALT >5xULN for ≥2wks or ≥3xULN and total bilirubin >2xULN. Monitor blood pressure every 2 weeks until stable dose established, then monthly thereafter. Interrupt or discontinue dose if hypertensive crisis (>180/120mmHg) occurs; discontinue if repeat BP >160/100mmHg for >4 weeks. Temporarily interrupt if severe diarrhea (Grade ≥3) occurs; resume at next lower daily dose if improved to Grade 1. Monitor ANC monthly and for infection. Temporarily interrupt if ANC <1x109/L occurs and remains low after 72hrs until resolved; resume at next lower daily dose. Use lowest effective dose. Embryo-fetal toxicity. Use effective contraception during and for ≥1 month after last dose. Pregnancy; confirm negative status prior to initiation. Nursing mothers: not recommended (during and for ≥1 month after last dose).

TAVALISSE Classification:

Tyrosine kinase inhibitor.

TAVALISSE Interactions:

Concomitant strong CYP3A4 inducers: not recommended. Concomitant strong CYP3A4 inhibitors or substrates; monitor for toxicity. May potentiate concomitant BCRP (eg, rosuvastatin) or P-gp (eg, digoxin) substrates: monitor for toxicity.

Adverse Reactions:

Diarrhea, hypertension, nausea, respiratory infection, dizziness, ALT/AST increase, rash, abdominal pain, fatigue, chest pain, neutropenia.


Tavalisse is metabolized in the gut by alkaline phosphatase to the major active metabolite, R406.

R406 is extensively metabolized, primarily through pathways of CYP450-mediated oxidation (by CYP3A4) and glucuronidation (by UDP glucuronosyltransferase [UGT]1A9). 

Drug Elimination:

The mean terminal half-life of R406 is ~15 (± 4.3) hours. Following an oral dose of Tavalisse, ~80% of the R406 metabolite is excreted in feces; ~20% excreted in the urine. The major component excreted in urine was R406 N-glucuronide. 

Generic Drug Availability:


How Supplied: