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63-YEAR-OLD MALE WITH CHRONIC ITP AND CARDIOVASCULAR DISEASE

Daniel*

BACKGROUND

AGE:	63
OCCUPATION:	Lawyer
DATE OF DIAGNOSIS:	May 1, 2018

COMORBIDITIES:

Unprovoked deep-vein thrombosis (DVT) in 2014; now controlled
Hypertension, controlled with bumetanide 1 mg QD, carvedilol 3.125 mg BID, losartan 25 mg QD
Hyperlipidemia, controlled with atorvastatin 40 mg QD
Diabetes mellitus type 2, controlled with empagliflozin 10 mg QD, glimepiride 4 mg QD, insulin glargine 20 U SC QD, linagliptin 5 mg QD, metformin 1 g QD

PATIENT WITH MILD EPISTAXIS, EASY BRUISING, AND MILD FATIGUE REFERRED TO HEMATOLOGY/ONCOLOGY SPECIALIST (HEM-ONC) BY PRIMARY CARE PHYSICIAN (PCP)

Platelet Counts
Treatment Summary

Daniel's Platelet Counts Over Time

Swipe/click right to explore the details for each time point

Date
Date Platelet Count
Clinical Observations
Laboratory Findings
Physician Notes
Treatment Plan

5/1/18

61 x 10⁹/L

Mild epistaxis, mild fatigue, easy bruising

Not reported

CBC revealed low platelet count; thrombocytopenia diagnosed

Referred to hem-onc for specialized care

5/17/18

43 x 10⁹/L

Mild epistaxis, mild fatigue, easy bruising

Not reported

Initial visit with hem-onc

Initiate dexamethasone 40 mg QD x 4 days

5/21/18

49 x 10⁹/L

Fewer bleeding incidents, reduced fatigue

Not reported

Dexamethasone demonstrated no meaningful response; patient reports sleep disturbance and headaches related to treatment

Rituximab and IVIG considered as treatment alternatives to dexamethasone

6/4/18

59 x 10⁹/L

No clinical observations available

WBC: 4.6 x 10⁹/L Hb: 13.1 g/dL

Diagnosis of ITP confirmed by bone marrow biopsy

No clinical notes available

7/13/18

45 x 10⁹/L

No clinical observations available

WBC: 4.4 x 10⁹/L; Hb: 12.9 g/dL; AST: 39 IU/L; ALT: 27 IU/L; bilirubin: 1.1 mg/dL

Need to increase platelet count (to ≥70 x 10⁹/L) for planned cardiac catheterization; treatment options discussed with patient

Determine protocol to provide rapid and robust platelet count increases for patient to undergo cardiac catheterization

8/1/18

45 x 10⁹/L

Negative for bleeding and bruising

WBC: 4.4 x 10⁹/L; Hb: 12.9 g/dL; AST: 39 IU/L; ALT: 27 IU/L; bilirubin: 1.1 mg/dL

Need to increase platelet count for planned cardiac catheterization

Initiate TAVALISSE 100 mg BID with goal of achieving rapid, robust platelet increase to ≥70 x 10⁹/L

8/15/18

94 x 10⁹/L

Negative for bleeding and bruising

Not available

No clinical notes available

Continue TAVALISSE 100 mg BID

9/21/18

73 x 10⁹/L

Negative for bleeding and bruising

WBC: 3.5 x 10⁹/L; Hb: 11.4 g/dL

Patient is tolerating therapy and reports no side effects; platelet counts within target range, no dose adjustment necessary

Continue TAVALISSE 100 mg BID

10/12/18

72 x 10⁹/L

Negative for bleeding and bruising

WBC: 3.3 x 10⁹/L; Hb: 10.6 g/dL; AST: 57 IU/L; ALT: 37 IU/L; bilirubin: 1.2 mg/dL

No clinical notes available

Continue TAVALISSE 100 mg BID

12/5/18

102 x 10⁹/L

Negative for bleeding and bruising

WBC: 4.9 x 10⁹/L; Hb: 8.0 g/dL

Cardiac catheterization and CABG x 3 vessels; indefinite antiplatelet therapy recommended by cardiologist

Continue TAVALISSE 100 mg BID; initiate aspirin 81 mg QD

1/14/19

135 x 10⁹/L

Negative for bleeding and bruising

WBC: 4.5 x 10⁹/L; Hb: 12.4 g/dL

No clinical notes available

Continue TAVALISSE 100 mg BID; continue aspirin 81 mg QD

2/21/19

103 x 10⁹/L

Negative for bleeding and bruising

WBC: 3.6 x 10⁹/L; Hb: 9.9 g/dL

Patient is tolerating therapy and reports no side effects

Continue TAVALISSE 100 mg BID; continue aspirin 81 mg QD

3/27/19

99 x 10⁹/L

Negative for bleeding and bruising

WBC: 3.8 x 10⁹/L; Hb: 10.8 g/dL; AST: 30 IU/L; ALT: 24 IU/L; bilirubin: 1.1 mg/dL

No clinical notes available

Continue TAVALISSE 100 mg BID; continue aspirin 81 mg QD

4/24/19

94 x 10⁹/L

Negative for bleeding and bruising

WBC: 3.7 x 10⁹/L; Hb: 10.6 g/dL; AST: 42 IU/L; ALT: 37 IU/L; bilirubin: 1.2 mg/dL

Patient has had ongoing response to TAVALISSE and will continue with therapy

Continue TAVALISSE 100 mg BID; continue aspirin 81 mg QD

8/3/19

91 x 10⁹/L

Negative for bleeding and bruising

Not available

Patient continues to tolerate therapy; patient continues to have no symptomatic bleeding, increases in BP, or diarrhea with treatment

Continue TAVALISSE 100 mg BID; continue aspirin 81 mg QD

11/12/2019

96 x 10⁹/L

Negative for bleeding and bruising

Hb: 11.7 g/dL

Platelet count remains stable; tolerating TAVALISSE without new symptoms; BP remains under good control

Continue TAVALISSE 100 mg BID

9/10/2020

88 x 10⁹/L

Negative for bleeding and bruising

AST: 47 IU/L; ALT: 36 IU/L;

Platelet count remains stable

Continue TAVALISSE 100 mg BID

1/25/2021

133 x 10⁹/L

Negative for bleeding and bruising

Hb: 8.9

Substantial increase in platelet count; tolerating TAVALISSE without new issues; BP remains controlled

Continue TAVALISSE 100 mg BID

6/23/2021

96 x 10⁹/L

Negative for bleeding and bruising

Not available

Daniel has been taking TAVALISSE 100 mg BID for 3 years and overall is very happy with this treatment; his platelet counts are stable, he is active, and he is doing well

Continue TAVALISSE 100 mg BID

Patient has been taking TAVALISSE 100 mg BID for 3 years. Overall, he is very happy with his treatment. His platelet counts are stable, and he is doing well.

ALT=alanine aminotransferase; AST=aspartate aminotransferase; CBC=complete blood count; Hb=hemoglobin; WBC=white blood cell.

*This case study contains data from an actual TAVALISSE patient. Patient name and image have been changed to protect privacy. This case study is intended for general medical education purposes only and is not a substitute for independent clinical medical judgment. The intent of this case study is to present the experience of a single patient, which may not represent the outcomes in the overall patient population. Response to treatment may vary from patient to patient.

Daniel's Treatment Summary

Headings:
Prior Treatment history

May-July 2018: While under the care of a hematology/oncology (hem-onc) specialist for ITP, cardiac workup reveals a need for cardiac catheterization
Headings:
treatment with tavalisse

August 1, 2018: TAVALISSE initiation
Platelet Count:
43 x 10⁹/L to 61 x 10⁹/L (fluctuating)
Platelet Count:
45 x 10⁹/L
Clinical Observations:
- Mild epistaxis, mild fatigue, easy bruising
Clinical Observations:
- Patient is clinically stable with no bleeding events
Laboratory Findings:
- Variable
Laboratory Findings:
- WBC: 4.4 x 10⁹/L
- Hb: 12.9 g/dL
- AST: 39 IU/L
- ALT: 27 IU/L
- Bilirubin: 1.1 mg/dL
- Negative for hepatitis B/C
Patient Discussion:
- PCP diagnoses Daniel with thrombocytopenia and refers him to hem-onc for further treatment
- Despite symptoms subsiding with initial treatment, patient is informed that he will require further treatment for immune thrombocytopenia (ITP) stemming from his need for cardiovascular surgery
Patient Discussion:
- Physician explained the need for rapid, robust platelet increase to ≥70 x 10⁹/L for planned cardiac catheterization
- Physician explained the mechanism of TAVALISSE and the potential efficacy and adverse events
- Patient has an active lifestyle; patient and physician agree that an oral medication that can be taken with or without food would be a good fit
Treatment Plan:
- Initiate dexamethasone 40 mg QD
- After it is determined that patient requires surgery, platelet target set at ≥70 x 10⁹/L
In view of Daniel’s need of an increase in platelet counts for a planned cardiac catheterization, the absence of meaningful clinical response to first-line steroids, and his active lifestyle, the hem-onc sought an oral medication in a different class of therapy.
Treatment Plan:
- Initiate TAVALISSE 100 mg BID and increase to 150 mg BID after week 4 if necessary
Patient has been taking TAVALISSE 100 mg BID for 3 years. Overall, he is very happy with his treatment. His platelet counts are stable, and he is doing well.

—Treating physician

ALT=alanine aminotransferase; AST=aspartate aminotransferase; CBC=complete blood count; Hb=hemoglobin; WBC=white blood cell.

*This case study contains data from an actual TAVALISSE patient. Patient name and image have been changed to protect privacy. This case study is intended for general medical education purposes only and is not a substitute for independent clinical medical judgment. The intent of this case study is to present the experience of a single patient, which may not represent the outcomes in the overall patient population. Response to treatment may vary from patient to patient.

TAVA_ITP-21210 1121

Indication and Important Safety Information

Indication

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.

Important Safety Information

Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.

Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.

Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.

Please see full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088).

Back to the top

Indication and Important Safety Information

Indication

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.

Important Safety Information

Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.

September is ITP Awareness month

Join Rigel in helping to raise awareness of immune thrombocytopenia (ITP) and showing support for ITP patients, care partners, and healthcare providers

TAVA_ITP-20158 0920