Tavlesse safety profile

The most common adverse reactions reported in Tavlesse versus placebo were categorised as mild, moderate and severe3

Incidence of common adverse reactions (≥5% of patients) - FIT-1 + FIT-23

Adverse reactions
Diarrhoeaa
Tavlesse (n=102)

Mild %: 21

Moderate %: 10

Severe %: 1

Placebo (n=48)

Mild %: 13

Moderate %: 2

Severe %: 0

Hypertensionb
Tavlesse (n=102)

Mild %: 17

Moderate %: 9

Severe %: 2

Placebo (n=48)

Mild %: 10

Moderate %: 0

Severe %: 2

Nausea
Tavlesse (n=102)

Mild %: 16

Moderate %: 3

Severe %: 0

Placebo (n=48)

Mild %: 8

Moderate %: 0

Severe %: 0

Dizziness
Tavlesse (n=102)

Mild %: 8

Moderate %: 2

Severe %: 1

Placebo (n=48)

Mild %: 6

Moderate %: 2

Severe %: 0

ALT increased
Tavlesse (n=102)

Mild %: 5

Moderate %: 6

Severe %: 0

Placebo (n=48)

Mild %: 0

Moderate %: 0

Severe %: 0

AST increased
Tavlesse (n=102)

Mild %: 5

Moderate %: 4

Severe %: 0

Placebo (n=48)

Mild %: 0

Moderate %: 0

Severe %: 0

Respiratory infectionc
Tavlesse (n=102)

Mild %: 7

Moderate %: 4

Severe %: 0

Placebo (n=48)

Mild %: 6

Moderate %: 0

Severe %: 0

Rashd
Tavlesse (n=102)

Mild %: 8

Moderate %: 1

Severe %: 0

Placebo (n=48)

Mild %: 2

Moderate %: 0

Severe %: 0

Abdominal paine
Tavlesse (n=102)

Mild %: 5

Moderate %: 1

Severe %: 0

Placebo (n=48)

Mild %: 2

Moderate %: 0

Severe %: 0

Fatigue
Tavlesse (n=102)

Mild %: 4

Moderate %: 2

Severe %: 0

Placebo (n=48)

Mild %: 0

Moderate %: 2

Severe %: 0

Chest pain
Tavlesse (n=102)

Mild %: 2

Moderate %: 3

Severe %: 1

Placebo (n=48)

Mild %: 2

Moderate %: 0

Severe %: 0

Neutropeniaf
Tavlesse (n=102)

Mild %: 3

Moderate %: 2

Severe %: 1

Placebo (n=48)

Mild %: 0

Moderate %: 0

Severe %: 0

ALT=alanine aminotransferase; AST=aspartate aminotransferase.

a. Includes diarrhoea and frequent bowel movement. b. Includes hypertension, blood pressure (BP) increased, BP diastolic abnormal, and BP diastolic increased. c. Includes upper respiratory tract infection, respiratory tract infection, lower respiratory tract infection, and viral upper respiratory tract infection. d. Includes rash, rash erythematous, and rash macular. e. Includes abdominal pain and abdominal pain upper. f. Includes neutropenia and neutrophil count decreased.

Adverse reactions Tavlesse (n=102) Placebo (n=48)
Mild % Moderate % Severe % Mild % Moderate % Severe %
Diarrhoeaa 21 10 1 13 2 0
Hypertensionb 17 9 2 10 0 2
Nausea 16 3 0 8 0 0
Dizziness 8 2 1 6 2 0
ALT increased 5 6 0 0 0 0
AST increased 5 4 0 0 0 0
Respiratory infectionc 7 4 0 6 0 0
Rashd 8 1 0 2 0 0
Abdominal paine 5 1 0 2 0 0
Fatigue 4 2 0 0 2 0
Chest pain 2 3 1 2 0 0
Neutropeniaf 3 2 1 0 0 0

No new or more frequent toxicities or intolerabilities were detected with prolonged use of Tavlesse in the FIT-3 open-label extension study4

Considerations when prescribing Tavlesse

Contraindications1, 2

  1. Hypersensitivity
  2. Pregnancy

Special warnings

Neutropenia

Patients with neutropenia may be more susceptible to infections. The physician should monitor the absolute neutrophil count monthly. The physician should manage toxicity with fostamatinib interruption, reduction or discontinuation1, 2

Hypertension

The patient’s blood pressure should be monitored every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy to ensure maintenance of blood pressure control during fostamatinib therapy. If increased blood pressure persists despite appropriate therapy, the physician should consider fostamatinib dose interruption, reduction or discontinuation1, 2

Liver function and hepatotoxicity

The physician should monitor liver function tests monthly during treatment. If ALT or AST increase more than 3 times the upper limit of normal (ULN), the physician should manage hepatotoxicity by treatment interruption, reduction or discontinuation. Concomitant total bilirubin increases greater than 2 x ULN should lead to treatment discontinuation1, 2

Complete blood counts (CBCs):

The physician should monitor CBCs, including platelet counts, monthly until a stable platelet count (of at least 50,000 /μL) is achieved. Thereafter, the physician should continue to monitor CBCs, including neutrophils, regularly1, 2

Diarrhoea

Patients should be monitored for the development of diarrhoea and managed by using supportive care measures (eg, dietary changes, hydration and/or antidiarrhoeal medication) early after the onset of symptoms. If diarrhoea becomes severe (Grade 3 or above), administration of fostamatinib should be interrupted, reduced, or discontinued1, 2

Infections

The patient should be monitored for infection during treatment. The benefit risk of continuing therapy during an infection should be evaluated by the physician1

Bone remodelling

Potential untargeted effects on bone remodelling or formation remain undetermined, in patients with osteoporosis, patients with fractures or young adults where epiphyseal fusion has not yet occurred. Closer monitoring in these patients is, therefore, recommended. The benefit risk of continuing therapy during the healing of a bone fracture should be thoroughly evaluated by the physician1, 2

Observations from the placebo-controlled FIT-1 + FIT-2 trials:

Diarrhoea was the most common adverse reaction1, 2

  • Diarrhoea should be managed with supportive measures (eg. dietary changes, hydration, and/or antidiarrhoeal medication). If diarrhoea becomes severe, interrupt, reduce, or discontinue Tavlesse (see Tavlesse Summary of Product Characteristics for further details)

Ten patients discontinued treatment with Tavlesse due to adverse reactions5

  • Five adverse reactions led to treatment withdrawal in the Tavlesse arm: syncope, pneumonia, chest pain, thrombocytopenia, and neutropenia
  • Five non-severe adverse reactions leading to withdrawal in the Tavlesse arm included: increased levels of alanine aminotransferase, diarrhoea, neutropenia, abdominal pain, and headache5

ITP: immune thrombocytopenia

References:

  1.  Tavlesse Summary of Product Characteristics. Great Britain. Grifols. Date of revision: January 2021. Available at https://www.medicines.org.uk/emc/product/11479 . Accessed on 14/2/2022.
  2. Tavlesse Summary of Product Characteristics. Northern Ireland. Grifols. Date of revision: August 2021. Available at https://www.emcmedicines.com/en-gb/northernireland/medicine?id=9c2f7cf0-129d-42a3-a61c-d729ae80e50c. Accessed on 14/2/2022
  3. Bussel J, Arnold DM, Grossbard E, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921-930
  4. Bussel J, Arnold DM, Boxer MA, et al. Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program. Am J Hematol. 2019;94(5):546-553
  5. Data on file, Grifols, 2018