Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Instituto Grifols, S.A., Can Guasc, 2 Parets del Vallès, 08150 Barcelona Spain
TAVLESSE is indicated for the treatment of chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments (see section 5.1).
Fostamatinib treatment should be initiated and remain under the supervision of a physician who is experienced in the treatment of haematological diseases.
Fostamatinib dosing requirements must be individualised based on the patient’s platelet counts. The lowest dose of fostamatinib to achieve and maintain a platelet count of at least 50,000/µL should be used. Dose adjustments are based upon the platelet count response and tolerability (see table 2).
The recommended starting dose of fostamatinib is 100 mg twice daily.
After initiating fostamatinib, the dose can be increased to 150 mg twice daily after 4 weeks based on platelet count and tolerability. A daily dose of 300 mg daily must not be exceeded.
In the case of a missed dose of fostamatinib, patients should take their next dose at its regularly scheduled time.
Treatment with fostamatinib should be discontinued after 12 weeks of fostamatinib therapy if the platelet count does not increase to a level sufficient to avoid clinically important bleeding.
Fostamatinib dose modification is recommended based on tolerability and platelet counts. Management of some adverse reactions may require dose interruption, reduction, or discontinuation (see table 1 and table 2).
Clinical haematology, blood pressure and liver function tests should be monitored regularly throughout therapy with fostamatinib (see section 4.4.) and the dosing should be adjusted as outlined in table 1. 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 mg1 | --- |
| 100 mg/day2 | 100 mg1 | --- |
1 Once daily fostamatinib should be taken in the morning.
2 If further dose reduction below 100 mg/day is required, discontinue fostamatinib.
The recommended dose modifications for adverse reactions are provided in table 2.
Table 2. Recommended dose modifications for adverse reactions:
| Adverse reaction | Recommended action |
|---|---|
| Hypertension | |
| Stage 1: systolic between 130-139 or diastolic between 80-89 mmHg | Initiate or increase dose of antihypertensive medicinal product for patients with increased cardiovascular risk, and adjust as needed until blood pressure (BP) is controlled. If the BP target is not met after 8 weeks, reduce fostamatinib to next lower daily dose (refer to table 1). |
| Stage 2: systolic at least 140 or diastolic at least 90 mmHg | Initiate or increase dose of antihypertensive medicinal product, and adjust as needed until BP is controlled. If BP remains 140/90 mmHg or higher for more than 8 weeks, reduce fostamatinib 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 fostamatinib. |
| Hypertensive crisis: systolic over 180 and/or diastolic over 120 mmHg | Interrupt or discontinue fostamatinib. Initiate or increase dose of antihypertensive medicinal product, and adjust as needed until BP is controlled. If BP returns to less than the target BP, resume fostamatinib at same daily dose. If repeat BP is 160/100 mmHg or higher for more than 4 weeks despite aggressive antihypertensive treatment, discontinue fostamatinib. |
| Hepatotoxicity | |
| AST/ALT is 3 x ULN or higher and less than 5 x ULN | If patient is symptomatic (e.g., nausea, vomiting, abdominal pain): Interrupt fostamatinib. Recheck LFTs every 72 hours until ALT/AST values are no longer elevated (below 1.5 x ULN) and total BL remains less than 2 x ULN. Resume fostamatinib 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 x ULN) and total BL remains less than 2 x ULN. Consider interruption or dose reduction of fostamatinib if ALT/AST and TBL remain in this category (AST/ALT is 3 to 5 x ULN; and total BL remains less than 2 x ULN). If interrupted, resume fostamatinib at next lower daily dose (refer to table 1) when ALT/AST are no longer elevated (below 1.5 x ULN) and total BL remains less than 2 x ULN. | |
| AST/ALT is 5 x ULN or higher and total BL is less than 2 x ULN | Interrupt fostamatinib. Recheck LFTs every 72 hours: If AST and ALT decrease, recheck until ALT and AST are no longer elevated (below 1.5 x ULN) and total BL remains less than 2 x ULN; resume fostamatinib at next lower daily dose (refer to table 1). If AST/ALT persist at 5 x ULN or higher for 2 weeks or more, discontinue fostamatinib. |
| AST/ALT is 3 x ULN or higher and total BL is greater than 2 x ULN | Discontinue fostamatinib. |
| Elevated unconjugated (indirect) BL in absence of other LFT abnormalities | Continue fostamatinib with frequent monitoring since isolated increase in unconjugated (indirect) BL may be due to UGT1A1 inhibition. |
| Diarrhoea | |
| Diarrhoea | Manage diarrhoea using supportive measures (e.g., dietary changes, hydration and/or antidiarrhoeal medicinal product) early after the onset until symptom(s) have resolved. If symptom(s) become severe (Grade 3 or above), temporarily interrupt fostamatinib. If diarrhoea improves to mild (Grade 1), resume fostamatinib 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 fostamatinib until resolved (ANC greater than 1.5 × 109/L). Resume fostamatinib 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; ANC = absolute neutrophil count
No dose adjustment is necessary in patients with renal impairment.
Fostamatinib should not be used in patients with severe hepatic impairment. In patients with mild or moderate hepatic impairment, monitoring of liver function throughout therapy with fostamatinib should be done. Dose regimen adjustment according to platelet counts and tolerability may be required (see table 1 and table 2, and section 4.4).
No dose adjustment is necessary in elderly patients.
Fostamatinib should not be used in children and adolescents less than 18 years of age because of adverse reactions on actively growing bones observed in nonclinical studies (see section 5.3).
Fostamatinib is for oral use.
The tablets should be taken twice daily, whole with or without food (see section 5.2). In the event of gastric upset, tablets may be taken with food.
There is no specific antidote for overdose with fostamatinib, and the amount of R406 cleared by dialysis is negligible. There has not been any experience of overdose in the clinical development program. In the event of an overdose, the physician should monitor the patient closely for signs and symptoms of adverse reactions as described in section 4.2, and treat the reactions with supportive care.
5 years.
This medicinal product does not require any special temperature storage conditions. Store in the original package to protect from moisture. Keep the bottle tightly closed.
White high density polyethylene (HDPE) bottle with an aluminium foil tamper evident seal and a white polypropylene (PP) child-resistant cap, together with two white opaque HDPE desiccant canisters containing silica gel.
Pack sizes of 30 and 60 film-coated tablets. Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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