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Tavlesse is a brand name for Fostamatinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: TAVLESSE is indicated for the treatment of chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments (see section 5.1).
Verbatim from this product's EMA label. Tap a section to expand.
Fostamatinib treatment should be initiated and remain under the supervision of a physician who is experienced in the treatment of haematological diseases. 3 Posology 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. Missed dose In the case of a missed dose of fostamatinib, patients should take their next dose at its regularly scheduled time.
Discontinuation 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. Monitoring and dose modifications 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). ) 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. 4 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.
Summary of the safety profile In the ITP placebo-controlled studies, serious adverse medicinal product reactions were febrile neutropenia, diarrhoea, pneumonia, and hypertensive crisis, which each occurred in 1% of patients receiving fostamatinib.
In addition, severe adverse reactions observed in patients receiving fostamatinib included dyspnea and hypertension (both 2%); and neutropenia, arthralgia, chest pain, diarrhoea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope and hypoxia (all 1%).
Tabulated list of adverse reactions The adverse reactions are presented from the placebo-controlled clinical studies and organised according to primary system organ class (SOC) for each preferred term in MedDRA. The adverse reactions are ranked by frequency within each SOC, and presented in order of decreasing seriousness.
Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000) and not known (cannot be estimated from the available data).
Table 3:
Tabulated list of the adverse reactions MedDRA SOC Frequency Adverse reactions Infections and infestations Uncommon Pneumonia Common Upper respiratory tract infection, respiratory tract infection, bronchitis, lower respiratory tract infection, viral upper respiratory tract infection Blood and lymphatic disorders Common Neutropenia, febrile neutropenia Nervous system disorders Very common Dizziness Common Dysgeusia, headache Vascular disorders Very Common Hypertension Uncommon Hypertensive crisis Gastrointestinal disorders Very common Diarrhoea, nausea, frequent bowel movement Common Abdominal pain upper, abdominal pain Skin and subcutaneous tissue disorders Common Rash, rash erythematous, rash macular General disorders and administration site conditions Common Chest pain, fatigue, influenza like illness Investigations Very common Alanine aminotransferase increased, aspartate aminotransferase increased, blood pressure (BP) increased, BP diastolic abnormal, BP diastolic increased, BP systolic increased, hepatic enzyme increased, liver function test abnormal Common Neutrophil count decreased Description of selected adverse reactions The most commonly reported adverse reactions associated with fostamatinib were hypertension, liver function test abnormaltities, diarrhoea, neutropenia and infections.
Information is based on ITP placebo-controlled population unless specified. Hypertension Over the range of doses studied in healthy volunteers, the effect of R406 (the major active metabolite of fostamatinib) on BP appears to be dose-dependent and varies among subjects.
In the ITP placebo- controlled population, increased blood pressure, including the development of hypertension, was reported in patients treated with fostamatinib. Hypertensive crisis occurred in 1 (1%) patient. Patients 6 with pre-existing hypertension may be more susceptible to the hypertensive effects of fostamatinib.
In clinical studies, the blood pressure effects resolved within a week of discontinuing treatment. The patient’s blood pressure should be monitored every two weeks until stable, then monthly, and adjust or initiate antihypertensive therapy to ensure maintenance of blood pressure control during fostamatinib therapy.
2). Liver function test abnormalities and risk of hepatotoxicity In the placebo-controlled studies, laboratory testing showed maximum ALT/AST levels more than 3 x the upper limit of normal (ULN) in 9% of patients receiving fostamatinib and no patients receiving placebo.
g. 2). For all patients, transaminases recovered generally to baseline levels within 2 to 6 weeks of dose- modification. The physician should monitor liver function tests monthly during treatment. If ALT or AST increase more than 3 x ULN, the physician should manage hepatotoxicity by treatment interruption, reduction or discontinuation.
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, regularly.
Diarrhoea Diarrhoea is the most common adverse reaction with fostamatinib treatment, but severe diarrhoea occurred in 1% of patients. , dietary changes, hydration and/or antidiarrhoeal medicinal product) early after the onset of symptoms.
1. 6).
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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. , nausea, vomiting, abdominal pain): Interrupt fostamatinib. 5 x ULN) and total BL remains less than 2 x ULN.
Resume fostamatinib at next lower daily dose (refer to table 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).
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. 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.
, dietary changes, hydration and/or antidiarrhoeal medicinal product) early after the onset until symptom(s) have resolved. 5 Adverse reaction Recommended action 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). 5 x 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 Special populations Renal impairment No dose adjustment is necessary in patients with renal impairment.
Hepatic impairment Fostamatinib should not be used in patients with severe hepatic impairment. In patients with mild or […]
4). Hypertension events were reversible within days after dose discontinuation in these subjects. 5% of patients receiving placebo in the placebo- controlled studies. Hypertension-related adverse reactions were mostly mild or moderate in severity, with 2 patients receiving fostamatinib and 1 subject receiving placebo experiencing severe hypertension.
Hypertensive crises was reported as a serious adverse reaction and occurred in 1 (1%) patient receiving fostamatinib. Dose modification (reduction or interruption) was required for 4 patients receiving fostamatinib and no placebo patients.
Study medicinal product was withdrawn due to a hypertension-related adverse reaction in 1 patient receiving placebo and no patients receiving fostamatinib. Approximately 20% of patients receiving fostamatinib required at least 1 intervention for hypertension-related events: increase in antihypertensive medicinal products and/or a new antihypertensive medicinal product.
Liver function test abnormalities and risk of hepatotoxicity Mild to moderate increases in liver enzymes (ALT and AST) were observed in fostamatinib treated subjects in phase 1 studies in healthy volunteers, occurring more frequently at the higher doses tested (250 mg oral twice daily).
4). In the ITP placebo-controlled population, transaminase elevation adverse reactions (ALT increased and AST increased) were reported in 11% and 9% of patients receiving fostamatinib. All transaminase elevations were mild or moderate in severity and dose modification (dose reduction or dose interruption) was required in 8 patients.
One patient discontinued fostamatinib due to a transaminase elevation (ALT increased); this event resolved after discontinuation of treatment. In the ITP placebo-controlled population, laboratory testing showed maximum ALT/AST levels more than 3 x the upper limit of normal (ULN) in 9% of patients receiving fostamatinib and no patients receiving placebo.
Maximum ALT and/or AST levels were > 10 x ULN in 1 patient receiving fostamatinib. Transaminase elevations recovered to baseline levels within 2 to 4 weeks of dose modification. 5 days (6 to 28 days). Diarrhoea Gastrointestinal complaints, specifically noninfectious diarrhoea events, were among the most common adverse reactions reported in patients treated with fostamatinib throughout the clinical development program.
4). In the placebo-controlled ITP population, noninfectious diarrhoea was the most commonly reported GI complaint, occurring in 31% of subjects receiving fostamatinib. Noninfectious diarrhoea events were most frequently mild-to-moderate in severity.
The majority of subjects with moderate diarrhoea received antidiarrhoeal agents (loperamide) to mitigate their symptoms. Severe diarrhoea was reported in 1% of patients receiving fostamatinib during the placebo-controlled period. Dose modification (interruption or reduction) was reported for approximately 5% of subjects receiving fostamatinib; however study medicinal product was discontinued because of […]
2). Neutropenia Neutropenia occurred in 7% of patients treated with fostamatinib; febrile neutropenia occurred in 1% of patients. Patients with neutropenia may be more susceptible to infections. The physician should monitor the absolute neutrophil count monthly.
2). 8). The patient should be monitored for infection during treatment. The benefit risk of continuing therapy during an infection should be evaluated by the physician. , VEGFR, RET), any potential untargeted effects on bone 7 remodelling or formation remain undetermined, especially 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 physician. 2% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
7% of the WHO recommended maximum daily intake of 2 g sodium for an adult.