Fostamatinib
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sonya Gelfand
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Overview
Fostamatinib is a tyrosine kinase inhibitor that is FDA approved for the treatment of chronic immune thrombocytopenia (ITP) in adults who have had an insufficient response to a previous treatment. Common adverse reactions include diarrhea, hypertension, nausea, respiratory infection, dizziness, ALT/AST increased, rash, abdominal pain, fatigue, chest pain and neutropenia.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
- Fostamatinib 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.
Recommended Dosage
- Initiate fostamatinib at a dose of 100 mg taken orally twice daily. After a month, if platelet count has not increased to at least 50 × 109/L, increase fostamatinib dose to 150 mg twice daily.
- Use the lowest dose of fostamatinib to achieve and maintain a platelet count at least 50 × 109/L as necessary to reduce the risk of bleeding.
- Fostamatinib may be taken with or without food. In the case of a missed dose of fostamatinib, instruct patients to take their next dose at its regularly scheduled time.
Dose Modification for Adverse Reactions
- Fostamatinib dose modification is recommended based on individual safety and tolerability. Management of some adverse reactions may require dose-interruption, reduction, or discontinuation.
- A dose reduction schedule is provided in Table 1, based on daily dose. 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.
- The recommended dose modifications for adverse reactions are provided in Table 2.
Dose Modification for Drug Interactions
- Concomitant use with a strong CYP3A4 inhibitor increases exposure to R406 (the major active metabolite). Monitor for toxicities of fostamatinib that may require fostamatinib dose modifications (see TABLE 1) when given concurrently with a strong CYP3A4 inhibitor
Discontinuation
- Discontinue fostamatinib after 12 weeks of treatment if the platelet count does not increase to a level sufficient to avoid clinically important bleeding.
Dosage Forms and Strengths
- Fostamatinib is available as:
- 100 mg tablet: orange, film-coated, round, biconvex tablets debossed with "100" on one side and "R" on the reverse side.
- 150 mg tablet: orange, film-coated, oval, biconvex tablets debossed with "150" on one side and "R" on the reverse side.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding fostamatinib Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.
Non–Guideline-Supported Use
There is limited information regarding fostamatinib Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Fostamatinib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding fostamatinib Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.
Non–Guideline-Supported Use
There is limited information regarding fostamatinib Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.
Contraindications
- None.
Warnings
Hypertension
- Hypertension can occur with fostamatinib treatment; hypertensive crisis occurred in 1% of patients. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects of fostamatinib.
- Monitor blood pressure 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, fostamatinib interruption, reduction or discontinuation may be necessary.
Hepatotoxicity
- Elevated liver function tests (LFTs), mainly ALT and AST, can occur with fostamatinib.
- In the placebo-controlled studies, laboratory testing showed maximum ALT/AST levels more than 3 × the upper limit of normal (ULN) in 9% of patients receiving fostamatinib. For most patients, transaminases recovered to baseline levels within 2 to 6 weeks of dose-modification.
- Monitor liver function tests monthly during treatment. If ALT or AST increase more than 3 × ULN, manage hepatotoxicity using fostamatinib interruption, reduction, or discontinuation.
Diarrhea
- Diarrhea occurred in 31% of patients treated with fostamatinib. Severe diarrhea occurred in 1% of patients treated with fostamatinib. Monitor patients for the development of diarrhea. Manage diarrhea using supportive care measures, including dietary changes, hydration and/or antidiarrheal medication, early after the onset of symptoms. Interrupt, dose reduce, or discontinue fostamatinib if diarrhea becomes severe (Grade 3 or above).
Neutropenia
- Neutropenia occurred in 6% of patients treated with fostamatinib; febrile neutropenia occurred in 1% of patients.
- Monitor the ANC monthly, and for infection during treatment. Manage toxicity with fostamatinib interruption, reduction or discontinuation.
Embryo-Fetal Toxicity
- Based on findings from animal studies and its mechanism of action, fostamatinib can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of fostamatinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes including embryo-fetal mortality (post-implantation loss), alterations to growth (lower fetal weights), and structural abnormalities (variations and malformations) at maternal exposures (AUCs) approximately 0.3 and 10 times the human exposure at the maximum recommended human dose (MRHD), respectively. Advise pregnant women of 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.
Adverse Reactions
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Fostamatinib was studied in two randomized, double-blind, placebo-controlled trials that were identical in design. The data described below reflect exposure to fostamatinib in 102 patients with chronic ITP who had received one or more prior ITP treatment(s). Groups were stratified with respect to splenectomy and severity of thrombocytopenia. Patients randomized to the fostamatinib arm received 100 mg orally twice daily. Based upon platelet count and tolerability, if a patient's platelet count did not increase to at least 50 × 109/L, the fostamatinib dose could be increased to 150 mg twice daily after one month. In the placebo controlled studies, the median duration of fostamatinib exposure in these studies was 86 days (range 8 to 183).
- In the ITP double-blind studies, serious adverse drug reactions were febrile neutropenia, diarrhea, 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, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope and hypoxia (all 1%). Table 3 presents the common adverse reactions from these studies.
Postmarketing Experience
There is limited information regarding Fostamatinib Postmarketing Experience in the drug label.
Drug Interactions
Effect of Other Drugs on Fostamatinib
- Strong CYP3A4 Inhibitors
- Strong CYP3A4 Inducers
Strong CYP3A4 Inhibitors
- Concomitant use with strong CYP3A4 inhibitors increases exposure to R406 (the major active metabolite), which may increase the risk of adverse reactions. Monitor for toxicities of fostamatinib that may require dose reduction when given concurrently with a strong CYP3A4 inhibitor.
Strong CYP3A4 Inducers
- Concomitant use with a strong CYP3A4 inducer reduces exposure to R406. Concomitant use of fostamatinib with strong CYP3A4 inducers is not recommended.
Effect of Fostamatinib on Other Drugs
- CYP3A4 Substrates
- BCRP Substrates
- P-Glycoprotein (P-gp) Substrates
CYP3A4 Substrates
- Concomitant use of fostamatinib may increase concentrations of some CYP3A4 substrate drugs. Monitor for toxicities of CYP3A4 substrate drug that may require dosage reduction when given concurrently with fostamatinib.
BCRP Substrates
- Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs (e.g., rosuvastatin). Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib
P-Glycoprotein (P-gp) Substrates
- Concomitant use of fostamatinib may increase concentrations of P-gp substrates (e.g., digoxin). Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib
Use in Specific Populations
Pregnancy
Risk Summary
- Based on findings from animal studies and the mechanism of action, fostamatinib can cause fetal harm when administered to a pregnant woman.
- There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of fostamatinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes that were directly attributed to exposure in utero to the major fostamatinib metabolite (R406) at maternal exposures (AUC) as low as 0.3 and 10 times the exposure in patients at the maximum recommended human dose (MRHD), respectively. Advise pregnant women of the potential risk to a fetus.
- All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. An estimated background risk of major birth defects and miscarriage for the chronic ITP population is 8% and 4-11%, respectively.
Data (Animal)
- In a fertility and early embryonic development study in female rats, fostamatinib was administered orally for 15 days before mating to Day 7 of pregnancy, which caused a slight decrease in pregnancy rates and an increase in post-implantation loss were seen at maternal doses approximately 4.2 times the dose in patients at the MRHD.
- In embryo-fetal development studies, pregnant animals were orally administered fostamatinib during the period of organogenesis at doses up to 25 and 50 mg/kg/day in rats and rabbits, respectively. The adverse developmental outcomes included an increase in embryo-fetal mortality (post-implantation loss), alterations to growth (lower fetal weights), and structural abnormalities (variations and malformations). These effects occurred at maternal exposures (AUCs) of 3,763 ng.h/mL in rats and 111,105 ng.h/mL in rabbits that were approximately 0.3 and 10 times the human exposure at the MRHD in rats and rabbits, respectively.
- In a peri and postnatal development study in rats, fostamatinib was orally administered at doses of 2.5, 12.5, and 25 mg/kg/day from gestation day 7 until lactation day 20. The dose of 25 mg/kg/day was associated with maternal toxicity, including decreased body weights, body weight gains, and food consumption. At doses as low as 12.5 mg/kg/day fostamatinib caused increases in newborn mortality (neonatal mortality), alterations in growth and/or development (lower neonatal weights into post-weaning and structural abnormalities [malformations]). Functional impairment (delayed sexual maturation) was observed at 25 mg/kg/day. There was no evidence of neurobehavioral defects (maze learning and shuttle box avoidance) or immunological compromise (influenza host resistance challenge) in the F1 generation or latent untoward effects in the F2 generation. The maternal doses were approximately 2.1 and 4.2 times the MHRD in patients.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Fostamatinib in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Fostamatinib during labor and delivery.
Nursing Mothers
Risk Summary
- There are no data on the presence of fostamatinib and/or its metabolites in human milk, the effects on the breastfed child, or on milk production. In rodents, R406 (the major active metabolite) was detected in maternal milk in concentrations 5- to 10-fold higher than in maternal plasma. Because of the potential for serious adverse reactions in a breastfed child from fostamatinib, advise a lactating woman not to breastfeed during treatment with fostamatinib and for at least 1 month after the last dose.
Pediatric Use
- Safety and effectiveness in pediatric patients have not been established. fostamatinib is not recommended for use in patients less than 18 years of age because adverse effects on actively growing bones were observed in nonclinical studies. In subchronic, chronic, and carcinogenicity studies of fostamatinib, chondrodystrophy of the femoral head was seen in rodents. In a study in juvenile rabbits, growth plate dysplasia was observed in the proximal femur and femoro-tibial joint, and bone marrow cellularity was reduced in the femur and sternum.
Geriatic Use
- Of the 102 patients with ITP who received fostamatinib, 28 (27%) were 65 years of age and older, while 11 (11%) were 75 years of age and older. In patients 65 years of age and older, 6 (21%) patients experienced serious adverse events and 5 (18%) experienced adverse events leading to treatment withdrawal while in patients under 65 years of age, 7 (9%) and 5 (7%) experienced serious adverse events and adverse events leading to treatment withdrawal, respectively. In patients 65 years of age and older who received fostamatinib, 11 (39%) patients experienced hypertension versus 2 (18%) placebo compared to 17 (23%) in patients under 65 of age versus 4 (11%) placebo. No overall differences in effectiveness were observed in these patients compared to younger patients.
Gender
There is no FDA guidance on the use of Fostamatinib with respect to specific gender populations.
Race
There is no FDA guidance on the use of Fostamatinib with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Fostamatinib in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Fostamatinib in patients with hepatic impairment.
Females of Reproductive Potential and Males
Pregnancy Testing
- Based on animal studies, fostamatinib can cause fetal harm when administered to a pregnant woman. For females of reproductive potential, verify pregnancy status prior to initiating fostamatinib.
Contraception
Females
- Based on animal studies, fostamatinib can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with fostamatinib and for at least 1 month after the last dose.
Infertility
- There are no data on the effect of fostamatinib on human fertility. Based on the finding of reduced pregnancy rates in animal studies, fostamatinib may affect female fertility
Immunocompromised Patients
There is no FDA guidance one the use of Fostamatinib in patients who are immunocompromised.
Administration and Monitoring
Administration
- Oral
Monitoring
- After obtaining baseline assessments:
- Monitor CBCs, including platelet counts, monthly until a stable platelet count (at least 50 × 109/L) is achieved. Thereafter, continue to monitor CBCs, including neutrophils, regularly.
- Monitor liver function tests (LFTs) (e.g., ALT, AST, and bilirubin) monthly.
- Monitor blood pressure every 2 weeks until establishment of a stable dose, then monthly thereafter.
IV Compatibility
There is limited information regarding the compatibility of Fostamatinib and IV administrations.
Overdosage
- There is no specific antidote for overdose with fostamatinib, and the amount of R406 (the pharmacologically active metabolite of fostamatinib) cleared by dialysis is negligible. In the event of an overdose, monitor patient closely for signs and symptoms of adverse reactions, and treat the reactions with supportive care.
Pharmacology
Mechanism of Action
- Fostamatinib is a tyrosine kinase inhibitor with demonstrated activity against spleen tyrosine kinase (SYK). The major metabolite of fostamatinib, R406, inhibits signal transduction of Fc-activating receptors and B-cell receptor. The fostamatinib metabolite R406 reduces antibody-mediated destruction of platelets.
Structure
Pharmacodynamics
- Mean treatment-related increases of 2.93 mmHg in systolic blood pressure and 3.53 mmHg in diastolic blood pressure over placebo were observed following fostamatinib doses of 100 mg twice daily for 28 days. About 31% of patients in the fostamatinib group experienced blood pressures ≥140/90 mmHg compared to 15% of patients in the placebo group. Blood pressure returned to baseline within 1 week following fostamatinib discontinuation in 58% (11 of 19) of patients in the fostamatinib group who had blood pressures ≥140/90 mmHg.
Cardiac Electrophysiology
- At 2 times the maximum recommended dose, fostamatinib did not prolong the QT interval to a clinically relevant extent.
Pharmacokinetics
- Fostamatinib is a prodrug that is converted in the gut to the major active metabolite, R406. Mean (± standard deviation [SD]) exposure estimates of R406 are 550 (± 270) ng/mL for Cmax and 7080 (± 2670) ng∙h/mL for AUC. R406 exposure is approximately dose proportional up to 200 mg twice daily (1.3 times the 150 mg dosage). R406 accumulates approximately 2- to 3-fold upon twice daily dosing at 100–160 mg (0.67 to 1.06 times the 150 mg dosage).
Absorption
Effect of Food
- Administration of fostamatinib with a high-calorie, high-fat meal (deriving approximately 150, 250, and 500–600 calories from protein, carbohydrate, and fat, respectively) increased R406 AUC by 23% and Cmax by 15%
Distribution
- In in vitro studies, the R406 is 98.3% protein bound in human plasma. The red blood cell to plasma concentration ratio is approximately 2.6. The mean (± SD) volume of distribution at steady-state of R406 is 256 (± 92) L.
Elimination
- The mean (± SD) terminal half-life of R406 is approximately 15 (± 4.3) hours.
Metabolism
- Fostamatinib 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). R406 is the predominant moiety in the systemic circulation, and there was minimal exposure to any R406 metabolites.
Excretion
- Following an oral dose of fostamatinib, approximately 80% of the R406 metabolite is excreted in feces with approximately 20% excreted in the urine. The major component excreted in urine was R406 N-glucuronide. The major components excreted in feces were R406, O-desmethyl R406 and a metabolite produced by gut bacteria from the O-desmethyl metabolite of R406.
Specific Populations
- Population pharmacokinetics analyses indicate fostamatinib is not altered based on age, sex, race/ethnicity. In addition, the pharmacokinetics of fostamatinib is not altered in patients with renal impairment (creatinine clearance [CLcr] ≥ 30 to < 50 mL/min, estimated by Cockcroft Gault equation and end stage renal disease requiring dialysis), or hepatic impairment (Child-Pugh Class A, B and C).
Drug Interaction Studies
- Clinical Pharmacology Studies
- No significant interactions were seen with concomitant use of fostamatinib with the following drugs: methotrexate (OAT1/3 transporters), midazolam (CYP3A4 substrate), microgynon (ethinyl estradiol and levonorgestrel), warfarin, pioglitazone (CYP2C8 substrate) and ranitidine (H2-antagonist that increases gastric pH).
Effect of Other Drugs on Fostamatinib
- Strong CYP3A4 inhibitor: Concomitant use of ketoconazole (200 mg twice daily for 3.5 days) with a single dose of 80 mg fostamatinib (0.53 times the 150 mg dosage) increased R406 AUC by 102% and Cmax by 37%.
- Moderate CYP3A4 Inhibitor: Concomitant use of verapamil (80 mg three times daily for 4 days) with a single dose of 150 mg fostamatinib increased R406 AUC by 39% and Cmax by 6%.
- CYP3A4 inducer: Concomitant use of rifampicin (600 mg once daily for 8 days) with a single dose of 150 mg fostamatinib decreased R406 AUC by 75% and Cmax by 59%.
Effect of Fostamatinib on Other Drugs
- CYP3A4 substrate: Concomitant use of simvastatin (single dose 40 mg) with 100 mg twice daily fostamatinib increased simvastatin AUC by 64% and Cmax by 113% and simvastatin acid AUC by 64% and Cmax by 83%.
- BCRP substrate: Concomitant use of rosuvastatin (single dose 20 mg) with 100 mg twice daily fostamatinib increased rosuvastatin AUC by 95% and Cmax by 88%.
- P-gp substrate: Concomitant use of digoxin (0.25 mg once daily) with 100 mg twice daily fostamatinib increased digoxin AUC by 37% and Cmax by 70%.
In Vitro Studies
- Fostamatinib is an inhibitor of the human P-gp efflux transporter in vitro.
- CYP3A4 and UGT1A9 are involved in the metabolism of R406. R406 is a substrate of P-gp but not of other major transporters (OAT1/3, OCT2, OATP1B1/3, MRP2, and BCRP). R406 can inhibit CYP3A4 and BCRP, and can induce CYP2C8 activity.
- R406 is an inhibitor of UGT1A1. Inhibition of UGT1A1 may result in increased unconjugated bilirubin in the absence of other LFT abnormalities.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
- Fostamatinib was not carcinogenic in a 2-year study in mice when administered daily by oral gavage at doses up to 500/250 mg/kg/day, and was not carcinogenic in rats when administered by oral gavage at 45 mg/kg/day.
- Fostamatinib and its major active metabolite (R406) were not mutagenic in an in vitro bacterial reverse mutation (Ames) assay or clastogenic in an in vitro human lymphocyte chromosomal aberration assay or an in vivo mouse bone marrow micronucleus assay.
- In a fertility study with oral fostamatinib, all mating (e.g., time to mating, breeding proficiency), sperm assessments (e.g., number and motility), and organ weight (e.g., paired testis weight) parameters in male rats were unaffected by dosages as high as 40 mg/kg/day, which is 6.7 times the MRHD. All mating and fertility parameters in female rats were unaffected by dosages as high as 11 mg/kg/day (which is 1.8 times the MRHD), but a slight decrease in pregnancy rates and an increase in post-implantation loss were seen at 25 mg/kg/day, which is 4.2 times the MRHD.
Clinical Studies
- Fostamitinib was studied in two placebo-controlled efficacy and safety studies (referred to as FIT-1 [NCT02076399] and FIT-2 [NCT02076412]), and in an open-label extension study referred to as FIT-3 (NCT 02077192).
Randomized, Placebo-Controlled Studies
- A total of 150 patients with persistent or chronic ITP, who had an insufficient response to previous treatment (which included corticosteroids, immunoglobulins, splenectomy, and/or a thrombopoietin receptor agonists) were enrolled in two identical, double-blind, placebo-controlled studies that were conducted in different countries. For each study, patients were randomized 2:1 to fostamatinib or placebo for 24 weeks; randomization was stratified with respect to prior splenectomy and severity of thrombocytopenia. Stable concurrent ITP therapy (glucocorticoids [< 20 mg prednisone equivalent per day], azathioprine, or danazol) was allowed, and rescue therapy was permitted, if needed. All patients initially received 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).
- Patients enrolled in the placebo-controlled studies had a median age of 54 years (range: 20 to 88), and the majority were female (61%) and were White (93%). Prior ITP treatments were varied, with the most common including corticosteroids (94%), immunoglobulins (53%), and thrombopoietin receptor agonists (TPO-RA) (48%). Most patients had chronic ITP (93%), with a median time since ITP diagnosis of 8.45 years, and 35% had undergone splenectomy. At baseline, the median platelet count was 16 × 109/L (with almost half [45]%) less than 15 × 109/L) and 47% were on stable ITP therapy.
- In Study FIT-1, 76 patients were randomized; 51 to the fostamatinib group and 25 to the placebo group. In Study FIT-2, 74 patients were randomized; 50 to the fostamatinib group and 24 to the placebo group. The efficacy of fostamatinib was based on stable platelet response (at least 50 ×109/L on at least 4 of the 6 visits between Weeks 14 to 24). Study outcomes for FIT-1 and FIT-2 are shown in Table 5.
- In the FIT-1 and FIT-2 studies a total of 47 patients in the fostamatinib arm had received a prior TPO-RA treatment; among these patients, 8 patients (17%) achieved a stable response to fostamatinib. All 8 patients had previously discontinued TPO-RA due to loss of effect. Rescue medication was required by 30% and 45% of patients receiving fostamatinib or placebo, respectively.
- During the placebo-controlled studies, the incidence of bleeding occurred in 29% and 37% of patients in the fostamatinib and placebo arms, respectively. Moderate, severe and serious bleeding events are described in Table 6. All severe events led to hospitalizations.
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 remained blinded to their treatment assignment from the previous study (fostamatinib or placebo), so their starting dose in this study was based on their final platelet count. 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 less than 50 × 109/L) received fostamatinib 100 mg twice daily regardless of their dose and regimen in the prior study.
- For the FIT-3 trial, 123 patients were enrolled, 44 patients previously randomized to placebo and 79 patients previously randomized to fostamatinib. Stable response in this study was prospectively defined as no 2 visits, at least 4 weeks apart, with a platelet count less than 50 × 109/L, without an intervening visit with a platelet count of at least 50 × 109/L (unrelated to rescue therapy), 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 a prospectively defined analysis, the 44 subjects treated with placebo in the prior study were evaluated for stable response for fostamatinib. Ten of these subjects (23%) (including a single subject who was classified as a placebo responder in the prior study) met the criteria for stable response.
- Among the subjects who achieved stable response in FIT-1, FIT-2 and FIT-3 trials, 18 subjects maintained the platelet count of at least 50 × 109/L for 12 months or longer.
How Supplied
- Fostamatinib 100 mg tablets are round, biconvex, orange, film-coated tablets debossed with "100" on one side and "R" on the reverse side.
- Fostamatinib 150 mg tablets are oval, biconvex, orange, film-coated tablets debossed with "150" on one side and "R" on the reverse side.
Storage
- Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not remove desiccants.
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Patient Counseling Information
- Advise the patient to read the FDA-approved patient labeling.
- Hypertension: Inform patients that periodic monitoring of their blood pressure is required, as high blood pressure has occurred in patients taking fostamatinib. Inform patients of the signs and symptoms of hypertension. Advise patients to undergo routine blood pressure monitoring and to contact their health care provider if blood pressure is elevated or if they experience signs or symptoms of hypertension.
- Hepatotoxicity: Inform patients that periodic monitoring of their liver enzymes is required, and any elevations (which may indicate liver injury) will be managed appropriately, including interruption, reduction, or discontinuation of fostamatinib.
- Diarrhea: Advise patients to use supportive care measures, and if diarrhea becomes severe, it may necessitate interruption, reduction, or discontinuation of fostamatinib.
- Neutropenia: Inform patients that monitoring of their complete blood counts is required, and a decrease in neutrophils may necessitate interruption, reduction, or discontinuation of fostamatinib.
- Advise patients to inform their healthcare providers of all their medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.
- Embryo-Fetal Toxicity: Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform female patients of the potential risk to a fetus.
- Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after receiving the last dose of fostamatinib.
- Lactation: Advise lactating women not to breastfeed during treatment with fostamatinib and for at least 1 month after the last dose.
- Inform patients that fostamatinib may be taken with or without food. In the case of a missed dose of fostamatinib, instruct patients to take their next dose at its regularly scheduled time.
Precautions with Alcohol
Alcohol-Fostamatinib interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
- Tavalisse
Look-Alike Drug Names
There is limited information regarding Fostamatinib Look-Alike Drug Names in the drug label.
Drug Shortage Status
Drug Shortage
Price
References
The contents of this FDA label are provided by the National Library of Medicine.