Note: Use the lowest dose necessary to achieve and maintain platelet count of at least 50,000/mm3 as necessary to reduce the risk of bleeding; discontinue after 12 weeks if platelet count does not increase to a level sufficient to avoid clinically important bleeding.
Immune thrombocytopenia, chronic, refractory: Initial: Oral: 100 mg twice daily; if platelet count has not increased to at least 50,000/mm3 after 1 month, increase dose to 150 mg twice daily (Bussel 2018, Bussel 2019).
Missed doses: If a dose is missed, the next scheduled dose should be administered at the regularly scheduled time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; renal impairment does not alter fostamatinib pharmacokinetics, therefore, dosage adjustment is not likely necessary.
Hepatic impairment at treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling; hepatic impairment does not alter fostamatinib pharmacokinetics, therefore, dosage adjustment is not likely necessary.
Hepatotoxicity during treatment:
Note: Refer to "Dosing - Adjustment for Toxicity" for fostamatinib dosage adjustment levels.
ALT, AST ≥3 and <5 times ULN and asymptomatic: Recheck LFTs every 72 hours until ALT, AST values are no longer elevated (<1.5 times ULN) and total bilirubin remains <2 times ULN; consider fostamatinib interruption or dose reduction if ALT, AST, and total bilirubin remain elevated (ALT, AST 3 to 5 times ULN with bilirubin <2 times ULN); if interrupted, resume fostamatinib at the next lower dosage level when ALT and AST are no longer elevated (<1.5 times ULN) and total bilirubin remains <2 times ULN.
ALT, AST ≥3 and <5 times ULN and symptomatic (eg, nausea, vomiting, abdominal pain): Interrupt fostamatinib. Recheck LFTs every 72 hours until ALT, AST values are no longer elevated (<1.5 times ULN) and total bilirubin remains <2 times ULN, then resume fostamatinib at the next lower dosage level.
ALT, AST ≥5 times ULN and total bilirubin <2 times ULN: Interrupt fostamatinib. Recheck LFTs every 72 hours. If ALT and AST decrease, recheck until ALT and AST are no longer elevated (<1.5 times ULN) and total bilirubin remains <2 times ULN, then resume fostamatinib at the next lower dosage level. If ALT, AST persist at ≥5 times ULN for ≥2 weeks, discontinue fostamatinib.
ALT, AST ≥3 times ULN and total bilirubin >2 times ULN: Discontinue fostamatinib.
Elevated unconjugated (indirect) bilirubin (in the absence of other LFT abnormalities): Continue fostamatinib; monitor frequently. Isolated increases in unconjugated bilirubin may be due to UGT1A1 inhibition.
Refer to adult dosing.
Usual maximum daily dose |
300 mg/day (150 mg twice daily) |
First dosage reduction level |
200 mg/day (100 mg twice daily) |
Second dosage reduction level |
150 mg/day (150 mg once daily in the morning) |
Third dosage reduction level |
100 mg/day (100 mg once daily in the morning) |
If further dosage reduction is required (at 100 mg/day), discontinue fostamatinib. |
Adverse Reaction |
Recommended Action |
---|---|
Hypertension | |
Stage 1: Systolic between 130 to 139 mm Hg or diastolic between 80 to 89 mm Hg |
Initiate or increase dosage of antihypertensive medication for patients with increased cardiovascular risk, and adjust as needed until BP is controlled. If the BP target is not met after 8 weeks, reduce fostamatinib to next lower daily dose level. |
Stage 2: Systolic ≥140 to 180 mm Hg or diastolic ≥90 to 120 mm Hg |
Initiate or increase dosage of antihypertensive medication, and adjust as needed until BP is controlled. If BP remains ≥140/90 mm Hg for >8 weeks, reduce fostamatinib to next lower daily dose level. If BP remains ≥160/100 mm Hg for >4 weeks despite aggressive antihypertensive therapy, interrupt or discontinue fostamatinib. |
Hypertensive crisis: Systolic >180 mm Hg and/or diastolic >120 mm Hg |
Interrupt or discontinue fostamatinib. Initiate or increase dosage of antihypertensive medication, 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 mm Hg for >4 weeks despite aggressive antihypertensive treatment, discontinue fostamatinib. |
Diarrhea | |
Diarrhea |
Manage diarrhea using supportive measures (eg, dietary changes, hydration and/or antidiarrheal medication) early after diarrhea onset until symptom(s) have resolved. If symptom(s) become severe (grade 3 or above), temporarily interrupt fostamatinib. If diarrhea improves to mild (grade 1), resume fostamatinib at the next lower daily dose level. |
Neutropenia | |
Neutropenia |
If absolute neutrophil count decreases (ANC <1,000/mm3) and remains low after 72 hours, temporarily interrupt fostamatinib until resolved (ANC >1,500/mm3). Resume fostamatinib at the next lower daily dose level. |
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as disodium hexahydrate:
Tavalisse: 100 mg, 150 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as disodium hexahydrate:
Tavalisse: 100 mg, 150 mg
Oral: Administer with or without food. Twice-daily doses should be administered in the morning and evening; once-daily doses (due to dose reduction for toxicity) should be administered in the morning.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Fostamatinib may cause teratogenicity and has a structural and/or toxicity profile similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Immune thrombocytopenia, chronic, refractory: Treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
Fostamatinib may be confused with afatinib, Fosamax, fosamprenavir, fosaprepitant, fosnetupitant, ifosfamide, imatinib, tafasitamab.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (28%)
Central nervous system: Dizziness (11%)
Gastrointestinal: Diarrhea (31%), nausea (19%)
Hepatic: Increased serum ALT (11%)
Respiratory: Respiratory tract infection (11%)
1% to 10%:
Cardiovascular: Chest pain (6%), hypertensive crisis (1%), syncope (1%, serious)
Central nervous system: Fatigue (6%)
Dermatologic: Skin rash (9%)
Gastrointestinal: Abdominal pain (6%), toothache (1%, serious)
Hematologic & oncologic: Neutropenia (6%), febrile neutropenia (1%)
Hepatic: Increased serum AST (9%)
Neuromuscular & skeletal: Arthralgia (1%, serious), limb pain (1%, serious)
Renal: Nephrolithiasis (1%, serious)
Respiratory: Dyspnea (2%, serious), hypoxia (1%, serious)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to fostamatinib or any component of the formulation; pregnancy.
Concerns related to adverse effects:
• GI toxicity: Diarrhea occurred in nearly one-third of patients treated with fostamatinib; severe diarrhea occurred rarely.
• Hepatotoxicity: Elevated liver function tests (predominantly ALT and AST) may occur with fostamatinib treatment; ALT and AST elevations >3 times the upper limit of normal (ULN) have been reported. Transaminases recovered to baseline levels within 2 to 6 weeks of dose modification in most patients.
• Hypertension: Hypertension may occur with fostamatinib; hypertensive crisis has been reported rarely. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects of fostamatinib.
• Neutropenia: Neutropenia has occurred with fostamatinib treatment; neutropenic fever has been reported rarely.
Disease-related concerns:
• Immune thrombocytopenia: If on a stable dose for 14 days prior to baseline, patients were allowed to continue one other concomitant immune thrombocytopenia medication (eg, corticosteroids at <20 mg/day prednisone equivalent, azathioprine, or danazol) throughout studies; rescue therapies (eg, IV immune globulin, Rho(D) immune globulin, corticosteroids, platelet transfusion) were also allowed (Bussel 2018).
Special populations:
• Pediatrics: Due to potential adverse effects on actively growing bones, use in patients under 18 years of age is not recommended.
Substrate of CYP3A4 (major), UGT1A9; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, P-glycoprotein/ABCB1
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Fostamatinib. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider therapy modification
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Rosuvastatin: Fostamatinib may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Simvastatin: Fostamatinib may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Evaluate pregnancy status prior to treatment in patients who could become pregnant; effective contraception should be used during treatment and for at least 1 month after the last fostamatinib dose.
Based on the mechanism of action and information from animal reproduction studies, fostamatinib may cause fetal harm if exposure occurs during pregnancy.
It is not known if fostamatinib is present in breast milk.
Due to the potential for serious adverse events in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for at least 1 month after the last fostamatinib dose.
CBC including platelets (baseline and monthly until a stable platelet count of ≥50,000/mm3 is achieved, then regularly); LFTs (ALT, AST, bilirubin [baseline and monthly; monitor every 72 hours if clinically indicated]). Evaluate pregnancy status (prior to treatment initiation in patients who could become pregnant). Monitor BP (baseline and every 2 weeks until stable dose is established, then monthly thereafter; monitor more frequently if clinically indicated). Monitor for signs/symptoms of diarrhea, infection, and hepatotoxicity. Monitor adherence.
Fostamatinib is a small molecule spleen tyrosine kinase (Syk) inhibitor. Syk affects cellular proliferation, differentiation, survival and immune regulation via IgG Fc-receptor signaling and is also linked to B-cell receptor signaling and autoantibody production (Bussel 2018). The major active metabolite of fostamatinib, R406, inhibits signal transduction of Fc-activating receptors and B-cell receptor and reduces antibody-mediated destruction of platelets.
Onset of action: Median time to response (platelets ≥50,000/mm3): 15 days (Bussel 2018)
Distribution: R406: 256 (± 92) L
Protein binding: R406: 98.3%
Metabolism: Fostamatinib: Metabolized in the gut (by alkaline phosphatase) to R406 (active metabolite); R406: Extensively metabolized, primarily via oxidation (by CYP3A4) and glucuronidation (by UGT1A9)
Bioavailability: R406: 55%
Half-life elimination: R406: 15 (± 4.3) hours
Time to peak: R406: ~1.5 hours (range: 1 to 4 hours)
Excretion: Feces (R406: ~80%); Urine (R406: ~20%)
Tablets (Tavalisse Oral)
100 mg (per each): $248.00
150 mg (per each): $248.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.