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Fostamatinib

Medically reviewed by Drugs.com. Last updated on May 9, 2020.

Pronunciation

(fos ta ma ti nib)

Index Terms

  • Fostamatinib Disodium Hexahydrate
  • R788
  • R935788
  • Syk Kinase Inhibitor R935788
  • Tavalisse

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as disodium hexahydrate:

Tavalisse: 100 mg, 150 mg

Brand Names: U.S.

  • Tavalisse

Pharmacologic Category

  • Spleen Tyrosine Kinase (Syk) Inhibitor
  • Tyrosine Kinase Inhibitor

Pharmacology

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.

Distribution

R406: 256 (± 92) L

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)

Excretion

Feces (R406: ~80%); Urine (R406: ~20%)

Onset of Action

Median time to response (platelets ≥50,000/mm3): 15 days (Bussel 2018)

Time to Peak

R406: ~1.5 hours (range: 1 to 4 hours)

Half-Life Elimination

R406: 15 (± 4.3) hours

Protein Binding

R406: 98.3%

Use: Labeled Indications

Immune thrombocytopenia (ITP) (chronic, refractory): Treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

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 (ITP) (chronic, refractory): Oral: Initial: 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).

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.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Recommended dose reduction schedule:

Usual maximum 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.

Gastrointestinal toxicity (diarrhea): Manage diarrhea with supportive measures (eg, dietary changes, hydration and/or antidiarrheal medication) early after the onset until symptom(s) have resolved. If symptom(s) become severe (grade 3 or higher), temporarily interrupt fostamatinib. If diarrhea improves to mild (grade 1), resume fostamatinib at the next lower dosage level.

Hypertension:

Stage 1 (systolic between 130 to 139 mm Hg or diastolic between 80 to 89 mm Hg): Initiate antihypertensive therapy (or increase antihypertensive dosage) for patients with increased cardiovascular risk; adjust as needed until blood pressure (BP) is controlled. If BP target is not met after 8 weeks, reduce fostamatinib dose to the next lower dosage level.

Stage 2 (systolic ≥140 to 180 mm Hg or diastolic ≥90 to 120 mm Hg): Initiate antihypertensive therapy (or increase antihypertensive dosage); adjust as needed until BP is controlled. If BP remains ≥140/90 mm Hg for >8 weeks, reduce fostamatinib dose to the next lower dosage 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 antihypertensive therapy (or increase antihypertensive dosage) and adjust as needed until BP is controlled. If BP returns to less than target BP, resume fostamatinib at the same dose. If BP remains ≥160/100 mm Hg for >4 weeks (despite aggressive antihypertensive therapy), discontinue fostamatinib.

Neutropenia: If ANC <1,000/mm3 and remains low after 72 hours, temporarily interrupt fostamatinib until resolved to ANC >1,500/mm3, then resume fostamatinib at the next lower dosage level.

Administration

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.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Do not remove desiccants from container.

Drug Interactions

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. Consider therapy modification

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. 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. Consider therapy modification

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-gp inhibitor. Avoid concomitant use of betrixaban and P-gp inhibitors in patients with severe renal impairment (CrCL less than 30 mL/min). Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Avoid combination

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. 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. Consider therapy modification

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. Consider therapy modification

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Fostamatinib. Avoid combination

CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Fostamatinib. Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digitoxin. 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. Consider therapy modification

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Avoid combination

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: Exceptions to this monograph are discussed in separate Lexi-Interact monographs. Monitor therapy

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. 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. Consider therapy modification

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

Ozanimod: BCRP/ABCG2 Inhibitors may increase serum concentrations of the active metabolite(s) of Ozanimod. Avoid combination

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination

Rimegepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination

RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Monitor therapy

Rosuvastatin: Fostamatinib may increase the serum concentration of Rosuvastatin. Monitor therapy

Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simvastatin: Fostamatinib may increase the serum concentration of Simvastatin. Monitor therapy

Sirolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus. 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. Consider therapy modification

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Monitor therapy

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tolvaptan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tolvaptan. Monitor therapy

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. 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. 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. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Adverse Reactions

>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)

Warnings/Precautions

Concerns related to adverse effects:

• Gastrointestinal toxicity: Diarrhea occurred in nearly one-third of patients treated with fostamatinib; severe diarrhea occurred rarely. Monitor for the development of diarrhea and manage supportively (eg, dietary changes, hydration, and/or antidiarrheal medication) early after the onset of symptoms. If diarrhea becomes severe (grade 3 or higher), may require treatment interruption, dosage reduction, and/or discontinuation.

• 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. Monitor liver function tests at baseline and monthly during treatment. If ALT or AST increase more than 3 times ULN, manage hepatotoxicity with treatment interruption, dose reduction, or discontinuation.

• 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. Monitor blood pressure every 2 weeks until stable and then monthly; adjust or initiate antihypertensive therapy to ensure blood pressure control during fostamatinib treatment. Fostamatinib treatment interruption, dosage reduction, and/or discontinuation may be indicated if hypertension persists despite appropriate antihypertensive therapy.

• Neutropenia: Neutropenia has occurred with fostamatinib treatment; neutropenic fever has been reported rarely. Monitor CBC at baseline and monthly; monitor for infection during treatment. Neutropenia may require fostamatinib treatment interruption, dosage reduction and/or discontinuation.

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.

Monitoring Parameters

CBC including platelets (baseline and monthly until a stable platelet count of ≥50,000/mm3 is achieved, then regularly); liver function tests (ALT, AST, bilirubin [baseline and monthly]); pregnancy test (prior to treatment initiation in females of reproductive potential); blood pressure (baseline and every 2 weeks until stable dose is established, then monthly thereafter). Monitor for signs/symptoms of diarrhea and hepatotoxicity. Monitor adherence.

Reproductive Considerations

Evaluate pregnancy status in females of reproductive potential prior to therapy; effective contraception should be used during treatment and for at least 1 month after the last fostamatinib dose.

Pregnancy Considerations

Based on the mechanism of action and information from animal reproduction studies, fostamatinib may cause fetal harm if exposure occurs during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat immune thrombocytopenia (ITP).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Common cold symptoms

• Abdominal pain

• Loss of strength and energy

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Severe headache

• Dizziness

• Passing out

• Vision changes

• Severe or persistent diarrhea

• Confusion

• Chest pain

• Shortness of breath

• Infection

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.