TAVALISSE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TAVALISSE (TAVALISSE).
Spleen tyrosine kinase (Syk) inhibitor; reduces antibody-mediated destruction of platelets by inhibiting Fcγ receptor signaling and B-cell receptor signaling.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP2C9 and CYP2C19. |
| Excretion | Primarily biliary/fecal elimination (approximately 87% of dose recovered in feces as unchanged drug and metabolites); renal excretion is minimal (approximately 8% of dose recovered in urine). |
| Half-life | Terminal elimination half-life is approximately 19 hours. This supports once-daily dosing; steady state is achieved within approximately 4 days. |
| Protein binding | Highly bound (approximately 99.4%) to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution is approximately 2.7 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 88% (based on mass balance data) with no significant food effect; can be taken with or without food. |
| Onset of Action | Time to clinical effect (platelet count improvement) is variable; initial increases in platelet counts may be observed within 1–2 weeks of starting therapy, with maximum response typically achieved by 8 weeks. |
| Duration of Action | Platelet count elevations are maintained with continued once-daily dosing; upon discontinuation, platelet counts generally return to baseline within 1–2 weeks. |
Oral, 150 mg once daily with or without food. If platelet count does not increase adequately after 3–4 weeks, dose may be increased to 200 mg once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or dialysis. |
| Liver impairment | Child-Pugh Class A: No dose adjustment. Child-Pugh Class B: Reduce to 100 mg once daily. Child-Pugh Class C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no approved pediatric dosing. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor platelet counts and adverse events closely due to potential age-related renal or hepatic impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TAVALISSE (TAVALISSE).
| Breastfeeding | There are no data on the presence of fostamatinib or its metabolites in human milk, effects on the breastfed infant, or effects on milk production. Fostamatinib and its active metabolite are present in rat milk at concentrations similar to maternal plasma. Because of the potential for serious adverse reactions in nursing infants, advise patients that breastfeeding is not recommended during treatment with TAVALISSE and for at least 1 month after the last dose. The milk-to-plasma ratio (M/P) in rats was approximately 0.7 for fostamatinib and 1.1 for the active metabolite, but human M/P ratio is unknown. |
| Teratogenic Risk | TAVALISSE (fostamatinib) is an oral spleen tyrosine kinase inhibitor. Based on animal studies and its mechanism of action, there is potential for fetal harm. In animal reproduction studies, administration of fostamatinib to pregnant rats and rabbits during organogenesis resulted in embryofetal toxicity (increased post-implantation loss, reduced fetal body weights, and skeletal anomalies) at exposures below the human exposure at the recommended dose. There are no adequate and well-controlled studies in pregnant women. Therefore, TAVALISSE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. First trimester risks include structural anomalies; second and third trimester risks include reduced fetal growth and potential adverse effects on immune development. |
■ FDA Black Box Warning
None.
| Serious Effects |
["None reported in prescribing information."]
| Precautions | ["Risk of hemorrhage (including fatal bleeding) in patients with thrombocytopenia.","Hepatotoxicity: monitor liver function tests.","Neutropenia and febrile neutropenia.","Hypertension and bradycardia.","Fetal harm based on animal data; advise females of reproductive potential to use effective contraception."] |
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| Fetal Monitoring | Monitor complete blood counts (CBC) monthly during treatment, as TAVALISSE can cause neutropenia, thrombocytopenia, and anemia. Monitor liver function tests (ALT, AST, bilirubin) monthly due to potential hepatotoxicity. Monitor blood pressure regularly as TAVALISSE can cause hypertension. In pregnant women, consider fetal ultrasound monitoring for growth and anatomy if exposure occurs. Monitor for signs of infection, especially neutropenic fever. No specific fetal monitoring is mandated; however, if used during pregnancy, close obstetric monitoring including fetal growth assessments is recommended. |
| Fertility Effects | Based on animal studies, TAVALISSE may impair fertility in both males and females. In female rats, fostamatinib caused disruption of estrous cycles and reduced fertility at exposures similar to human exposure. In male rats, decreased sperm count and motility were observed at exposures below the human exposure. The effects on human fertility are unknown; however, caution is warranted. Reversibility of these effects has not been studied in animals or humans. |