FOSTAMATINIB Drug Interactions: What You Need to Know

INTERACTIONS Strong CYP3A4 Inhibitors: Concomitant use with a strong CYP3A4 inhibitor increases exposure to R406 (the major active metabolite).( 7 ) Strong CYP3A4 Inducers: Concomitant use is not recommended. ( 7 )

7.1 Effect of Other Drugs on TAVALISSE 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 TAVALISSE that may require dose reduction (see Table 1 ) when given concurrently with a strong CYP3A4 inhibitor <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ]</span> . Strong CYP3A4 Inducers Concomitant use with a strong CYP3A4 inducer reduces exposure to R406. Concomitant use of TAVALISSE with strong CYP3A4 inducers is not recommended <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> .

7.2 Effect of TAVALISSE on Other Drugs CYP3A4 Substrates Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs. Monitor for toxicities of CYP3A4 substrate drug that may require dosage reduction when given concurrently with TAVALISSE <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> .

Bcrp

Substrates Concomitant use of TAVALISSE 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 TAVALISSE [see Clinical Pharmacology (12.3) ] . P-Glycoprotein (P-gp)

Substrates

Concomitant use of TAVALISSE 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 TAVALISSE [see Clinical Pharmacology (12.3) ] .

None. None. ( 4 )

AND PRECAUTIONS Hypertension: Monitor blood pressure every 2 weeks until stable, then monthly. Manage hypertension using standard antihypertensive treatment and, if needed, interrupt, reduce or discontinue TAVALISSE. ( 5.1 ) Hepatotoxicity: Monitor LFTs monthly. If LFT levels are elevated, interrupt, reduce or discontinue TAVALISSE. ( 5.2 ) Diarrhea: Manage diarrhea with supportive measures. If diarrhea becomes severe, interrupt, reduce or discontinue TAVALISSE. ( 5.3 ) Neutropenia: Monitor ANC monthly, and for infection. If neutrophil count decreases below 1.0 × 10 9 /L, interrupt, reduce or discontinue TAVALISSE. ( 5.4 ) Embryo-Fetal Toxicity: TAVALISSE can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.5 )

5.1 Hypertension Hypertension can occur with TAVALISSE treatment; hypertensive crisis occurred in 1% of patients. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects of TAVALISSE. Monitor blood pressure every 2 weeks until stable, then monthly and adjust or initiate antihypertensive therapy to ensure maintenance of blood pressure control during TAVALISSE therapy. If increased blood pressure persists despite appropriate therapy, TAVALISSE interruption, reduction or discontinuation may be necessary <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .

5.2 Hepatotoxicity Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. 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 TAVALISSE <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . 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 TAVALISSE interruption, reduction, or discontinuation <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .

5.3 Diarrhea Diarrhea occurred in 31% of patients treated with TAVALISSE. Severe diarrhea occurred in 1% of patients treated with TAVALISSE. 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 TAVALISSE if diarrhea becomes severe (Grade 3 or above) <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .

5.4 Neutropenia Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly, and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction or discontinuation <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .

5.5 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, TAVALISSE 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. <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1) and Clinical Pharmacology (12.1) ]</span>.