AYVAKIT

Avapritinib C max and AUC increased approximately proportionally over the dose range of 25 mg to 400 mg once daily. Steady state concentrations of avapritinib were reached prior to day 15 following daily dosing. Steady state pharmacokinetic parameters per recommended dosing regimen are described in Table 10. Table 10. Steady State Pharmacokinetic Parameters of AYVAKIT Following Different Dosing Regimen Pharmacokinetic Parameters 25 mg once daily (ISM) 200 mg once daily (AdvSM) 300 mg once daily ...

14.1 Gastrointestinal Stromal Tumors The efficacy of AYVAKIT was demonstrated in NAVIGATOR (NCT02508532), a multi-center, single-arm, open-label clinical trial. Eligible patients were required to have a confirmed diagnosis of GIST and an ECOG performance status (PS) of 0 to 2. Patients received AYVAKIT 300 mg or 400 mg (1.33 times the recommended dose) orally once daily until disease progression or unacceptable toxicity. The trial initially enrolled patients at a starting dose of 400 mg, which was later reduced to the recommended dose of 300 mg due to toxicity. As there was no apparent differe...

The following clinically significant adverse reactions are described elsewhere in the labeling: Intracranial hemorrhage [see Warnings and Precautions (5.1) ] Cognitive effects [see Warnings and Precautions (5.2) ] Photosensitivity [see Warnings and Precautions (5.3) ] The most common adverse reactions are: GIST (≥20% incidence): edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, increased lacrimation, abdominal pain, constipation, rash, dizziness, and ...

None. None. ( 4 )

Intracranial Hemorrhage : Permanently discontinue for any occurrence of any grade. ( 2.5 , 5.1 ) Cognitive Effects : A broad spectrum of cognitive adverse reactions can occur in patients receiving AYVAKIT. In patients with GIST, AdvSM, or ISM depending on the severity, continue AYVAKIT at same dose, withhold and then resume at same or reduced dose upon improvement, or permanently discontinue. ( 2.5 , 5.2 ) Photosensitivity: May cause photosensitivity reactions. Advise patients to limit direct ul...

7 DRUG INTERACTIONS Strong and Moderate CYP3A Inhibitors : Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration of AYVAKIT with a moderate inhibitor cannot be avoided, reduce dose of AYVAKIT in patients with GIST or AdvSM. ( 2.6 , 7.1 ) Strong and Moderate CYP3A Inducers : Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers. ( 7.1 )...