FRUZAQLA

1 Dosing Considerations FRUZAQLA should be initiated by a physician experienced in the administration of anticancer therapy. 2 Recommended Dose and Dosage Adjustment The recommended dose of FRUZAQLA is 5 mg (one 5 mg capsule) administered orally once daily at approximately the same time each day for 21 consecutive days, followed by a 7 day rest period to comprise a complete cycle of 28 days.

Treatment with FRUZAQLA should be continued until disease progression or unacceptable toxicity occurs. Dose Adjustments for Adverse Reactions FRUZAQLA should be permanently discontinued in patients unable to tolerate a dose of 3 mg once daily.

The recommended dose reduction schedule for adverse reactions is provided in Table 1. Table 1 Recommended FRUZAQLA dose reduction schedule Dose Reduction Schedule Dose and schedule Number and strength of capsules First dose reduction 4 mg once daily Four 1 mg capsules once daily Second dose reduction 3 mg once daily Three 1 mg capsules once daily FRUZAQLA (fruquintinib) capsules Page 5 of 36 The recommended dose modifications for adverse reactions are provided in Table 2.

Table 2 Recommended dose modifications for FRUZAQLA for adverse reactions Adverse Reaction Severity1 Dose modification Hypertension Grade 3 • Withhold if Grade 3 hypertension persists despite initiation or modification of antihypertensive treatment.

• If hypertension recovers to Grade 1 or baseline, resume at a reduced dose as per Table 1. • If the patient still experiences Grade 3 hypertension after taking 3 mg daily, permanently discontinue. Grade 4 Permanently discontinue. Haemorrhagic Events Grade 2 • Withhold until bleeding fully resolves or recovers to Grade 1 or baseline.

• Resume at a reduced dose as per Table 1. • If the patient still experiences Grade 2 hemorrhagic events after taking 3 mg daily, permanently discontinue. Grade ≥3 Permanently discontinue. Proteinuria ≥2 g / 24 hours • Withhold until proteinuria fully resolves or is <1 g / 24 hours (Grade 1).

• Resume at a reduced dose as per Table 1. • If the patient still experiences ≥ 2 g / 24 hours proteinuria after taking 3 mg daily, permanently discontinue. Permanently discontinue for nephrotic syndrome. 5 times ULN • Withhold until liver function test abnormality recovers to Grade 1 or baseline.

• Resume at a reduced dose as per Table 1. • If the patient still experiences Grade 2 or Grade 3 liver function test abnormalities after taking 3 mg daily, permanently discontinue. ALT or AST greater than 3 times ULN with concurrent total bilirubin greater than 2 times ULN (in the Permanently discontinue.

). Exercise caution when driving or operating a vehicle or potentially dangerous machinery. 5% of patients. 1% of patients treated with FRUZAQLA. 7%). 2% of patients treated with FRUZAQLA, GI perforation events led to dose discontinuation.

Symptoms of GI perforation should be monitored periodically during treatment with FRUZAQLA. FRUZAQLA should be permanently discontinued in patients developing GI perforation. Hepatic Liver function test abnormalities FRUZAQLA can cause liver injury.

7% of patients treated with FRUZAQLA, including fatal events in clinical studies (see 8 ADVERSE REACTIONS). Most hepatobiliary disorders in patients treated with FRUZAQLA were mild to moderate in severity. 8%. 5%). Median time to onset in FRUZAQLA treated patients was 27 days (range: 4 days to 12 months).

4% of patients. 2% of patients. 9% of patients. Liver function test abnormalities should be monitored before initiation and throughout the treatment with FRUZAQLA. Based on the severity and persistence of liver function abnormalities as manifested by elevated liver function tests, treatment should be withheld, and then reduced or permanently discontinued.

Infections Infections, including fatalities, have been reported in patients treated with FRUZAQLA. 4% of the patients (see 8 ADVERSE REACTIONS). Most infection events in patients treated with FRUZAQLA were mild to moderate in severity.

9%. 7% of patients. 8%. 5%). 4% respectively). FRUZAQLA should be withheld for Grade 3 or 4 infections or worsening of the infection of any grade. FRUZAQLA to be resumed at the same dose when infection is resolved. Monitoring and Laboratory Tests Hypertension should be monitored and managed using standard antihypertensive therapy during treatment with FRUZAQLA as clinically indicated.

The pregnancy status of females of reproductive potential should be verified prior to starting treatment with FRUZAQLA. Urine protein should be monitored regularly. Monitor hematologic and coagulation parameters in patients at risk of bleeding.

4% of patients treated with FRUZAQLA. Approximately half of these events occurred during the first 2 weeks after initiating treatment with FRUZAQLA. 1%. 6 months). 3%) treated with FRUZAQLA experienced life-threatening hypertension. The majority of the events resolved.

7% of patients, respectively. 5% of patients treated with FRUZAQLA, hypertension led to permanent treatment discontinuation. Preexisting hypertension should be adequately controlled before starting FRUZAQLA treatment. Hypertension should be medically managed with antihypertensive medicinal products and adjustment of the FRUZAQLA dose, if necessary (see 4 DOSAGE AND ADMINISTRATION).

FRUZAQLA should be permanently discontinued for hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis. Driving and Operating Machinery Studies to evaluate the effects of FRUZAQLA on the ability to drive or operate machinery have not been conducted.

FRUZAQLA may have a minor influence on the ability to drive and use machines. Fatigue may occur following administration of FRUZAQLA (see

FRUZAQLA is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.