FRUZAQLA

FRUZAQLA should be initiated by a physician experienced in the administration of anticancer therapy. Posology The recommended dose of fruquintinib is 5 mg (one 5 mg capsule) 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.

Duration of treatment Treatment with fruquintinib should be continued until disease progression or unacceptable toxicity occurs. Missed doses or vomiting If a dose is missed by less than 12 hours, it should be taken, and the next dose should be taken as scheduled.

If a dose is missed by more than 12 hours, it should be skipped, and the next dose should be taken as scheduled. If a patient vomits after taking a dose, the patient should not repeat the dose on the same day, but resume the usual dosing as scheduled on the following day.

Dose Adjustments for Adverse Reactions The dose should be modified based on safety and tolerability. Fruquintinib 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 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 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. Hypertension Grade 4 Permanently discontinue. Grade 2 • Withhold until bleeding fully resolves or recovers to Grade 1. • Resume at a reduced dose as per Table 1.

If the patient still experiences Grade 2 haemorrhagic events after taking 3 mg daily, permanently discontinue. Haemorrhagic Events Grade ≥ 3 Permanently discontinue. Proteinuria ≥ 2 g / 24 hours • Withhold until proteinuria fully resolves or is < 1 g / 24 hours (Grade 1).

Summary of the safety profile The overall safety profile of fruquintinib is based on pooled data from clinical studies with 911 patients with mCRC. 68 months. 5%), the majority of which were of Grades 1 or 2 severity. 3%). 4). 6%. 6%). 5%.

4%). Tabulated list of adverse reactions Adverse reactions reported in clinical studies of fruquintinib are listed in Table 3. These reactions are presented by system organ class and by frequency. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first.

Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 3:

Adverse Reactions Reported in Clinical Studies in Patients with mCRC Treated with Fruquintinib (N=911) System Organ Class Frequency Category Adverse Reactions All Grades Infections and infestations Common Pneumonia Upper respiratory tract infection1 Very Common Thrombocytopenia2 Blood and lymphatic system disorders Common Leukopenia3 Neutropenia4 Endocrine disorders Very Common Hypothyroidism5 Very Common Anorexia6 Metabolism and Nutrition disorders Common Hypokalaemia Nervous system disorders Uncommon Posterior reversible encephalopathy syndrome Vascular disorders Very Common Hypertension7 Very Common Dysphonia8 Respiratory, thoracic and mediastinal disorders Common Epistaxis Throat pain9 Very Common Diarrhoea Stomatitis10 Common Gastrointestinal haemorrhage11 Gastrointestinal perforation12 Pancreatic enzymes increased13 Oral pain14 Gastrointestinal disorders Uncommon Pancreatitis15 Hepatobiliary disorders Very Common Aspartate aminotransferase increased Total bilirubin increased16 Alanine aminotransferase increased Very Common Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders Common Rash17 Musculoskeletal and connective tissue disorders Very Common Musculoskeletal discomfort18 Arthralgia Renal and urinary disorders Very Common Proteinuria19 Very Common Asthenia Fatigue General disorders and administrative site conditions Common Mucosal inflammation The safety data is based on all patients with mCRC who received at least 1 dose (5 mg) of fruquintinib (5 mg once daily 3 weeks on/1 week off) in the following pooled studies: 2012-013-00CH1; 2013-013-00CH1/ FRESCO; 2019-013- GLOB1/FRESCO-2 including the open-label Japanese safety lead-in cohort; 2009- 013-00CH1; 2012 013-00CH3; 2015-013-00US1.

Hypertension Hypertension, including hypertensive crisis, has been reported in patients treated with fruquintinib. 8). Pre-existing hypertension should be adequately controlled before starting fruquintinib treatment. 2). Fruquintinib should be permanently discontinued for hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis.

8). Serious and sometimes fatal bleeding events have been reported in patients after treatment with fruquintinib. Monitor haematologic and coagulation profiles more frequently in patients at risk for bleeding, including those treated with anticoagulants or other concomitant medicinal products that increase the risk of bleeding.

2). 8). Fruquintinib should be withheld for Grade 3 or 4 infections or worsening of the infection of any grade. Fruquintinib to be resumed at the same dose when infection is resolved. 8). Symptoms of GI perforation should be periodically monitored during treatment with fruquintinib.

Fruquintinib should be permanently discontinued in patients developing GI perforation. 8). The liver function test abnormalities should be monitored before initiation and throughout the treatment with fruquintinib. 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.

Proteinuria Proteinuria events have occurred in patients treated with fruquintinib. Urine protein should be monitored regularly. If urine dipstick proteinuria ≥2 g / 24 hours is detected, dose interruptions, adjustments, or discontinuation may be necessary.

2). 8). 2). 8). PRES is a rare neurologic disorder that can present with headache, seizure, lethargy, confusion, altered mental function, blindness, and other visual or neurological disturbances, with or without associated hypertension.

1.