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 prescribed 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 modification 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. 4 Haemorrhagic events 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. Grade ≥ 3 Permanently discontinue. Proteinuria ≥ 2 g / 24 hours • Withhold until proteinuria fully resolves or is < 1 g / 24 hours (Grade 1).

5%). 3%). 3%). 6%. 6%). 5%. 4%). Tabulated list of adverse reactions The frequencies of adverse reactions are based on pooled data from clinical studies with 911 patients with previously treated mCRC. 68 months. Adverse reactions reported in clinical studies or from post-marketing use of fruquintinib are listed in Table 3 by MedDRA 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 frequency not known (cannot be estimated from available post-marketing data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 3:

Adverse reactions reported 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 Bacterial infections2 Blood and lymphatic system disorders Very common Thrombocytopaenia3 Common Leukopenia4 Neutropenia5 Endocrine disorders Very common Hypothyroidism6 Metabolism and nutrition disorders Very common Anorexia7 Common Hypokalaemia Nervous system disorders Uncommon Posterior reversible encephalopathy syndrome* Vascular disorders Very common Hypertension8 Not known Aortic dissection† Respiratory, thoracic and mediastinal disorders Very common Dysphonia9 Common Epistaxis Throat pain10 Gastrointestinal disorders Very common Diarrhoea Stomatitis11 Common Gastrointestinal haemorrhage12 Gastrointestinal perforation13 Pancreatic enzymes increased14 Oral pain15 Uncommon Pancreatitis16 Hepatobiliary disorders Very common Aspartate aminotransferase increased Total bilirubin increased17 Alanine aminotransferase increased Uncommon Cholecystitis18 Very common Palmar-plantar erythrodysaesthesia syndrome 10 Skin and subcutaneous tissue disorders Common Rash19 Musculoskeletal and connective tissue disorders Very common Musculoskeletal discomfort20 Arthralgia Renal and urinary disorders Very common Proteinuria21 General disorders and administrative site conditions Very common Asthenia Fatigue Common Mucosal inflammation Uncommon Impaired wound healing*, 22 The safety data is based on all patients with mCRC who received at least 1 dose (5 mg) of fruquintinib monotherapy (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.

8). Pre-existing hypertension should be monitored and adequately controlled in accordance with standard medical practices 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. Haematologic and coagulation profiles should be monitored in accordance with standard medical practices in patients at risk for bleeding, including those treated with anticoagulants or other concomitant medicinal products that increase the risk of bleeding.

2). 8). Symptoms of GI perforation should be periodically monitored during treatment with fruquintinib. Fruquintinib should be permanently discontinued in patients developing GI perforation. Proteinuria Proteinuria events have occurred in patients treated with fruquintinib.

Proteinuria should be monitored before initiation and during treatment with fruquintinib in accordance with standard medical practices. 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.

A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). In patients developing PRES, discontinuation of 7 fruquintinib, along with control of hypertension and supportive medical management of other symptoms, are recommended.

1%) treated with fruquintinib in clinical studies. Patients are recommended to withhold fruquintinib for at least 2 weeks prior to surgery. Fruquintinib should not be resumed for at least 2 weeks after surgery, as clinically indicated when there is evidence of adequate wound healing.

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