4.1. Therapeutic indications

FRUZAQLA is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with available therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, with or without an anti-VEGF therapy, and, if RAS wildtype and medically appropriate, an anti-EGFR therapy.

4.2. Posology and method of administration

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

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.

• 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).

• 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.

Liver Function Test Abnormalities

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times upper limit of normal (ULN) if baseline was normal, or greater than 3.0 times baseline if baseline was abnormal; or bilirubin greater than 1.5 times ULN if baseline was normal, or greater than 1.5 times baseline if baseline was abnormal

• 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 absence of alternative etiologies)

Permanently discontinue.

AST or ALT greater than 20 times ULN if baseline was normal, or greater than 20 times baseline if baseline was abnormal; or bilirubin greater than 10 times ULN if baseline was normal, or greater than 10 times baseline if baseline was abnormal

Permanently discontinue.

Palmar-plantar Erythrodysesthesia Syndrome (PPES)

Grade 2

• Administer supportive treatment.

• Withhold until PPES recovers to Grade 1 or baseline.

• Resume at the same dose level.

Grade 3

• Administer supportive treatment.

• Withhold until PPES recovers to Grade 1 or baseline.

• Resume at a reduced dose as per Table 1.

If the patient still experiences Grade 3 PPES after taking 3 mg daily, permanently discontinue.

Other Adverse Reactions

Grade 3

• Withhold until the reaction recovers to Grade 1 or baseline.

• Resume at a reduced dose as per Table 1.

If the patient still experiences Grade 3 other adverse reactions after taking 3 mg daily, permanently discontinue.

Grade 4

Discontinue.

Consider resuming at a reduced dose as per Table 1 if the toxicity recovers to Grade 1 or baseline and the potential benefit outweighs the risks.

1Graded per national cancer institute common terminology criteria for adverse events. Version 5.0 (NCI CTCAE v5).

Special Populations

Renal Impairment

No dose adjustment is required for patients with mild, moderate, or severe renal impairment (see section 5.2).

Hepatic Impairment

No dose adjustment is required for patients with mild or moderate hepatic impairment (see section 5.2).

FRUZAQLA is not recommended for use in patients with severe hepatic impairment as FRUZAQLA has not been studied in this population.

Elderly Population

No dose adjustment is required in patients aged 65 years or above.

Paediatric Population

The safety and efficacy of FRUZAQLA in children aged 0 to <18 years have not been established. No data are available.

Method of Administration

FRUZAQLA is for oral use.

FRUZAQLA capsules can be taken with or without food and should be swallowed whole.

4.3. Contraindications

Hypersensitivity to the active substance or any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Hypertension

Hypertension, including hypertensive crisis, has been reported in patients treated with fruquintinib. (see section 4.8). Pre‑existing hypertension should be adequately controlled before starting fruquintinib treatment.

Hypertension should be medically managed with antihypertensive medicinal products and adjustment of the fruquintinib dose, if necessary (see section 4.2). Fruquintinib should be permanently discontinued for hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis.

Haemorrhagic events

Haemorrhagic events have been reported in patients treated with fruquintinib, including gastrointestinal (GI) tract events (see section 4.8). 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. In the event of severe bleeding requiring immediate medical intervention, fruquintinib should be permanently discontinued (see section 4.2).

Infections

Infections have been reported in in patients treated with fruquintinib, including fatal events (1%) in clinical studies (see section 4.8).

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.

Gastrointestinal (GI) perforation

GI perforation events, including fatal events, have been reported in patients treated with fruquintinib (see section 4.8).

Symptoms of GI perforation should be periodically monitored during treatment with fruquintinib.

Fruquintinib should be permanently discontinued in patients developing GI perforation.

Hepatotoxicity

Liver function test abnormalities have been reported in patients treated with fruquintinib, including fatal events in clinical studies (see section 4.8).

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. Fruquintinib should be permanently discontinued in patients developing nephrotic syndrome (see section 4.2).

Palmar-plantar erythrodysesthesia syndrome (PPES)

PPES is the most frequently reported dermatological adverse reaction (see section 4.8).

If Grade ≥2 skin reactions are detected, dose interruptions, adjustments, or discontinuation may be necessary (see section 4.2).

Posterior reversible encephalopathy syndrome (PRES)

PRES has been reported with the use of fruquintinib (0.1%) (see section 4.8). 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 fruquintinib, along with control of hypertension and supportive medical management of other symptoms, are recommended.

Impaired wound healing

No formal studies of the effect of fruquintinib on wound healing have been conducted.

Impaired wound healing has been reported in 1 patient (0.1%) treated with fruquintinib.

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.

Arterial thromboembolic events

It is recommended to avoid starting treatment with fruquintinib in patients with a history of thromboembolic events (including deep vein thrombosis and pulmonary embolism) within the past 6 months or if they have a history of stroke and/or transient ischemic attack within the last 12 months. If arterial thrombosis is suspected, fruquintinib should be discontinued immediately.

Aneurysms and artery dissections

The use of VEGF pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections. Before initiating fruquintinib, this risk should be carefully considered in patients with a history of risk factors such as hypertension or aneurysm.

Excipients

Fruquintinib 5 mg capsules contain Allura red AC (E129), which may cause allergic reactions.

4.5. Interaction with other medicinal products and other forms of interaction

In vitro results indicated that fruquintinib was metabolised by CYP and non-CYP enzymes. CYP3A4 was the main enzyme among the CYP isoforms involved in the metabolism of fruquintinib, with minor contributions from CYP2C8, CYP2C9 and CYP2C19. Fruquintinib inhibited P-gp and BCRP in a dose-dependent manner in vitro and demonstrated pH-dependent aqueous solubility.

Effects of other medicinal products on the pharmacokinetics of fruquintinib

CYP3A inhibitors

Co-administration of fruquintinib with itraconazole (a strong CYP3A inhibitor) 200 mg twice daily did not result in clinically meaningful changes in the area under the concentration‑time curve (AUC) and Cmax of fruquintinib.

CYP3A inducers

Co-administration of fruquintinib with rifampicin (a strong CYP3A inducer) 600 mg once daily decreased fruquintinib AUC by 65% and decreased fruquintinib Cmax by 12%. Co-administration of fruquintinib with efavirenz (a moderate CYP3A inducer) 600 mg once daily is predicted to decrease fruquintinib AUC by 32% and fruquintinib Cmax by 4%. No clinically meaningful differences in the AUC of fruquintinib are predicted when fruquintinib is co-administered with dexamethasone (a weak CYP3A inducer) 8 mg twice daily. The concomitant use of fruquintinib with strong and moderate CYP3A inducers should be avoided.

Gastric acid lowering agents

Co-administration of fruquintinib with rabeprazole (a proton pump inhibitor) 40 mg once daily did not result in clinically meaningful changes in the AUC of fruquintinib.

Effect of fruquintinib on the pharmacokinetics of other medicinal products

Medicinal products that are substrates of P-glycoprotein (P‑gp)

Co-administration of a single dose of dabigatran etexilate 150 mg (a P‑gp substrate) with a single dose of fruquintinib 5 mg decreased AUC of dabigatran by 9%. Co‑administration of a single dose of digoxin (a P‑gp substrate) 0.5 mg with multiple doses of fruquintinib is predicted to result in a 6% increase in AUC of digoxin.

Medicinal products that are substrates of breast cancer resistance protein (BCRP)

Co-administration of a single 10 mg dose of rosuvastatin (a BCRP substrate) with a single 5 mg dose of fruquintinib decreased AUC of rosuvastatin by 19%. Co‑administration of a single 20 mg dose of rosuvastatin with multiple doses of fruquintinib is predicted to result in a 19% increase in AUC of rosuvastatin (a BCRP substrate).

4.6. Fertility, pregnancy and lactation

Women of childbearing potential/Contraception in males and females

Women of childbearing potential and male patients with female partners of childbearing potential should be advised to use effective contraception during and for at least 2 weeks following the last dose of fruquintinib.

Pregnancy

There are no clinical data available on the use of fruquintinib in pregnant women.

Based on its mechanism of action, fruquintinib has the potential to cause foetal harm. Studies in animals have shown reproductive toxicity, including foetal malformations (see section 5.3). FRUZAQLA should not be used during pregnancy unless the woman's clinical condition requires treatment with this medicinal product and after careful consideration of the benefits for the mother and the risk to the foetus.

If fruquintinib is used during pregnancy or if the patient becomes pregnant while on treatment, the patient must be informed of the potential hazard to the foetus.

Breast-feeding

It is unknown whether FRUZAQLA or its metabolites are excreted in human milk. A risk to newborns/infants cannot be excluded.

Breast-feeding should be discontinued during treatment with FRUZAQLA and for at least 2 weeks after the last dose.

Fertility

There are no data on the effects of fruquintinib on human fertility. Results from animal studies indicate that fruquintinib may impair male and female fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

Studies to evaluate the effects of fruquintinib on the ability to drive or operate machinery have not been conducted. Fruquintinib may have a minor influence on the ability to drive and use machines. Fatigue may occur following administration of fruquintinib (see section 4.8).

4.8. Undesirable effects

Summary of the safety profile

The overall safety profile of fruquintinib is based on pooled data from clinical studies with 911 patients with mCRC. Patients were exposed to at least one dose (5 mg) of fruquintinib (5 mg once daily 3 weeks on/1 week off) during a median of 3.68 months. In this patient population, the most common adverse reactions of any grade (incidence ≥ 20%) were hypertension (49.3%), anorexia (35.6%), proteinuria (35.5%), PPES (34.6%), hypothyroidism (32.4%), dysphonia (28.6%), diarrhoea (26.3%), and asthenia (24.5%), the majority of which were of Grades 1 or 2 severity. The most common adverse reactions of Grade 3/4 (incidence ≥ 5%) were hypertension (19.1%) and PPES (8.3%). The most common serious adverse reactions (incidence ≥ 1%) were gastrointestinal haemorrhage (1.5%), pneumonia (1.5%), hypertension (1.5%), and gastrointestinal perforation (1.3%) (see section 4.4).

The frequency of treatment discontinuation due to adverse reactions was 7.6%. The most common adverse reaction leading to treatment discontinuation was proteinuria (1.6%).

The frequency of dose reduction due to adverse reactions was 20.5%. The most common adverse reactions leading to dose reduction were PPES (6.4%), hypertension (3.7%), and proteinuria (3.4%).

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

PneumoniaUpper respiratory tract infection1

Blood and lymphatic system disorders

Very Common

Thrombocytopenia2

Common

Leukopenia3Neutropenia4

Endocrine disorders

Very Common

Hypothyroidism5

Metabolism and Nutrition disorders

Very Common

Anorexia6

Common

Hypokalaemia

Nervous system disorders

Uncommon

Posterior reversible encephalopathy syndrome

Vascular disorders

Very Common

Hypertension7

Respiratory, thoracic and mediastinal disorders

Very Common

Dysphonia8

Common

EpistaxisThroat pain9

Gastrointestinal disorders

Very Common

DiarrhoeaStomatitis10

Common

Gastrointestinal haemorrhage11

Gastrointestinal perforation12Pancreatic enzymes increased13Oral pain14

Uncommon

Pancreatitis15

Hepatobiliary disorders

Very Common

Aspartate aminotransferase increased

Total bilirubin increased16

Alanine aminotransferase increased

Skin and subcutaneous tissue disorders

Very Common

Palmar-plantar erythrodysaesthesia syndrome

Common

Rash17

Musculoskeletal and connective tissue disorders

Very Common

Musculoskeletal discomfort18Arthralgia

Renal and urinary disorders

Very Common

Proteinuria19

General disorders and administrative site conditions

Very Common

AstheniaFatigue

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. MedDRA 25.0.

The following terms represent a group of related events that describe a medical condition rather than a single event:

1Upper respiratory tract infection includes nasopharyngitis, pharyngitis, upper respiratory tract infection

2Thrombocytopenia includes platelet count decreased and thrombocytopenia

3Leukopenia includes leukopenia and white blood cell count decreased

4Neutropenia includes neutropenia and neutrophil count decreased

5Hypothyroidism includes blood thyroid stimulating hormone increased, hypothyroidism

6Anorexia includes appetite decreased and weight loss

7Hypertension includes blood pressure diastolic increased, blood pressure increased, diastolic hypertension, hypertension, hypertensive crisis

8Dysphonia includes aphonia and dysphonia

9Throat pain includes laryngeal discomfort, laryngeal pain, oropharyngeal discomfort, oropharyngeal pain

10Stomatitis includes aphthous ulcer, gingival ulceration, mouth ulceration, stomatitis, tongue ulceration

11Gastrointestinal haemorrhage includes anal haemorrhage, anastomotic haemorrhage, gastric haemorrhage, gastrointestinal haemorrhage, haematochezia, haemorrhoidal haemorrhage, intestinal haemorrhage, lower gastrointestinal haemorrhage, rectal haemorrhage, upper gastrointestinal haemorrhage

12Gastrointestinal perforation includes gastric perforation, gastric ulcer perforation, gastrointestinal perforation, intestinal perforation, large intestine perforation, rectal perforation, small intestinal perforation

13Pancreatic enzymes increased includes amylase increased, hyperamylasaemia, hyperlipasaemia, lipase increased

14Oral pain includes gingival pain, oral pain, toothache

15Pancreatitis includes pancreatitis, pancreatitis acute

16 Total bilirubin increased includes bilirubin conjugated increased, blood bilirubin increased, blood bilirubin unconjugated increased, hyperbilirubinaemia, jaundice, jaundice cholestatic

17Rash includes rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic

18Musculoskeletal discomfort includes bone pain, muscle spasms, musculoskeletal chest pain, musculoskeletal pain, neck pain, pain in extremity

19Proteinuria includes albuminuria, protein urine present, proteinuria

Description of selected adverse reactions

Data for the following selected adverse reactions are based on patients who received at least 1 dose (5 mg) of fruquintinib (5 mg once daily 3 weeks on/1 week off) across three randomised placebo-controlled studies (2012-013-00CH1; 2013-013-00CH1/ FRESCO; 2019-013-GLOB1/FRESCO-2). The management guidelines for these adverse reactions are described in section 4.4.

Hypertension

Hypertension was reported in 47.4% of patients in the fruquintinib arm and 11.8% in the placebo arm. Approximately half of these events occurred during the first 2 weeks after initiating treatment with fruquintinib. The incidence of Grade ≥3 hypertension events were 18.4% in the fruquintinib arm and 1.3% in the placebo arm. Median time to onset in fruquintinib-treated patients was 15 days (range: 1 day to 7.6 months). Two patients (0.3%) treated with fruquintinib experienced life-threatening hypertension. The majority of the events recovered or resolved following dose interruption or reduction, which occurred in 3.1% and 3.7% of patients, respectively. In 0.5% of patients treated with fruquintinib, hypertension led to permanent treatment discontinuation.

Haemorrhagic events

Haemorrhagic events were reported in 26.5% of patients in the fruquintinib arm and 14.6% in the placebo arm. Most haemorrhagic events in patients treated with fruquintinib were mild to moderate in severity; the incidence of Grade ≥ 3 haemorrhagic events were 2.0% in the fruquintinib arm and 1.0% in the placebo arm. Median time to onset in fruquintinib treated patients was 23 days (range: 1 day to 9.8 months). Fatal haemorrhagic events were reported in 0.5% of patients in the fruquintinib arm. In 1.2% of patients treated with fruquintinib, haemorrhagic events led to dose discontinuation. The most common haemorrhagic reactions were gastrointestinal haemorrhage (7%) and epistaxis (5.6%). The most frequently reported serious haemorrhagic event was gastrointestinal haemorrhage, which was reported in 1.5% of patients in the fruquintinib arm compared with 0.5% in the placebo arm.

Gastrointestinal (GI) perforation

GI perforation events were reported in 1.5% of patients in the fruquintinib arm, and no events were reported in the placebo arm. Fatal GI perforation was reported in 0.1% of patients treated with fruquintinib. The most common GI perforation event was intestinal perforation (0.8%). In 1.0% of patients treated with fruquintinib, GI perforation events led to dose discontinuation.

Hepatotoxicity

Liver function test abnormalities were reported in 36.4% of the patients on the fruquintinib arm and 23.5% in the placebo arm. Most hepatobiliary disorders in patients treated with fruquintinib were mild to moderate in severity (incidence of Grade ≥ 3 liver function test abnormalities were 8.8% in the fruquintinib arm and 9.5% in the placebo arm). The most common liver function test abnormality events were AST increase (18.1%), total bilirubin increase (18.3%), and ALT increase (15.5%). Median time to onset in fruquintinib treated patients was 28 days (range: 4 days to 12 months). Serious liver function test abnormalities were reported in 2.3% of patients in the fruquintinib arm and 3.1% in the placebo arm. Fatal liver function test abnormalities were reported in 0.3% of patients in the fruquintinib arm and 0.8% in the placebo arm. Liver function test abnormalities led to dose interruption and reduction in 4.6% and 2.0% of patients, respectively, and to permanent discontinuation in 1.5% of patients.

Proteinuria

Proteinuria was reported in 32.9% of the patients in the fruquintinib arm and 15.1% in the placebo arm. Most of the events in patients treated with fruquintinib were mild to moderate in severity; the incidence of Grade ≥ 3 proteinuria events were 2.8% in the fruquintinib arm and 0.5% in the placebo arm. Median time to onset in fruquintinibtreated patients was 28 days (range: 6 days to 1.3 years). The majority of the events recovered or resolved following dose interruption or reduction. In 1.8% of patients treated with fruquintinib, proteinuria led to permanent treatment discontinuation.

Palmar-plantar erythrodysesthesia syndrome (PPES)

Palmar-plantar erythrodysaesthesia syndrome was reported in 32.7% of patients in the fruquintinib arm and 3.1% in the placebo arm. The incidence of Grade ≥3 PPES events were 8.5% in the fruquintinib arm and 0.3% in the placebo arm. Median time to onset in fruquintinib-treated patients was 20 days (range: 1 day to 7.4 months). The majority of the events recovered or resolved following dose interruption or reduction, which occurred 6.4% and 6.3%, respectively. In 0.5% of patients treated with fruquintinib, PPES led to permanent treatment discontinuation.

Hypothyroidism

Hypothyroidism was reported in 31.5% of the patients in the fruquintinib arm and 2.8% in the placebo arm. Most of the events in patients treated with fruquintinib were mild to moderate in severity; the incidence of Grade ≥3 hypothyroidism in the fruquintinib arm was low (0.3%). Median time to onset in fruquintinib-treated patients was 56 days (range: 18 days to 1.4 years). No events led to dose reduction or discontinuation.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

The highest dose of fruquintinib studied in clinical studies was 6 mg per day.

The effects of fruquintinib overdose are unknown, and there is no known antidote for fruquintinib overdose. In the event of an overdose, interrupt fruquintinib, general supportive measures should be undertaken and observe until clinical stabilisation.