{ "meta": { "disclaimer": "Do not rely on openFDA to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. We may limit or otherwise restrict your access to the API in line with our Terms of Service.", "terms": "https://open.fda.gov/terms/", "license": "https://open.fda.gov/license/", "last_updated": "2026-06-01", "results": { "skip": 0, "limit": 1, "total": 1 } }, "results": [ { "spl_product_data_elements": [ "Fruzaqla fruquintinib FRUQUINTINIB FRUQUINTINIB TALC MICROCRYSTALLINE CELLULOSE STARCH, CORN GELATIN, UNSPECIFIED TITANIUM DIOXIDE FD&C YELLOW NO. 5 FD&C YELLOW NO. 6 yellow opaque cap and white opaque body HM013;1mg Fruzaqla fruquintinib FRUQUINTINIB FRUQUINTINIB TALC MICROCRYSTALLINE CELLULOSE STARCH, CORN GELATIN, UNSPECIFIED TITANIUM DIOXIDE FD&C RED NO. 40 FD&C BLUE NO. 1 red opaque cap and white opaque body HM013;5mg" ], "recent_major_changes": [ "Dosage and Administration ( 2.2 ) 2/2025" ], "recent_major_changes_table": [ "
Dosage and Administration (2.2)2/2025
" ], "indications_and_usage": [ "1. INDICATIONS AND USAGE FRUZAQLA is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy, an anti‑VEGF therapy, and, if RAS wild‑type and medically appropriate, an anti-EGFR therapy. FRUZAQLA is a kinase inhibitor indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy, an anti‑VEGF therapy, and, if RAS wild‑type and medically appropriate, an anti-EGFR therapy. ( 1 )" ], "dosage_and_administration": [ "2. DOSAGE AND ADMINISTRATION The recommended dose of FRUZAQLA is 5 mg orally once daily, with or without food for the first 21 days of each 28-day cycle. ( 2.1 ) 2.1. Recommended Dosage The recommended dose of FRUZAQLA is 5 mg orally once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. Take FRUZAQLA with or without food [see Clinical Pharmacology (12.3) ] at approximately the same time each day. Swallow the FRUZAQLA capsule whole. Take a missed dose if less than 12 hours have passed since the missed scheduled dose. Do not take two doses on the same day to make up for a missed dose. Do not take an additional dose if vomiting occurs after taking FRUZAQLA but continue with the next scheduled dose. 2.2. Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are provided in Table 1. Table 1: Recommended Dose Reductions for FRUZAQLA Dose Level FRUZAQLA Dosage First dose reduction 4 mg orally once daily Second dose reduction 3 mg orally once daily Permanently discontinue FRUZAQLA in patients unable to tolerate 3 mg orally once daily. The recommended dosage modifications for adverse reactions are provided in Table 2. Table 2: Recommended Dosage Modifications for FRUZAQLA Adverse Reaction Severity Severity as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. FRUZAQLA Dosage Modification Hypertension [see Warnings and Precautions (5.1) ] Grade 3 Withhold FRUZAQLA for Grade 3 hypertension that persists despite optimal anti-hypertensive therapy. If hypertension fully resolves or recovers to Grade 1, resume at the next lower dose level. Grade 4 Permanently discontinue FRUZAQLA. Hemorrhagic Events [see Warnings and Precautions (5.2) ] Grade 2 Withhold FRUZAQLA until bleeding fully resolves or recovers to Grade 1. Resume at the next lower dose level. Grade 3 or Grade 4 Permanently discontinue FRUZAQLA. Hepatotoxicity [see Warnings and Precautions (5.5) ] Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times upper limit of normal (ULN), or greater than 3 times baseline if baseline was abnormal; or bilirubin greater than 1.5 times ULN, or greater than 1.5 times baseline if baseline was abnormal Withhold FRUZAQLA and monitor AST, ALT and total bilirubin until resolution to Grade 1 or baseline. Resume at the next lower dose level. ALT or AST greater than 3 times ULN with concurrent total bilirubin greater than 2 times ULN (in the absence of cholestasis or hemolysis) Permanently discontinue FRUZAQLA. 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 FRUZAQLA. Proteinuria [see Warnings and Precautions (5.6) ] 2 grams or greater proteinuria in 24 hours Withhold FRUZAQLA until proteinuria fully resolves or is <1 gram/24 hours. Upon recovery, resume at the next lower dose level. Permanently discontinue FRUZAQLA for nephrotic syndrome or if proteinuria does not recover to <1 gram/24 hours. Palmar-plantar erythrodysesthesia (PPE) [see Warnings and Precautions (5.7) ] Grade 2 Withhold FRUZAQLA and initiate supportive treatment. If toxicity fully resolves or recovers to Grade 1, resume at the same dose level. Grade 3 Withhold FRUZAQLA and initiate supportive treatment. If toxicity fully resolves or recovers to Grade 1, resume at the next lower dose level. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 3 Withhold FRUZAQLA. If toxicity fully resolves or recovers to Grade 1, resume at the next lower dose level. Grade 4 Discontinue FRUZAQLA. Consider resuming FRUZAQLA at the next lower dose level only if the toxicity is non-life threatening and fully resolves or recovers to Grade 1 and the potential benefit outweighs the risks." ], "dosage_and_administration_table": [ "
Table 1: Recommended Dose Reductions for FRUZAQLA
Dose LevelFRUZAQLA Dosage
First dose reduction4 mg orally once daily
Second dose reduction3 mg orally once daily
", "
Table 2: Recommended Dosage Modifications for FRUZAQLA
Adverse ReactionSeveritySeverity as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.FRUZAQLA Dosage Modification
Hypertension [see Warnings and Precautions (5.1)]Grade 3Withhold FRUZAQLA for Grade 3 hypertension that persists despite optimal anti-hypertensive therapy.If hypertension fully resolves or recovers to Grade 1, resume at the next lower dose level.
Grade 4Permanently discontinue FRUZAQLA.
Hemorrhagic Events [see Warnings and Precautions (5.2)]Grade 2Withhold FRUZAQLA until bleeding fully resolves or recovers to Grade 1.Resume at the next lower dose level.
Grade 3 or Grade 4Permanently discontinue FRUZAQLA.
Hepatotoxicity [see Warnings and Precautions (5.5)]Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times upper limit of normal (ULN), or greater than 3 times baseline if baseline was abnormal; or bilirubin greater than 1.5 times ULN, or greater than 1.5 times baseline if baseline was abnormalWithhold FRUZAQLA and monitor AST, ALT and total bilirubin until resolution to Grade 1 or baseline.Resume at the next lower dose level.
ALT or AST greater than 3 times ULN with concurrent total bilirubin greater than 2 times ULN (in the absence of cholestasis or hemolysis)Permanently discontinue FRUZAQLA.
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 abnormalPermanently discontinue FRUZAQLA.
Proteinuria [see Warnings and Precautions (5.6)]2 grams or greater proteinuria in 24 hoursWithhold FRUZAQLA until proteinuria fully resolves or is <1 gram/24 hours.Upon recovery, resume at the next lower dose level.Permanently discontinue FRUZAQLA for nephrotic syndrome or if proteinuria does not recover to <1 gram/24 hours.
Palmar-plantar erythrodysesthesia (PPE) [see Warnings and Precautions (5.7)]Grade 2Withhold FRUZAQLA and initiate supportive treatment.If toxicity fully resolves or recovers to Grade 1, resume at the same dose level.
Grade 3Withhold FRUZAQLA and initiate supportive treatment.If toxicity fully resolves or recovers to Grade 1, resume at the next lower dose level.
Other Adverse Reactions [see Adverse Reactions (6.1)]Grade 3Withhold FRUZAQLA.If toxicity fully resolves or recovers to Grade 1, resume at the next lower dose level.
Grade 4Discontinue FRUZAQLA. Consider resuming FRUZAQLA at the next lower dose level only if the toxicity is non-life threatening and fully resolves or recovers to Grade 1 and the potential benefit outweighs the risks.
" ], "dosage_forms_and_strengths": [ "3. DOSAGE FORMS AND STRENGTHS Capsules: 1 mg: size 3 hard gelatin capsule with standard yellow opaque cap and white opaque body, imprinted with “HM013” over “1 mg” on the body in black ink. 5 mg: size 1 hard gelatin capsule with a red opaque cap and white opaque body, imprinted with “HM013” over “5 mg” on the body in black ink. Capsules: 1 mg and 5 mg. ( 3 )" ], "contraindications": [ "4. CONTRAINDICATIONS None. None. ( 4 )" ], "warnings_and_cautions": [ "5. WARNINGS AND PRECAUTIONS Hypertension: Control blood pressure prior to treatment and monitor during treatment. Manage with anti-hypertensive medications and adjustment of the dose of FRUZAQLA, if necessary. Withhold, dose reduce, or permanently discontinue based on severity of hypertension. ( 2.2 , 5.1 ) Hemorrhagic Events: Closely monitor patients who are at risk for bleeding. Withhold, reduce dose, or permanently discontinue FRUZAQLA based on severity and persistence of hemorrhage. ( 2.2 , 5.2 ) Infections: Monitor for infection during treatment and withhold FRUZAQLA during active infections. Do not start FRUZAQLA in patients with active infections. ( 5.3 ) Gastrointestinal (GI) Perforation: Periodically monitor for GI perforation. Permanently discontinue FRUZAQLA in patients who develop GI perforation or fistula. ( 5.4 ) Hepatotoxicity: Monitor liver laboratory tests prior to the start of FRUZAQLA and periodically during treatment. Withhold, reduce the dose, or permanently discontinue based on severity. ( 2.2 , 5.5 ) Proteinuria: Monitor urine protein. Discontinue FRUZAQLA for nephrotic syndrome ( 2.2 , 5.6 ) Palmar-Plantar Erythrodysesthesia: Withhold FRUZAQLA based on severity. ( 2.2 , 5.7 ) Posterior Reversible Encephalopathy Syndrome (PRES): Immediately discontinue FRUZAQLA if PRES is suspected and confirmed via Magnetic Resonance Imaging (MRI). ( 5.8 ) Impaired Wound Healing: Withhold FRUZAQLA for 2 weeks before major surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of FRUZAQLA after resolution of wound healing complications has not been established. ( 5.9 ) Arterial Thromboembolic Events: Initiation of FRUZAQLA in patients with a recent history of thromboembolic events should be carefully considered. Discontinue FRUZAQLA in patients who develop arterial thromboembolism. ( 5.10 ) Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF): Contains FD&C Yellow No. 5 (tartrazine) and No. 6 (sunset yellow FCF) as color additives, which may cause allergic reactions (including bronchial asthma) in certain susceptible patients. ( 5.11 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.12 , 8.1 , 8.3 ) 5.1. Hypertension FRUZAQLA can cause hypertension. Hypertension occurred in 450 of 911 (49%) patients with mCRC treated with FRUZAQLA, including Grade 3-4 events in 19%, and hypertensive crisis in three patients (0.3%). The median time to first onset of hypertension was 14 days from first dose of FRUZAQLA. Do not initiate FRUZAQLA unless blood pressure is adequately controlled. Monitor blood pressure weekly the first month, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue FRUZAQLA based on the severity of hypertension [see Dosage and Administration (2.2) ] . 5.2. Hemorrhagic Events FRUZAQLA can cause serious hemorrhagic events, which may be fatal. In 911 patients with mCRC treated with FRUZAQLA, 6% of patients experienced a gastrointestinal hemorrhage, including 13 patients (1%) with a Grade ≥3 event and 2 patients with fatal hemorrhages. Permanently discontinue FRUZAQLA in patients with severe or life-threatening hemorrhage. Monitor the International Normalized Ratio (INR) levels in patients receiving anticoagulants [see Dosage and Administration (2.2) ] . 5.3. Infections FRUZAQLA can cause an increased risk of infections, including fatal infections. In 781 patients treated with FRUZAQLA across three randomized, placebo-controlled trials, the overall incidence of infections was higher (18% vs. 12%) including for fatal infections (1% vs. 0.3%) as compared to the placebo arms (n=391). In 911 patients with mCRC treated with FRUZAQLA, the most common infections were urinary tract infections (6.8%), upper respiratory tract infections (3.2%) and pneumonia (2.5%); fatal infections included pneumonia (0.4%), sepsis (0.2%), bacterial infection (0.1%), lower respiratory tract infection (0.1%), and septic shock (0.1%). Withhold FRUZAQLA for Grade 3 or 4 infections, or worsening infection of any grade. Resume FRUZAQLA at the same dose when the infection has resolved. 5.4. Gastrointestinal Perforation FRUZAQLA can cause gastrointestinal perforation. In 911 patients with mCRC treated with FRUZAQLA, 12 patients (1.3%) experienced a Grade ≥3 gastrointestinal perforation, including one fatal event. Permanently discontinue FRUZAQLA in patients who develop gastrointestinal perforation or fistula. 5.5. Hepatotoxicity FRUZAQLA can cause liver injury. In 911 patients with mCRC treated with FRUZAQLA, 48% experienced increased ALT or AST, including Grade ≥3 events in 5%, and fatal events in 0.2%. Median time to first onset of elevated liver enzymes was 29 days from first dose of FRUZAQLA. Monitor liver function tests (ALT, AST, and bilirubin) before initiation and periodically throughout treatment with FRUZAQLA. Temporarily hold and then reduce or permanently discontinue FRUZAQLA depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests [see Dosage and Administration (2.2) and Use in Specific Populations (8.6) ] . 5.6. Proteinuria FRUZAQLA can cause proteinuria. In 911 patients with mCRC treated with FRUZAQLA, 36% experienced proteinuria and 2.5% of patients experienced Grade ≥3 events. Median time to first onset of proteinuria was 22 days from first dose of FRUZAQLA. Monitor for proteinuria before initiation and periodically throughout treatment with FRUZAQLA. For proteinuria ≥2 g/24 hours, withhold FRUZAQLA until improvement to ≤Grade 1 proteinuria, resume FRUZAQLA at a reduced dose. Discontinue FRUZAQLA in patients who develop nephrotic syndrome [see Dosage and Administration (2.2) ]. 5.7. Palmar-Plantar Erythrodysesthesia (PPE) FRUZAQLA can cause PPE. In 911 patients with mCRC treated with FRUZAQLA, PPE occurred in 35%, including 8% with Grade 3 events. Median time to first onset of PPE was 19 days from first dose of FRUZAQLA. Based on severity, withhold FRUZAQLA and then resume at the same or reduced dose [see Dosage and Administration (2.2) ]. 5.8. Posterior Reversible Encephalopathy Syndrome (PRES) FRUZAQLA can cause PRES, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI. PRES occurred in one of 911 patients with mCRC treated with FRUZAQLA. Perform an evaluation for PRES in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue FRUZAQLA in patients who develop PRES. 5.9. Impaired Wound Healing Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. In 911 patients with mCRC treated with FRUZAQLA, 1 patient experienced a Grade 2 event of wound dehiscence. Do not administer FRUZAQLA for at least 2 weeks prior to major surgery. Do not administer FRUZAQLA for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of FRUZAQLA after resolution of wound healing complications has not been established. 5.10. Arterial Thromboembolic Events FRUZAQLA may increase the risk of arterial thromboembolic events. In 911 patients with mCRC treated with FRUZAQLA, 7 patients (0.8%) experienced an arterial thromboembolic event; additionally, FRUZAQLA studies excluded patients with clinically significant cardiovascular disease, uncontrolled hypertension, or with thromboembolic events within the prior 6 months. Initiation of FRUZAQLA in patients with a recent history of thromboembolic events should be carefully considered. In patients who develop arterial thromboembolism discontinue FRUZAQLA. 5.11. Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF) FRUZAQLA 1 mg capsules contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. FRUZAQLA 1 mg contains FD&C Yellow No. 6 (sunset yellow FCF), which may cause allergic reactions. 5.12. Embryo-Fetal Toxicity Based on findings in animal studies and its mechanism of action, FRUZAQLA can cause fetal harm when administered to pregnant women. In an embryo-fetal developmental study in rats, embryotoxic and teratogenic effects were observed at exposures below the clinical exposure [see Use in Specific Populations (8.1) ] . Advise pregnant women of the potential risk to a fetus. Advise females of childbearing potential and males with female partners of childbearing potential to use effective contraception during treatment with FRUZAQLA and for 2 weeks after the last dose [see Use in Specific Populations (8.1 , 8.3) ] ." ], "adverse_reactions": [ "6. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypertension [see Warnings and Precautions (5.1) ] . Hemorrhagic Events [see Warnings and Precautions (5.2) ] . Infections [see Warnings and Precautions (5.3) ] . Gastrointestinal Perforation [see Warnings and Precautions (5.4) ] . Hepatotoxicity [see Warnings and Precautions (5.5) ]. Proteinuria [see Warnings and Precautions (5.6) ] . Palmar-Plantar Erythrodysesthesia (PPE) [see Warnings and Precautions (5.7) ] . Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions (5.8) ] . Most common adverse reactions (incidence ≥20%) are hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals America, Inc. at 1-844-662-8532 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS and below reflects exposure to FRUZAQLA as a single agent in 911 patients with mCRC who were enrolled in three randomized, placebo-controlled studies (FRESCO-2, FRESCO and 2012-013-00CH1) (N=781); three open-label studies (2009-013-00CH1, 2012-013-00CH3 and 2015-013-00US1) (N=124); and an open-label lead-in cohort of FRESCO-2 (N=6). Among the 911 patients who received FRUZAQLA, 23% were exposed for 6 months or longer and 3.5% were exposed for greater than one year. These patients received at least one dose of FRUZAQLA at the recommended dosage of 5 mg daily for the first 21 days of each 28-day cycle. The median age was 60 years (range: 23 to 82) and 34% were 65 years of age or older. The most common adverse reactions (incidence ≥20%) that occurred in pooled monotherapy studies were hypertension, PPE, proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia. Metastatic Colorectal Cancer FRESCO-2 Study The safety of FRUZAQLA was evaluated in FRESCO-2, a randomized, double-blind, placebo-controlled study [see Clinical Studies (14.1) ] . Patients received either FRUZAQLA 5 mg daily for the first 21 days of each 28-day cycle plus best supportive care (BSC) (n=456) or matching placebo plus BSC (n=230). The median duration of therapy with FRUZAQLA was 3 months (range: 0.3 to 19.1 months). Serious adverse reactions occurred in 38% of patients treated with FRUZAQLA. Serious adverse reactions in ≥2% of patients treated with FRUZAQLA included hemorrhage (2.2%) and gastrointestinal perforation (2.0%). Fatal adverse reaction(s) occurred in 14 (3.1%) patients who received FRUZAQLA. Fatal adverse reactions occurring in ≥2 patients include pneumonia (n=3), sepsis/septic shock (n=2), and hepatic failure/encephalopathy (n=2). Adverse reactions leading to treatment discontinuation occurred in 20% of patients treated with FRUZAQLA. Adverse reactions leading to treatment discontinuations of FRUZAQLA in ≥1% of patients were asthenia and gastrointestinal perforation. Dose interruptions of FRUZAQLA due to an adverse reaction occurred in 47% of patients. Adverse reactions leading to dose interruptions of FRUZAQLA in ≥2% of patients were PPE, proteinuria, asthenia, abdominal pain, hypertension, vomiting, and diarrhea. Dose reductions of FRUZAQLA due to an adverse reaction occurred in 24% of patients. Adverse reactions leading to dose reductions of FRUZAQLA in ≥2% of patients were PPE, hypertension and asthenia. Table 3 summarizes the adverse reactions in FRESCO-2. Table 3: Adverse Reactions (≥10%) in Patients who Received FRUZAQLA and with a Difference Between Arms of ≥5% Compared to Placebo in FRESCO-2 (All Grades) Adverse Reaction FRUZAQLA (N=456) Placebo (N=230) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) General Fatigue Represents a composite of multiple related terms. 53 12 39 4.8 Vascular Hypertension 38 14 9 0.9 Gastrointestinal Stomatitis 31 2.2 7.8 0.4 Abdominal Pain 25 3.5 20 3 Diarrhea 24 3.7 11 0 Endocrine Disorders Hypothyroidism 21 0.4 0.4 0 Skin and Subcutaneous Palmar-plantar erythrodysesthesia (hand-foot skin reactions) 19 6 2.6 0 Renal Proteinuria 18 1.8 5 0.9 Respiratory Dysphonia 18 0 5 0 Musculoskeletal Musculoskeletal Pain 16 1.1 7 0 Arthralgia 11 0.9 4.3 0 Other important adverse reactions (all grades) that occurred in <10% of patients treated with FRUZAQLA included urinary tract infection (4.6%), epistaxis (3.9%), proctalgia (3.5%), pneumonia (2.4%), gastrointestinal hemorrhage (1.5%), gastrointestinal perforation (1.3%), pancreatitis (0.7%), thrombotic microangiopathy (0.2%), and posterior reversible encephalopathy syndrome (0.2%). Table 4 provides laboratory abnormalities observed in FRESCO-2. Table 4: Select Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients in FRESCO-2 Laboratory Graded according to NCI CTCAE version 5.0. Abnormality FRUZAQLA (N=456) Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: FRUZAQLA (range: 409-444) and placebo (range: 195-216). Placebo (N=230) All Grade (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Triglycerides Increased 53 2.8 22 1.0 Cholesterol Increased 37 1.9 22 1.9 Aspartate Aminotransferase Increased 36 4.3 24 1.9 Albumin Decreased 35 1.6 32 1.4 Sodium Decreased 35 1.1 27 0.9 Alanine Aminotransferase Increased 34 5 22 1.4 Bilirubin Increased 30 7 21 8 Alkaline Phosphatase Increased 20 1.6 27 0.5 Magnesium Decreased 20 0.5 10 0.5 Hematology Lymphocytes Decreased 30 6 32 4.7 Platelets Decreased 30 0.2 4.7 0 Activated Partial Thromboplastin Time Increased 21 2.7 18 1.5 Other clinically relevant laboratory abnormalities (all grades) that occurred in <20% of patients treated with FRUZAQLA included pancreatic enzymes increased (3.9%). FRESCO Study The safety of FRUZAQLA was evaluated in FRESCO, a randomized, double-blind, placebo-controlled study [see Clinical Studies (14.1) ] . Patients received either FRUZAQLA 5 mg daily for the first 21 days of each 28-day cycle plus BSC (n=278) or matching placebo plus BSC (n=137). The median duration of therapy with FRUZAQLA was 3.68 months (range: 0.3 to 22.1 months). Serious adverse reactions occurred in 15% of patients treated with FRUZAQLA. Serious adverse reactions in ≥2% of patients included intestinal obstruction (2.9%) and hemorrhage (2.2%). Fatal adverse reaction(s) occurred in 7 (2.5%) patients who received FRUZAQLA including cerebral infarction (n=1), gastrointestinal hemorrhage (n=1), hemoptysis (n=1), bacterial infection (n=1), lung/lower respiratory infection (n=2), and multiple organ dysfunction (n=1). Adverse reactions leading to treatment discontinuation occurred in 15% of patients who received FRUZAQLA. Adverse reactions leading to treatment discontinuations of FRUZAQLA in ≥1% were intestinal obstruction, proteinuria and hepatic function abnormalities. Dose interruptions of FRUZAQLA due to an adverse reaction occurred in 35% of patients. Adverse reactions leading to dose interruptions of FRUZAQLA in ≥2% of patients were PPE, proteinuria, platelet count decreased, ALT increased, hypertension, and diarrhea. Dose reductions of FRUZAQLA due to an adverse reaction occurred in 24% of patients. Adverse reactions leading to dose reduction of FRUZAQLA in ≥2% of patients were PPE, proteinuria, and hypertension. Table 5 summarizes the adverse reactions in FRESCO. Table 5: Adverse Reactions (≥10%) in Patients who Received FRUZAQLA and with a Difference Between Arms of ≥5% Compared to Placebo in FRESCO (All Grades) Adverse Reaction Fruquintinib (N=278) Placebo (N=137) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Vascular Hypertension Represents a composite of multiple related terms. 61 23 17 2.2 Hemorrhage 28 1.1 14 0 Renal Proteinuria 55 4.7 30 0 Skin and Subcutaneous Palmar-plantar erythrodysesthesia (hand-foot skin reactions) 49 11 2.9 0 Respiratory Dysphonia 38 0 1.5 0 Throat Pain 10 0 1.5 0 Gastrointestinal Stomatitis 33 0.7 2.9 0 Abdominal Pain 29 4 17 1.5 Diarrhea 25 3.6 5 0 General Fatigue 25 2.5 13 1.5 Metabolism Anorexia 21 1.4 9 0 Musculoskeletal Musculoskeletal Pain 22 2.2 6 1.5 Back Pain 15 1.8 7 0 Arthralgia 13 0.4 2.2 0 Endocrine Disorders Hypothyroidism 17 0 2.2 0 Other clinically important adverse reactions (all grades) that occurred in <10% of patients treated with FRUZAQLA included urinary tract infection (9%), rash (9%), upper respiratory tract infection (4.7%), proctalgia (3.6%), pneumonia (2.9%), and gastrointestinal perforation or fistula (2.2%). Table 6 provides laboratory abnormalities observed in FRESCO. Table 6: Select Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients in FRESCO Laboratory Graded according to NCI CTCAE version 4.03. Abnormality FRUZAQLA (N=278) Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: FRUZAQLA (range: 257-277) and placebo (range: 126-134). Placebo (N=137) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Creatinine Increased 87 0.7 75 1.5 Glucose Increased 43 1.1 31 3.0 Aspartate Aminotransferase Increased 42 3.6 31 1.5 Alkaline Phosphatase Increased 40 4.3 34 6 Bilirubin Increased 39 4.7 34 8 Alanine Aminotransferase Increased 33 2.2 18 1.5 Sodium Decreased 33 6 31 5 Urate Increased 26 26 22 22 Calcium Decreased 25 0.4 13 0 Potassium Decreased 22 1.8 15 2.3 Hematology Platelets Decreased 29 3.6 6 0.7 Hemoglobin Decreased 23 0.7 33 4.5 Other clinically relevant laboratory abnormalities (all grades) that occurred in <20% of patients treated with FRUZAQLA included pancreatic enzymes increased (4.3%)." ], "adverse_reactions_table": [ "
Table 3: Adverse Reactions (≥10%) in Patients who Received FRUZAQLA and with a Difference Between Arms of ≥5% Compared to Placebo in FRESCO-2 (All Grades)
Adverse ReactionFRUZAQLA (N=456)Placebo (N=230)
All Grades (%)Grade 3 or 4 (%)All Grades (%)Grade 3 or 4 (%)
General
FatigueRepresents a composite of multiple related terms.5312394.8
Vascular
Hypertension381490.9
Gastrointestinal
Stomatitis312.27.80.4
Abdominal Pain253.5203
Diarrhea243.7110
Endocrine Disorders
Hypothyroidism210.40.40
Skin and Subcutaneous
Palmar-plantar erythrodysesthesia (hand-foot skin reactions)1962.60
Renal
Proteinuria181.850.9
Respiratory
Dysphonia18050
Musculoskeletal
Musculoskeletal Pain161.170
Arthralgia110.94.30
", "
Table 4: Select Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients in FRESCO-2
LaboratoryGraded according to NCI CTCAE version 5.0. AbnormalityFRUZAQLA (N=456)Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: FRUZAQLA (range: 409-444) and placebo (range: 195-216).Placebo (N=230)
All Grade (%)Grade 3 or 4 (%)All Grades (%)Grade 3 or 4 (%)
Chemistry
Triglycerides Increased532.8221.0
Cholesterol Increased371.9221.9
Aspartate Aminotransferase Increased364.3241.9
Albumin Decreased351.6321.4
Sodium Decreased351.1270.9
Alanine Aminotransferase Increased345221.4
Bilirubin Increased307218
Alkaline Phosphatase Increased201.6270.5
Magnesium Decreased200.5100.5
Hematology
Lymphocytes Decreased306324.7
Platelets Decreased300.24.70
Activated Partial Thromboplastin Time Increased212.7181.5
", "
Table 5: Adverse Reactions (≥10%) in Patients who Received FRUZAQLA and with a Difference Between Arms of ≥5% Compared to Placebo in FRESCO (All Grades)
Adverse ReactionFruquintinib (N=278)Placebo (N=137)
All Grades (%)Grade 3 or 4 (%)All Grades (%)Grade 3 or 4 (%)
Vascular
HypertensionRepresents a composite of multiple related terms.6123172.2
Hemorrhage281.1140
Renal
Proteinuria554.7300
Skin and Subcutaneous
Palmar-plantar erythrodysesthesia (hand-foot skin reactions)49112.90
Respiratory
Dysphonia3801.50
Throat Pain1001.50
Gastrointestinal
Stomatitis330.72.90
Abdominal Pain294171.5
Diarrhea253.650
General
Fatigue252.5131.5
Metabolism
Anorexia211.490
Musculoskeletal
Musculoskeletal Pain222.261.5
Back Pain151.870
Arthralgia130.42.20
Endocrine Disorders
Hypothyroidism1702.20
", "
Table 6: Select Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients in FRESCO
LaboratoryGraded according to NCI CTCAE version 4.03. AbnormalityFRUZAQLA (N=278)Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: FRUZAQLA (range: 257-277) and placebo (range: 126-134).Placebo (N=137)
All Grades (%)Grade 3 or 4 (%)All Grades (%)Grade 3 or 4 (%)
Chemistry
Creatinine Increased870.7751.5
Glucose Increased431.1313.0
Aspartate Aminotransferase Increased423.6311.5
Alkaline Phosphatase Increased404.3346
Bilirubin Increased394.7348
Alanine Aminotransferase Increased332.2181.5
Sodium Decreased336315
Urate Increased26262222
Calcium Decreased250.4130
Potassium Decreased221.8152.3
Hematology
Platelets Decreased293.660.7
Hemoglobin Decreased230.7334.5
" ], "drug_interactions": [ "7. DRUG INTERACTIONS Strong or Moderate CYP3A Inducers: Avoid concomitant use. ( 7.1 ) 7.1. Effects of Other Drugs on FRUZAQLA Strong CYP3A Inducers Avoid concomitant use of drugs that are strong CYP3A inducers with FRUZAQLA. Concomitant use with a strong CYP3A inducer may decrease fruquintinib C max and AUC [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of FRUZAQLA. Moderate CYP3A Inducers If possible, avoid concomitant use of drugs that are moderate CYP3A inducers with FRUZAQLA. If it is not possible to avoid concomitant use of a moderate CYP3A inducer and fruquintinib, continue to administer FRUZAQLA at the recommended dosage. Concomitant use with a moderate CYP3A inducer may decrease fruquintinib C max and AUC [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of FRUZAQLA." ], "use_in_specific_populations": [ "8. USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1. Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, FRUZAQLA can cause fetal harm when administered to a pregnant woman. In an embryo-fetal developmental study in pregnant rats, oral administration of fruquintinib during the period of organogenesis resulted in teratogenicity and embryo lethality at exposures below the clinical exposure (see Data ) . There are no data on the use of FRUZAQLA in pregnant women. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal developmental study in pregnant rats, daily oral administration of fruquintinib at doses ≥0.1 mg/kg [approximately 0.2 times the recommended clinical dose of 5 mg based on body surface area (BSA)] during the period of organogenesis resulted in fetal external (edema and head and tail abnormalities), visceral, and skeletal malformations. At doses of 0.25 mg/kg (approximately 0.5 times the recommended clinical dose of 5 mg based on BSA), an increase in post-implantation loss and reduction in live fetuses was observed. 8.2. Lactation Risk Summary There are no data regarding the presence of fruquintinib or its metabolites in human milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with FRUZAQLA and for 2 weeks after the last dose. 8.3. Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating FRUZAQLA. Contraception Females and Males Females of childbearing potential and males with female partners of childbearing potential should use effective contraception during treatment and for 2 weeks after the last dose of FRUZAQLA [see Warnings and Precautions (5.11) and Nonclinical Toxicology (13.1) ] . Infertility Females and Males There are no data on the effects of fruquintinib on human fertility. Based on findings in animal studies, FRUZAQLA may impair female fertility [see Nonclinical Toxicology (13.1) ] . 8.4. Pediatric Use The safety and efficacy of FRUZAQLA in patients younger than 18 years of age have not been established. 8.5. Geriatric Use In FRESCO-2, 212 (46%) patients who received FRUZAQLA were ≥65 years of age and older, of whom 43 (20%) of patients were ≥75 years. There were no observed overall differences in safety and effectiveness of FRUZAQLA in geriatric compared to younger patients. Of the total number of FRUZAQLA-treated patients in the FRESCO study, 50 (18%) were 65 years of age and older, and one patient was ≥75 years. There were no observed overall differences in safety and effectiveness of FRUZAQLA in geriatric compared to younger patients. 8.6. Hepatic Impairment No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin less than or equal to the ULN with AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN with any AST [see Clinical Pharmacology (12.3) ] . FRUZAQLA has not been sufficiently studied in patients with moderate hepatic impairment (total bilirubin greater than 1.5 times and less than 3 times ULN and any AST). FRUZAQLA is not recommended for use in patients with severe hepatic impairment (total bilirubin greater than 3 times ULN and any AST)." ], "pregnancy": [ "8.1. Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, FRUZAQLA can cause fetal harm when administered to a pregnant woman. In an embryo-fetal developmental study in pregnant rats, oral administration of fruquintinib during the period of organogenesis resulted in teratogenicity and embryo lethality at exposures below the clinical exposure (see Data ) . There are no data on the use of FRUZAQLA in pregnant women. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal developmental study in pregnant rats, daily oral administration of fruquintinib at doses ≥0.1 mg/kg [approximately 0.2 times the recommended clinical dose of 5 mg based on body surface area (BSA)] during the period of organogenesis resulted in fetal external (edema and head and tail abnormalities), visceral, and skeletal malformations. At doses of 0.25 mg/kg (approximately 0.5 times the recommended clinical dose of 5 mg based on BSA), an increase in post-implantation loss and reduction in live fetuses was observed." ], "pediatric_use": [ "8.4. Pediatric Use The safety and efficacy of FRUZAQLA in patients younger than 18 years of age have not been established." ], "geriatric_use": [ "8.5. Geriatric Use In FRESCO-2, 212 (46%) patients who received FRUZAQLA were ≥65 years of age and older, of whom 43 (20%) of patients were ≥75 years. There were no observed overall differences in safety and effectiveness of FRUZAQLA in geriatric compared to younger patients. Of the total number of FRUZAQLA-treated patients in the FRESCO study, 50 (18%) were 65 years of age and older, and one patient was ≥75 years. There were no observed overall differences in safety and effectiveness of FRUZAQLA in geriatric compared to younger patients." ], "description": [ "11. DESCRIPTION Fruquintinib is a kinase inhibitor with the chemical name 6-[(6,7-dimethoxyquinazolin-4-yl)oxy]- N ,2-dimethyl-1-benzofuran-3-carboxamide. Its molecular formula is C 21 H 19 N 3 O 5 , which corresponds to a molecular weight of 393.39 g/mol. Fruquintinib has the following chemical structure: Fruquintinib is a white to off-white powder with a dissociation constant (pK a ) of 2.78. The aqueous solubility of fruquintinib is pH-dependent with a solubility of 0.9 μg/mL at pH 6.8 that increases under acidic conditions to 129.9 μg/mL at pH 1. FRUZAQLA (fruquintinib) capsules for oral administration contain 1 mg or 5 mg of fruquintinib. The inactive ingredients are corn starch, microcrystalline cellulose, and talc. The 1 mg capsule shell contains FD&C Yellow No. 5 (tartrazine), FD&C Yellow No. 6 (sunset yellow FCF), gelatin, and titanium dioxide. The 5 mg capsule shell contains FD&C Blue No. 1 (brilliant blue FCF), FD&C Red No. 40 (allura red AC), gelatin, and titanium dioxide. The printing ink for 1 mg and 5 mg capsules contains butanol, dehydrated alcohol, ferrosoferric oxide, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac and strong ammonia solution. Chemical Structure" ], "clinical_pharmacology": [ "12. CLINICAL PHARMACOLOGY 12.1. Mechanism of Action Fruquintinib is a small molecule kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 with IC 50 values of 33, 35, and 0.5 nM, respectively. In vitro studies showed fruquintinib inhibited VEGF-mediated endothelial cell proliferation and tubular formation. In vitro and in vivo studies showed fruquintinib inhibited VEGF-induced VEGFR-2 phosphorylation. In vivo studies showed fruquintinib inhibited tumor growth in a tumor xenograft mouse model of colon cancer. 12.2. Pharmacodynamics Fruquintinib exposure-response relationships and the time course of pharmacodynamic response are unknown. Cardiac Electrophysiology A mean increase in QTc interval >20 milliseconds (ms) was not observed at the approved recommended dosage. 12.3. Pharmacokinetics The fruquintinib steady-state geometric mean (% coefficient of variation [CV]) maximum concentration (C max ) is 300 ng/mL (28%) and area under the concentration-time curve for the dosing interval (AUC 0-24h ) is 5880 ng∙h/mL (29%) at the recommended dosage. The fruquintinib C max and AUC 0-24h are dose-proportional across the dosage range of 1 to 6 mg (0.2 to 1.2 times the recommended dosage). Fruquintinib steady state is achieved after 14 days with a mean AUC 0-24h accumulation of 4-fold. Absorption The fruquintinib median (min, max) time to C max is approximately 2 hours (0, 26 hours). Effect of Food No clinically significant differences in fruquintinib pharmacokinetics were observed following administration of a high-fat meal (800 to 1000 calories, 50% fat). Distribution The mean (SD) apparent volume of distribution of fruquintinib is approximately 46 (13) L. Plasma protein binding of fruquintinib is approximately 95%. Elimination The fruquintinib mean (SD) elimination half-life is approximately 42 (11) hours and the apparent clearance is 14.8 (4.4) mL/min. Metabolism Fruquintinib is primarily eliminated by CYP450 and non-CYP450 (i.e., sulfation and glucuronidation) metabolism. CYP3A and to a lesser extent CYP2C8, CYP2C9, and CYP2C19 are the CYP450 enzymes involved in fruquintinib metabolism. Excretion Following oral administration of a 5 mg radiolabeled fruquintinib dose, approximately 60% of the dose was recovered in urine (0.5% unchanged) and 30% of the dose was recovered in feces (5% unchanged). Specific Populations No clinically significant differences in the pharmacokinetics of fruquintinib were observed based on age (18 to 82 years), sex, race (Asian, Black, and White), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), body weight (48 to 108 kg), mild to severe renal impairment (CLcr 15 to 89 mL/min estimated by the Cockcroft-Gault equation), mild hepatic impairment (total bilirubin less than or equal to ULN with AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN with any AST). The effect of moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN and any AST) on fruquintinib pharmacokinetics is unknown. Drug Interaction Studies Clinical Studies and Model-Informed Approaches Strong CYP3A inducers: Fruquintinib C max decreased by 12% and AUC inf by 65% following concomitant use with rifampin (strong CYP3A inducer). Moderate CYP3A inducers: Fruquintinib C max is predicted to decrease by 4% and AUC inf by 32% following concomitant use with efavirenz (moderate CYP3A inducer). Other Drugs: No clinically significant differences in fruquintinib pharmacokinetics were observed when used concomitantly with itraconazole (strong CYP3A inhibitor) or rabeprazole (proton pump inhibitor; gastric acid reducing agent). No clinically significant differences in the pharmacokinetics of the following drugs were observed when used concomitantly with fruquintinib: dabigatran etexilate (P-gp substrate), or rosuvastatin (BCRP substrate). In Vitro Studies Cytochrome P450 Enzymes: Fruquintinib is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A, or an inducer of CYP1A2, CYP2B6, CYP3A. Transporter Systems: Fruquintinib is not a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP)1B1 or OATP1B3. Fruquintinib is not an inhibitor of OATP1B1, OATP1B3, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)2, multidrug and toxin extrusion protein (MATE)1, or MATE2-K." ], "mechanism_of_action": [ "12.1. Mechanism of Action Fruquintinib is a small molecule kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 with IC 50 values of 33, 35, and 0.5 nM, respectively. In vitro studies showed fruquintinib inhibited VEGF-mediated endothelial cell proliferation and tubular formation. In vitro and in vivo studies showed fruquintinib inhibited VEGF-induced VEGFR-2 phosphorylation. In vivo studies showed fruquintinib inhibited tumor growth in a tumor xenograft mouse model of colon cancer." ], "pharmacodynamics": [ "12.2. Pharmacodynamics Fruquintinib exposure-response relationships and the time course of pharmacodynamic response are unknown. Cardiac Electrophysiology A mean increase in QTc interval >20 milliseconds (ms) was not observed at the approved recommended dosage." ], "pharmacokinetics": [ "12.3. Pharmacokinetics The fruquintinib steady-state geometric mean (% coefficient of variation [CV]) maximum concentration (C max ) is 300 ng/mL (28%) and area under the concentration-time curve for the dosing interval (AUC 0-24h ) is 5880 ng∙h/mL (29%) at the recommended dosage. The fruquintinib C max and AUC 0-24h are dose-proportional across the dosage range of 1 to 6 mg (0.2 to 1.2 times the recommended dosage). Fruquintinib steady state is achieved after 14 days with a mean AUC 0-24h accumulation of 4-fold. Absorption The fruquintinib median (min, max) time to C max is approximately 2 hours (0, 26 hours). Effect of Food No clinically significant differences in fruquintinib pharmacokinetics were observed following administration of a high-fat meal (800 to 1000 calories, 50% fat). Distribution The mean (SD) apparent volume of distribution of fruquintinib is approximately 46 (13) L. Plasma protein binding of fruquintinib is approximately 95%. Elimination The fruquintinib mean (SD) elimination half-life is approximately 42 (11) hours and the apparent clearance is 14.8 (4.4) mL/min. Metabolism Fruquintinib is primarily eliminated by CYP450 and non-CYP450 (i.e., sulfation and glucuronidation) metabolism. CYP3A and to a lesser extent CYP2C8, CYP2C9, and CYP2C19 are the CYP450 enzymes involved in fruquintinib metabolism. Excretion Following oral administration of a 5 mg radiolabeled fruquintinib dose, approximately 60% of the dose was recovered in urine (0.5% unchanged) and 30% of the dose was recovered in feces (5% unchanged). Specific Populations No clinically significant differences in the pharmacokinetics of fruquintinib were observed based on age (18 to 82 years), sex, race (Asian, Black, and White), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), body weight (48 to 108 kg), mild to severe renal impairment (CLcr 15 to 89 mL/min estimated by the Cockcroft-Gault equation), mild hepatic impairment (total bilirubin less than or equal to ULN with AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN with any AST). The effect of moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN and any AST) on fruquintinib pharmacokinetics is unknown. Drug Interaction Studies Clinical Studies and Model-Informed Approaches Strong CYP3A inducers: Fruquintinib C max decreased by 12% and AUC inf by 65% following concomitant use with rifampin (strong CYP3A inducer). Moderate CYP3A inducers: Fruquintinib C max is predicted to decrease by 4% and AUC inf by 32% following concomitant use with efavirenz (moderate CYP3A inducer). Other Drugs: No clinically significant differences in fruquintinib pharmacokinetics were observed when used concomitantly with itraconazole (strong CYP3A inhibitor) or rabeprazole (proton pump inhibitor; gastric acid reducing agent). No clinically significant differences in the pharmacokinetics of the following drugs were observed when used concomitantly with fruquintinib: dabigatran etexilate (P-gp substrate), or rosuvastatin (BCRP substrate). In Vitro Studies Cytochrome P450 Enzymes: Fruquintinib is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A, or an inducer of CYP1A2, CYP2B6, CYP3A. Transporter Systems: Fruquintinib is not a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP)1B1 or OATP1B3. Fruquintinib is not an inhibitor of OATP1B1, OATP1B3, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)2, multidrug and toxin extrusion protein (MATE)1, or MATE2-K." ], "nonclinical_toxicology": [ "13. NONCLINICAL TOXICOLOGY 13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with fruquintinib. Fruquintinib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay or clastogenic in the in vitro Chinese hamster ovary chromosome aberration assay. Fruquintinib was not genotoxic in the in vivo rat micronucleus or alkaline comet assays. In a fertility and early embryonic development study in rats, post-implantation loss was observed at doses approximately equal to the recommended clinical dose of 5 mg based on BSA. 13.2. Animal Toxicology and/or Pharmacology In repeat dose toxicity studies in rats, daily oral administration of fruquintinib at doses ≥0.6 mg/kg (approximately 1.2 times the recommended clinical dose of 5 mg based on BSA) resulted in broken or lost teeth." ], "carcinogenesis_and_mutagenesis_and_impairment_of_fertility": [ "13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with fruquintinib. Fruquintinib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay or clastogenic in the in vitro Chinese hamster ovary chromosome aberration assay. Fruquintinib was not genotoxic in the in vivo rat micronucleus or alkaline comet assays. In a fertility and early embryonic development study in rats, post-implantation loss was observed at doses approximately equal to the recommended clinical dose of 5 mg based on BSA." ], "animal_pharmacology_and_or_toxicology": [ "13.2. Animal Toxicology and/or Pharmacology In repeat dose toxicity studies in rats, daily oral administration of fruquintinib at doses ≥0.6 mg/kg (approximately 1.2 times the recommended clinical dose of 5 mg based on BSA) resulted in broken or lost teeth." ], "clinical_studies": [ "14. CLINICAL STUDIES 14.1. Metastatic Colorectal Cancer FRESCO-2 Study The efficacy of FRUZAQLA was evaluated in FRESCO-2 (NCT04322539), an international, multicenter, randomized, double-blind, placebo-controlled study that enrolled 691 patients with metastatic colorectal cancer who had disease progression during or after prior treatment with fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapy, an anti-VEGF biological therapy, if RAS wild type, an anti-EGFR biological therapy, and trifluridine/tipiracil, regorafenib, or both. Patients with an ECOG PS ≥2, left ventricular fraction ≤50%, systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, urine protein ≥1 g/24h, or untreated brain metastases were ineligible. Randomization was stratified by prior use of trifluridine/tipiracil or regorafenib (trifluridine/tipiracil vs. regorafenib vs. trifluridine/tipiracil and regorafenib), RAS status (wild type vs. mutant), and duration of metastatic disease (≤18 months vs. >18 months). Patients were randomized (2:1) to receive FRUZAQLA 5 mg orally once daily (N=461) for the first 21 days of each 28-day cycle plus BSC or placebo (N=230) plus BSC. Patients received either FRUZAQLA or placebo until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall survival (OS) and an additional efficacy outcome measure was progression-free survival (PFS) as determined by investigators according to RECIST v1.1. The study population characteristics were median age of 64 years (range: 25 to 86), with 47% ≥65 years of age; 56% male; 81% White, 9% Asian, 2.9% Black or African American, and 0.7% Native Hawaiian/Pacific Islander; 43% had an ECOG PS of 0 and 57% had an ECOG PS of 1, and 63% had RAS -mutant tumors. Eighteen percent of the patients were enrolled in North America, 72% in Europe, and 10% in Asia Pacific (Japan and Australia) region. All patients received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy; 96% received prior anti-VEGF therapy, 39% received prior anti-EGFR therapy, 91% received trifluridine/tipiracil, 48% received regorafenib, and 39% received both trifluridine/tipiracil and regorafenib. The addition of FRUZAQLA to BSC resulted in a statistically significant improvement in OS and PFS compared to placebo plus BSC (see Table 7 , Figure 1 ). FRESCO Study The efficacy of FRUZAQLA was evaluated in FRESCO (NCT02314819), a multicenter, randomized, double-blind, placebo-controlled study conducted in China that enrolled 416 patients with metastatic colorectal cancer who had disease progression during or after prior treatment with fluoropyrimidine-, oxaliplatin, or irinotecan-based chemotherapy. Patients older than 75 years of age, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, left ventricular ejection fraction ≤50%, systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, urine protein ≥1 g/24h, or brain metastases were ineligible. Randomization was stratified by prior use of VEGF inhibitors (yes vs. no) and K-RAS status (wild type vs. mutant). Patients were randomized (2:1) to receive FRUZAQLA 5 mg orally once daily (N=278) for the first 21 days of each 28-day cycle plus BSC or placebo (N=138) plus BSC. Patients received either FRUZAQLA or placebo until disease progression or unacceptable toxicity. The major efficacy outcome measure was OS and an additional efficacy outcome measure was PFS as determined by investigators according to RECIST v1.1. The study population characteristics were median age of 56 years (range: 23 to 75), with 19% ≥65 years of age; 61% male; 100% Asian; 27% had an ECOG PS of 0 and 73% had an ECOG PS of 1 (73%), and 44% had K-RAS mutant tumors. All patients received prior treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy; 30% of patients received prior anti-VEGF therapy, and 14% received prior anti-EGFR therapy. The addition of FRUZAQLA to BSC resulted in a statistically significant improvement in OS compared to placebo plus BSC (see Table 7 , Figure 2 ). Table 7: Efficacy Results from FRESCO-2 and FRESCO Studies FRESCO-2 FRESCO Endpoint FRUZAQLA + BSC N=461 Placebo + BSC N=230 FRUZAQLA + BSC N=278 Placebo + BSC N=138 Abbreviations: CI=confidence interval; N=number of patients; OS=overall survival; PFS=progression-free survival OS Number of patients with event (%) 317 (69%) 173 (75%) 188 (68%) 109 (79%) Median in months (95% CI) 7.4 (6.7, 8.2) 4.8 (4.0, 5.8) 9.3 (8.2, 10.5) 6.6 (5.9, 8.1) Hazard Ratio The Hazard Ratio and its 95% CI were estimated using a stratified Cox proportional hazards model. (95% CI) 0.66 (0.55, 0.80) 0.65 (0.51, 0.83) P -Value P -Value (2-sided) was calculated using a stratified log-rank test. <0.001 <0.001 PFS Number of patients with event (%) 392 (85%) 213 (93%) 235 (85%) 125 (91%) Median in months (95% CI) 3.7 (3.5, 3.8) 1.8 (1.8, 1.9) 3.7 (3.7,4.6) 1.8 (1.8, 1.8) Hazard Ratio (95% CI) 0.32 (0.27, 0.39) 0.26 (0.21, 0.34) P -Value P -Value for the PFS analysis in FRESCO was not included due to lack of multiplicity adjustment for this analysis. <0.001 - Figure 1: Kaplan-Meier Curve for Overall Survival in FRESCO-2 Figure 2: Kaplan-Meier Curve for Overall Survival in FRESCO figure1 figure2" ], "clinical_studies_table": [ "
Table 7: Efficacy Results from FRESCO-2 and FRESCO Studies
FRESCO-2FRESCO
EndpointFRUZAQLA + BSC N=461Placebo + BSC N=230FRUZAQLA + BSC N=278Placebo + BSC N=138
Abbreviations: CI=confidence interval; N=number of patients; OS=overall survival; PFS=progression-free survival
OS
Number of patients with event (%)317 (69%)173 (75%)188 (68%)109 (79%)
Median in months (95% CI)7.4 (6.7, 8.2)4.8 (4.0, 5.8)9.3 (8.2, 10.5)6.6 (5.9, 8.1)
Hazard RatioThe Hazard Ratio and its 95% CI were estimated using a stratified Cox proportional hazards model. (95% CI)0.66 (0.55, 0.80)0.65 (0.51, 0.83)
P-ValueP-Value (2-sided) was calculated using a stratified log-rank test.<0.001<0.001
PFS
Number of patients with event (%)392 (85%)213 (93%)235 (85%)125 (91%)
Median in months (95% CI)3.7 (3.5, 3.8)1.8 (1.8, 1.9)3.7 (3.7,4.6)1.8 (1.8, 1.8)
Hazard Ratio (95% CI)0.32 (0.27, 0.39)0.26 (0.21, 0.34)
P-ValueP-Value for the PFS analysis in FRESCO was not included due to lack of multiplicity adjustment for this analysis.<0.001-
", "
Figure 1: Kaplan-Meier Curve for Overall Survival in FRESCO-2
", "
Figure 2: Kaplan-Meier Curve for Overall Survival in FRESCO
" ], "how_supplied": [ "16. HOW SUPPLIED/STORAGE AND HANDLING How Supplied Capsule Strength Description Package Configuration NDC Number 1 mg Size 3 hard gelatin capsule with yellow opaque cap and white opaque body, imprinted with “HM013” over “1 mg” on the body in black ink White high-density polyethylene (HDPE) bottle with child-resistant closure packaged in a carton. Each bottle contains 21 capsules. 63020-210-21 5 mg Size 1 hard gelatin capsule with a red opaque cap and white opaque body, imprinted with “HM013” over “5 mg” on the body in black ink 63020-225-21 Storage and handling Store at 20°C to 25°C (68°F to 77°F). Brief exposure to 15°C and 30°C (59°F to 86°F) permitted (see USP Controlled Room Temperature). Any unused medicinal product or waste material should be disposed of in accordance with local requirements." ], "how_supplied_table": [ "
Capsule StrengthDescriptionPackage ConfigurationNDC Number
1 mgSize 3 hard gelatin capsule with yellow opaque cap and white opaque body, imprinted with “HM013” over “1 mg” on the body in black inkWhite high-density polyethylene (HDPE) bottle with child-resistant closure packaged in a carton. Each bottle contains 21 capsules.63020-210-21
5 mgSize 1 hard gelatin capsule with a red opaque cap and white opaque body, imprinted with “HM013” over “5 mg” on the body in black ink63020-225-21
" ], "storage_and_handling": [ "Storage and handling Store at 20°C to 25°C (68°F to 77°F). Brief exposure to 15°C and 30°C (59°F to 86°F) permitted (see USP Controlled Room Temperature). Any unused medicinal product or waste material should be disposed of in accordance with local requirements." ], "information_for_patients": [ "17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Hypertension Advise patients to undergo regular blood pressure monitoring and to contact their health care provider if blood pressure is elevated or if symptoms from hypertension occur including severe headache, lightheadedness, or new neurologic symptoms [see Warnings and Precautions (5.1) ] . Hemorrhages Advise patients that FRUZAQLA may increase the risk of bleeding and to contact their healthcare provider for unusual, severe, or persistent bleeding, bruising, or symptoms of bleeding, such as lightheadedness [see Warnings and Precautions (5.2) ] . Infections Advise patients to contact their healthcare provider if they experience signs and symptoms of infection [see Warnings and Precautions (5.3) ] . Gastrointestinal Perforation Advise patients to contact a healthcare provider immediately if they experience severe abdominal pains, or other symptoms of gastrointestinal perforation or fistula [see Warnings and Precautions (5.4) ] . Hepatotoxicity Advise patients that they will need to undergo laboratory tests to monitor liver function and to report any new symptoms indicating hepatic toxicity or failure [see Warnings and Precautions (5.5) ] . Proteinuria Advise patients that they will need to undergo laboratory tests to monitor for proteinuria and to contact their healthcare provider for signs or symptoms of proteinuria [see Warnings and Precautions (5.6) ] . Palmar-plantar erythrodysesthesia (PPE) Advise patients to contact their healthcare provider for progressive or intolerable rash [see Warnings and Precautions (5.7) ] . Posterior Reversible Encephalopathy Syndrome (PRES) Advise patients to immediately contact their healthcare provider for new onset or worsening neurological function [see Warnings and Precautions (5.8) ] . Impaired Wound Healing Advise patients that FRUZAQLA may impair wound healing. Advise patients to inform their healthcare provider of any planned surgical procedure [see Warnings and Precautions (5.9) ] . Arterial Thrombosis Advise patients to seek immediate medical attention for new onset chest pain or acute neurologic symptoms consistent with myocardial infarction or stroke [see Warnings and Precautions (5.10) ] . Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF) Advise patients that FRUZAQLA 1 mg contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons or in patients who also have aspirin hypersensitivity [see Warnings and Precautions (5.11) ] . Advise patients FRUZAQLA 1 mg contains FD&C Yellow No. 6 (sunset yellow FCF) which may cause allergic-type reactions [see Warnings and Precautions (5.11) ] . Embryo-Fetal Toxicity Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform females of the risk to a fetus and potential loss of pregnancy [see Warnings and Precautions (5.12) and Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment and for 2 weeks after the last dose of FRUZAQLA [see Warnings and Precautions (5.12) and Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment and for 2 weeks following the last dose of FRUZAQLA [see Warnings and Precautions (5.11) and Use in Specific Populations (8.3) ] . Lactation Advise patients not to breastfeed during treatment with FRUZAQLA and for 2 weeks after the last dose of FRUZAQLA [see Use in Specific Populations (8.2) ] . Infertility Advise females of reproductive potential that FRUZAQLA may cause post-implantation loss [see Use in Specific Populations (8.3) , Nonclinical Toxicology (13.1) ] ." ], "spl_unclassified_section": [ "Distributed by: Takeda Pharmaceuticals America, Inc. Cambridge, MA 02142 FRUZAQLA and are trademarks of HUTCHMED Group Enterprises Limited, used under license. TAKEDA and are registered trademarks of Takeda Pharmaceutical Company Limited. ©2025 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved. FRU380 R2 logo1 logo2" ], "spl_patient_package_insert": [ "This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 2/2025 PATIENT INFORMATION FRUZAQLA ® (fru-zahk-la) (fruquintinib) capsules What is FRUZAQLA? FRUZAQLA is a prescription medicine used to treat adults with colon or rectal cancer that has spread to other parts of the body (metastatic colorectal cancer [mCRC]) and who have received previous treatment with certain anti-cancer medicines. It is not known if FRUZAQLA is safe and effective in children. Before taking FRUZAQLA, tell your healthcare provider about all of your medical conditions, including if you: have high blood pressure. have bleeding problems. have an infection. have liver or kidney problems. plan to have surgery or have had recent surgery. You should stop taking FRUZAQLA at least 2 weeks before your planned surgery. Your healthcare provider will tell you when you can start FRUZAQLA again after your surgery. See “What are the possible side effects of FRUZAQLA?” have recently had a blood clot, stroke, or heart attack. are allergic to FD&C Yellow No. 5 (tartrazine) or FD&C Yellow No. 6 (sunset yellow FCF). See “What are the possible side effects of FRUZAQLA?” are pregnant or plan to become pregnant. FRUZAQLA can harm your unborn baby. You should not become pregnant during treatment with FRUZAQLA. Females who can become pregnant: Your healthcare provider will do a pregnancy test before you start treatment with FRUZAQLA. Use effective birth control (contraception) during treatment and for 2 weeks after your last dose of FRUZAQLA. Tell your healthcare provider right away if you become pregnant during treatment with FRUZAQLA. Males with female partners who can become pregnant: Use effective birth control during treatment and for 2 weeks after your last dose of FRUZAQLA. Tell your healthcare provider right away if your partner becomes pregnant during your treatment with FRUZAQLA. are breastfeeding or plan to breastfeed. It is not known if FRUZAQLA passes into your breast milk. Do not breastfeed during treatment and for 2 weeks after your last dose of FRUZAQLA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. FRUZAQLA may affect the way other medicines work, and other medicines may affect how FRUZAQLA works. Especially tell your healthcare provider if you take blood thinners (anticoagulants). Know the medicines you take. Keep a list of your medicines to show to your healthcare provider and pharmacist when you get a new medicine. How should I take FRUZAQLA? Take FRUZAQLA exactly as your healthcare provider tells you. Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with FRUZAQLA if you have certain side effects. Do not change your dose or stop taking FRUZAQLA unless your healthcare provider tells you. You will usually take FRUZAQLA 1 time a day for 21 days (3 weeks) and then stop for 7 days (1 week). This is 1 cycle of treatment. Repeat this cycle for as long as your healthcare provider tells you. Take FRUZAQLA about the same time each day with or without food and swallow the capsule whole. If you miss a dose of FRUZAQLA, you can take the missed dose within 12 hours on the same day. If more than 12 hours have passed, take your regularly scheduled dose the next day at the usual time. Do not take 2 doses at the same time to make up for the missed dose. Do not take another dose if you vomit after taking FRUZAQLA. Take your regularly scheduled dose the next day at the usual time. If you take too much FRUZAQLA, call your healthcare provider or go to the nearest hospital emergency room right away. What are the possible side effects of FRUZAQLA? FRUZAQLA may cause serious side effects, including: High blood pressure (hypertension). High blood pressure is common with FRUZAQLA and can also be severe. Your healthcare provider will check your blood pressure before starting treatment with FRUZAQLA, 1 time every week for the first month of treatment, and then at least 1 time a month or more often if needed during treatment. Your healthcare provider may prescribe medicine to treat your high blood pressure if needed. Tell your healthcare provider if you get any of the following symptoms of hypertension during treatment: severe headache lightheadedness or dizziness confusion changes in vision chest pain trouble breathing nosebleeds vomiting Severe bleeding (hemorrhage). FRUZAQLA can cause bleeding that can be serious and may lead to death. Tell your healthcare provider if you get any of the following symptoms of bleeding during treatment: unusual, severe, or bleeding that will not stop bruising lightheadedness vomiting blood or your vomit looks like coffee grinds blood in the stool or black stool that looks like tar blood in the urine or urine that looks red, pink or brown coughing up blood or blood clots menstrual bleeding that is heavier than normal unusual vaginal bleeding nose bleeds that happen often Infections. FRUZAQLA can increase the risk of infections, including serious infections that can lead to death. The most common infections with FRUZAQLA happened in the urinary tract, nose or throat, and lungs. Tell your healthcare provider if you get any of the following symptoms of infection during treatment: fever severe cough with or without an increase in mucus (sputum) production severe sore throat trouble breathing burning or pain when you urinate redness, swelling or pain in any part of the body A tear in your stomach or intestinal wall (gastrointestinal perforation). FRUZAQLA can cause gastrointestinal perforation that can be serious and may lead to death. Tell your healthcare provider right away, if you get any of the following symptoms of gastrointestinal perforation during treatment: severe stomach (abdominal) pain or stomach pain that does not go away vomiting or vomiting blood blood in the stool or black stool that looks like tar fever or chills nausea Liver problems . Increased liver enzymes in your blood are common with FRUZAQLA and can also be severe and may lead to death. Your healthcare provider will do blood tests before and during treatment with FRUZAQLA to check for liver problems. Tell your healthcare provider if you get any of the following symptoms of liver problems during treatment: yellowing of your skin or the white part of your eyes dark colored (tea colored) urine pain in your right upper stomach-area (abdomen) loss of appetite nausea or vomiting bleeding or bruising Protein in your urine (proteinuria) . Protein in your urine is common with FRUZAQLA and can also be severe. Your healthcare provider will check your urine for protein before starting and during treatment with FRUZAQLA. Tell your healthcare provider if you have to urinate more than usual, or if you get swelling of your face, hands, arms, legs, or feet during treatment. Hand-foot skin reactions (Palmar-Plantar Erythrodysesthesia [PPE]) . Hand-foot skin reactions are common with FRUZAQLA and can also be severe. Tell your healthcare provider if you get a severe rash or redness, pain, blisters, bleeding, or swelling on the palms of your hands or soles of your feet during treatment. Posterior Reversible Encephalopathy Syndrome (PRES). PRES is a serious condition that can happen in your brain during treatment with FRUZAQLA. Tell your healthcare provider right away if you get any of the following symptoms during treatment: headache seizures confusion changes in vision problems thinking Wound healing problems. Wounds may not heal properly during treatment with FRUZAQLA. Tell your healthcare provider if you plan to have any surgery before starting FRUZAQLA or during treatment. You should stop taking FRUZAQLA at least 2 weeks before planned surgery. Your healthcare provider will tell you when you may start taking FRUZAQLA again after surgery. Blood clots in your blood vessels (arteries). FRUZAQLA can cause blood clots or blockage in your blood vessels that may lead to heart attack, stroke, or death. Get medical help right away if you get any of the following symptoms during treatment: severe chest pain or pressure pain in your arms, legs, back, neck or jaw shortness of breath numbness or weakness of your face, arm, or leg, especially on one side of your body feeling lightheaded or faint sweating more than usual sudden confusion, trouble talking, or understanding things trouble walking sudden severe headache sudden vision changes in one or both eyes dizziness, or loss of balance or coordination Allergic reactions to FD&C Yellow No. 5 and FD&C Yellow No. 6 . FRUZAQLA 1 mg capsules contain the inactive ingredients FD&C Yellow No. 5 (tartrazine) and FD&C Yellow No. 6 (sunset yellow FCF). FD&C Yellow No. 5 (tartrazine) can cause allergic-type reactions (including bronchial asthma) in certain people, especially people who also have an allergy to aspirin. FD&C Yellow No. 6 (sunset yellow FCF) can also cause allergic reactions. Tell your healthcare provider if you get hives, rash, or trouble breathing during treatment with FRUZAQLA. The most common side effects of FRUZAQLA include: voice changes or hoarseness stomach-area (abdominal) pain diarrhea weakness, lack of strength and energy, and feeling very tired or sleepy (asthenia) FRUZAQLA may cause fertility problems in females, which may affect your ability to have children. Talk to your healthcare provider if you have concerns about fertility. These are not all of the possible side effects of FRUZAQLA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store FRUZAQLA? Store FRUZAQLA at room temperature between 68°F to 77°F (20°C to 25°C). Keep FRUZAQLA dry and away from moisture. The FRUZAQLA bottle comes with a child resistant closure. Safely throw away (discard of) any unused FRUZAQLA. Keep FRUZAQLA and all medicines out of the reach of children. General information about the safe and effective use of FRUZAQLA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use FRUZAQLA for a condition for which it was not prescribed. Do not give FRUZAQLA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about FRUZAQLA that is written for health professionals. What are the ingredients in FRUZAQLA? Active ingredient: fruquintinib Inactive ingredients: corn starch, microcrystalline cellulose, talc Capsule shell: 1 mg capsule: FD&C Yellow No. 5 (tartrazine), FD&C Yellow No. 6 (sunset yellow FCF), gelatin, and titanium dioxide 5 mg capsule: FD&C Blue No. 1 (brilliant blue FCF), FD&C Red No. 40 (allura red AC), gelatin, and titanium dioxide Printing ink: butanol, dehydrated alcohol, ferrosoferric oxide, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution. Distributed by: Takeda Pharmaceuticals America, Inc. Cambridge, MA 02142 FRUZAQLA and are trademarks of HUTCHMED Group Enterprises Limited, used under license. TAKEDA and are registered trademarks of Takeda Pharmaceutical Company Limited. ©2025 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved. For more information, go to www.fruzaqla.com or call 1-844-217-6468. FRU380 R2" ], "spl_patient_package_insert_table": [ "
This Patient Information has been approved by the U.S. Food and Drug Administration.Revised: 2/2025
PATIENT INFORMATION FRUZAQLA® (fru-zahk-la) (fruquintinib) capsules
What is FRUZAQLA? FRUZAQLA is a prescription medicine used to treat adults with colon or rectal cancer that has spread to other parts of the body (metastatic colorectal cancer [mCRC]) and who have received previous treatment with certain anti-cancer medicines. It is not known if FRUZAQLA is safe and effective in children.
Before taking FRUZAQLA, tell your healthcare provider about all of your medical conditions, including if you:have high blood pressure.have bleeding problems.have an infection.have liver or kidney problems.plan to have surgery or have had recent surgery. You should stop taking FRUZAQLA at least 2 weeks before your planned surgery. Your healthcare provider will tell you when you can start FRUZAQLA again after your surgery. See “What are the possible side effects of FRUZAQLA?”have recently had a blood clot, stroke, or heart attack.are allergic to FD&C Yellow No. 5 (tartrazine) or FD&C Yellow No. 6 (sunset yellow FCF). See “What are the possible side effects of FRUZAQLA?”are pregnant or plan to become pregnant. FRUZAQLA can harm your unborn baby. You should not become pregnant during treatment with FRUZAQLA. Females who can become pregnant:Your healthcare provider will do a pregnancy test before you start treatment with FRUZAQLA.Use effective birth control (contraception) during treatment and for 2 weeks after your last dose of FRUZAQLA.Tell your healthcare provider right away if you become pregnant during treatment with FRUZAQLA.Males with female partners who can become pregnant:Use effective birth control during treatment and for 2 weeks after your last dose of FRUZAQLA.Tell your healthcare provider right away if your partner becomes pregnant during your treatment with FRUZAQLA.are breastfeeding or plan to breastfeed. It is not known if FRUZAQLA passes into your breast milk. Do not breastfeed during treatment and for 2 weeks after your last dose of FRUZAQLA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. FRUZAQLA may affect the way other medicines work, and other medicines may affect how FRUZAQLA works. Especially tell your healthcare provider if you take blood thinners (anticoagulants). Know the medicines you take. Keep a list of your medicines to show to your healthcare provider and pharmacist when you get a new medicine.
How should I take FRUZAQLA?Take FRUZAQLA exactly as your healthcare provider tells you.Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with FRUZAQLA if you have certain side effects. Do not change your dose or stop taking FRUZAQLA unless your healthcare provider tells you.You will usually take FRUZAQLA 1 time a day for 21 days (3 weeks) and then stop for 7 days (1 week). This is 1 cycle of treatment. Repeat this cycle for as long as your healthcare provider tells you.Take FRUZAQLA about the same time each day with or without food and swallow the capsule whole.If you miss a dose of FRUZAQLA, you can take the missed dose within 12 hours on the same day. If more than 12 hours have passed, take your regularly scheduled dose the next day at the usual time. Do not take 2 doses at the same time to make up for the missed dose.Do not take another dose if you vomit after taking FRUZAQLA. Take your regularly scheduled dose the next day at the usual time.If you take too much FRUZAQLA, call your healthcare provider or go to the nearest hospital emergency room right away.
What are the possible side effects of FRUZAQLA? FRUZAQLA may cause serious side effects, including:High blood pressure (hypertension). High blood pressure is common with FRUZAQLA and can also be severe. Your healthcare provider will check your blood pressure before starting treatment with FRUZAQLA, 1 time every week for the first month of treatment, and then at least 1 time a month or more often if needed during treatment. Your healthcare provider may prescribe medicine to treat your high blood pressure if needed. Tell your healthcare provider if you get any of the following symptoms of hypertension during treatment:
severe headachelightheadedness or dizzinessconfusionchanges in visionchest paintrouble breathingnosebleedsvomiting
Severe bleeding (hemorrhage). FRUZAQLA can cause bleeding that can be serious and may lead to death. Tell your healthcare provider if you get any of the following symptoms of bleeding during treatment:
unusual, severe, or bleeding that will not stopbruisinglightheadednessvomiting blood or your vomit looks like coffee grindsblood in the stool or black stool that looks like tarblood in the urine or urine that looks red, pink or browncoughing up blood or blood clotsmenstrual bleeding that is heavier than normalunusual vaginal bleedingnose bleeds that happen often
Infections. FRUZAQLA can increase the risk of infections, including serious infections that can lead to death. The most common infections with FRUZAQLA happened in the urinary tract, nose or throat, and lungs. Tell your healthcare provider if you get any of the following symptoms of infection during treatment:
fever severe cough with or without an increase in mucus (sputum) production severe sore throattrouble breathingburning or pain when you urinateredness, swelling or pain in any part of the body
A tear in your stomach or intestinal wall (gastrointestinal perforation). FRUZAQLA can cause gastrointestinal perforation that can be serious and may lead to death. Tell your healthcare provider right away, if you get any of the following symptoms of gastrointestinal perforation during treatment:
severe stomach (abdominal) pain or stomach pain that does not go awayvomiting or vomiting bloodblood in the stool or black stool that looks like tarfever or chillsnausea
Liver problems. Increased liver enzymes in your blood are common with FRUZAQLA and can also be severe and may lead to death. Your healthcare provider will do blood tests before and during treatment with FRUZAQLA to check for liver problems. Tell your healthcare provider if you get any of the following symptoms of liver problems during treatment:
yellowing of your skin or the white part of your eyesdark colored (tea colored) urinepain in your right upper stomach-area (abdomen)loss of appetitenausea or vomitingbleeding or bruising
Protein in your urine (proteinuria). Protein in your urine is common with FRUZAQLA and can also be severe. Your healthcare provider will check your urine for protein before starting and during treatment with FRUZAQLA. Tell your healthcare provider if you have to urinate more than usual, or if you get swelling of your face, hands, arms, legs, or feet during treatment.
Hand-foot skin reactions (Palmar-Plantar Erythrodysesthesia [PPE]). Hand-foot skin reactions are common with FRUZAQLA and can also be severe. Tell your healthcare provider if you get a severe rash or redness, pain, blisters, bleeding, or swelling on the palms of your hands or soles of your feet during treatment.
Posterior Reversible Encephalopathy Syndrome (PRES). PRES is a serious condition that can happen in your brain during treatment with FRUZAQLA. Tell your healthcare provider right away if you get any of the following symptoms during treatment:
headacheseizuresconfusionchanges in vision problems thinking
Wound healing problems. Wounds may not heal properly during treatment with FRUZAQLA. Tell your healthcare provider if you plan to have any surgery before starting FRUZAQLA or during treatment.
You should stop taking FRUZAQLA at least 2 weeks before planned surgery.Your healthcare provider will tell you when you may start taking FRUZAQLA again after surgery.
Blood clots in your blood vessels (arteries). FRUZAQLA can cause blood clots or blockage in your blood vessels that may lead to heart attack, stroke, or death. Get medical help right away if you get any of the following symptoms during treatment:
severe chest pain or pressurepain in your arms, legs, back, neck or jawshortness of breathnumbness or weakness of your face, arm, or leg, especially on one side of your bodyfeeling lightheaded or faintsweating more than usualsudden confusion, trouble talking, or understanding thingstrouble walkingsudden severe headachesudden vision changes in one or both eyesdizziness, or loss of balance or coordination
Allergic reactions to FD&C Yellow No. 5 and FD&C Yellow No. 6. FRUZAQLA 1 mg capsules contain the inactive ingredients FD&C Yellow No. 5 (tartrazine) and FD&C Yellow No. 6 (sunset yellow FCF). FD&C Yellow No. 5 (tartrazine) can cause allergic-type reactions (including bronchial asthma) in certain people, especially people who also have an allergy to aspirin. FD&C Yellow No. 6 (sunset yellow FCF) can also cause allergic reactions. Tell your healthcare provider if you get hives, rash, or trouble breathing during treatment with FRUZAQLA.
The most common side effects of FRUZAQLA include:
voice changes or hoarsenessstomach-area (abdominal) paindiarrheaweakness, lack of strength and energy, and feeling very tired or sleepy (asthenia)
FRUZAQLA may cause fertility problems in females, which may affect your ability to have children. Talk to your healthcare provider if you have concerns about fertility. These are not all of the possible side effects of FRUZAQLA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store FRUZAQLA?Store FRUZAQLA at room temperature between 68°F to 77°F (20°C to 25°C).Keep FRUZAQLA dry and away from moisture.The FRUZAQLA bottle comes with a child resistant closure.Safely throw away (discard of) any unused FRUZAQLA.Keep FRUZAQLA and all medicines out of the reach of children.
General information about the safe and effective use of FRUZAQLA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use FRUZAQLA for a condition for which it was not prescribed. Do not give FRUZAQLA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about FRUZAQLA that is written for health professionals.
What are the ingredients in FRUZAQLA? Active ingredient: fruquintinib Inactive ingredients: corn starch, microcrystalline cellulose, talc Capsule shell: 1 mg capsule: FD&C Yellow No. 5 (tartrazine), FD&C Yellow No. 6 (sunset yellow FCF), gelatin, and titanium dioxide5 mg capsule: FD&C Blue No. 1 (brilliant blue FCF), FD&C Red No. 40 (allura red AC), gelatin, and titanium dioxide Printing ink: butanol, dehydrated alcohol, ferrosoferric oxide, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution. Distributed by: Takeda Pharmaceuticals America, Inc. Cambridge, MA 02142 FRUZAQLA and are trademarks of HUTCHMED Group Enterprises Limited, used under license. TAKEDA and are registered trademarks of Takeda Pharmaceutical Company Limited. ©2025 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved. For more information, go to www.fruzaqla.com or call 1-844-217-6468. FRU380 R2
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