Dosing & Uses
Dosage Forms & Strengths
capsule
- 1mg
- 5mg
Colorectal Cancer
Indicated for treatment of adults 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
Each cycle is 28 days
5 mg PO qDay on first 21 days of each cycle
Continue until disease progression or unacceptable toxicity
Dosage Modifications
Recommended dose reductions
- First dose reduction: 4 mg PO qDay
- Second dose reduction: 3 mg PO qDay
- Unable to tolerate 3 mg PO qDay: Permanently discontinue
Hypertension
- Grade 3 that persists despite optimal antihypertensive therapy: Withhold until blood pressure (BP) elevation fully resolves or recovers to Grade 1, then resume at next lower dose level
- Grade 4: Permanently discontinue
Hemorrhagic events
- Grade 2: Withhold until bleeding fully resolves or recovers to Grade 1, resume at next lower dose level
- Grade 3 or 4: Permanently discontinue
Hepatotoxicity
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x upper limit of normal (ULN) with total bilirubin (TB) ≤2x ULN: Withhold and monitor AST/ALT and TB until resolution to Grade 1 or baseline, then resume at next lower dose level
-
Permanently discontinue
- ALT/AST >3x ULN WITH bilirubin >2x ULN (with no cholestasis or hemolysis)
- ALT/AST >20x ULN OR bilirubin >10x ULN
Proteinuria
- ≥2 grams/24 hr: Withhold until proteinuria fully resolves or <1 gram/24 hr, resume at next lower dose level once recovered
- Permanently discontinue for nephrotic syndrome or if proteinuria does not recover to <1 gram/24 hr
Palmoplantar erythrodysesthesia
- Withhold and initiate supportive treatment
- Grade 2: If fully resolves or recovers to Grade 1, resume at same dose level
- Grade 3: If fully resolves or recovers to Grade 1, resume at next lower dose level
Other adverse reactions
- Grade 3: Withhold until toxicity fully resolves or recovers to Grade 1, resume at next lower dose level
- Grade 4: Discontinue; consider resuming at next lower dose level only if toxicity is non–life-threatening and fully resolves or recovers to Grade 1 and potential benefit outweighs risks
Strong or moderate CYP3A4 inducers
- Avoid coadministration of strong or moderate CYP3A4 inducers with fruquintinib
Renal impairment
- Mild or moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
Hepatic impairment
- Mild (total bilirubin ≤ULN with AST >ULN or total bilirubin >1-1.5x ULN with any AST): No dosage adjustment necessary
- Moderate (total bilirubin >1.5x to <3x ULN and any AST): Not studied
- Severe hepatic impairment (total bilirubin >3x ULN and any AST): Fruquintinib not recommended
Dosing Considerations
Verify pregnancy status for females of childbearing potential
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (42)
- amobarbital
amobarbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- apalutamide
apalutamide will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- armodafinil
armodafinil will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- belzutifan
belzutifan will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- bexarotene
bexarotene will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- bosentan
bosentan will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butabarbital
butabarbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- butalbital
butalbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- carbamazepine
carbamazepine will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cenobamate
cenobamate will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- dabrafenib
dabrafenib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- duvelisib
duvelisib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- efavirenz
efavirenz will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- elagolix
elagolix will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- encorafenib
encorafenib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- enzalutamide
enzalutamide will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- etrasimod
etrasimod, fruquintinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod.
- etravirine
etravirine will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- fosphenytoin
fosphenytoin will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ivosidenib
ivosidenib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- lorlatinib
lorlatinib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mavacamten
mavacamten will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- mitapivat
mitapivat will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- mitotane
mitotane will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mobocertinib
mobocertinib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- modafinil
modafinil will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- nafcillin
nafcillin will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- olutasidenib
olutasidenib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- pentobarbital
pentobarbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- pexidartinib
pexidartinib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- phenobarbital
phenobarbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenytoin
phenytoin will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- primidone
primidone will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifabutin
rifabutin will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- rifampin
rifampin will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- secobarbital
secobarbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- sotorasib
sotorasib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- St John's Wort
St John's Wort will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- telotristat ethyl
telotristat ethyl will increase the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
Monitor Closely (1)
- warfarin
fruquintinib, warfarin. Other (see comment). Use Caution/Monitor. Comment: Fruquintinib may cause serious hemorrhagic events. Monitor INR in patients receiving anticoagulants.
Minor (0)
Adverse Effects
>10%
All grades
- Creatinine increased (87%)
- Hypertension (38-61%)
- Proteinuria (18-55%)
- Triglycerides increased (53%)
- Fatigue (53%)
- Palmoplantar erythrodysesthesia (19-49%)
- Glucose increased (43%)
- AST increased (36-42%)
- Alkaline phosphatase increased (20-40%)
- Bilirubin increased (30-39%)
- Dysphonia (38%)
- Cholesterol increased (37%)
- Albumin decreased (35%)
- Sodium decreased (33-35%)
- ALT increased (33-34%)
- Stomatitis (31-33%)
- Lymphocytes decreased (30%)
- Platelets decreased (29-30%)
- Abdominal pain (25-29%)
- Hemorrhage (28%)
- Urate increased (26%)
- Calcium decreased (25%)
- Diarrhea (24-25%)
- Hemoglobin decreased (23%)
- Musculoskeletal pain (16-22%)
- Potassium decreased (22%)
- Hypothyroidism (17-21%)
- Activated partial thromboplastin time (aPTT) increased (21%)
- Anorexia (21%)
- Magnesium increased (20%)
- Dysphonia (18%)
- Back pain (15%)
- Arthralgia (11%)
Grade 3 or 4
- Urate increased (26%)
- Hypertension (14-23%)
- Fatigue (12%)
- Palmoplantar erythrodysesthesia (6-11%)
1-10%
All grades
- Throat pain (10%)
- Urinary tract infection (4.6%)
- Epistaxis (3.9%)
- Proctalgia (3.5%)
- Pneumonia (2.4%)
- Albumin decreased (1.6%)
- Gastrointestinal hemorrhage (1.5%)
- Gastrointestinal perforation (1.3%)
Grade 3 or 4
- Bilirubin increased (4.7-7%)
- Sodium decreased (1.1-6%)
- ALT increased (2.2-5%)
- Proteinuria (1.8-4.7%)
- AST increased (3.6-4.3%)
- Alkaline phosphatase increased (1.6-4.3%)
- Platelets decreased (3.6%)
- Abdominal pain (3.5-4%)
- Diarrhea (3.6-3.7%)
- Triglycerides increased (2.8%)
- aPTT increased (2.7%)
- Stomatitis (0.7-2.2%)
- Cholesterol increased (1.9%)
- Back pain (1.8%)
- Potassium decreased (1.8%)
- Anorexia (1.4%)
- Musculoskeletal pain (1.1-2.2%)
- Hemorrhage (1.1%)
- Glucose increased (1.1%)
<1%
All grades
- Thrombotic microangiopathy (0.2%)
- Posterior reversible encephalopathy syndrome (0.2%)
Grade 3 or 4
- Arthralgia (0.9%)
- Hemoglobin decreased (0.7%)
- Creatinine increased (0.7%)
- Magnesium decreased (0.5%)
- Hypothyroidism (0.4%)
- Calcium decreased (0.4%)
- Lymphocytes decreased (0.2%)
Warnings
Contraindications
None
Cautions
May cause serious hemorrhagic events, which may be fatal; permanently discontinue if severe or life-threatening hemorrhaging occurs; monitor international normalized ratio (INR) levels in patients receiving anticoagulants
Increased risk of infections reported, including fatal infections; withhold for Grade 3 or 4 infections, or worsening infection of any grade, then resume at same dose when infection has resolved
Gastrointestinal (GI) perforation reported; permanently discontinue if GI perforation or fistula develops
Palmoplantar erythrodysesthesia may occur; based on severity, withhold and then resume at same or reduced dose
Posterior reversible encephalopathy syndrome (PRES) reported; PRES is a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI; evaluate for PRES if seizures, headache, visual disturbances, confusion, or altered mental function develops; discontinue if PRES develops
May increase risk of arterial thromboembolic events; carefully consider initiating in patients with recent history of thromboembolic events; discontinue if arterial thromboembolism develops
1-mg capsules contain FD&C yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons
Based on animal studies and its mechanism of action, fetal harm may occur when administered to pregnant females
Hypertension
- May cause hypertension
- Median time from first dose to hypertension onset was 14 days
- Do not initiate unless BP is adequately controlled
- Monitor BP weekly for first month, at least monthly thereafter, and as clinically indicated
- Initiate or adjust antihypertensive therapy as appropriate
- Withhold, reduce dose, or permanently discontinue based on hypertension severity
Hepatotoxicity
- Liver injury may occur
- Median time from first dose to onset of elevated liver enzymes was 29 days
- Monitor liver function tests (ALT, AST, and bilirubin) before initiation and periodically during treatment
- Temporarily hold and then reduce or permanently discontinue depending on severity and persistence of hepatotoxicity
Impaired wound healing
- Impaired wound healing can occur in patients who receive vascular endothelial growth factor (VEGF) signaling pathway inhibitors
- Do not administer for at least 2 weeks before major surgery
- Do not administer for at least 2 weeks after major surgery and until adequate wound healing
- Safety of resuming treatment after wound healing complications resolve has not been established
Drug interaction overview
- Substrate of CYP3A4
-
Strong or moderate CYP3A inducers
- Strong CYP3A4 inducers: Avoid use
- For moderate CYP3A4 inducers, avoid use if possible
- If unavoidable, continue to administer at recommended dosage
- Strong or moderate CYP3A inducers may decrease fruquintinib levels and efficacy
Pregnancy & Lactation
Pregnancy
Based on animal studies and its mechanism of action, fetal harm may occur when administered to pregnant females
Contraception
- Females of childbearing potential and males with female partners of childbearing potential: Use effective contraception during treatment and for 2 weeks after last dose
Animal data
- In pregnant rats, oral administration during organogenesis resulted in teratogenicity and embryo lethality at exposures below clinical exposure
Lactation
No data are available regarding presence of fruquintinib or its metabolites in human milk or its effects on a breastfed child or on milk production
Advise women not to breastfeed during treatment and for 2 weeks after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Oral, small molecule inhibitor of vascular endothelial growth factor receptors (VEGFRs), with potential anti-angiogenic and antineoplastic activities
Fruquintinib inhibits VEGF-induced phosphorylation of VEGFRs 1, 2, and 3, which may result in inhibition of migration, proliferation, and survival of endothelial cells; micro-vessel formation; and tumor cell proliferation, resulting in tumor cell death
Absorption
Peak plasma concentration: 300 ng/mL
Peak plasma time: ~2 hr
AUC: 5,880 ng⋅hr/mL
Steady-state achieved at 14 days
Distribution
Vd: 46 L
Protein bound: ~95%
Metabolism
Primarily eliminated by CYP450 and non-CYP450 (ie, sulfation and glucuronidation) metabolism
Metabolized by CYP3A and to a lesser extent CYP2C8, CYP2C9, and CYP2C19
Elimination
Clearance: 14.8 mL/min
Half-life: 42 hr
Excretion: 60% (urine, 0.5% unchanged); 30% (feces, 5% unchanged)
Administration
Oral Administration
Take with or without food at approximately the same time each day
Swallow capsule whole
Missed or vomited dose
- <12 hr since missed dose: Take missed dose; do not take 2 doses on the same day to make up for a missed dose
- Vomited dose: Do not take additional dose, but continue with next dose at next scheduled time
Storage
Store at 20-25ºC (68-77ºF), excursion permitted to 15-30ºC (59-86°F) permitted
Any unused medicinal product or waste material should be disposed of in accordance with local requirements
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