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Fruquintinib (Monograph)

Brand name: Fruzaqla
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

[Web]

Introduction

Antineoplastic agent; inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3.

Uses for Fruquintinib

Colorectal Cancer

Used for treatment of metastatic colorectal cancer in adults previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens; an anti-VEGF therapy; and in those bearing the wild-type (nonmutated) RAS genes, and when medically appropriate, an epidermal growth factor receptor inhibitor (anti-EGFR therapy).

American Society of Clinical Oncology (ASCO) guidelines on metastatic colorectal cancer and late-stage colorectal cancer do not discuss the specific place in therapy for fruquintinib.

Fruquintinib Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Other General Considerations

Administration

Oral Administration

Available as capsules containing 1 or 5 mg of fruquintinib.

Administer with or without food, at approximately same time each day. Swallow capsules whole.

If a dose is missed, take missed dose if <12 hours have elapsed; do not take 2 doses on same day to make up for missed dose.

If vomiting occurs after taking a dose, do not administer an additional dose but continue with next scheduled dose.

Dosage

Adults

Metastatic Colorectal Cancer
Oral

5 mg once daily for first 21 days of each 28-day cycle. Continue until disease progression or unacceptable toxicity.

Dosage Modification for Toxicity

Temporary interruption, dosage reduction, and/or permanent discontinuance of fruquintinib may be necessary if adverse effects occur.

If dosage modification required, reduce dosage of fruquintinib as described in Table 1.

Permanently discontinue fruquintinib in patients unable to tolerate dosage of 3 mg orally once daily.

Table 1. Recommended Dosage Reduction for Fruquintinib Toxicity.1

Dosage Reduction Level

Recommended Dosage

First dose reduction

4 mg orally once daily

Second dose reduction

3 mg orally once daily

Refer to Table 2 for recommended fruquintinib dosage modifications based on adverse reaction.

Level of severity as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Table 2. Recommended Dosage Modification for Fruquintinib Adverse Reactions.1

Adverse Reaction

Fruquintinib Dosage Modification Based on Severity

Hypertension

Grade 3:Temporarily withhold fruquintinib for grade 3 hypertension that persists despite antihypertensive therapy. Upon full resolution of hypertension or recovery to grade 1, resume fruquintinib at the next lower dosage level.

Grade 4: Permanently discontinue fruquintinib.

Hemorrhagic events

Grade 2:Temporarily withhold fruquintinib until full bleeding resolution or recovery to grade 1, then resume fruquintinib at the next lower dosage level.

Grade 3 or 4: Permanently discontinue fruquintinib.

Hepatotoxicity

ALT or AST >3 times ULN with total bilirubin ≤2 times ULN:Temporarily withhold fruquintinib and monitor AST/ALT and total bilirubin until total resolution to grade 1 or baseline, then resume fruquintinib at the next lower dosage level.

ALT or AST >3 times ULN with concurrent total bilirubin >2 times ULN (without cholestasis or hemolysis):Permanently discontinue fruquintinib.

AST or ALT >20 times ULN or bilirubin >10 times ULN:Permanently discontinue fruquintinib.

Proteinuria

Proteinuria ≥2 grams/24 hours:Temporarily withhold fruquintinib until proteinuria fully resolves or is <1 gram/24 hours. Upon recovery of proteinuria, resume fruquintinib at the next lower dosage level.

Presence of nephrotic syndrome or if proteinuria does not recover to <1 gram/24 hours:Permanently discontinue fruquintinib.

Palmar-plantar erythrodysesthesia (PPE)

Grade 2:Temporarily withhold fruquintinib and initiate supportive care. Upon full resolution of PPE or recovery to grade 1, resume fruquintinib at the same dosage level.

Grade 3:Temporarily withhold fruquintinib and initiate supportive care. Upon full resolution of PPE or recovery to grade 1, resume fruquintinib at the next lower dosage level.

Other adverse reactions

Grade 3:Temporarily withhold fruquintinib; upon full resolution of toxicity or recovery to grade 1, resume fruquintinib at the next lower dosage level.

Grade 4: Discontinue fruquintinib. Consider resumption of fruquintinib at the next lower dosage level only if the toxicity is non-life threatening and fully resolves or recovers to grade 1 and the potential benefits of therapy outweigh the risks.

Special Populations

Hepatic Impairment

Mild hepatic impairment (total bilirubin less than or equal to ULN with AST greater than ULN, or total bilirubin >1–1.5 times ULN and any AST): No dosage adjustment necessary.

Moderate hepatic impairment (total bilirubin >1.5 times and <3 times ULN and any AST): Not adequately studied.

Severe hepatic impairment (total bilirubin >3 times ULN and any AST): Not recommended.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Fruquintinib

Contraindications

Warnings/Precautions

Hypertension

Hypertension, including hypertensive crisis, reported.

Do not initiate fruquintinib unless BP adequately controlled. Monitor BP weekly during first month of therapy, then at least once monthly and as clinically indicated. Initiate or adjust antihypertensive therapy as needed. Withhold, reduce dosage, or permanently discontinue fruquintinib based on severity of hypertension.

Hemorrhagic Events

Serious hemorrhagic events, some fatal, reported.

Permanently discontinue fruquintinib if severe or life-threatening hemorrhage occurs. Monitor INR in patients receiving anticoagulants.

Infections

Increased risk for infections, including fatal infections. Infections reported include urinary tract infections, upper respiratory tract infections, and pneumonia; fatal infections reported include pneumonia, sepsis, bacterial infection, lower respiratory tract infection, and septic shock.

Withhold fruquintinib if grade 3 or 4 infections occur, or if there is worsening infection of any grade. Upon resolution of infection, resume fruquintinib at same dosage.

Gastrointestinal Perforation

Gastrointestinal perforation reported.

Permanently discontinue fruquintinib in patients who develop GI perforation or fistula.

Hepatotoxicity

Liver injury can occur; ALT or AST increases reported.

Monitor liver function tests (ALT, AST, and bilirubin) before initiating fruquintinib and periodically during therapy. Temporarily withhold and then reduce or permanently discontinue fruquintinib based on severity and persistence of hepatotoxicity.

Proteinuria

Proteinuria reported.

Monitor for proteinuria before initiating fruquintinib and periodically during therapy. Withhold fruquintinib in patients with proteinuria ≥2 g/24 hours until improvement to grade 1 proteinuria or lower, then resume at reduced dosage. Discontinue fruquintinib if nephrotic syndrome occurs.

Palmar-plantar Erythrodysesthesia

Palmar-plantar erythrodyesthesia (PPE) reported.

Based on PPE severity, withhold fruquintinib and resume at same or reduced dosage.

Posterior Reversible Encephalopathy Syndrome

Posterior reversible encephalopathy syndrome (PRES) reported.

Evaluate for PRES in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue fruquintinib in patients who develop PRES.

Impaired Wound Healing

Potential for impaired wound healing.

Withhold fruquintinib for ≥2 weeks prior to major surgery. Withhold fruquintinib for ≥2 weeks after major surgery and until adequate wound healing. Safety of resuming fruquintinib after resolution of wound healing complications not established.

Arterial Thrombotic Events

Potential increased risk of arterial thrombotic events. Clinical trials of fruquintinib excluded patients with clinically important cardiovascular disease, uncontrolled hypertension, or prior thromboembolic events within last 6 months.

Carefully consider initiation of fruquintinib in patients with recent history of thromboembolic events. Discontinue fruquintinib if arterial thromboembolism occurs.

Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF)

Fruquintinib 1 mg capsules contain FD&C Yellow No. 5 (tartrazine), which can lead to allergic-type reactions (including bronchial asthma) in susceptible patients. Tartrazine sensitivity more frequently observed in patients who also have aspirin hypersensitivity.

Fruquintinib 1 mg capsules also contain FD&C Yellow No. 6 (sunset yellow FCF), which can cause allergic reactions.

Fetal/Neonatal Morbidity and Mortality

Can cause fetal harm based on animal data and drug mechanism of action. Embryotoxic and teratogenic effects demonstrated in animals.

Verify pregnancy status in females of reproductive potential before initiating fruquintinib. Advise pregnant women of potential fetal risk.

Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 2 weeks after the last dose.

Specific Populations

Pregnancy

May cause fetal harm based on animal data and drug mechanism of action.

No data available on use in pregnant women. Embryotoxic and teratogenic effects demonstrated in animals.

Verify pregnancy status in females of reproductive potential prior to initiating fruquintinib. Advise pregnant women of potential fetal risk.

Lactation

Not known whether fruquintinib or its metabolites present in milk. Effects on breast-fed child or on milk production also unknown.

Advise women to avoid breast-feeding during treatment and for 2 weeks following the last dose.

Females and Males of Reproductive Potential

Verify pregnancy status in females of reproductive potential prior to initiation.

No genotoxicity demonstrated in animals.

Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 2 weeks after the last dose.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

Clinical studies included patients ≥65 years of age, including those ≥75 years of age.

No overall differences in safety or effectiveness observed between geriatric and younger patients.

Hepatic Impairment

No clinically important differences in fruquintinib pharmacokinetics observed in mild hepatic impairment (total bilirubin less than or equal to ULN with AST greater than ULN, or total bilirubin >1–1.5 times ULN with any AST).

Not adequately studied in moderate hepatic impairment (total bilirubin >1.5 times and <3 times ULN and any AST).

Not recommended for use in severe hepatic impairment (total bilirubin >3 times ULN and any AST).

Effect of moderate to severe hepatic impairment on fruquintinib pharmacokinetics unknown.

Renal Impairment

No clinically important differences in fruquintinib pharmacokinetics observed in mild to moderate renal impairment (Clcr30–89 mL/minute).

Common Adverse Effects

Common adverse effects (incidence ≥20%): hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, abdominal pain, diarrhea, asthenia.

Drug Interactions

Metabolized principally by CYP3A, and to a lesser extent by CYP2C8, CYP2C9, and CYP2C19. Also metabolized via non-CYP mediated routes (i.e., sulfation, glucuronidation).

Does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A. Does not induce CYP1A2, CYP2B6, or CYP3A.

Not a substrate of P-glycoprotein (P-gp), organic anion transporting polypeptide (OATP) 1B1, or OATP1B3. Does not inhibit OATP1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, multidrug and toxin extrusion protein (MATE) 1, or MATE2-K.

Drugs Affecting Hepatic Microsomal Enzymes

Strong CYP3A Inducers

Concomitant use may decrease fruquintinib peak plasma concentration and AUC, which may reduce efficacy of fruquintinib.

Avoid concomitant use.

Moderate CYP3A Inducers

Concomitant use may decrease fruquintinib peak plasma concentration and AUC, which may reduce efficacy of fruquintinib.

If possible, avoid concomitant use. If concomitant use unavoidable, continue to administer fruquintinib at recommended dosage.

Specific Drugs

Drug

Interaction

Comments

Dabigatran etexilate

No clinically important effect on pharmacokinetics of dabigatran etexilate (P-gp substrate) observed

Efavirenz

Efavirenz (moderate CYP3A inducer) expected to decrease peak plasma concentration and AUC of fruquintinib by 4 and 32%, respectively

Avoid concomitant use if possible; if concomitant use unavoidable, continue to administer fruquintinib at recommended dosage

Itraconazole

No clinically important effect on fruquintinib pharmacokinetics observed when used concomitantly with itraconazole (strong CYP3A inhibitor)

Rabeprazole

No clinically important effect on fruquintinib pharmacokinetics observed when used concomitantly with rabeprazole (proton pump inhibitor)

Rifampin

Rifampin (strong CYP3A inducer) decreased peak plasma concentration and AUC of fruquintinib by 12 and 65%, respectively

Avoid concomitant use

Rosuvastatin

No clinically important effect on pharmacokinetics of rosuvastatin (breast cancer resistance protein [BCRP] substrate) observed

Fruquintinib Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentration and AUC dose-proportional over dosage range of 1–6 mg.

Median time to peak plasma concentration: approximately 2 hours.

Steady-state concentrations achieved after 14 days; accumulation based on AUC is 4-fold.

Food

Administration of high-fat meal (800–1000 calories, 50% fat) did not substantially affect pharmacokinetics.

Distribution

Extent

Not known whether fruquintinib or its metabolites distribute into human milk.

Plasma Protein Binding

Approximately 95%.

Elimination

Metabolism

Metabolized principally via CYP pathway (by CYP3A, and to a lesser extent by CYP2C8, CYP2C9, and CYP2C19) and non-CYP pathway (sulfation and glucuronidation).

Elimination Route

Eliminated in urine (60% [0.5% as unchanged drug]) and in feces (30% [5% as unchanged drug]).

Half-life

Approximately 42 hours.

Special Populations

Age (18–82 years), sex, race (Asian, Black, and white), ethnicity (Hispanic/Latino versus non-Hispanic/Latino), and body weight (48–108 kg) do not substantially affect pharmacokinetics.

Stability

Storage

Oral

Capsules

20–25°C; brief excursions permitted to 15–30°C.

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Fruquintinib is obtained through designated specialty pharmacies. Visit the Fruzaqla website ([Web]) for specific availability information.

Fruquintinib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

1 mg

Fruzaqla

Takeda Pharmaceuticals America

5 mg

Fruzaqla

Takeda Pharmaceuticals America

AHFS DI Essentials™. © Copyright 2025, Selected Revisions December 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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