Version July 2025
Dosage guidance:
Safety: Do not initiate fruquintinib unless BP is adequately controlled. Temporarily withhold fruquintinib for ≥2 weeks prior to major surgery; do not resume fruquintinib for ≥2 weeks after major surgery and until adequate wound healing has occurred.
Colorectal cancer, metastatic : Oral: 5 mg once daily on days 1 to 21 of each 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Missed doses: Administer a missed dose if <12 hours have passed since scheduled dose; do not administer 2 doses on the same day to make up for a missed dose. Do not administer an additional dose if vomiting occurs after fruquintinib administration; resume with the next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney function impairment prior to treatment initiation :
Note: Kidney function estimated by the Cockcroft-Gault equation.
CrCl ≥15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in fruquintinib pharmacokinetics were observed.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
Acute kidney toxicity during treatment:
Proteinuria (≥2 g in 24 hours): Withhold fruquintinib until proteinuria fully resolves or is <1 g in 24 hours; resume fruquintinib at the next lower dose level.
Nephrotic syndrome or if proteinuria does not recover to <1 g in 24 hours: Permanently discontinue fruquintinib.
Hepatic impairment prior to treatment initiation:
Mild (total bilirubin ≤ ULN with AST > ULN or total bilirubin >1 to 1.5 times ULN with any AST) impairment: No dosage adjustment necessary.
Moderate (total bilirubin >1.5 to <3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Severe (total bilirubin >3 times ULN and any AST): Use is not recommended (has not been studied).
Acute hepatotoxicity during treatment:
AST or ALT >3 times ULN or >3 times baseline (if baseline was abnormal) or total bilirubin >1.5 times ULN or >1.5 times baseline (if baseline was abnormal): Withhold fruquintinib and monitor AST, ALT, and total bilirubin until resolution to ≤ grade 1 or baseline; resume therapy at next lower dose level.
AST or ALT >3 times ULN with concurrent total bilirubin >2 times ULN (without cholestasis or hemolysis): Permanently discontinue fruquintinib.
AST or ALT >20 times ULN (if baseline was normal) or >20 times baseline (if baseline was abnormal) or total bilirubin >10 times ULN (if baseline was normal) or >10 times baseline (if baseline was abnormal): Permanently discontinue fruquintinib.
|
Dosage reduction level |
Recommended fruquintinib dosage and schedule |
|---|---|
|
Initial (usual) dosage |
5 mg once daily |
|
First dosage reduction |
4 mg once daily |
|
Second dosage reduction |
3 mg once daily |
|
Subsequent modification |
If unable to tolerate 3 mg once daily, permanently discontinue fruquintinib. |
|
Adverse reaction |
Severity |
Fruquintinib dosage modification |
|---|---|---|
|
Dermatologic toxicity: Palmar-plantar erythrodysesthesia |
Grade 2 |
Withhold fruquintinib and initiate supportive treatment. If toxicity fully resolves or recovers to grade 1, resume fruquintinib at the same dose level. |
|
Grade 3 |
Withhold fruquintinib and initiate supportive treatment. If toxicity fully resolves or recovers to grade 1, resume fruquintinib at the next lower dose level. | |
|
GI perforation/fistula |
Any |
Permanently discontinue fruquintinib. |
|
Hemorrhage |
Grade 2 |
Withhold fruquintinib until bleeding fully resolves or recovers to grade 1; resume fruquintinib at the next lower dose level. |
|
Grade 3 or 4 (severe or life-threatening) |
Permanently discontinue fruquintinib. | |
|
Hypertension |
Grade 3 |
Initiate or adjust anti-hypertensive therapy as appropriate. Withhold fruquintinib for persistent grade 3 hypertension despite optimal anti-hypertensive therapy. If hypertension fully resolves or recovers to grade 1, resume fruquintinib at the next lower dose level. |
|
Grade 4 |
Initiate or adjust anti-hypertensive therapy as appropriate. Permanently discontinue fruquintinib. | |
|
Infection |
Grade 3 or 4, or worsening infection of any grade |
Withhold fruquintinib until infection has resolved; resume fruquintinib at the same dose level. |
|
Posterior reversible encephalopathy syndrome |
Suspected |
Perform an evaluation in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental status. |
|
Confirmed |
Permanently discontinue fruquintinib. | |
|
Thromboembolism (arterial) |
Any |
Permanently discontinue fruquintinib. |
|
Wound healing complications |
Any |
The safety of resuming fruquintinib after resolution of wound healing complications has not been established. |
|
Other toxicity |
Grade 3 |
Withhold fruquintinib. If toxicity fully resolves or recovers to grade 1, resume fruquintinib at the next lower dose level. |
|
Grade 4 |
Discontinue fruquintinib. If toxicity is non-life threatening, fully resolves or recovers to grade 1, and the potential benefits outweigh risks, consider resuming fruquintinib at the next lower dose level. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Hypertension (38% to 61%)
Dermatologic: Palmar-plantar erythrodysesthesia (19% to 49%)
Endocrine & metabolic: Decreased serum albumin (35%), decreased serum calcium (25%), decreased serum magnesium (20%), decreased serum potassium (22%), decreased serum sodium (33% to 35%), hypercholesterolemia (37%), hypothyroidism (17% to 21%), increased serum glucose (43%), increased serum triglycerides (53%), increased uric acid (26%)
Gastrointestinal: Abdominal pain (25% to 29%), anorexia (21%), diarrhea (24% to 25%; grades 3/4: 4%), stomatitis (31% to 33%; grades 3/4: ≤2%)
Genitourinary: Proteinuria (18% to 55%)
Hematologic & oncologic: Decreased platelet count (29% to 30%; grades 3/4: ≤4%), hemorrhage (2% to 28%; grades 3/4: 1%), prolonged partial thromboplastin time (21%; grades 3/4: 3%)
Hepatic: Increased serum alanine aminotransferase (33% to 34%), increased serum alkaline phosphatase (20% to 40%), increased serum aspartate aminotransferase (36% to 42%), increased serum bilirubin (30% to 39%)
Infection: Infection (18%; including bacterial infection, sepsis, septic shock)
Nervous system: Fatigue (25% to 53%), voice disorder (18% to 38%)
Neuromuscular & skeletal: Arthralgia (11% to 13%), back pain (15%), musculoskeletal pain (16% to 22%)
Renal: Increased serum creatinine (87%)
1% to 10%:
Dermatologic: Skin rash (9%)
Gastrointestinal: Gastrointestinal fistula (≤2%), gastrointestinal hemorrhage (2%), gastrointestinal perforation (≤2%), increased pancreatic enzymes (4%), intestinal obstruction (3%), rectal pain (4%)
Genitourinary: Urinary tract infection (5% to 9%)
Respiratory: Epistaxis (4%), pharyngitis (10%), pneumonia (2% to 3%), respiratory tract infection (including lower respiratory tract infection, upper respiratory tract infection [3% to 5%])
<1%:
Gastrointestinal: Pancreatitis
Hematologic & oncologic: Thrombotic microangiopathy
Nervous system: Posterior reversible encephalopathy syndrome
Frequency not defined:
Cardiovascular: Arterial thromboembolism, hypertensive crisis
Nervous system: Asthenia
Miscellaneous: Wound dehiscence
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to fruquintinib or any component of the formulation.
Concerns related to adverse effects:
• Dermatologic toxicity: Skin reactions, including palmar-plantar erythrodysesthesia (PPE) with grade 3 events, may occur with fruquintinib. Median time to onset of PPE from first dose of fruquintinib was 19 days.
• GI perforation: GI perforation has occurred in a small number of patients treated with fruquintinib; some cases were ≥ grade 3 or fatal.
• Hemorrhage: Severe or life-threatening hemorrhage may occur with fruquintinib; some cases were fatal.
• Hepatotoxicity: Fruquintinib may cause hepatic dysfunction and liver injury. Elevations of AST or ALT occurred in approximately half of patients treated with fruquintinib in clinical trials; ≥ grade 3 and fatal events occurred rarely. Median time to onset of elevated liver enzymes from first dose of fruquintinib was 29 days.
• Hypertension: Elevated BP was observed in ~50% of patients treated with fruquintinib. Grade 3 or 4 elevations of BP and hypertensive crisis have been observed. Median time to onset of hypertension from first dose of fruquintinib was 14 days.
• Infection: An increased risk of infection, including fatal infections, was observed in fruquintinib-treated patients in clinical trials when compared to placebo. The most commonly observed infections were urinary tract infections, upper respiratory infections, and pneumonia. Fatal infections included pneumonia, sepsis/septic shock, bacterial infection, and lower respiratory tract infection.
• Proteinuria: Fruquintinib is associated with an increased risk of proteinuria, including ≥ grade 3 events. Median time to onset of proteinuria from first dose of fruquintinib was 22 days.
• Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome, a syndrome of subcortical vasogenic edema diagnosed via characteristic finding on MRI, occurred very rarely with fruquintinib.
• Thromboembolism: Fruquintinib may be associated with an increased risk of arterial thromboembolic events. Clinical trials of fruquintinib excluded patients with clinically significant cardiovascular disease, uncontrolled hypertension, or with thromboembolic events within the prior 6 months. Carefully consider initiation of fruquintinib in patients with recent history of thromboembolic events.
• Wound healing complications: Medications that inhibit the vascular endothelial growth factor (VEGF) signaling pathway are associated with impaired wound healing. The safety of resuming fruquintinib after resolution of wound healing complications has not been established.
Dosage form specific issues:
• Yellow dye: Fruquintinib 1 mg capsules contain FD&C Yellow No. 5 (tartrazine) and No. 6 (sunset yellow FCF). Tartrazine may cause allergic-type reactions, including bronchial asthma; tartrazine sensitivity is frequently observed in patients who also have aspirin hypersensitivity. FD&C Yellow No. 6 may also cause allergic reactions.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Fruzaqla: 1 mg [contains corn starch, fd&c yellow #5 (tartrazine), fd&c yellow #6 (sunset yellow)]
Fruzaqla: 5 mg [contains corn starch, fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
No
Capsules (Fruzaqla Oral)
1 mg (per each): $369.03
5 mg (per each): $1,476.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Fruzaqla: 1 mg [contains corn starch, fd&c yellow #5 (tartrazine), fd&c yellow #6 (sunset yellow)]
Fruzaqla: 5 mg [contains corn starch, fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Fruquintinib is available through specialty pharmacies and various specialty institutions/accounts. Examples from the manufacturer may be found at: https://www.fruzaqlahcp.com/sites/default/files/resources/access-guide.pdf.
Oral: Administer with or without food at approximately the same time each day. Swallow capsules whole.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Fruquintinib may cause developmental toxicity (including teratogenicity), reproductive toxicity, and has structural and/or toxicity profiles similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Colorectal cancer, metastatic: Treatment (as a single agent) of metastatic colorectal cancer in adults who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy (if RAS wild type and medically appropriate).
Fruquintinib may be confused with fedratinib, futibatinib, fostamatinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP2C19 (Minor), CYP2C8 (Minor), CYP2C9 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Bisphosphonate Derivatives: Angiogenesis Inhibitors (Systemic) may increase adverse/toxic effects of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: Monitor
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Fruquintinib. Management: Avoid this combination when possible. If combined, continue the same fruquintinib dose, but monitor for reduced fruquintinib efficacy. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Strong): May decrease serum concentration of Fruquintinib. Risk X: Avoid
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to treatment initiation.
Patients who could become pregnant should use effective contraception during therapy and for 2 weeks after the last dose of fruquintinib. Patients with partners who could become pregnant should also use effective contraception during therapy and for 2 weeks after the last dose of fruquintinib.
Adverse effects to fertility were observed in animal toxicology studies; data are lacking on possible fertility effects in humans.
Based on the mechanism of action and data from animal reproduction studies using doses lower than the recommended human dose (based on BSA), in utero exposure to fruquintinib may cause fetal harm.
It is not known if fruquintinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 2 weeks after the last dose of fruquintinib.
Obtain liver function tests (AST, ALT, and total bilirubin) and evaluate for the presence of proteinuria at baseline and periodically during treatment. Monitor INR in patients receiving anticoagulants. Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Monitor BP weekly in the first month, at least monthly thereafter and as clinically indicated. Monitor for signs/symptoms of dermatologic toxicity (palmar-plantar erythrodysesthesia), GI perforation/fistula, hemorrhage, hepatotoxicity, uncontrolled hypertension, impaired wound healing, infection, posterior reversible encephalopathy syndrome (seizures, headache, visual disturbances, confusion, or altered mental status; evaluate with MRI), and thromboembolic (arterial) events. Monitor adherence.
Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]). BP at each clinical visit (as well as daily home monitoring for first cycle, after dose increases, and every 2 to 3 weeks thereafter); baseline echocardiography in high- and very high-risk patients (repeat every 3 months during the first year and every 6 to 12 months thereafter); consider baseline echocardiography in low- and moderate-risk patients (consider repeating every 4 months during the first year for moderate-risk patients and every 6 to 12 months thereafter) (ESC [Lyon 2022]).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow up.
Fruquintinib is a potent, highly selective, small molecule kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3, which are key regulators of angiogenesis associated with tumor growth and metastasis. Through inhibition of VEGFR, fruquintinib has demonstrated through in vitro and in vivo analyses to inhibit VEGF-mediated endothelial cell proliferation, tubular formation, VEGFR-2 phosphorylation, and tumor growth (Dasari 2023; Li 2018; manufacturer's labeling).
Distribution: Vd: ~46 L.
Protein binding: ~95% to plasma proteins.
Metabolism: Hepatic via CYP450 (CYP3A and to a lesser extent CYP2C8, CYP2C9, and CYP2C19) and non-CYP450 mechanisms (eg, sulfation and glucuronidation).
Half-life elimination: ~42 hours.
Time to peak: Median: ~2 hours.
Excretion: Urine (~60%, 0.5% as unchanged drug); Feces (30%, 5% as unchanged drug).
Clearance: 14.8 mL/minute.
