Fruquintinib

Fruquintinib is a prescription medication indicated for the treatment of adults with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy, and, if RAS wild-type and medically appropriate, an anti-epidermal growth factor receptor therapy.

• Fruquintinib is available under the following different brand names: Fruzaqla

Common side effects of Fruquintinib include:

• voice changes or hoarseness
• diarrhea
• stomach-area (abdominal) pain 
• weakness, lack of strength and energy, and feeling very tired or sleepy (asthenia)

Serious side effects of Fruquintinib include:

• high blood pressure (hypertension)
• severe bleeding (hemorrhage)
• protein in your urine (proteinuria)
• hand-foot skin reactions
• posterior reversible encephalopathy syndrome
• wound healing problems
• blood clots in your blood vessels
• liver problems such as yellowing of the skin or the white part of the eyes, loss of appetite, nausea or vomiting, dark colored (tea-colored) urine, bleeding or bruising, pain in the right upper stomach area

Rare side effects of Fruquintinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 1 mg
• 5 mg

Colorectal cancer

Adult dosage

• Each cycle is 28 days
• 5 mg orally once a day on the first 21 days of each cycle
• Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Fruquintinib has severe interactions with no other drugs
• Fruquintinib has serious interactions with at least 42 other drugs
• Fruquintinib has moderate interactions with the following drug:
  • warfarin
• Fruquintinib has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Fruquintinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Fruquintinib?”

Cautions

• May cause serious hemorrhagic events, which may be fatal; permanently discontinue if severe or life-threatening hemorrhaging occurs; monitor international normalized ratio levels in patients receiving anticoagulants
• Increased risk for infections, including fatal ones, reported; withhold for Grade 3 or 4 infections, or worsening infection of any grade, then resume at the same dose after the 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 the same or reduced dose
• Posterior reversible encephalopathy syndrome (PRES) reported; PRES is a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI; evaluate for PRES if seizures, headache, visual disturbances, confusion, or altered mental function develop; discontinue if PRES develops
• May increase the risk for arterial thromboembolic events; carefully consider initiating the drug in patients with a 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 the drug’s mechanism of action, fetal harm may occur if fruquintinib is administered to pregnant women
• Hypertension
  • Fruquintinib may cause hypertension
  • The median time from the first dose to hypertension onset was 14 days
  • Do not initiate unless blood pressure (BP) is adequately controlled
  • Monitor BP weekly for the 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
  • The median time from the first dose to the 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 the severity and persistence of hepatotoxicity
• Impaired wound healing
  • Impaired wound healing can occur in patients who receive VEGF signaling pathway inhibitors
  • Do not administer for at least 2 weeks before a major surgery
  • Do not administer for at least 2 weeks after a major surgery and until adequate wound healing
  • The safety of resuming treatment after wound healing complications are resolved 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 the recommended dosage
  • Strong or moderate CYP3A inducers may decrease Fruquintinib levels and efficacy

Pregnancy and Lactation

• Based on animal studies and the drug’s mechanism of action, fetal harm may occur when administered to pregnant women
• Contraception
• Women of childbearing potential and males with female partners of childbearing potential: Use effective contraception during treatment and for 2 weeks after the last dose
• Lactation
  • No data are available regarding the presence of fruquintinib or its metabolites in human milk and its effects on a breastfed child or milk production
  • Advise women not to breastfeed during treatment and for 2 weeks after the last dose