Fruquintinib was developed during the 2010s as a targeted anticancer drug for the treatment of metastatic colorectal cancer. It was first approved in China in 2018 under the brand name Elunate and later received approval from the United States Food and Drug Administration (FDA) on November 8, 2023, under the brand name Fruzaqla. Its development focused on selectively inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2 and VEGFR-3), thereby blocking tumour angiogenesis and restricting tumour growth. Its approval was supported by clinical trials demonstrating improved overall survival and progression-free survival in patients with previously treated metastatic colorectal cancer.
BRAND NAMES
Fruzaqla® – The internationally recognized brand name of fruquintinib, approved by the US FDA in 2023 for previously treated metastatic colorectal cancer.
Elunate® – The original Chinese brand name of fruquintinib, first approved in China in 2018 for the treatment of metastatic colorectal cancer.
MECHANISM OF ACTION
It inhibits VEGF-mediated signalling, thereby preventing the formation of new blood vessels (angiogenesis) that supply oxygen and nutrients to tumour cells. This reduces tumour blood supply, inhibits cancer cell growth and proliferation, and slows tumour progression, particularly in metastatic colorectal cancer.
PHARMACOKINETICS
Absorption
Fruquintinib is administered orally and is well absorbed from the gastrointestinal tract. It reaches peak plasma concentration (Tmax) approximately 2 hours after administration. Food does not significantly affect its absorption, so it can be taken with or without food. It has an absolute bioavailability of approximately 30%.
Distribution
Fruquintinib is widely distributed throughout the body and has a large apparent volume of distribution. It is highly bound to plasma proteins (approximately 95%), mainly albumin. It reaches tumour tissues, where it inhibits VEGFR activity and reduces the formation of new blood vessels, thereby restricting tumour growth.
Metabolism
Fruquintinib is primarily metabolized in the liver by cytochrome P450 enzymes, mainly CYP3A4. It undergoes oxidation and other metabolic reactions to form several metabolites. Its metabolism may be affected by drugs that inhibit or induce CYP3A4, which can alter its blood concentration and therapeutic effects.
Elimination
Fruquintinib is eliminated mainly through feces and, to a lesser extent, through urine. It is excreted primarily as metabolites, with a small amount eliminated unchanged. Its terminal elimination half-life is approximately 42 hours, allowing once-daily administration.
PHARMACODYNAMICS
It blocks VEGFR-1, VEGFR-2 and VEGFR-3, thereby inhibiting angiogenesis (formation of new blood vessels). This reduces the supply of oxygen and nutrients to tumour cells, suppresses tumour growth and progression, and helps control metastatic colorectal cancer.
ADMINISTRATION
Fruquintinib is administered orally in the form of capsules, usually once daily for 21 consecutive days, followed by 7 days without treatment, completing a 28-day treatment cycle. It can be taken with or without food and should be swallowed whole with water.. Regular monitoring of blood pressure, liver function and urine protein is recommended during treatment.
DOSAGE AND STRENGTH
Fruquintinib is available as oral capsules in strengths of 1 mg and 5 mg. The recommended adult dose is 5 mg once daily for 21 consecutive days, followed by 7 days without treatment, completing a 28-day cycle. Dosage may be reduced to 4 mg or 3 mg once daily depending on the patient's tolerance and adverse effects.
DRUG INTERACTIONS
Fruquintinib may interact with drugs that affect the CYP3A4 enzyme system. Strong CYP3A4 inhibitors, such as ketoconazole and clarithromycin, may increase fruquintinib levels and the risk of toxicity, while CYP3A4 inducers, such as rifampicin and carbamazepine, may reduce its effectiveness. Concurrent use with anticoagulants and antiplatelet drugs may increase the risk of bleeding. Therefore, careful monitoring is recommended during treatment.
FOOD INTERACTIONS
Fruquintinib can be taken with or without food, as food does not significantly affect its absorption. Grapefruit and grapefruit juice should be avoided because they may interfere with drug metabolism and potentially increase drug levels. Patients are advised to maintain a balanced diet, avoid herbal supplements that affect CYP3A4 activity, and take the medication at the same time each day.
CONTRAINDICATIONS
It should be avoided during pregnancy due to the risk of fetal harm. Caution is required in patients with severe liver impairment, uncontrolled hypertension, active bleeding, recent surgery and impaired wound healing. It is not recommended during breastfeeding, and careful monitoring is necessary in patients with cardiovascular disorders.
SIDE EFFECTS
Hypertension (high blood pressure).
Fatigue and weakness.
Diarrhea.
Nausea and vomiting.
Loss of appetite.
Abdominal pain.
Hand-foot syndrome (palmar-plantar erythrodysesthesia).
Proteinuria (protein in urine).
OVER DOSAGE
Management involves immediate discontinuation of the drug, monitoring of blood pressure and liver function, and providing appropriate supportive and symptomatic treatment. There is no specific antidote for fruquintinib overdose.
TOXICITY
Fruquintinib toxicity may cause severe hypertension, hepatotoxicity, proteinuria, bleeding and delayed wound healing. Other toxic effects include diarrhea, fatigue, hand-foot syndrome and gastrointestinal disturbances. Regular monitoring of blood pressure, liver function and urine protein is essential to prevent serious complications.
