FRUZAQLA

/ Takeda

The recommended dose of fruquintinib is 5 mg orally once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity.

For treatment of adult patients 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.
See prescribing information for full details.

Hypersensitivity to the active substance or to any of the excipients

Hypertension

FRUZAQLA can cause hypertension. Hypertension occurred in 450 of 911 (49%) patients with mCRC treated with FRUZAQLA, including Grade 3-4 events in 19%, and hypertensive crisis in three patients (0.3%). The median time to first onset of hypertension was 14 days from first dose of FRUZAQLA. Do not initiate FRUZAQLA unless blood pressure is adequately controlled. Monitor blood pressure
weekly the first month, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue FRUZAQLA based on the severity of hypertension
Hemorrhagic Events

FRUZAQLA can cause serious hemorrhagic events, which may be fatal. In 911 patients with mCRC treated with FRUZAQLA, 6% of patients experienced a gastrointestinal hemorrhage, including 13 patients (1%) with a Grade ≥3 event and 2 patients with fatal hemorrhages.
Permanently discontinue FRUZAQLA in patients with severe or life-threatening hemorrhage. Monitor the International Normalized Ratio (INR) levels in patients receiving anticoagulants
Infections
FRUZAQLA can cause an increased risk of infections, including fatal infections.
In 911 patients with mCRC treated with FRUZAQLA, the most common infections were urinary tract infections (6.8%), upper respiratory tract infections (3.2%) and pneumonia (2.5%); fatal infections included pneumonia (0.4%), sepsis (0.2%), bacterial infection (0.1%), lower respiratory tract infection (0.1%), and septic shock (0.1%). Withhold FRUZAQLA for Grade 3 or 4 infections, or worsening infection of any grade. Resume FRUZAQLA at the same dose when the infection has resolved.
Gastrointestinal Perforation
FRUZAQLA can cause gastrointestinal perforation. In 911 patients with mCRC treated with FRUZAQLA, 12 patients (1.3%) experienced a Grade ≥3 gastrointestinal perforation, including one fatal event. Permanently discontinue FRUZAQLA in patients who develop gastrointestinal perforation or fistula.
Hepatotoxicity
FRUZAQLA can cause liver injury. In 911 patients with mCRC treated with FRUZAQLA, 48% experienced increased ALT or AST, including Grade ≥3 events in 5%, and fatal events in 0.2%. Median time to first onset of elevated liver enzymes was 29 days from first dose of FRUZAQLA. Monitor liver function tests (ALT, AST, and bilirubin) before initiation and periodically throughout treatment with FRUZAQLA. Temporarily hold and then reduce or permanently discontinue FRUZAQLA depending on the severity and persistence of hepatotoxicity as manifested by elevated
liver function tests.
Proteinuria
FRUZAQLA can cause proteinuria. In 911 patients with mCRC treated with FRUZAQLA, 36% experienced proteinuria and 2.5% of patients experienced Grade ≥3 events. Median time to first onset of proteinuria was 22 days from first dose of FRUZAQLA.
Monitor for proteinuria before initiation and periodically throughout treatment with FRUZAQLA. For proteinuria ≥2 g/24 hours, withhold FRUZAQLA until improvement to ≤Grade 1 proteinuria, resume FRUZAQLA at a reduced dose. Discontinue FRUZAQLA in patients who develop nephrotic syndrome.
Palmar-Plantar Erythrodysesthesia (PPE)
FRUZAQLA can cause PPE. In 911 patients with mCRC treated with FRUZAQLA, PPE occurred in 35%, including 8% with Grade 3 events. Median time to first onset of PPE was 19 days from first dose of FRUZAQLA.
Based on severity, withhold FRUZAQLA and then resume at the same or reduced dose.
Posterior Reversible Encephalopathy Syndrome (PRES)
FRUZAQLA can cause PRES, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI. PRES occurred in one of 911 patients with mCRC treated with FRUZAQLA.
Perform an evaluation for PRES in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue FRUZAQLA in patients who develop PRES.
Impaired Wound Healing
Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. In 911 patients with mCRC treated with FRUZAQLA, 1 patient experienced a Grade 2 event of wound dehiscence.
Do not administer FRUZAQLA for at least 2 weeks prior to major surgery. Do not administer FRUZAQLA for at least 2 weeks after major surgery and until adequate wound healing.
Arterial Thromboembolic Events
Initiation of FRUZAQLA in patients with a recent history of thromboembolic events should be carefully considered. In patients who develop arterial thromboembolism discontinue FRUZAQLA.
See prescribing information for full details.

clinically significant adverse reactions: hypertension, hemorrhagic events, infections, gastrointestinal perforation, hepatotoxicity, proteinuria, Palmar-Plantar Erythrodysesthesia (PPE), Posterior Reversible Encephalopathy Syndrome (PRES).
See prescribing information for full details.

Pregnancy: There are no data on the use of FRUZAQLA in pregnant women. Advise pregnant women of the potential risk to a fetus.
Verify pregnancy status of females of reproductive potential prior to initiating FRUZAQLA.
Contraception
Females of childbearing potential and males with female partners of childbearing potential should use effective contraception during treatment and for 2 weeks after the last dose of FRUZAQLA.
Lactation: There are no data regarding the presence of fruquintinib or its metabolites in human milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with FRUZAQLA and for 2 weeks after the last dose.