fruquintinib

Absorption: Extent of absorption unknown.

Distribution: Well distributed to extravascular tissues.

Protein Binding: 95%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme, and to a lesser extent by the CYP2C8, CYP2C9, and CYP2C19 isoenzymes. Primarily excreted in the urine (60%) as metabolites, with 30% being excreted in the feces (5% as unchanged drug).

Half-Life: 42 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Uncontrolled hypertension;
Cardiovascular disease;
History of thromboembolism;
Aspirin hypersensitivity (contains tartrazine);
Moderate hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension

Derm: palmar plantar erythrodysesthesia, impaired wound healing, rash

EENT: dysphonia, throat pain

Endo: hyperglycemia, hypothyroidism

F and E: hypocalcemia, hypokalemia, hypomagenesemia, hyponatremia

GI: ↑liver enzymes, abdominal pain, anorexia, diarrhea, hepatotoxicity, hyperbilirubinemia, hypoalbuminemia, stomatitis, GI PERFORATION

GU: ↑serum creatinine, proteinuria

Hemat: ↑activated partial thromboplastin time, anemia, bleeding, lymphopenia, thrombocytopenia, ARTERIAL THROMBOEMBOLIC EVENTS

Metab: hypercholesterolemia, hypertriglyceridemia, hyperuricemia

MS: arthralgia, pain

Neuro: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

Misc: fatigue, infection, HYPERSENSITIVITY REACTIONS, proctalgia

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inducers, including rifampin, may significantly ↓ levels and effectiveness; avoid concurrent use.
Moderate CYP3A inducers, including efavirenz, may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 5 mg once daily for 21 days of each 28-day cycle; continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Capsules: 1 mg; 5 mg

Assessment ⬆ ⬇

Monitor and control BP prior to and during therapy. Assess weekly during the 1st mo, at least monthly thereafter, and then as clinically indicated. Manage with antihypertensives and adjustment of dose. If Grade 3 hypertension persists despite optimal antihypertensive therapy, hold therapy; when hypertension ≤Grade 1, resume at next ↓ dose. If Grade 4 occurs, permanently discontinue fruquintinib.
Monitor for easy bruising and bleeding, especially from the GI tract. If Grade 2 hemorrhage occurs, hold therapy until bleeding resolves or recovers to ≤Grade 1; then resume at next lower ↓ dose. If Grade 3 or 4 hemorrhage occurs, permanently discontinue fruquintinib.
Monitor for signs and symptoms of infection, especially of the urinary and respiratory tracts. If any infection worsens or Grade 3 or 4 infection occurs, hold therapy; then resume at same dose when infection has resolved.
Monitor for signs and symptoms of GI perforation and fistula during therapy. If GI perforation or fistula occurs, permanently discontinue fruquintinib.
Assess for signs and symptoms of palmar-plantar erythrodysesthesia (swelling, skin color change, pain or blisters to palms or plantar surfaces). If Grade 2 or 3 symptoms occur, hold therapy and provide supportive treatment. If Grade 2 symptoms resolve to ≤Grade 1, resume at same dose. If Grade 3 symptoms resolve to ≤Grade 1, resume at next ↓ dose.
Monitor for signs and symptoms of PRES (headache, seizure, lethargy, confusion, blindness, mild hypertension). If PRES confirmed, permanently discontinue fruquintinib.
Monitor for signs and symptoms of arterial thromboembolic events (MI, stroke). If thromboembolism occurs, permanently discontinue fruquintinib.
Monitor for hypersensitivity reactions, especially in patients with known aspirin or food dye allergies.

Lab Test Considerations:

Verify negative pregnancy status prior to starting therapy.
Monitor ALT, AST, and bilirubin before initiation and periodically throughout therapy. If ALT or AST >3 times upper limit of normal (ULN) and bilirubin ≤2 times ULN, hold therapy; monitor until ≤Grade 1; then resume at next lower ↓ dose. If ALT or AST >3 times ULN and bilirubin >2 times ULN in the absence of cholestasis or hemolysis, permanently discontinue fruquintinib. If ALT or AST >20 times ULN or bilirubin >10 times ULN, permanently discontinue fruquintinib.
Obtain baseline and periodic urinalysis; perform 24-hr urine protein as indicated. If proteinuria ≥2 g/24 hr, hold therapy until improved to <1 g/24 hr; then resume at next ↓ dose. If nephrotic syndrome occurs or proteinuria does not recover to <1 g/24 hr, permanently discontinue fruquintinib.
Monitor INR as clinically indicated and in patients on warfarin.

Implementation ⬆ ⬇

May impair wound healing. Hold fruquintinib ≥2 wk prior to and ≥2 wk after major surgery, and until adequate wound healing.
Recommended Dose Reductions: 1st dose reduction: 4 mg orally once daily. 2nd dose reduction: 3 mg orally once daily. Permanently discontinue fruquintinib if unable to tolerate 3 mg once daily.
PO: Administer without regard to food and at approximately the same time each day. DNC: Swallow capsules whole; do not crush or open.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Instruct patient to take missed doses as soon as remembered; if <12 hr before next dose, omit dose.
Advise patient to notify health care professional immediately if signs and symptoms of liver problems (yellowing of skin or whites of eyes, dark urine, tiredness, right upper abdominal pain); heart attack or stroke (chest pain or pressure; pain in arms, back, neck, or jaw; shortness of breath; numbness or weakness on one side of body; trouble talking; headache; dizziness); easy bleeding or bruising; wounds that do not heal; GI perforation or fistula (abdominal pain and bloating, hematemesis, tarry stools); PRES (headache, seizure, confusion, ↑ BP, loss of speech, visual changes); changes to skin on palms or bottom of feet; or severe infections occur.
Advise patient to notify health care professional of ↑ urination or if swelling of face, arms, legs or feet occurs.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential and male patients with partners of reproductive potential to use effective contraception during and for 2 wk after therapy. Notify health care professional immediately if pregnancy is suspected. Advise patient to avoid breastfeeding during therapy and for 2 wk after final dose of fruquintinib.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇