FLUOTREX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FLUOTREX (FLUOTREX).

How it works

The active metabolite of FLUOTREX, 5-fluorouracil (5-FU), inhibits thymidylate synthase, leading to depletion of thymidine triphosphate and inhibition of DNA synthesis. Additionally, it incorporates into RNA, disrupting RNA function.

What the body does with it

Metabolism	Primarily metabolized via the dihydropyrimidine dehydrogenase (DPD) pathway to dihydrofluorouracil (DHFU). Hepatic metabolism contributes to inactivation.
Excretion	Primarily renal excretion as unchanged drug (approximately 60-70% of administered dose), with the remainder eliminated via biliary/fecal routes (20-30%) and minor metabolic clearance.
Half-life	Terminal elimination half-life is approximately 3-5 hours in adults with normal renal function. In patients with renal impairment, half-life may be prolonged up to 10-15 hours, necessitating dose adjustment.
Protein binding	Approximately 80-90% bound to serum albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is 0.2-0.3 L/kg, indicating limited extravascular distribution, consistent with a drug that is primarily confined to the vascular and interstitial spaces.
Bioavailability	Oral bioavailability is 70-90% (with high interindividual variability due to first-pass metabolism); intramuscular bioavailability is nearly 100%.
Onset of Action	Intravenous: Within 5-10 minutes; Oral: 30-60 minutes; Intramuscular: 15-30 minutes.
Duration of Action	Therapeutic effects persist for 4-6 hours following a single dose. Clinical monitoring for efficacy and toxicity should be conducted accordingly.

Classification & Brands

Dosing & administration

20 mg/m2 intramuscularly once weekly, not to exceed 30 mg/m2 per week.

Dosage form	CREAM
Renal impairment	GFR > 50 mL/min: no adjustment; GFR 10-50 mL/min: 50% dose reduction; GFR < 10 mL/min: avoid use.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 50% dose reduction; Child-Pugh C: avoid use.
Pediatric use	15-20 mg/m2 intramuscularly once weekly, maximum 25 mg/m2.
Geriatric use	Reduce initial dose by 25-30% due to increased toxicity risk; monitor renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FLUOTREX (FLUOTREX).

Breastfeeding	Contraindicated. Excreted into breast milk; M/P ratio not established. Potential for serious adverse effects in nursing infant, including immunosuppression and gastrointestinal toxicity. Avoid breastfeeding during and for at least 1 week after last dose.
Teratogenic Risk	FDA Category D. First trimester: High risk of neural tube defects, craniofacial anomalies, and limb malformations due to folate antagonism. Second/third trimesters: Risk of intrauterine growth restriction, preterm birth, and fetal methotrexate syndrome (including developmental delay and skeletal abnormalities).

Warnings & precautions

■ FDA Black Box Warning

FLUOTREX (5-fluorouracil) should be administered under the supervision of a qualified physician experienced in cancer chemotherapy. Severe toxic reactions including myelosuppression, mucositis, and neurotoxicity have been reported. Dosage modifications are required for patients with dihydropyrimidine dehydrogenase (DPD) deficiency, which can lead to life-threatening toxicity.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known DPD deficiency (complete or near-complete absence)","Pregnancy (teratogenic)","Breastfeeding","Severe bone marrow depression (unless benefit outweighs risk)","Severe hepatic or renal impairment (relative)","Active severe infections"]

Clinical Precautions

Precautions

["Myelosuppression (neutropenia, thrombocytopenia, anemia) - monitor CBCs frequently","Gastrointestinal toxicity (mucositis, diarrhea, nausea/vomiting) - dose reduction or discontinuation","Neurotoxicity (cerebellar ataxia, confusion, encephalopathy) - more common with high doses or DPD deficiency","Cardiotoxicity (angina, myocardial ischemia, arrhythmias)","Hand-foot syndrome (palmar-plantar erythrodysesthesia)","Hepatotoxicity (elevated transaminases, bilirubin)","Dermatologic reactions (photosensitivity, rash)","Immunosuppression leading to infection"]

Clinical Tips & Counseling

Drug interactions

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FLUOTREX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FLUOTREX (FLUOTREX).

How it works

What the body does with it

Metabolism	Primarily metabolized via the dihydropyrimidine dehydrogenase (DPD) pathway to dihydrofluorouracil (DHFU). Hepatic metabolism contributes to inactivation.
Excretion	Primarily renal excretion as unchanged drug (approximately 60-70% of administered dose), with the remainder eliminated via biliary/fecal routes (20-30%) and minor metabolic clearance.
Half-life	Terminal elimination half-life is approximately 3-5 hours in adults with normal renal function. In patients with renal impairment, half-life may be prolonged up to 10-15 hours, necessitating dose adjustment.
Protein binding	Approximately 80-90% bound to serum albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is 0.2-0.3 L/kg, indicating limited extravascular distribution, consistent with a drug that is primarily confined to the vascular and interstitial spaces.
Bioavailability	Oral bioavailability is 70-90% (with high interindividual variability due to first-pass metabolism); intramuscular bioavailability is nearly 100%.
Onset of Action	Intravenous: Within 5-10 minutes; Oral: 30-60 minutes; Intramuscular: 15-30 minutes.
Duration of Action	Therapeutic effects persist for 4-6 hours following a single dose. Clinical monitoring for efficacy and toxicity should be conducted accordingly.

Classification & Brands

Dosing & administration

20 mg/m2 intramuscularly once weekly, not to exceed 30 mg/m2 per week.

Dosage form	CREAM
Renal impairment	GFR > 50 mL/min: no adjustment; GFR 10-50 mL/min: 50% dose reduction; GFR < 10 mL/min: avoid use.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 50% dose reduction; Child-Pugh C: avoid use.
Pediatric use	15-20 mg/m2 intramuscularly once weekly, maximum 25 mg/m2.
Geriatric use	Reduce initial dose by 25-30% due to increased toxicity risk; monitor renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FLUOTREX (FLUOTREX).

Breastfeeding	Contraindicated. Excreted into breast milk; M/P ratio not established. Potential for serious adverse effects in nursing infant, including immunosuppression and gastrointestinal toxicity. Avoid breastfeeding during and for at least 1 week after last dose.
Teratogenic Risk	FDA Category D. First trimester: High risk of neural tube defects, craniofacial anomalies, and limb malformations due to folate antagonism. Second/third trimesters: Risk of intrauterine growth restriction, preterm birth, and fetal methotrexate syndrome (including developmental delay and skeletal abnormalities).