FLUOTREX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FLUOTREX (FLUOTREX).
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.
| 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. |
| Molecular Weight | 476.45 Da |
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. |
| 1st trimester | FLUOTREX is contraindicated in the first trimester due to high risk of teratogenicity. Methotrexate, a related compound, is associated with fetal death and malformations. |
| 2nd trimester | Use is contraindicated in the second trimester as it carries risks of fetal toxicity and pregnancy loss. |
| 3rd trimester | Contraindicated in the third trimester due to risks of fetal toxicity and neonatal complications, including myelosuppression and pneumonitis. |
Clinical note
Comprehensive clinical and safety monograph for FLUOTREX (FLUOTREX).
| Placental transfer | FLUOTREX readily crosses the placenta. Methotrexate, a related antifolate, is known to cross the placenta and accumulate in fetal tissues, with transfer documented in both animal and human studies. |
| Breastfeeding | FLUOTREX is excreted into human milk at low concentrations. However, due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy. Discontinue nursing or the drug, taking into account the importance of the drug to the mother. |
■ 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.
| Serious Effects |
PregnancyBreastfeedingSevere hepatic impairmentSevere renal impairment (CrCl < 30 mL/min)Active peptic ulcer diseaseSevere bone marrow suppressionHypersensitivity to fluorouracil or any excipients
| 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 |
| Food/Dietary |
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| Lactation Rating | L5 - Contraindicated |
| 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). |
| Fetal Monitoring | Maternal: Complete blood count with differential, liver function tests, renal function tests, and serum methotrexate levels at baseline and periodically. Fetal: First-trimester ultrasound for neural tube defects, detailed anatomy scan at 18-20 weeks, and serial growth ultrasounds every 4-6 weeks. Consider amniocentesis for karyotyping if anomalies detected. |
| Fertility Effects | Reversible infertility in both sexes. In females: ovulatory dysfunction, amenorrhea, and premature ovarian failure. In males: oligospermia, azoospermia, and testicular atrophy. Effects may persist for months after discontinuation. Preconception counseling recommended. |
| Avoid alcohol completely. Limit caffeine intake as it may decrease methotrexate efficacy. Maintain adequate folate intake; folic acid supplements are often prescribed. No specific food interactions, but avoid folic acid-rich foods in excess unless directed. |
| Clinical Pearls | FLUOTREX (methotrexate) is a folate analog antimetabolite. Administer once weekly for rheumatoid arthritis or psoriasis; daily dosing can cause severe toxicity. Ensure adequate hydration and urine alkalinization to prevent renal crystallization. Monitor CBC, LFTs, and creatinine at baseline and monthly. Avoid in significant hepatic fibrosis, alcoholism, or severe renal impairment. Folic acid 1 mg daily reduces GI and hepatic side effects without compromising efficacy. Give leucovorin rescue for accidental overdose. |
| Patient Advice | Take FLUOTREX exactly as prescribed—usually once a week, not daily. · Use a calendar or reminder to keep track of your weekly dose. · Do not share this medication with others; it can be dangerous. · Avoid alcohol completely; it increases risk of liver damage. · Report signs of infection (fever, sore throat), mouth sores, cough, or unusual bleeding. · Use effective contraception during treatment and for at least 3 months after stopping. · Take folic acid as directed to help reduce side effects. · Drink plenty of fluids to help prevent kidney problems. · Avoid live vaccines while on this medication. · Keep all appointments for blood tests to monitor for toxicity. |