Dosing and uses of Adrucil (fluorouracil)
Adult dosage forms and strengths
injectable solution
- 50mg/mL
Cancers of Colon, Breast, Ovary, Liver, Pancreas, Rectum, Stomach
Various protocols exist
500 mg/sq.meter IV on Days 1-5, Or
450-600 mg/sq.meter IV weekly, Or
200-400 mg/sq.meter IV continuous infusion qd
Not to exceed 800 mg/day
Glioblastoma Multiforme (Orphan)
Orphan indication sponsor
- Ethypharm SA; 194 Bureaux de la Colline - Batiment D; 92213 Saint-Cloud Cedex
Advanced Colorectal Carcinoma (Orphan)
Use in combination with recombinant interferon alpha-2a
Orphan indication sponsor
- Hoffmann-La Roche, Inc; 340 Kingsland Street; Nutley, NJ 07110-1199
Esophageal Carcinoma (Orphan)
Use in combination with recombinant interferon alpha-2a
Orphan indication sponsor
- Hoffmann-La Roche, Inc; 340 Kingsland Street; Nutley, NJ 07110-1199
Other Information
May use leucovorin concomitantly
Monitor: CBC
Other Indications & Uses
Off-label use for cervical, bladder, hepatic, prostate, endometrial, and head and neck carcinoma
Pediatric dosage forms and strengths
Safety & efficacy not established
Adrucil (fluorouracil) adverse (side) effects
1-10%
Loss of appetite
Headache
Nausea
Vomiting
Diarrhea
Mucositis
Myelosuppression
Alopecia
Photosensitivity
Hand-foot syndrome
Maculopapular eruption (pruritic)
Frequency not defined
Angina
Coronary arteriosclerosis
Thrombophlebitis
Darkening of veins
Gastrointestinal ulcer
Increased alkaline phosphatase
Increased LFTs
Hyperbilirubinemia
Hypercholesterolemia (increased LDH)
Anaphylaxis
Nystagmus
Ophthalmic findings
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician because of the possibility of severe toxic reactions
Patient should be hospitalized for initiation of the therapy because of the risk for severe toxic reactions
Contraindications
Hypersensitivity
Poor nutritional status
Myelosuppression
Serious infection
Recent serious surgery
Dihydropyrimidine Dehydrogenase (DPD) deficiency
Cautions
Discontinue in case of stomatitis, esophagopharyngitis, leukopenia, thrombocytopenia, intractable vomiting, GI bleeding, hemorrhage, diarrhea
Prior alkylating agent use, CAD, hepatic/renal impairment
Avoid pregnancy
Cardiotoxicity, usually ischemic in nature, has been seen with highdose infusions
Case reports of cardiomyopathy and acute decreases in LVEF Cardiotoxicity is more common with IV 5FU compared to oral capecitabine
Pregnancy and lactation
Pregnancy category: d
Lactation: excretion in milk unknown; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Adrucil (fluorouracil)
Half-Life: 16 min
Onset: 2-7 d, but may take up to 12 wk
Duration: 24 hr
Metabolism: liver
Metabolites: urea, fluorouracil, dihydrofluorouracil, expired CO2 metabolite
Excretion: urine
Pharmacogenomics
Dihydropyrimidine dehydrogenase (DPD), an enzyme encoded by the DPYD gene, is the rate-limiting step in pyrimidine catabolism and deactivates >80% of 5FU standard doses and the 5FU prodrug capecitabine
Contraindicated in patients with DPD deficiency; causes severe toxicity with conventional doses (ie, grade III/IV toxicity and potentially fatal neutropenia, mucositis, and diarrhea)
Because true DPD deficiency is rare and because the clinical implications of partial deficiency are still unclear, screening for mutations prior to initiating therapy is not warranted
Genetic testing laboratories
- The following companies currently offer testing for DPYD*2A mutations
- EntroGen (https://www.entrogen.com)
- Myriad (https://www.myriadtests.com)
- LabCorp (https://www.labcorp.com)
- Molecular Diagnostics Laboratories (https://www.mdl-labs.com)
Mechanism of action
Inhibits DNA synthesis during S phase by inhibition of thymidylate synthetase
Administration
IV Incompatibilities
Additive: carboplatin, cisplatin, cytarabine, diazepam, doxorubicin, epirubicin, fentanyl, leucovorin, metoclopramide, morphine sulfate
Syringe: doxorubicin (at high conc of doxo & 5FU, compatible at lower conc), droperidol, epirubicin
Y-site: aldesleukin, amphotericin B cholesteryl SO4, droperidol, filgrastim, ondansetron(?), topotecan, vinorelbine
IV Compatibilities
Solution: compatible w/ most common solvents
Additive: bleomycin, cyclophosphamide, cyclophosphamide/methotrexate, etoposide, floxuridine, hydromorphone, ifosfamide, methotrexate, mitoxantrone, vincristine
Syringe: bleomycin, cisplatin, cyclophosphamide, furosemide, heparin, leucovorin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine
Y-site: (partial list) allopurinol, furosemide, granisetron, heparin, hydrocortisone-Na-succinate, leucovorin, linezolid, metoclopramide, piperacillin/tazobactam, KCl, propofol, vit B/C
IV Preparation
IV Push: dose/syringe (concentration: 50 mg/mL); max syringe size for IVP is 30 mL syringe and syringe should be <75% fulL
Continuous IV Infusion/IVPB: dose/50-1000 mL D5W or NS; syringe and solution are stable for 72 hr at 4 to 25°C
IV Administration
Direct IV push injection (50 mg/mL solution needs no further dilution) or by IV infusion
Toxicity may be reduced by giving the drug as a constant infusion
Bolus doses may be administered by slow IVP or IVPB
Warm to body temperature before using
Continuous IV infusion may be administered in D5W or Ns
Solution should be protected from direct sunlight
5-FU may also be administered intra-arterially or intra-hepatically
Use plastic IV containers for continuous infusions (stable in plastic IV bags than in glass bottles)
Storage
Store intact vials at room temp & protect from light
Slight discoloration does not usually denote decomposition
Don't use cloudy solutions
- If crystals form, redissolve by warming
Don't refrigerate
