Monograph
L01BC02 - Fluorouracil |
Not porphyrinogenic |
NP |
Rationale
Non-CYP metabolism. Reported to be tolerated by 5 patients with AIP. Side effects such as nausea, vomiting and anorexia may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Fluorouracil is an analogue of the pyrimidine uracil.
Therapeutic characteristics
Fluorouracil is used for the palliative treatment of carcinoma of the colon, rectum, breast, stomach, and pancreas that is not amenable to surgery or irradiation. The drug also is used as an adjunct to surgery for the treatment of various solid tumors (e.g., adenocarcinoma of the colon, rectal carcinoma, or breast cancer)Administered as as an intravenous injection or infusion. Common adverse reactions of fluorouracil that can be confused with an acute porphyric attack are nausea, vomiting, diarrhoes,and cerebral ataxia. Side effects such as nausea, vomiting and anorexia may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmacokinetics
Fluorouracil is metabolized by dihydropyrimidine dehydrogenase, a non-CYP enzyme (Collins, J. M., 2000). Baumhakel et al (2001) states that fluorouracil has no inhibitory effect on CYP3A4. No observations pointing to clinical CYP-induction. Rendic (2002) reports fluorouracil to be a substrate for several smaller CYP-groups (1A2,2A6, 2C8, 2E1, 3A5), but not an inducer or inhibitor. In spite of reports of fluorouracil leading to increased effect of warfarin, Park et al found that fluorouracil has no inhibitory effect on CYP-isoforms or drug metabolism causing drug interaction
with fluorouracil, and concludes that the mechanism that causes drug interaction may not be related to direct CYP-inhibition by fluorouracil.
Published experience
Samuels et al (1984) reported unevenful use of 5-fluorouracil in 2 patients with VP. De Wet (1992) reported uneventtful use in a 56 year old woman with quiescent VP.
IPNet drug reports
Uneventful use reported twice in male VP patient, baseline PBG level was measured and then daily monitoring for a few days and then weekly until finished chemotherapy without any increase in PBG levels. Uneventful use reported in 62 year-old AIP female.
References
# | Citation details | PMID |
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* | Scientific articles | |
1. | Baumhakel, M., Kasel, D. et al. Screening for inhibitory effecs on antineoplastic agents on CYP3A4 in human liver microsomes. International Journal of Clinical Pharmacology and Therapeutics 2001; 39(12):517-28.
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2. | Park JY, Kim, KA. Inhibitory effect of 5-fluorouracil on human cytochrome P(450) isoforms in human liver microsomes. Eur J Clin Pharmacol 2003; 59:407â-9.
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12904931 |
3. | Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448.
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11996015 |
4. | Samuels, B., Bezwoda, W.R., et al. Chemotherapy in porphyria. S Afr Med J 1984; 65:924-6.
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5. | Ondansetron in a patient with porphyria. S Afr Med J 1992; 82(6):480.
De Wet M, Jooste R. et al. |
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* | Drug reference publications | |
6. | McEvoy GK, editor. Fluorouracil. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (03.12.09).
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7. | Sweetman SC, editor. Martindale: The complete drug reference. Fluorouracil. Pharmaceutical Press 2009.
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Similar drugs
Tradenames and packages
From some sources, we get a list of packages (United Kingdom, Ireland, Estonia).
Other sources contain more or less "clean" versions of the trade name (Denmark, Finland, Iceland, Lithuania, Norway).
What you see here is the raw data we get from each country, so there will appear to be duplicates. The bold names
are the searchable terms. The gray names that follow are all mapped to the bolded term.
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Netherlands
Efudix · Efudix crème, 50 mg/g · Efudix, creme 50 mg/g · Efudix, crème 50 mg/g · Fluorouracil · Fluorouracil Accord 50 mg/ml, oplossing voor injectie of infusie · Tolak · Tolak 40 mg/g crèmeBelgium
Efflurak · Efflurak 40 mg/g crème · Efudix · Efudix 5 % pommade · Fluorouracil · Fluorouracil Accord Healthcare 50 mg/ml sol. inj./perf. i.artér./i.v. flac. · Fluracedyl · Fluracedyl 50 mg/ml sol. inj. i.artér./i.v. flac.United Kingdom
Carac · Carac 0.5% cream · Efudix · Efudix 5% cream · Fluoroplex · Fluoroplex 1% cream · Fluorouracil · Fluorouracil 1.1g/44ml solution for injection pre-filled syringes · Fluorouracil 1.2g/48ml solution for injection pre-filled syringes · Fluorouracil 1000mg/40ml solution for injection pre-filled syringes · Fluorouracil 10mg/0.2ml solution for injection pre-filled syringes · Fluorouracil 1350mg/1000ml in Sodium chloride 0.9% infusion bags · Fluorouracil 1350mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 1500mg/1000ml in Sodium chloride 0.9% infusion bags · Fluorouracil 1650mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 1800mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 1g/20ml solution for injection vials · Fluorouracil 2.5g/100ml solution for infusion vials · Fluorouracil 2.5g/50ml solution for infusion vials · Fluorouracil 2000mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 2000mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 200mg/8ml solution for injection pre-filled syringes · Fluorouracil 2250mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 2250mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 2500mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 2500mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 250mg capsules · Fluorouracil 250mg/10ml solution for injection vials · Fluorouracil 250mg/5ml solution for injection vials · Fluorouracil 2800mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 2800mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 2800mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 3150mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 3150mg/120ml (2.5ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 3150mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 3150mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 3500mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 3500mg/120ml (2.5ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 3500mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 3500mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 3950mg/105ml (0.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV0.5 elastomeric devices · Fluorouracil 3950mg/120ml (2.5ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 3950mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 3950mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 4450mg/120ml (2.5ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 4450mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 4450mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 5000mg/120ml (2.5ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 5000mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 5000mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 500mg/10ml solution for injection vials · Fluorouracil 500mg/20ml solution for injection pre-filled syringes · Fluorouracil 500mg/20ml solution for injection vials · Fluorouracil 5650mg/130ml (2.5ml/hour) in Sodium chloride 0.9% infusion FOLFusor SV2.5 elastomeric devices · Fluorouracil 5650mg/200ml (2ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 5650mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 5g/100ml solution for infusion vials · Fluorouracil 600mg/24ml solution for injection pre-filled syringes · Fluorouracil 6400mg/200ml (2ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 6400mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 7250mg/200ml (2ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 7250mg/300ml (5ml/hour) in Sodium chloride 0.9% infusion FOLFusor LV5 elastomeric devices · Fluorouracil 800mg/32ml solution for injection pre-filled syringes · Fluorouracil 8200mg/200ml (2ml/hour) in Sodium chloride 0.9% infusion AutoFuser elastomeric devices · Fluorouracil 900mg/36ml solution for injection pre-filled syringes · Fluorouracil 950mg/38ml solution for injection pre-filled syringes · Tolak · Tolak 40mg/g creamDenmark
Fluorouracil · Fluorouracil "Accord" · Fluorouracil "Paranova" · Fluorouracil "Pfizer" · TolakNorway
Efudix specific · Fluorouracil Accord · TolakPoland
5-Fluorouracil-Ebewe · Efudix · Fluorouracil Accord · Fluorouracil medac · TOLAKLuxembourg
Efflurak · EFUDIX · FLURACEDYLIceland
Flúoróúracil · Flúoróúracil AccordFinland
Fluorouracil Accord · TolerakLatvia
Fluorouracil · Fluorouracil AccordSerbia
5-Fluorouracil · 5-Fluorouracil Ebewe® · Efudix · Efudix® · Fluorouracil · Fluorouracil Accord · Fluorouracil Quatalia
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