Acute Porphyria Drug Database

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.
Similar drugs
Explore alternative drugs in similar therapeutic classes L01B / L01BC or go back.

References

# Citation details PMID
*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.
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.
12904931
3. Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448.
11996015
4. Samuels, B., Bezwoda, W.R., et al. Chemotherapy in porphyria. S Afr Med J 1984; 65:924-6.
5. Ondansetron in a patient with porphyria. S Afr Med J 1992; 82(6):480.
De Wet M, Jooste R. et al.
*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).
7. Sweetman SC, editor. Martindale: The complete drug reference. Fluorouracil. Pharmaceutical Press 2009.

Tradenames
This list comprises raw data collected from different countries. In some cases, a more comprehensive list of available drug packages is included. Consequently, very similar terms may therefore appear multiple times. Bold names are the searchable terms, while the gray names that follow are all mapped to the bolded term.
Note: The cleaning is done automatically by a proprietary algorithm, and it may produce errors. We strive to improve it continuously.


Efudix · Fluorouracil · Tolak Efflurak · Efudix · Fluorouracil · Fluracedyl Fluorouracilo · Tolak Tolerak 5 - Fluorouracil · Fluorouracil Carac · Efudix · Fluoroplex · Fluorouracil · Tolak Fluorouracil · Tolak Efudix · Fluorouracil · Tolak 5-Fluorouracil · Efudix · Fluorouracil · Tolak Efflurak · Efudix · Fluracedyl Flúoróúracil Fluorouracil · Tolerak Fluorouracil 5-Fluorouracil · Efudix · Fluorouracil
 
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