Fomepizole

Structural formula
General
Non-proprietary name	Fomepizole
other names	4-methylpyrazole ( IUPAC ); Fomepizolum ( Latin );
Molecular formula	C 4 H 6 N 2
External identifiers / databases
EC number	231-445-0
ECHA InfoCard	100,028,587
PubChem	3406
DrugBank	DB01213
Wikidata	Q416410
Drug information
ATC code	V03 AB34
Drug class	Antidote
Mechanism of action	competitive inhibition of alcohol dehydrogenase
properties
Molar mass	82,10 g · mol -1
Physical state	firmly
density	0.99 g cm −3 (at 20 ° C)
Melting point	15.5-18.5 ° C
boiling point	204-205 ° C (97.3 kPa)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302-315-319-335
	P: 261-305 + 351 + 338
Toxicological data	534 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fomepizole is an antidote that is used to treat acute poisoning (intoxication) with ethylene glycol . It has been on the WHO Essential Medicines List since 2013 .

Mode of action

Fomepizole is a competitive inhibitor of alcohol dehydrogenase . Alcohol dehydrogenase (ADH) is an enzyme that catalyzes the reaction of alcohols to the corresponding aldehydes, as well as the reverse reaction. Alcohol (ethanol) contained in alcoholic beverages is broken down into acetaldehyde with the help of alcohol dehydrogenase . Other alcohols, on the other hand, are converted into toxic degradation products by alcohol dehydrogenase: methanol to formaldehyde , ethylene glycol to glycolaldehyde , propylene glycol to lactaldehyde and isopropanol to acetone . The affinity of fomepizole for alcohol dehydrogenase is about 500 to 1000 times higher than that of ethanol. Therefore, alcohol dehydrogenase can be completely inhibited by fomepizole at considerably lower concentrations. Although fomepizole is also effective when taken orally , it is only approved for use in medicine in the form of a parenteral infusion solution , as the dosage is easier to control. Fomepizole can also be given to unconscious patients this way .

properties

Fomepizole has a volume of distribution of 0.6 to 1.0 l / kg. The protein binding is low. Fomepizole is removed by breakdown in the liver (hepatic metabolism) and excretion via the kidneys (renal excretion).

application

According to the specialist information , fomepizole is only approved in Germany for the treatment of acute intoxication caused by ethylene glycol. In the USA there is also an approval for the treatment of intoxication with methanol . Outside of the approval, fomepizole was also used to treat intoxication with diethylene glycol ( off-label use ). Fomepizole is removed by dialysis . If dialysis treatment is used at the same time, the dose must therefore be adjusted. In the Czech Republic, fomepizole has been used successfully for methanol poisoning.

rating

Benefits of fomepizole (compared to treatment with ethanol as an antidote) are:

the high affinity for alcohol dehydrogenase,
the effectiveness even at low serum concentrations,
only minimal side effects,
no effect on mental activity, which makes it easier to assess the clinical course,
monitoring ( Monitoring ) of the blood levels is not required,
treatment in the intensive care unit is not absolutely necessary,
the serum osmolality is not affected, so it can be used to monitor the concentration of toxic alcohol levels.

Disadvantages of fomepizole are

that it is not immediately available everywhere,
the high price (945 € for 5 × 20 ml),
that it is only available as an intravenous preparation,
that it is formally approved in Germany only for the treatment of ethylene glycol intoxication, but not for the treatment of intoxication with other alcohols.

literature

Kraut, Jeffrey A., Kurtz, Ira: Toxic Alcohol Ingestions: Clinical Features, Diagnosis, and Management . In: Clin J Am Soc Nephrol . No. 3 , 2008, p. 208-225 ( abstract ).

Individual evidence

↑ Fomepizole data sheet from AlfaAesar, accessed on December 15, 2010 ( PDF )(JavaScript required) .

^ ^A ^b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .

↑ ^a ^b Fomepizole data sheet from Sigma-Aldrich , accessed on April 2, 2011 ( PDF ).

↑ Entry on fomepizole in the ChemIDplus database of the United States National Library of Medicine (NLM) .

↑ Brigitte Gensthaler, Kerstin Gräfe: Fomepizol, galsulfase and rotigotine. Article in the Pharmazeutische Zeitung , issue 14/2006.

^ Battistella M: Fomepizole as an antidote for ethylene glycol poisoning . In: Ann Pharmacother . 36, No. 6, June 2002, pp. 1085-1089. PMID 12022913 .

↑ Rob Cameron: Norwegian doctor brings hope - and antidote - to methanol poison victims. Radio Prague, September 14, 2012, accessed September 15, 2012 .

Trade names

Antizol (CDN, USA), Fomepizole OPi (D)

[alfa-1] Fomepizole data sheet from AlfaAesar, accessed on December 15, 2010 ( PDF )(JavaScript required) .

[MERCK_Index-2] A ^b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .

[Sigma-3] Fomepizole data sheet from Sigma-Aldrich , accessed on April 2, 2011 ( PDF ).

[ChemIDplus-4] Entry on fomepizole in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[5] Brigitte Gensthaler, Kerstin Gräfe: Fomepizol, galsulfase and rotigotine. Article in the Pharmazeutische Zeitung , issue 14/2006.

[6] Battistella M: Fomepizole as an antidote for ethylene glycol poisoning . In: Ann Pharmacother . 36, No. 6, June 2002, pp. 1085-1089. PMID 12022913 .

[7] Rob Cameron: Norwegian doctor brings hope - and antidote - to methanol poison victims. Radio Prague, September 14, 2012, accessed September 15, 2012 .