Fomepizole

• IUPAC: 4 -methylpyrazole
• Latin: Fomepizolum

V03AB34

Antidote

Competitive inhibition of alcohol dehydrogenase

0.99 g · cm -3 ( at 20 ° C)

15.5 to 18.5 ° C

204-205 ° C ( 97.3 kPa)

Attention

534 mg · kg -1 ( LD50, rat, oral)

Template: Infobox chemical / molecular formula search available

Fomepizole is an antidote ( antidote ), for the treatment of acute poisoning ( intoxication ) is used with ethylene glycol.

Operation

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. Alcoholic beverages contained in alcohol (ethanol) is reduced by means of alcohol dehydrogenase to acetaldehyde. Other alcohols are, however, transformed by alcohol dehydrogenase in the toxic breakdown products: methanol to formaldehyde, ethylene glycol to glycolaldehyde, propylene glycol and isopropanol to acetone to lactaldehyde. The affinity of alcohol dehydrogenase for Fomepizole compared to ethanol about 500 to 1000 times higher. Therefore, the alcohol can be completely inhibited by fomepizole at significantly lower concentrations. Although fomepizole is also effective when taken orally, it is approved for use in medicine only in the form of a parenteral infusion solution, since the dosage is easier to control. In addition, fomepizole can be given in this way the patient is unconscious.

Properties

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

Application

According to prescribing information fomepizole is approved in Germany only for the treatment of acute intoxication by ethylene glycol. In the U.S., in addition, there is an approval for the treatment of intoxication with methanol. Outside the approval fomepizole with diethylene glycol was also used for the treatment of intoxication ( off- label use ). Fomepizole is removed by dialysis. With simultaneous dialysis treatment, therefore a dose adjustment is required. In the Czech Republic fomepizole has been used successfully in methanol poisoning.

Assessment

Advantages of Fomepizole (compared to the treatment with ethanol as an antidote ) are:

• The high affinity for alcohol dehydrogenase,
• Efficacy was observed at low serum concentrations,
• Minimal side effects,
• No effect on the mental activity, which facilitates the assessment of the clinical course,
• Monitoring (monitoring) the blood level is not required,
• Treatment in intensive care is not mandatory,
• Serum osmolality will not be affected, so that it can be used for monitoring the concentration of toxic alcohol level.

Disadvantages of fomepizole are

• That it is immediately available for use everywhere,
• The high price ( € 945 for 5 x 20 ml),
• That it is only available in an intravenous formulation,
• That it is approved in Germany formally only for the treatment of ethylene glycol intoxication, but not for the treatment of intoxications with other alcohols.