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Fomepizole

Fomepizole or 4-methylpyrazole is indicated for use as an antidote in confirmed or suspected methanol or ethylene glycol poisoning. It may be used alone or in combination with hemodialysis. {03} more...

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Uses

Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Ethylene glycol is first metabolized to glycoaldehyde which then undergoes further oxidation to glycolate, glyoxylate, and oxalate. It is glycolate and oxalate that are primarily responsible for the metabolic acidosis and renal damage that are seen in ethylene glycol poisoning. Methanol is first metabolized to formaldehyde and then undergoes subsequent oxidation via formaldehyde dehydrogenase to become formic acid. It is formic acid that is primarily responsible for the metabolic acidosis and visual disturbances that are associated with methanol poisoning.

Dosage

Fomepizole distributes rapidly into total body water. The volume of distribution is between 0.6 and 1.02 L/kg. The theraputic concentration is from 8.2 to 24.6 mg (100 to 300 micromoles) per liter. Peak concentration following single oral doses of 7 to 50 mg/kg of body weight occurred in 1 to 2 hours. The half-life varies with dose and therefore has not been calculated.

Transformation and elimination

Hepatic; the primary metabolite is 4-carboxypyrazole (approximately 80 to 85% of an administered dose). Other metabolites include the pyrazoles 4-hydroxymethylpyrazole and the N -glucuronide conjugates of 4-carboxypyrazole and 4-hydroxymethylpyrazole.

Following multiple doses, fomepizole rapidly induces its own metabolism via the cytochrome P450 mixed-function oxidase system.

In healthy volunteers, 1 to 3.5% of an administered dose was excreted unchanged in the urine. The metabolites also are excreted unchanged in the urine.

Fomepizole is dialyzable.

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Clinical quiz - continuing medical education
From American Family Physician, 9/1/02

Clinical Quiz questions are based on selected articles in this issue. Answers appear in this issue.

American Family Physician has been approved by the American Academy of Family Physicians as having educational content acceptable for Prescribed credit hours. Term of approval covers issues published within one year from the beginning distribution date of January 2002. This issue has been reviewed and is acceptable for up to 4 Prescribed credit hours. One half hour of these credit hours conforms to AAFP criteria for evidence-based CME clinical content. Credit may be claimed for one year from the date of this issue. When reporting CME credit hours, AAFP members should report total Prescribed credit hours earned for this activity. It is not necessary for members to label credit hours as evidence-based or Prescribed for CME reporting purposes.

The American Academy of Family Physicians is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The AAFP designates this educational activity for a maximum of 4 hours in Category 1 credit toward the American Medical Association Physician's Recognition Award. Each physician should claim only those hours of credit that he or she actually spent in the educational activity.

AAFP Credit

Each copy of AFP contains a Clinical Quiz answer card. AAFP members may use this card to obtain the designated number of Prescribed credit hours for the year in which the card is postmarked.

AMA/PRA Category 1 Credit

AAFP members who satisfy the Academy's continuing medical education requirements are automatically eligible for the AMA/PRA.

Physicians who are not members of the AAFP are eligible to receive the designated number of credit hours in Category 1 of the AMA/PRA on completion and return of the Clinical Quiz answer card. AFP keeps a record of AMA/PRA Category 1 credit hours for nonmember physicians. This record will be provided on request; however, nonmembers are responsible for reporting their own Category 1 CME credits when applying for the AMA/PRA or other certificates or credentials.

For health care professionals who are not physicians and are AFP subscribers, a record of CME credit is kept by AAFP and will be provided to you on written request. You are responsible for reporting CME hours to your professional organization.

NOTE: The full text of AFP is available online (www.aafp.org/afp), including each issue's Clinical Quiz. The table of contents for each online issue will link you to the Clinical Quiz. Just follow the online directions to take the quiz and, if you're an AAFP member, you can submit your answers for CME credit.

INSTRUCTIONS

(1) Read each article, answer all questions on the quiz pages, and transfer your answers to the Clinical Quiz answer card (bound into your copy of AFP). This will help you avoid errors and permit you to check your answers against the correct answers.

(2) A Mail the Clinical Quiz answer card within one year (by September 30, 2003). The bar code on the answer card contains your identification for CME credit hours.

Before beginning the test, please note:

Each Clinical Quiz includes two types of questions: Type A and Type X.

Type A questions have only one correct answer and may have four or five choices. Here is a typical Type A question:

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