candies [20:<20 mg/dL and patient is asymptomatic with normal pH. a Example 2: Patient is given a loading dose of 15 mg/kg. a Hemodialysis starts 7 hours after loading dose and lasts for 45 minutes. a Patient would receive a dose of 10 mg/kg prior to initiation of hemodialysis. a Because length of time between the last fomepizole dose and end of hemodialysis is> <1 hour, patient should receive a 10 mg/kg dose 12 hours after the dose given prior to initiation of hemodialysis. a Administer fomepizole every 12 hours thereafter until ethylene glycol or methanol concentration is> <20 mg/dL and the patient is asymptomatic with normal pH. a Table 1. Fomepizole Dosing in Patients Requiring Hemodialysis Dose at the Beginning of Hemodialysis If> <6 hours since last fomepizole dose If 6 hours since last fomepizole dose Do not administer dose Administer next scheduled dose Dose during Hemodialysis Dose every 4 hours Dose at the Time Hemodialysis Is Completed Time between last dose and the end of hemodialysis> <1 hour Do not administer dose at the end of hemodialysis 1 3 hours Administer half of next scheduled dose> 3 hours Administer next scheduled dose Maintenance Dosing off Hemodialysis Give next scheduled dose 12 hours from last dose administered Special Populations Geriatric Patients Select dosage with caution because of age-related decrease in renal function. 1 21 Cautions for Antizol Contraindications Known severe hypersensitivity to fomepizole or other pyrazoles. 1 8 11 21 Warnings/Precautions Sensitivity Reactions Hypersensitivity Reactions Mild rash and eosinophilia reported. b Monitor for manifestations of an allergic reaction. 1 Major Toxicities Hepatic Effects Transient increases in serum transaminase concentrations reported following repeated dosing. b Monitor hepatic enzyme concentrations during therapy. b Hematologic Effects Eosinophilia reported following repeated dosing. b Monitor WBC counts during therapy. b Local Effects Vein irritation and phlebosclerosis reported following rapid (i.e., <30 minutes) IV infusion or IV injection (i.e., over 5 minutes) of a 25-mg/mL solution. 1 16 21 b General Precautions Adequate Patient Evaluation and Monitoring Frequently monitor arterial blood gases, pH, electrolytes, BUN, creatinine, and urinalysis to determine response to therapy. b Frequently monitor serum and urine ethylene glycol concentrations and monitor for presence of urinary oxalate crystals in patients with ethylene glycol intoxication. b In patients with methanol intoxication, monitor serum methanol concentrations. b Perform ECG because acidosis and electrolyte imbalances can affect the cardiovascular system. b Electroencephalography also may be required in comatose patients. b Monitor hepatic enzyme (i.e., serum transaminase) concentrations and WBC counts. b (See Major Toxicities under Cautions.) Concomitant Use with Alcohol Consider potential interaction with alcohol, which often is ingested concomitantly by patients with ethylene glycol intoxication or used initially in the treatment of ethylene glycol or methanol intoxication. 1 2 4 5 7 22 23 24 25 26 33 (See Alcohol under Interactions.) Specific Populations Pregnancy Category C. b Lactation Not know whether fomepizole is distributed into milk. b Caution if used in nursing women. b Pediatric Use Safety and efficacy not established. b Geriatric Use Safety and efficacy not established. b Common Adverse Effects Headache, nausea, dizziness, increased drowsiness, bad/metallic taste. b Interactions for Antizol Metabolized by mixed-function oxidases (cytochrome P-450 system). b Potent inducer of CYP-mediated drug elimination; induces own metabolism. a b Drugs Affecting Hepatic Microsomal Enzymes Inhibitors or inducers of CYP isoenzymes: Potential pharmacokinetic interaction; however, no studies to date. b Specific Drugs Drug Interaction Comments Alcohol Decreased elimination rate of fomepizole and alcohol (possibly due to inhibition of alcohol dehydrogenase) 1 2 4 5 7 22 23 24 25 26 33 b Antizol Pharmacokinetics Absorption Bioavailability Immediately and completely bioavailable following IV administration. a Distribution Extent Rapidly distributes to total body water following IV infusion. b Not known whether fomepizole is distributed into milk. b Elimination Metabolism Metabolized in the liver. b Induces own metabolism; elimination rate increases after about 30 40 hours. b Elimination Route Excreted in urine mainly as metabolites; only 1 3.5% of administered dose excreted in urine as unchanged drug. b Fomepizole is dialyzable. 1 25 Half-life Not determined, but varies with dose. b Special Populations Pharmacokinetics not studied in patients with hepatic or renal impairment or in geriatric patients. 1 Stability Storage Parenteral Injection Concentrate for IV Infusion 20-25 C. 1 Fomepizole concentrate solidifies at temperatures> <25 C. 1 If solidification occurs, pass vial under warm water or hold vial in the hand to liquify solution before dilution. 1 Solidification does not affect efficacy, safety, or stability of fomepizole. 1 Following dilution with 0.9% sodium chloride or 5% dextrose injection, stable for 24 hours when refrigerated or stored at controlled room temperature (20 25 C). 1 However, because product contains no preservatives, manufacturer recommends using within 24 hours after dilution. 1 Discard if solutions become hazy, discolored, or contain a precipitate or if they exhibit leakage. 1 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Solution Compatibility 1 Compatible Dextrose 5% in water Sodium chloride 0.9% Actions Competitively inhibits alcohol dehydrogenase, 1 2 3 4 5 6 7 8 9 11 12 14 16 18 the enzyme that catalyzes the oxidation of alcohol to acetaldehyde and the initial steps in the metabolism of ethylene glycol and methanol to toxic metabolites. 1 4 6 7 9 11 15 16 Blocks metabolism of ethylene glycol (main component of most antifreezes and coolants) to glycoaldehyde, which undergoes subsequent sequential oxidations to yield glycolate, glyoxylate, and oxalate. 1 2 4 9 11 15 17 Glycolate and oxalate are toxic metabolites principally responsible for the metabolic acidosis and renal damage associated with ethylene glycol intoxication. 1 2 3 4 8 9 12 15 17 20 24 28 Lethal dose of ethylene glycol in humans is approximately 1.4 1.6 mL/kg (about 100 mL in an adult); 1 11 20 however, as little as 30 mL may be fatal. a Blocks metabolism of methanol (main component of windshield wiper fluid) to formaldehyde, which undergoes subsequent oxidation to yield formic acid. 1 4 9 11 17 Formic acid is principally responsible for the metabolic acidosis and visual disturbances (e.g., decreased visual acuity, potential blindness) associated with methanol intoxication. 1 4 9 14 17 20 23 Lethal dose of pure methanol in humans is approximately 1 2 mL/kg; 1 11 20 however, permanent blindness and death reported with as little as 0.1 mL/kg (6 10 mL in adults). a Fomepizole has approximately 8000 or 80,000 times greater affinity for alcohol dehydrogenase than alcohol or methanol, respectively. 14 Advice to Patients Risk of hypersensitivity reactions. 1 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and/or herbal products, as well as any concomitant illnesses. 1 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Fomepizole Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, concentrate, for IV infusion 1 g/mL Antizol (preservative-free) Jazz AHFS DI Essentials. Copyright 2017, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. Use is not currently included in the labeling approved by the US Food and Drug Administration. References 1. Orphan Medical. Antizol (fomepizole) injection prescribing information. Minnetonka, MN; 1997 Dec. 2. Baud FJ, Galliot M, Astier A et al. Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med . 1988; 319:97-100. [PubMed 3380132] 3. Jobard E, Harry P, Turcant A et al. 4-Methylpyrazole and hemodialysis in ethylene glycol poisoning. J Toxicol Clin Toxicol . 1996; 34:373-7. [PubMed 8699550] 4. Jacobsen D, McMartin KE. Antidotes for methanol and ethylene glycol poisoning. J Toxicol Clin Toxicol . 1997; 35:127-43. [PubMed 9120880] 5. Jacobsen D, McMartin K. 4-Methylpyrazole present status. J Toxicol Clin Toxicol . 1996; 34:379-81. [PubMed 8699551] 6. Jacobsen D, Barron SK, Sebastian CS et al. Non-linear kinetics of 4-methylpyrazole in healthy human subjects. Eur J Clin Pharmacol . 1989; 37:599-604. [PubMed 2693117] 7. Jacobsen D, Sebastian CS, Dies DF et al. Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans. Alcohol Clin Exp Res . 1996; 20:804-9. [PubMed 8865952] 8. Baud FJ, Bismuth C, Garnier R et al. 4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man. J Toxicol Clin Toxicol . 1986; 24:463-83. [PubMed 3573122] 9. Anon. Ethylene glycol and methanol poisoning simplified. N Z Med J . 1988; 101:591. 10. Jacobsen D, Sebastian CS, Blomstrand R et al. 4-Methylpyrazole: a controlled study of safety in healthy human subjects after single, ascending doses. Alcohol Clin Exp Res . 1988; 12:516-22. [PubMed 3056073] 11. Orphan Medical. Antizol (fomepizole) injection product monograph. Minnetonka, MN; 1997 Dec. 12. Harry P, Turcant A, Bouachour G et al. Efficacy of 4-methylpyrazole in ethylene glycol poisoning: clinical and toxicokinetic aspects. Hum Exp Toxicol . 1994; 13:61-4. [PubMed 8198831] 13. Jacobsen D, Sebastian CS, Barron SK et al. Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans. J Emerg Med . 1990; 8:455-61. [PubMed 2212566] 14. Burns MJ, Graudins A, Aaron CK et al. Treatment of methanol poisoning with intravenous 4-methylpyrazole. Ann Emerg Med . 1997; 30:829-32. [PubMed 9398786] 15. Davis DP, Bramwell KJ, Hamilton RS et al. Ethylene glycol poisoning: case report of a record-high level and a review. J Emerg Med . 1997; 15:653-67. [PubMed 9348055] 16. Antidotes. In: Ellenhorn MJ, ed. Medical Toxicology Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore: Williams & Wilkins; 1997:99-100. 17. Alcohols and Glycols. In: Ellenhorn MJ, Barceloux DG, eds. Medical Toxicology Diagnosis and Treatment of Human Poisoning. New York: Elsevier Science; 1988:805-9. 18. Woolf AD, The Haitian diethylene glycol poisoning tragedy: a dark wood revisited. JAMA . 1998; 279:1215-6. 19. Grauer GF, Thrall MA, Henre BA et al. Comparison of the effects of ethanol and 4-methylpyrazole on the pharmacokinetics and toxicity of ethylene glycol in the dog. Toxicol Lett . 1987; 35:307-14. [PubMed 3824418] 20. Gosselin RE, Smith RP, Hodge HC. Clinical toxicology of commercial products. 5th ed. Baltimore: The Williams & Wilkins CO; 1984:III-172-9. 21. Orphan Medical, Minnetonka, MN: Personal communication. 22. Brent J, McMartin K, Phillips S et al. Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med . 1999; 340:832-8. [PubMed 10080845] 23. Brent J, McMartin K, Phillips S et al. Fomepizole for the treatment of methanol poisoning. N Engl J Med . 2001; 344:424-9. [PubMed 11172179] 24. Jacobsen D. New treatment for ethylene glycol poisoning. N Engl J Med . 1999; 340:879-81. [PubMed 10080853] 25. Barceloux DG, Krenzelok EP, Olson K et al. American academy of clinical toxicology practice guideline on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol . 1999; 37:537-60. [PubMed 10497633] 26. Casavant MJ. Fomepizole in the treatment of poisoning. Pediatrics . 2001; 107:170-1. [PubMed 11134450] 27. Watson WA. Ethylene glycol toxicity: closing in on rational evidence based treatment. Ann Emerg Med . 2000; 36:139-41. [PubMed 10918105] 28. Sivilotti MA, Burns MJ, McMartin KE et al. Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. Ann Emerg Med . 2000; 36:114-125. [PubMed 10918102] 29. Baum CR, Langman CB, Oker EE et al. Fomepizole treatment of ethylene glycol poisoning in an infant. Pediatrics . 2000; 106:1489-91. [PubMed 11099610] 30. Harry P, Jobard E, Briand M et al. Ethylene glycol poisoning in a child treated with 4-methylpyrazole. Pediatrics . 1998; 102:E1. [PubMed 9724679] 31. Boyer EW, Mejia M, Woolf A et al. Severe ethylene glycol ingestion treated without hemodialysis. Pediatrics . 2001; 107:172-3. [PubMed 11134452] 32. Benitez JG, Swanson-Biearman B, Krenzelok EP. Nystagmus secondary to fomepizole administration in a pediatric patient. J Toxicol Clin Toxicol . 2000; 38:795-8. [PubMed 11192468] 33. Boron SW, Mégarbane B, Baud FJ. Fomepizole in treatment of uncomplicated ethylene glycol poisoning. Lancet . 1999; 354:831. [PubMed 10485727] 34. Megarbane B, Borron SW, Trout H et al. Treatment of acute methanol poisoning with fomepizole. Intensive Care Med . 2001; 27:1370-8. [PubMed 11511951] 35. Girault C, Tamion F, Moritz F et al. Fomepizole (4-methylpyrazole) in fatal methanol poisoning with early CT scan cerebral lesions. J Toxicol Clin Toxicol . 1999; 37:777-80. [PubMed 10584591] 36. Davis DP, Bramwell KJ, Hamilton RS et al. Ethylene glycol poisoning: case report of a record-high level and a review. J Emerg Med . 1997; 15:653-67. [PubMed 9348055] a. Orphan Medical. Antizol (fomepizole) injection product monograph. Minnetonka, MN; 2001 Apr. b. Jazz Pharmaceuticals, Inc. Antizol (fomepizole) injection prescribing information. Palo Alto, CA; 2006 Apr. Next Interactions Print this page Add to My Med List More about Antizol (fomepizole) Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 0 Reviews Add your own review/rating Generic Availability Drug class: antidotes Consumer resources Antizol Professional resources Antizol (FDA) Fomepizole (AHFS Monograph) Related treatment guides Ethylene Glycol Poisoning Methanol Poisoning> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturer Paladin Labs Inc. Drug Class Antidotes Related Drugs Methanol Poisoning fomepizole , More... Ethylene Glycol Poisoning fomepizole , More... Antizol Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } to admit
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