Canadian antidote guide

Fomepizole

• 4-MP
• 4-methylpyrazole
• Antizol™

• Methanol poisoning if serum concentration is equal or greater to 6 mmol/L (19,2 mg/dL).
• Ethylene glycol poisoning if serum concentration is equal or greater to 3 mmol/L (18,6 mg/dL).
• Circumstances suggestion one of these poisonings, pending testing, i.e.:
  • Metabolic acidosis with unexplained osmolar gap greater than 10.
  • History, signs or symptoms suggestive of exposure.
• On a case-by-case basis, after consulting with your poison centre for other substances metabolized by alcohol dehydrogenase, such as diethylene glycol, 1.4-butanediol, or various glycol ethers, when metabolic acidosis develops.

• Headaches, nausea, dizziness.
• Transient hypotension and bradycardia has been reported during hemodialysis.

• Plasma concentrations of ethylene glycol or methanol
  • Conversion factors:
    • Methanol: 1 mmol/L = 3.20 mg/dL; 1 mg/dL = 0.3121 mmol/l
    • Ethylene glycol: 1 mmol/L = 6.21 mg/dL; 1 mg/dL= 0.1611 mmol/L.
• Hepatic and liver function
• Serum electrolytes
• EKG
• Blood gases
• Anion and osmolar gaps

• Methanol Poisoning: Serum concentration less than 6 mmol/L and absence of metabolic acidosis (if patient is on hemodialysis, the test must be done at least 4 - 6 h after the end of the hemodialysis session).
• Ethylene Glycol Poisoning: Serum concentration less than 3 mmol/L and absence of metabolic acidosis (if patient is on hemodialysis, the test must be done at least 4 - 6 h after the end of the hemodialysis session).
• Poisoning with other substances: Generally several hours after the metabolic acidosis has subsided (quantitative testing generally not readily available).

Intravenous Route (IV)

• Direct IV:
  • Not recommended.
  • May cause venous irritation and phlebosclerosis in cases of rapid administration (less than 5 minutes) of a concentrated 25 mg/ml solution.
• IV infusion over 30 minutes:
  • Dilute the dose in 100 ml of compatible solution.
  • Pediatric doses can be diluted in a compatible solution for a final concentration less than 25 mg/ml.
  • Administer by IV infusion over 30 minutes using a volumetric pump.
• Continuous IV Infusion:
  • Dilute 1000 mg (1 ml) in 99 ml of compatible solution.
  • Final volume: 100 ml.
  • Final concentration: 10 mg/ml.
  • Administer by IV infusion using a volumetric pump.

Subcutaneous Route (SC)

• Not a recommended route of administration.

Intramuscular Route (IM)

• Not a recommended route of administration.

Intraosseous Route (IO)

• No data available.

Enteral Route (PO or NG Tube)

• Intravenous route is preferred route.
• Possible alternative to IV route. Consult your poison centre before using the enteral route.
• Use solution for injection to administer by enteral route.
  • PO
    • Fomepizole has a particularly unpleasant smell and taste.
    • Dilute the dose in 100 ml of orange juice or tomato juice.
  • NG Tube
    • Collect the dose of fomepizole, then add SWFI until a total volume of 10 ml is reached.
    • Administer the antidote through the NG tube.
    • Rinse NG tube with 5 - 10 ml of SWFI, then clamp.

Compatibility

Partial list only. Consult the pharmacist on duty at your health care facility.

• Compatible solutions: D5W, NS
• Y-site compatibility: No data available.
• Y-site incompatibility: No data available.

Stability

• Store unopened vials at room temperature.
• Fomepizole solidifies at temperatures below 25°C (melting point). If the solution has solidified in the vial, it should be liquified by placing the vial under warm running tap water or warming by holding the vial int the hand. Solidification does not compromise the efficacy, safety or stability of the product.
• After dilution, the diluted solution is stable for 24 hours at room temperature or in the refrigerator.

• Antizol 1 g/ml, vials of 1.5 ml, Inj. Sol., Paladin Labs Inc, DIN 02242980
• Fomepizole for injection 1 g/ml, vials of 1.5 ml, Inj. Sol., Sterimax Inc., DIN 02435667

• At least 6 g.

Brent, Jeffrey. 2009. “Fomepizole for Ethylene Glycol and Methanol Poisoning.” The New England Journal of Medicine 360 (21):2216–23.

Lepik, Katherine J., Adrian R. Levy, Boris G. Sobolev, Roy A. Purssell, Christopher R. DeWitt, Gunnar D. Erhardt, James R. Kennedy, Derek E. Daws, and Jane L. Brignall. 2009. “Adverse Drug Events Associated with the Antidotes for Methanol and Ethylene Glycol Poisoning: A Comparison of Ethanol and Fomepizole.” Annals of Emergency Medicine 53 (4):439–50.e10.

Levine, Michael, Steven C. Curry, Anne-Michelle Ruha, Anthony F. Pizon, Edward Boyer, Jarrett Burns, Dale Bikin, and Richard D. Gerkin. 2012. “Ethylene Glycol Elimination Kinetics and Outcomes in Patients Managed without Hemodialysis.” Annals of Emergency Medicine 59 (6):527–31.

McMartin, Kenneth, Knut Erik Hovda, and Dag Jacobsen. 2016. “Fomepizole.” In Critical Care Toxicology, edited by Jeffrey Brent, Keith Burkhart, Paul Dargan, Benjamin Hatten, Bruno Megarbane, and Robert Palmer, 23:1–14. Cham: Springer International Publishing.

Osterhoudt, Kevin C. 2002. “Fomepizole Therapy for Pediatric Butoxyethanol Intoxication.” Journal of Toxicology. Clinical Toxicology 40 (7):929–30.

Roberts, Darren M., Christopher Yates, Bruno Megarbane, James F. Winchester, Robert Maclaren, Sophie Gosselin, Thomas D. Nolin, et al. 2015. “Recommendations for the Role of Extracorporeal Treatments in the Management of Acute Methanol Poisoning: A Systematic Review and Consensus Statement.” Critical Care Medicine 43 (2):461–72.

Schep, Leo J., Robin J. Slaughter, Wayne A. Temple, and D. Michael G. Beasley. 2009. “Diethylene Glycol Poisoning.” Clinical Toxicology 47 (6):525–35.

Sivilotti, Marco L. A. 2009. “Ethanol: Tastes Great! Fomepizole: Less Filling!” Annals of Emergency Medicine 53 (4):451–53.

Zuckerman, Matthew, Howard A. Greller, and Kavita M. Babu. 2015. “A Review of the Toxicologic Implications of Obesity.” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 11 (3):342–54.