Swedish Orphan Biovitrum distributes this product in the Nordic countries.
Therapeutic Indications
Fomepizole EUSA Pharma is an antidote used in the treatment of acute ethylene glycol poisoning.
Ethylene glycol poisoning in its severe forms is expressed by metabolic acidosis (anion gap > 16 mmol/l), convulsive coma and renal failure. Treatment with Fomepizole OPi should start immediately upon either documented ethylene glycol poisoning (plasma ethylene glycol greater than 0.2 g/l (3.2 mmol/l)) or suspicion of ethylene glycol ingestion based on patient’s history and/or anion gap metabolic acidosis, increased osmolar gap or oxalate crystals in the urine. Treatment of ethylene glycol intoxication involves prevention of the metabolism of ethylene glycol to its toxic metabolites, correction of metabolic acidosis, sufficient hydration (oral or venous if applicable) to prevent the risks of dehydration and hypernatremia and to increase urine clearance of ethylene glycol, and if necessary, removal of toxic metabolites with hemodialysis. Monitoring requires frequent measurements of plasma ethylene glycol, blood gas, pH, electrolytes, serum creatinine, urine analysis and presence of urinary oxalate crystals.
Posology and administration
The treatment should begin whenever ethylene glycol poisoning is suspected, as early as possible after its ingestion, even in the absence of signs of toxicity. In the absence of ethylene glycol assay, ethylene glycol poisoning should be suspected on the following criteria:
- patient’s history ;
- osmolar gap > 20 mOsm/kg H20 ;
- metabolic acidosis with anion gap > 16 mmol/l (presence of high levels of glycolates) ;
- calcium oxalate crystals in the urine.
- elderly patients : Clinical experience in elderly patients is limited. The regimen has to be adjusted to the renal function (see above).
- children : There is no available data regarding the pharmacokinetics of fomepizole in children. Clinical experience is limited and based on similar weight-adjusted doses.
- patients with impaired liver function : No clinical data are available.
Special warnings and precautions for use
Previous treatment of ethylene glycol poisoning with ethanol does not preclude the use of fomepizole. Nevertheless, the combination of ethanol and fomepizole is usually not recommended.
Minor hypersensitivity reactions have been reported in a few patients (rash, hypereosinophilia). These symptoms should be monitored. Management should be modified in case of a major hypersensitivity reaction (angioedema, bronchospasms, anaphylactic shock). In these cases, the fomepizole sulphate infusion should be immediately discontinued in the absence of another established cause; symptomatic treatment should start and fomepizole sulphate should not be re-administered to the patient. Treatment by ethanol should be started and hemodialysis considered.
Evaluation of hepatic transaminases and blood cell counts before and one month after treatment is recommended. Pre-existing impaired liver function requires careful monitoring of hepatic transaminases.
Interactions
Association with ethanol
Alcohol consumption does not impair fomepizole efficacy in case of ethylene glycol intoxication.
Pregnancy and lactation
No clinical data on exposed pregnancies are available. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Fomepizole should not be used during pregnancy unless clearly necessary. There are no data on the extent to which fomepizole is excreted in milk. It is advised to stop breastfeeding temporarily during treatment with fomepizole.
Effects on ability to drive and use machines
The possible risks of dizziness and vertigo related to the treatment should be pointed out. It is not advisable to drive or use machines during the first few days after treatment is discontinued.
Undesirable effects
The most commonly reported adverse effects (>10 %) were dizziness and headaches. The commonly reported adverse reactions (1 to 10 %) were:
- Cardiovascular: bradycardia, tachycardia, increase of blood pressure;
- Nervous: vertigo, seizures, visual disturbances, nystagmus, speech disturbances, anxiety, agitation;
- Liver: transient increase of transaminases;
- Gastrointestinal: nausea, vomiting, diarrhea, dyspepsia, hiccups;
- Administration site: injection site reaction, venous inflammation;
- Skin : pruritus, rash ;
- Blood : hypereosinophilia, anemia ;
- Metabolic : increased CPK.
Overdose
Dizziness, drunkenness, nausea, vertigo, headaches, nystagmus and speech disturbances have been observed for doses of 50 to 100 mg/kg in healthy volunteers. In case of a substantial overdose, as fomepizole sulphate is dialysable, hemodialysis could be considered