Fomepizole: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Fomepizole, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Antizol-Vet® (NADA/ANADA 141-075)
Antizol-Vet® NADA 141-075, Original approval, November 25, 1996; sponsor Paladin Labs (USA), Inc.; species: Dogs; foi_id 612; FDA PDF
Indication
Antidote for ethylene glycol (antifreeze) poisoning in dogs that have ingested or are suspected of having ingested ethylene glycol.
Dose regimen
20 mg/kg initial dose, then 15 mg/kg at 12 and 24 hours, then 5 mg/kg at 36 hours, intravenous (5% solution, 50 mg/mL, diluted in 0.9% sodium chloride injection), four doses over 36 hours, starting as soon as practical upon suspicion of poisoning, If not recovered and ethylene glycol remains in the bloodstream, continue 5 mg/kg every 12 hours until ethylene glycol is cleared or the animal has visibly recovered.
Initial dose: 20 mg/kg IV Dose 2 (12 hours after initial dose): 15 mg/kg IV Dose 3 (24 hours after initial dose): 15 mg/kg IV Dose 4 (36 hours after initial dose): 5 mg/kg IV
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | dose-proportional increase in plasma fomepizole after a single dose at 10, 20 and 30 mg/kg | IV infusion twice daily for 14 days, Beagle dogs (subacute toxicity study) | Pharmacokinetics Results from this twice daily 14 day intravenous study evaluating doses of 10, 20, and 30 mg/kg in dogs showed a dose proportional increase in plasma levels of fomepizole after a single (first) dose. |
| half-life | terminal elimination half-life increases with dose after multiple doses (nonlinear kinetics); not quantified | repeated twice-daily IV dosing; most evident at 30 mg/kg and in four of eight dogs at 20 mg/kg | However, the terminal elimination half life appears to increase (nonlinear kinetics) with dose following multiple administrations. |
| other | greater-than-dose-proportional plasma accumulation after fourteen days of dosing, attributed to a saturable elimination process | 20 and 30 mg/kg twice daily x 14 days | Accordingly, after the fourteen day dosing regimen in these animals, plasma fomepizole concentrations accumulated in a greater than dose proportional manner. |
| other | linear pharmacokinetics with no plasma accumulation at 10 mg/kg | 10 mg/kg twice daily x 14 days | In contrast, linear pharmacokinetics and an NADA 141-075 FOI Summary page 10 absence of plasma fomepizole accumulation was observed following the fourteen days of dosing in the 10 mg/kg dose group. |
Target-animal safety
dose multiples 10 mg/kg twice daily, 20 mg/kg twice daily, 30 mg/kg twice daily; duration 30-minute IV infusions twice daily for 14 days (subacute toxicity study); 6 dogs/group necropsied at Day 14, remainder after 28-day recovery (Day 42); animals Thirty-two (four groups of 8: 4 males and 4 females each).
Dogs were randomly separated into four groups of 4 males and 4 females each (8 dogs/group). Dosage levels of 10 (Group 2), 20 (Group 3), and 30 (Group 4) mg/kg fomepizole were selected for the study based on the results from the overdosing toxicity study.
| Finding | Quote |
|---|---|
| Hypoactivity in one high-dose (30 mg/kg) female, considered treatment related; vomiting, diarrhea and injected sclera seen in treated and vehicle-control dogs. | Hypoactivity was observed in a single female animal in the high-dose group and was considered treatment-related. Vomiting, diarrhea and injected sclera were seen in treated males and females throughout the dosing period. |
| Elevated bicarbonate and decreased potassium at 30 mg/kg on day 14, normal by day 42; increased urine volume and decreased specific gravity at 20 and 30 mg/kg. | Mean bicarbonate values were elevated and mean potassium values were decreased in the 30 mg/kg group at day 14, but returned to normal by day 42. |
| Pale/swollen livers and increased mean liver weight in the 30 mg/kg group at day 14; no treatment effects at day 42. | At necropsy on day 14, two males and two females in the 30 mg/kg group had pale livers and one 30 mg/kg male had a swollen liver. |
| Conclusion: safe intravenously at doses up to 20 mg/kg. | Conclusion: The study demonstrates that fomepizole is safe when administered intravenously at doses up to 20 mg/kg. |
| Dose range-finding study (25-150 mg/kg IV twice daily, 10 six-week-old Beagles): 25 mg/kg caused decreased food consumption, weight loss and sweet-odored breath; 50 mg/kg or greater caused ataxia, hypoactivity, hypothermia, tremors/prostration and marked clinical chemistry elevations. | administered at 25 mg/kg resulted in decreased food consumption, body weight loss, and breaths with sweet odors. |
Effectiveness
Retrospective open-label clinical field study at Colorado State University Veterinary Teaching Hospital (Sept 1983-April 1995): 105 dogs (54 males, 51 females; 3 months to 15 years) treated IV with fomepizole for suspected or confirmed ethylene glycol poisoning (69 with regimen 1: 20/15/5/5 mg/kg at 0/17/25/36 h; 5 with the labeled regimen 2; 31 with variations); no control group. Supported by two published laboratory studies (Grauer 1987, n=9; Dial 1994, n=11) and a prospective open-label clinical study (Dial 1989, n=8).; n = One-hundred five; primary endpoint: Survival; result: 84 (80%) survived, 20 (19%) were euthanized (17 azotemic at admission) and 1 (1%) died; only 1 of 21 azotemic dogs survived, while all 84 non-azotemic dogs survived except one confirmed case euthanized. Fomepizole must be given before substantial ethylene glycol metabolism to prevent renal failure.
Eighty-four (80%) animals survived, 20 (19%) were euthanized and 1 (1%) died (See diagram 1).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Anaphylactic-type reaction (tachypnea, gagging, excessive salivation, trembling) in one dog after the second dose; dosing discontinued, dog survived | One animal experienced an anaphylactic type reaction following the second dose of fomepizole. |
Extraction notes: 1996 summary with no parsed sections; extracted from raw text. n_dogs for the field study is spelled out in the summary ('One-hundred five'); 105 also appears in the flow diagram. Target animal safety is the 14-day subacute IV toxicity study; doses are absolute (10/20/30 mg/kg twice daily) rather than label multiples, and the summary gives no X-multiples. PK statements are qualitative; no numeric half-life or Cmax is reported. The product name is rendered 'Antizol-Vetä' in the extracted text; quotes avoid that token.
Reproduce: foi_structured_search(query="Fomepizole") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).