Isoniazid

From Dog

Isoniazid (isonicotinylhydrazine) is an antibacterial prodrug which is metabolized in vivo to isonicotinic acyl-NADH complex which blocks the synthesis of mycolic acid, required for mycobacterial cell walls.

This drug was primarily used in the treatment of canine tuberculosis[1] in combination with other antimicrobials such as rifampicin[2] but has been discontinued.

Pyridoxine has been used as an adjunct treatment of side-effects associated with this drug[3].

Side-effects associated with toxicity with this drug are associated with excessive cytochrome P450 induction[4] and include acute renal injury, seizures[5], myocarditis and metabolic acidosis[6]. The LD50 of this drug in dogs is 150 mg/kg[7].

Recommended dose rate is 10 - 20 mg/kg given orally once daily every 24 hrs (max < 100mg total/day).

References

  1. Sagalovich VI et al (1987) Effectiveness of single and fractional administration of isoniazid in the treatment of dogs infected with isoniazid-resistant strains of Mycobacterium tuberculosis. Probl Tuberk 7:49-53
  2. Wang Y et al (2013) Design and evaluation of enteric-coated tablets for rifampicin and isoniazid combinations. Pharm Dev Technol 18(2):401-406
  3. Villar D et al (1995) Treatment of acute isoniazid overdose in dogs. Vet Hum Toxicol 37(5):473-477
  4. Graham RA et al (2002) In vivo and in vitro induction of cytochrome P450 enzymes in beagle dogs. Drug Metab Dispos 30(11):1206-1213
  5. Haburjak JJ & Spangler WL (2002) Isoniazid-induced seizures with secondary rhabdomyolysis and associated acute renal failure in a dog. J Small Anim Pract 43(4):182-186
  6. Frank I et al (2002) Myocardial necrosis and severe metabolic acidosis associated with isoniazid poisoning in a dog. Vet Rec 151(21):638-639
  7. Inchem.org