The Toxic Effect of Intravenous Application of the Trypanocide Isometamidium (Samorin®)

Abstract

Summary For the trypanocide isometamidium chloride (Samorin®, May & Baker) the intramuscular route is recommended by the suppliers but application by this route is followed by local tissue irritation and necrosis. The intravenous administration leads to a dose‐dependent acute systemic toxicity, which can be fatal. These side effects can be avoided by intravenous administration of a precise dose based upon the known maximal tolerated dose (MTD). The MTD for the goat was found to be 0.5 mg/kg, for cattle 1.5 mg/kg, for the camel 1.0 mg/kg and for the dog 2.0 mg/kg. The clinical picture of the acute toxicity is characterized by muscle weakness, increased heart rate, salivation and diarrhoea. These clinical signs were associated with decreased serum cation (Ca, Mg, Na, K) concentrations. Intravenous dosage exceeding the MTD may cause shock followed by death. Zusammenfassung Toxizität des Trypanozides Isometamidium (Samorin®) nach intravenöser Applikation Die vom Hersteller empfohlene intramuskuläre Applikation des Trypanozides Isometamidiumchlorid (Samorin®, May & Baker) verursacht Gewebereizungen und ‐nekrosen. Die intravenöse Verabreichung ist dosisabhängig von einer akuten systemischen Toxizität mit zum Teil letalem Ausgang begleitet. Eine Vermeidung der lokalen Gewebsschädigung durch intravenöse Injektion ist nur bei Kenntnis der maximal tolerierten Dosis (MTD) möglich. Diese betrug für die Ziege 0.5 mg/kg Körpergewicht, für das Rind 1.5 mg/kg, für das Kamel 1.0 mg/kg und für den Hund 2.0 mg/kg. Das Vergiftungsbild ist durch Parese der Skelettmuskulatur, Tachykardie, Speicheln und Diarrhoe gekennzeichnet. Diese klinischen Symptome waren von einem Konzentrationsabfall der Serumkationen Ca, Mg, Na und K begleitet. Die MTD übersteigenden intravenösen Dosen können ein Schockgeschehen mit letalem Ausgang zur Folge haben. Résumé Effet toxique d'une application intraveineuse de l'isometamidium trypanocide (Samorin®) L'application intramusculaire recommandée par le fabricant du chlorure d'isometamidium trypanocide (Samorin®, May et Baker) provoque des irritations et des nécroses du tissu. L'application intraveineuse est accompagnée d'une toxicité systémique aiguë en fonction de la dose avec une issue en partie létale. On pourra éviter la lésions tissulaire locale par une injection intraveineuse seulement en connaissant la dose maximale tolérée (MTD). Celle‐ci est de 0,5 mg/kg de poids pour la chèvre, de 1,5 mg/kg pour le bovin, de 1,0 mg/kg pour le dromadaire et de 2,0 mg/kg pour le chien. L'empoissonement se reconnaît par une parésie de la musculature du squelette, une tachycardie, de la salivation et une diarrhée. Ces symptômes cliniques étaient accompagnés par une diminution de la concentration des cations sjriques Ca, Mg, Na et K. Les doses intraveineuses dépassant la MTD peuvent être suivies d'un choc et d'une issue fatale. Resumen El efecto tóxico de la aplicación intravenosa del tripanocida isometamidio (Samorin®) La aplicación intramuscular del tripanocida cloruro de isometamidio (Samorin®, May y Baker), recomend...

Safety and efficacy of three trypanocides in confirmed field cases of trypanosomiasis in working equines in The Gambia: a prospective, randomised, non-inferiority trial

“…A low therapeutic index and dose-dependent toxicity [67] related to an anticholinesterase effect [68] has been documented in other species, producing similar signs. The adverse reaction is associated with decreased serum cations (calcium, magnesium, sodium and potassium) [69] consistent with third space losses and occasional deaths have been reported in cattle [70]. The small stature of donkeys could render them more vulnerable to over-estimation of body weight.…”

“…Division of the drug dose into two fractions given an hour apart, or reducing the total dose could both decrease the occurrence of adverse effects if they are related to peak plasma concentration. The use of intramuscular isometamidium administration was discounted in equines due to reported associated severe muscle necrosis [69]. Further work is required to investigate isometamidium pharmacokinetics in equines.…”

The health of working dogs in conservation in Africa

“…Intravenous administration is an effective treatment for trypanosomiasis in horses and avoids the muscular necrosis from intramuscular administration ( 56 ). This route of administration in dogs could be a way of avoiding side effects, which would be possible in an experimental trial but would need training in intravenous catheter placement and accurate dosing to limit potential toxicities ( 57 ). Regular screening as a means of detecting infection early, treating early and thereby reducing morbidity was reported to be successful by one of the participants who lived in an area with a high tsetse challenge (in combination with fly repellent strategies).…”