Milbemycin oxime is a broad-spectrum antiparasitic active ingredient used in veterinary medicine in dogs and cats against internal parasites (e.g. roundworms). It is not used against agricultural and household pests. It belongs to the chemical class of the macrocyclic lactones.
Common name: MILBEMYCIN OXIME
Type: veterinary medicine
Chemical class: macrocyclic lactone
EFFICACY AGAINST PARASITES
Type of action: Systemic & contact broad-spectrum endoparasiticide and ectoparasiticide.
Main veterinary parasites controlled: roundworms (nematodes), incl. heartworm prevention (Dirofilaria spp), mites.
Efficacy against a specific parasite depends on the delivery form and on the dose administered.
Click here for general information on features and characteristics of PARASITICIDES.
Click here to view the article in this site with the most common dosing recommendations for milbemycin oxime used in domestic animals.
Oral LD50, rat, acute*: 980 mg/kg mg/kg
Dermal LD50, rat, acute*: not found
* These values refer to the active ingredient. Toxicity has to be determined for each formulation as well. Formulations are usually significantly less toxic than the active ingredients.
MRL (maximum residue limit): Not applicable: not approved for livestock
Withholding periods for meat, milk, eggs: Not applicable: not approved for livestock
WARNING: Dogs of some breeds do not tolerate macrocyclic lactones or other medicines (e.g. emodepside) that can cross the blood-brain barrier. They can suffer more or less serious adverse effects if treated at dose rates slightly higher than the recommended ones. Consequently dosing must be as accurate as possible. This is the case for Collies and related breeds, which have a mutation in the MDR-1 gene that affects the blood-brain barrier and makes it more permeable to such compounds than in dogs without this mutation. Besides Collies, other dog breeds have shown similar problems, although the MDR-1 mutation has not been confirmed in all of them.
The breeds more affected by this mutation are (% frequency): Collie (70%), Long-haired Whippet (65%), Australian Shepherd (50%, also mini), McNab (30%), Silken Windhound (30%), English Shepherd (15%), Shetland Sheepdog (15%), English Shepherd (15%), German Shepherd (10%), Herding Breed Cross (10%). Other less affected breeds are: Old English Sheepdog, Border Collie, Berger Blanc Suisse, Bobtail, Wäller. The only may to be sure that a dog is affected or not is to test for it. As more dogs are tested it is likely that the mutation is discovered in other breeds, or that the frequencies change.
Learn more about milbemycin oxime safety.
General information on the safety of veterinary antiparasitics is available in specific articles in this site (click to visit):
- General safety of antiparasitics for domestic animals
- General safety of antiparasitics for humans
- General safety of antiparasitics for the environment
It is obvious that veterinary products are not intended for and should never be used on humans!!!
MARKETING & USAGE
Decade of introduction: 1990
Introduced by: CIBA-GEIGY → NOVARTIS → ELANCO
Some original brands: INTERCEPTOR, SENTINEL, MILBEMAX
Patent: Expired (particular formulations may be still patent-protected)
Use in LIVESTOCK: No
Use in HORSES: NO
Use in DOGS and CATS: Yes, moderate
Main delivery forms:
Use in human medicine: No
Use in public/domestic hygiene: No
Use in agriculture: No
Generics available: Yes, rather few
SELECTION OF COMMERCIAL BRANDS WITH MILBEMYCIN OXIME
- INTERCEPTOR: for DOGS and CATS - tablets against HEARTWORMS and ROUNDWORMS - milbemycin oxime
- MILBEMAX: for DOGS and CATS - tablets against HEARTWORMS, ROUNDWORMS and TAPEWORMS - milbemycin oxime + praziquantel
- NEXGARD SPECTRA: for DOGS - tablets against FLEAS, TICKS, HEARTWORMS and ROUNDWORMS - afoxolaner + milbemycin oxime
- PROGRAM PLUS: for DOGS - tablets against FLEAS, HEARTWORMS and ROUNDWORMS - lufenuron + milbemycin oxime
- SENTINEL: for DOGS- tablets against FLEAS, HEARTWORMS and ROUNDWORMS - lufenuron + milbemycin oxime
- SENTINEL SPECTRUM: for DOGS - tablets against FLEAS, HEARTWORM, ROUNDWORMS and TAPE WORMS - lufenuron + milbemycin oxime + praziquantel
- TRIFEXIS: for DOGS - tablets against FLEAS, HEARTWORMS and ROUNDWORMS - spinosad + milbemycin oxime
- PANORAMIS: for DOGS - tablets against FLEAS, HEARTWORMS and ROUNDWORMS - spinosad + milbemycin oxime
In pets: Yes, reported to ivermectin in heartworm microfilariae in the USA (mainly in the South), with cross-resistance to other macrocyclic lactones, including milbemycin oxime.
Visit also the section in this site about parasite resistance to antiparasitics and more specifically to milbemycin oxime.
Milbemycin oxime is a macrocyclic lactone obtained from fermentation products of the soil microorganism Streptomyces hygroscopicus var. aureolacrimosus. It is a derivative of the milbemycins and not of avermectins as several other macrocyclic lactones (e.g. ivermectin). It is used only on dogs and cats, alone or in combination products (e.g. with lufenuron, a flea development inhibitor; or with praziquantel, a taenicide). NOVARTIS has not developed a livestock product with milbemycin oxime.
Efficacy of milbemycin oxime
Milbemycin oxime at the therapeutic dose is an effective heartworm (Dirofilaria spp) preventative and it controls a few other roundworms (e.g. Ancylostoma spp, Angiostrongylus vasorum, Crenosoma vulpis, Toxocara canis, Toxocara cati, Trichuris spp). Some mite species may be controlled at higher doses.
Milbemycin oxime alone at the therapeutic dose is ineffective against tapeworms, flukes, fleas, ticks, lice, mosquitoes and flies. There are combination products to broaden the spectrum of activity: with lufenuron or spinosad to control fleas, and with praziquantel to control tapeworms.
Pharmacokinetics of milbemycin oxime
After oral administration to dogs milbemycin oxime is quickly and almost completely absorbed. Peak plasma concentration is reached 2 to 4 hours later, and subsequently declines with a half-life of 1-3 days. Bioavailability is about 80%.
In rats, metabolism seems to be complete, since unchanged milbemycin oxime was not found in urine or feces. High concentrations of milbemycin oxime are found in the liver and in body fat.
As a general rule, due to a different pharmacokinetic behavior the anthelmintic effect is longer for milbemycin oxime than for ivermectin, although this strongly depends on the delivery form and the administered dose.
Mechanism of action
As all macrocyclic lactone milbemycin oxime acts as agonist of the GABA (gamma-aminobutyric acid) neurotransmitter in nerve cells and also binds to glutamate-gated chloride channels in nerve and muscle cells of invertebrates. In both cases it blocks the transmission of neuronal signals of the parasites, which are either paralyzed and expelled out of the body, or they starve. It also affects the reproduction of some parasites by diminishing oviposition or inducing an abnormal oogenesis.
In mammals the GABA receptors occur only in the central nervous system (CNS), i.e. in the brain and the spinal chord. But mammals have a so-called blood-brain barrier that prevents microscopic objects and large molecules to get into the brain. Consequently macrocyclic lactones are much less toxic to mammals than to the parasites that do not have such a barrier, which allows quite high safety margins for use on livestock and pets. A notable exception to this are those dogs that carry the MDR-1 mutation previously mentioned.
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