Ivermectin and Moxidectin
Ivermectin and moxidectin belong to the group of macrocyclic lactones, which are used as antiparasitics in veterinary medicine. These active ingredients are highly effective substances against ecto- and endoparasites and are primarily used in livestock such as horses and cattle. Both substances work by enhancing GABA-mediated (gamma-aminobutyric acid) signal transmission in the nervous system of parasites, leading to paralysis and ultimately the death of the parasites.
In mammals, the blood-brain barrier normally prevents these substances from entering the central nervous system, thus ensuring high therapeutic safety. However, certain animal species and breeds may have genetic peculiarities that impair this protective barrier, potentially leading to severe poisonings.
Of particular importance here is the MDR1 gene defect (Multi-Drug Resistance-1 gene, also referred to as ABCB1 gene), which occurs in various dog breeds. This gene codes for a transport protein called P-glycoprotein, which plays a crucial role in the function of the blood-brain barrier by actively transporting potentially harmful substances out of the brain tissue. In animals with the MDR1 gene defect, this protective system is impaired, allowing ivermectin and moxidectin to enter the brain unimpeded and exert their toxic effects there.
The most important facts at a glance
Ivermectin and moxidectin poisonings pose a serious threat to dogs and cats, especially for dogs with the MDR1 gene defect. These macrocyclic lactones, primarily used for parasite control in livestock, can cause severe neurological symptoms in sensitive animals even at low doses.
The MDR1 gene defect, which is common in certain dog breeds such as Collies, Australian Shepherds, and German Shepherds, leads to impaired function of the blood-brain barrier, allowing these active ingredients to enter the brain unimpeded. There, they enhance GABA-mediated signal transmission, leading to an inhibition of the central nervous system.
Clinical symptoms range from mild signs such as salivation and ataxia to life-threatening conditions with seizures, coma, and respiratory depression. Diagnosis is primarily based on anamnesis, clinical symptoms, and the exclusion of other causes of neurological disorders.
Since no specific antidote exists, therapy consists of decontamination, symptomatic treatment, and intensive medical support. Innovative approaches such as Lipid-Rescue Therapy can support detoxification. The prognosis depends on the ingested dose, the timing of therapy initiation, and the intensity of supportive measures.
Preventive measures such as MDR1 gene tests in predisposed breeds, careful medication selection, and pet owner education are crucial to prevent poisonings. In case of suspected poisoning, immediate veterinary treatment is required, as time is a critical factor for therapeutic success.
Causes, development and progression
Ivermectin and moxidectin are antiparasitics used in veterinary medicine. Both substances are used for deworming in horses.
There is a natural blood-brain barrier, so these substances normally cannot reach the brain, thus providing a large therapeutic safety margin for mammals.
The main cause of ivermectin and moxidectin poisoning in dogs and cats is the improper use of these active ingredients. Since these substances are generally not approved for dogs and cats (with the exception of some specific formulations in very low doses), poisonings frequently result from:
- Incorrect dosages during off-label use by veterinarians or pet owners
- Accidental ingestion of preparations intended for other animal species
- Ingestion of feces from recently dewormed horses or other livestock
- Self-medication by pet owners with human or veterinary preparations
The MDR1 gene defect is particularly common in herding dog breeds such as Collie, Border Collie, Australian Shepherd, Shetland Sheepdog, as well as German and White Shepherds. The prevalence of the defect varies considerably depending on the breed:
- In Collies, the prevalence is approximately 70–80%
- In Australian Shepherds, about 50%
- In Border Collies, about 10%
- In German Shepherds, about 6–10%
The gene defect is inherited in an autosomal recessive manner, meaning that animals can be either homozygous affected (MDR1-/-), heterozygous (MDR1+/-), or homozygous intact (MDR1+/+). Homozygous affected animals are most at risk, but heterozygous animals also show increased sensitivity to these active ingredients.
The minimum toxic dose for ivermectin in dogs with the MDR1 gene defect is less than 0.1 mg/kg body weight, while dogs without this defect can tolerate doses up to 2.5 mg/kg without clinical symptoms. For moxidectin, the acute LD50 (dose at which 50% of animals die) in dogs with the gene defect is approximately 0.2 mg/kg, while in dogs without the gene defect, it is approximately 80 mg/kg. Cats generally tolerate ivermectin better than dogs, with an LD50 of approximately 1.0 mg/kg.
Mechanism of action
For many dogs, ivermectin and moxidectin are highly toxic.
This is due to a specific gene defect found in German Shepherds and White Shepherds, as well as many herding dog breeds (Collies, Border Collies, Australian Shepherds, Shelties, Bobtails, and others).
This results in many substances overcoming the blood-brain barrier that normally protects the brain, and can thus trigger severe poisonings.
Ivermectin and moxidectin exert their toxic effect in the brain by increasing the effect of various neurotransmitters (GABA).
Even the ingestion of feces from horses that have been dewormed with ivermectin or moxidectin can lead to poisoning in these dogs.
The minimum toxic dose for ivermectin in dogs of these breeds when ingested orally is < 0.1 mg/kg body weight.
Moxidectin is better tolerated in sensitive breeds than ivermectin.
The acute LD50 when administered orally is 80 mg/kg body weight in dogs without the gene defect and 0.2 mg/kg body weight in dogs with the gene defect under the same conditions.
Cats tolerate ivermectin better than dogs. For them, the LD50 is 1.0 mg/kg.
Ivermectin and moxidectin are not approved for dogs and cats.
An exception is the treatment of heartworm infection. In this case, if other medications fail, ivermectin is used at a dosage of 0.006 mg/kg body weight.
Supplements
A) Crossing the Blood-Brain Barrier
- In case of overdose or genetic defect of the MDR1 gene (Multidrug Resistance 1), which codes for P-glycoprotein, ivermectin or moxidectin enters the CNS.
- There, the active ingredients bind to GABA-gated chloride channels in the brain, which are present in the CNS of mammals.
- GABAergic neurons are inhibitory. Excessive stimulation leads to strong inhibition of neuronal activity.
B) CNS Depression and Neurotoxicity
- This results in pronounced central depression:
- Ataxia
- Lethargy
- Muscle Twitches
- Coma
- In severe cases: respiratory arrest and death
C) MDR1 Mutation
- Particularly affected are dog breeds such as Collies, Shelties, Australian Shepherds, Border Collies, Bobtails, among others, in which a defective MDR1 gene (also known as ABCB1) occurs.
- These animals can suffer life-threatening poisoning even at a therapeutic dose.
- Symptoms can also occur in young animals or older, sick animals with an immature or damaged BBB.
Differences between Ivermectin and Moxidectin
| Property | Ivermectin | Moxidectin |
| Potency | Less lipophilic, faster elimination | More lipophilic, longer half-life |
| Toxicity in MDR1 | High | High, potentially even more severe |
| Application | Tablets, spot-on, injections | Spot-on, injections, oral preparations |
| Characteristic | Narrow therapeutic window in dogs | Accumulates in fatty tissue |
Species-specific Characteristics
Dog:
- Relatively sensitive to ivermectin and moxidectin.
- MDR1 defects are the largest risk factor group.
- Toxic dose of Ivermectin:
- from 0.2 mg/kg in MDR1-affected dogs
- from 2–5 mg/kg in healthy dogs
- Toxic dose of Moxidectin: similar, but with prolonged duration of action due to the longer half-life.
Cat:
- Generally less sensitive, but sensitive to high spot-on doses, e.g., when products for large dogs are mistakenly applied to cats.
- Symptoms similar to those in dogs, possibly with more pronounced salivation and ataxia.
Summary of the Toxic Mechanism of Action
| Target Structure | Effect |
| GABA receptors in the CNS | Increased inhibition → central depression, unconsciousness, respiratory arrest |
| MDR1 transporter (if defective) | No protection against CNS exposure → increased neurotoxicity |
| Glutamate-gated chloride channels (only in parasites) | therapeutic target mechanism (irrelevant for vertebrates) |
Conclusion
Ivermectin or moxidectin poisoning in dogs and cats occurs due to overdose or genetic predisposition (MDR1 defect) and, via increased GABAergic inhibition in the CNS, leads to severe neurological symptoms, up to death from respiratory arrest. Collie-type dog breeds are particularly at risk. Immediate veterinary care is essential – with early intervention, recovery is possible, but the course can be protracted.
Symptoms of intoxication
Symptoms begin a few hours to 1 day after ingestion and, depending on the dose, intensify over the next few hours to days.
- Salivation
- Pupil dilation (Ivermectin)
- Vomiting
- Decreased heart rate (bradycardia)
- Disruption of temperature regulation (hypo- or hyperthermia)
- Disorientation
- Balance disorders (ataxia)
- Tremor
- Seizures.
With the progression of intoxication, there is
- Weakness
- Lateral recumbency
- Dizziness
- Coma
- Respiratory depression
Supplements
The clinical symptoms of ivermectin or moxidectin poisoning typically develop within 4 to 12 hours after ingestion, but depending on the ingested dose and individual sensitivity, they may also appear only after 24 hours. The severity of symptoms correlates with the concentration of the active ingredients in the central nervous system and increases over time.
Symptoms can be categorized into different stages:
Early phase (mild to moderate poisoning):
- Increased salivation (hypersalivation)
- Mydriasis (pupil dilation, especially with ivermectin)
- Vomiting and nausea
- Bradycardia (slowed heart rate)
- Disorders of temperature regulation (both hypo- and hyperthermia)
- Behavioral changes and disorientation
- Ataxia (balance and coordination disorders)
- Muscle tremors (tremor)
Late phase (severe poisoning):
- Pronounced muscle weakness
- Lateral recumbency with inability to stand
- Seizures and convulsions
- Progressive dullness of consciousness up to coma
- Respiratory depression
- Circulatory failure
In cats, neurological symptoms may differ slightly and more frequently include hyperesthesia (exaggerated sensitivity to tactile stimuli), hypersalivation, and agitation, before progressing to depression and coma.
Symptoms can persist for several days to weeks, depending on the ingested dose and presence of the MDR1 gene defect, as ivermectin and moxidectin have a long half-life in the body and can accumulate in fatty tissue.
Diagnosis
The diagnosis of ivermectin or moxidectin poisoning is primarily based on anamnesis, clinical symptoms, and the exclusion of other causes of neurological disorders. Early and precise diagnosis is crucial for successful treatment.
Anamnesis:
A thorough questioning of the pet owner is essential to identify possible sources of exposure. Important questions include:
- Did the animal have access to dewormers for horses or other livestock?
- Was the animal recently treated with antiparasitics?
- Is it possible that the animal ingested feces from recently dewormed horses?
- Does the animal belong to a breed commonly affected by the MDR1 gene defect?
Clinical Examination:
The neurological examination typically shows symptoms of diffuse CNS depression with ataxia, mydriasis, decreased consciousness, and possibly seizures. Vital parameters may include bradycardia, hypotension, and respiratory depression.
Laboratory Diagnostics:
- General blood tests (complete blood count, serum biochemistry) are usually unremarkable, but can be helpful for ruling out other diseases and assessing the general condition.
- Toxicological analyses for the direct detection of ivermectin or moxidectin in blood or urine are possible, but often not readily available in practice.
- MDR1 Gene Test: In cases of suspected MDR1 gene defect, a gene test can be performed, which is usually too time-consuming for acute treatment but can be relevant for future medication selection.
Differential Diagnoses:
Other causes for neurological symptoms must be ruled out, such as:
- Poisoning by other neurotoxins (organophosphates, metaldehyde, strychnine)
- Metabolic disorders (hypoglycemia, hepatic encephalopathy)
- Infectious encephalitides
- Traumatic brain injuries
- Epileptic seizures of other etiologies
The combination of typical symptoms, breed predisposition, and exposure history is usually sufficient for a presumptive diagnosis that requires immediate therapeutic measures.
Therapeutic principles
Gastrointestinal decontamination is performed by immediate gastric emptying through inducing vomiting or repeated gastric lavage, and intestinal cleansing by repeated administration of activated charcoal and bowel irrigation with Glauber’s salt.
There is no specific antidote.
Physostigmine can be attempted, but the effect lasts only for a very short time.
The therapy is symptomatic.
In the advanced stage of intoxication, only supportive measures are possible to stabilize vital functions and treat symptoms such as antiemetics, anticonvulsant medications, and maintaining body temperature.
Special attention, as with all intoxications, must be paid to water, electrolyte, and acid-base balance.
Due to the mechanism of action of ivermectin and moxidectin in the brain, the anticonvulsant medications (benzodiazepines, barbiturates) usually primarily used to control seizures are not suitable. Anesthetics such as propofol are preferred, initially as a bolus to control seizures and then continued as a low-dose continuous drip infusion until symptoms subside.
The administration of lipids to bind fat-soluble toxins from tissues into a form that can be transported via the blood is also part of supportive therapy.
Supplements
Prognosis & follow-up care
The prognosis is guarded to good and depends on the ingested dose, the time of presentation to the veterinarian, and the duration of consistent therapy.
The prognosis for ivermectin or moxidectin poisoning depends on several factors, including the ingested dose, the time of therapy initiation, the presence of an MDR1 gene defect, and the intensity of supportive measures.
Prognostic factors:
- Mild to moderate poisonings have a good prognosis with adequate therapy.
- Severe poisonings with coma and respiratory depression have a guarded to poor prognosis.
- The earlier therapy begins, the better the prospects for success.
- Animals that show clinical improvement within the first 48-72 hours have a more favorable prognosis.
- The recovery phase for severe poisonings can last several weeks.
Follow-up care:
After the acute phase of poisoning, careful follow-up care is essential:
- Regular follow-up examinations:
- Neurological examinations to assess recovery
- Monitoring of organ functions, especially liver and kidneys
- Physiotherapy:
- In cases of prolonged neurological deficits, physiotherapy can support rehabilitation
- Passive range of motion exercises to maintain joint function
- Later, active exercises to restore coordination and muscle strength
- Nutritional management:
- Tailored diet during the recovery phase
- Support with food intake if necessary
- Preventive measures:
- MDR1 gene test for animals with unknown status
- Owner education on the safe handling of antiparasitics
- Creation of a list of medications that should be avoided in MDR1-affected animals
- Identification of the animal (e.g., by a tag on the collar) with a note on the MDR1 status for emergencies
- Long-term prognosis:
Most animals recover completely if they survive the acute phase. However, in some cases, subtle neurological deficits may persist, such as mild coordination disorders or altered behaviors. These residual symptoms usually improve over time but can be permanent in rare cases.
Follow-up care should be individually tailored to the patient and can last several weeks to months depending on the severity of the poisoning and recovery progress.
Research outlook
Research in the field of ivermectin and moxidectin poisonings in small animals is continuously evolving, with promising approaches for improved diagnostics, therapy, and prevention.
Genetic Research:
Recent studies are investigating the genetic basis of the MDR1 mutation in more detail and have identified further polymorphisms that can influence sensitivity to macrocyclic lactones. Scientists are working on more comprehensive gene tests that capture not only the classic MDR1 gene defect but also other relevant genetic variants that affect drug sensitivity.
Rapid Diagnostics:
Researchers are developing point-of-care tests that aim to enable rapid detection of MDR1 status, which would be particularly valuable in emergency situations. These tests could be available in every veterinary practice in the future and allow for immediate risk assessment.
Therapeutic Innovations:
Lipid-Rescue Therapy continues to be researched, with a focus on optimal dosing protocols and timing of administration. Studies show promising results, especially when therapy is initiated early.
Furthermore, specific antagonists for macrocyclic lactones are being investigated, which could directly reach the site of action in the brain and block excessive GABA activation. Such substances could serve as true antidotes in the future.
Pharmacokinetic Models:
Advances in pharmacokinetics enable more precise predictions about the distribution and elimination of ivermectin and moxidectin in various animal species and genetic variants. These models can help develop individualized treatment protocols and better estimate the duration of therapy.
International Collaboration:
Global databases on poisoning cases are being established to better document rarer manifestations and long-term consequences. These collaborative approaches enable a more comprehensive understanding of toxicity and more effective treatment strategies.
Prevention Strategies:
Innovative approaches to prevention include the development of smartphone apps that assist pet owners in medication selection, as well as improved labeling systems for animals with known MDR1 status. Some research groups are working on biosensors that can detect the presence of macrocyclic lactones in animal feed or environments.
Ongoing research in this field promises to significantly improve the diagnosis, treatment, and prevention of ivermectin and moxidectin poisonings in small animals in the coming years, ultimately leading to better care for affected animals.
Frequently asked questions (FAQs)
- Which dog breeds are particularly at risk for ivermectin and moxidectin poisoning?
Particularly at risk are dog breeds with a high prevalence of the MDR1 gene defect, including Collies (70–80%), Australian Shepherds (50%), Shetland Sheepdogs, Border Collies (10%), German Shepherds (6–10%), White Shepherds, Bobtails (Old English Sheepdogs), and other herding dog breeds. Mixed-breed dogs with ancestry from these breeds can also be affected.
- How can I determine if my dog has the MDR1 gene defect?
The MDR1 status can be determined by a gene test. This test is offered by various laboratories and only requires a saliva or blood sample. For dogs from at-risk breeds, this test is recommended before administering medications that may be problematic for MDR1-affected animals.
- Is it dangerous if my dog eats horse feces?
If horses have recently been dewormed with ivermectin or moxidectin, their feces may contain sufficient amounts of these active ingredients to cause poisoning in sensitive dogs, especially those with the MDR1 gene defect. Therefore, dogs should not have access to feces from recently dewormed horses.
- What immediate measures should I take if I suspect my pet has ingested ivermectin or moxidectin?
Contact your veterinarian or a veterinary emergency clinic immediately. If ingestion occurred within the last 1–2 hours and the animal shows no symptoms, the veterinarian may induce vomiting. Transport the animal calmly and avoid additional stressors. If possible, bring the packaging of the ingested product with you.
- How long does recovery take after ivermectin or moxidectin poisoning?
The recovery time is highly variable and depends on the ingested dose, MDR1 status, and the severity of symptoms. Mild cases can recover within 24–48 hours, while severe poisonings may require a recovery period of several weeks. Complete elimination of the active ingredients from the body can take 1-4 weeks due to their long half-life and accumulation in fatty tissue.
- Are there safe alternatives to ivermectin and moxidectin for dogs with MDR1 gene defect?
Yes, there are various antiparasitics that can be safely used in dogs with MDR1 gene defect, including certain formulations with milbemycin oxime, selamectin, pyrantel, fenbendazole, and praziquantel. The selection should always be made in consultation with a veterinarian, who can consider the individual needs and risks.
- Can cats also have the MDR1 gene defect?
In cats, the MDR1 gene defect has not yet been clinically proven to be relevant. Cats are generally less sensitive to ivermectin than dogs with the MDR1 defect, but can still develop poisoning symptoms if overdosed. The LD50 for ivermectin in cats is approximately 1.0 mg/kg.
- Which other medications are problematic for dogs with MDR1 gene defect?
In addition to ivermectin and moxidectin, other medications can also be problematic for MDR1-deficient dogs, including loperamide, certain chemotherapeutics (vincristine, vinblastine, doxorubicin), some antibiotics (e.g., doxycycline in high doses), acepromazine, and others. A complete list should be discussed with the veterinarian.
- Is Lipid-Rescue Therapy effective in all poisoning cases?
Lipid-Rescue Therapy shows promising results in poisonings with lipophilic substances such as ivermectin and moxidectin, but it is not equally effective in all cases. Success depends on the timing of administration, the dose ingested, and the individual response. It is used as a supplementary therapy and does not replace other supportive measures.
- Can ivermectin or moxidectin poisoning cause permanent damage?
With timely and adequate treatment, most animals recover completely. However, in severe poisonings or delayed onset of therapy, permanent neurological deficits may occur in rare cases. These can range from subtle behavioral changes to persistent coordination disorders. Thorough aftercare and rehabilitation can help minimize possible long-term consequences.
Literature
- Linek, J., Spiess, C., Dallmeyer, J., & Geyer, J. (2007). Ivermectin intoxication in three dogs with and without MDR1 gene defect due to an oral antiparasitic approved for horses. Tierärztl. Prax, 35.
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