The EPA issued an advisory a couple years ago about spot-on products after receiving over 44,000 reports of adverse reactions, including 600 deaths. Don't be another statistic.
Bravecto has an active ingredient called Fluralaner. Due to the recent introduction, there is very little knowledge on tolerance in different dog breeds or in young, old or otherwise weak animals. Although there are reports of toxicity and death. Within 9 days of being given the product the dog developed anorexia, vomiting, and bloody diarrhea. This was followed by elevated calcium levels and multi-organ failure. Once you put them in you can’t get them out. Most owners and veterinarians do not associate the side effects with the chemicals because the side effects may not show up for days to weeks after the drug is given. Many times the side effects do not show up until the second or third dose is given.
As Clayton Veterinary Associates put it: "Protect your pets and don’t give in to the scare tactics of big pharma and the media."
Do not use flea and tick products unless they are all natural. See all natural products here...
As Clayton Veterinary Associates put it: "Protect your pets and don’t give in to the scare tactics of big pharma and the media."
Do not use flea and tick products unless they are all natural. See all natural products here...
Acute Toxicity and Tolerance of Fluralaner
Sourced from: Parasitipedia
LD50 acute, rats, p.o. >2000 mg/kg
LD50 acute, rats, dermal >2000 mg/kg.
In rats the main target organ in the repeated dose toxicity studies was the liver. Increased organ weight, hepatocellular fatty change and effects in related blood parameters were observed mainly in the highest dose groups, thus at large overdoses relative to recommended/proposed use in the dogs. At the dose of 400 mg/kg bw/day effects on thymus and adrenal weight and microscopic changes in lung and thymus were observed. Comparable effects were reported after dermal administration at very high doses.
In Beagle puppies treated at 1x, 3x and 5x the maximum recommended dose (= 25 to ~60 mg/kg bw) three times with a 56 day interval, fluralaner was well tolerated. There was no evidence of product-related effects in food consumption, body weight, clinical parameters or physical examination variables, or clinical pathology findings.
Sourced from: Parasitipedia
LD50 acute, rats, p.o. >2000 mg/kg
LD50 acute, rats, dermal >2000 mg/kg.
In rats the main target organ in the repeated dose toxicity studies was the liver. Increased organ weight, hepatocellular fatty change and effects in related blood parameters were observed mainly in the highest dose groups, thus at large overdoses relative to recommended/proposed use in the dogs. At the dose of 400 mg/kg bw/day effects on thymus and adrenal weight and microscopic changes in lung and thymus were observed. Comparable effects were reported after dermal administration at very high doses.
In Beagle puppies treated at 1x, 3x and 5x the maximum recommended dose (= 25 to ~60 mg/kg bw) three times with a 56 day interval, fluralaner was well tolerated. There was no evidence of product-related effects in food consumption, body weight, clinical parameters or physical examination variables, or clinical pathology findings.
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In a pivotal reproductive study Beagle dogs were treated up to 3X the recommended dose 3 times at 8 weeks intervals starting 12 weeks (males) and 4 weeks (females) before expected mating. Treatment continued until the females had whelped (males) or the puppies were weaned (females). No adverse reactions were observed in adult dogs and no detrimental effect on reproductive functions, number of puppies and puppy survival was detected.
Safety data collected during field studies in Europe and the USA showed that the product was in general well tolerated. In the European field study mild and transient diarrhea, vomiting, lack of appetite and drooling were recorded in 1.6% of dogs in the first days after treatment. Toxic Symptoms, Side Effects, Adverse Drug Reactions (ADRs) caused by Fluralaner |
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The most frequent ADRs to be expected are:
Vomiting (~7%)
Decreased appetite (~6.7%)
Diarrhea (~5%)
Lethargy (~5.5%)
Excessive thirst (polydipsia) (~2%)
Excessive gas in stomach or intestine (flatulence) (~1%)
A potential administration error in dogs is administration to small dogs of tablets approved for larger animals.
In general dogs tolerate very well fluralaner at the therapeutic dose range (25 to ~57 mg/kg) apart from the ADRs previously indicated.
Vomiting (~7%)
Decreased appetite (~6.7%)
Diarrhea (~5%)
Lethargy (~5.5%)
Excessive thirst (polydipsia) (~2%)
Excessive gas in stomach or intestine (flatulence) (~1%)
A potential administration error in dogs is administration to small dogs of tablets approved for larger animals.
In general dogs tolerate very well fluralaner at the therapeutic dose range (25 to ~57 mg/kg) apart from the ADRs previously indicated.
Antidote and Treatment of Fluralaner Intoxication
There is no antidote for fluralaner poisoning.
Treatment consists in preventing further exposure together with supportive and symptomatic measures.
After accidental ingestion stomach lavage as well as administration of active charcoal administration and laxatives may be advisable.
There is no antidote for fluralaner poisoning.
Treatment consists in preventing further exposure together with supportive and symptomatic measures.
After accidental ingestion stomach lavage as well as administration of active charcoal administration and laxatives may be advisable.
Pharmacokinetics of Fluralaner
Fluralaner orally administered to dogs was rapidly absorbed into blood. Max. blood levels were reached 24 hours after administration. Mean half-life in blood was 12 to 15 days. Bioavailability was higher when fluralaner was administered to fed animals.
After absorption fluralaner was well distributed to tissues. Highest concentrations were found in fat, followed by liver, kidney and muscle. Fluralaner was also quantifiable in hair and skin. Clearance from tissues was very low.
Absorbed fluralaner binds strongly (~100%) to blood proteins but it seems not to cause displacement of other drugs with high protein binding capacities.
Excretion occurs mainly in the form of unchanged parent molecule, primarily in the feces (~90% of the dose). Less than 0.01% of the dose was found in urine, indicating that renal excretion plays a marginal role.
Fluralaner orally administered to dogs was rapidly absorbed into blood. Max. blood levels were reached 24 hours after administration. Mean half-life in blood was 12 to 15 days. Bioavailability was higher when fluralaner was administered to fed animals.
After absorption fluralaner was well distributed to tissues. Highest concentrations were found in fat, followed by liver, kidney and muscle. Fluralaner was also quantifiable in hair and skin. Clearance from tissues was very low.
Absorbed fluralaner binds strongly (~100%) to blood proteins but it seems not to cause displacement of other drugs with high protein binding capacities.
Excretion occurs mainly in the form of unchanged parent molecule, primarily in the feces (~90% of the dose). Less than 0.01% of the dose was found in urine, indicating that renal excretion plays a marginal role.
Environmental Toxicity of Fluralaner
Little to nothing has been published yet regarding the environmental toxicity of fluralaner. Its use in dogs as recommended is unlikely to pose a risk for the environment, and for this reason no environmental studies have been carried out for the approval of its use on dogs.
Based on its mode of action it must be assumed that fluralaner is highly toxic to both aquatic and terrestrial arthropods (insects, ticks, spiders, crustaceans, etc).
Little to nothing has been published yet regarding the environmental toxicity of fluralaner. Its use in dogs as recommended is unlikely to pose a risk for the environment, and for this reason no environmental studies have been carried out for the approval of its use on dogs.
Based on its mode of action it must be assumed that fluralaner is highly toxic to both aquatic and terrestrial arthropods (insects, ticks, spiders, crustaceans, etc).
Nexgard
The active ingredient in Nexgard is Afoxolaner. There have been reports of toxicity and death as stated above with Bravecto.
Acute Toxicity and Tolerance of Afoxolaner
LD50 acute, rats, p.o. >1000 mg/kg
LD50 acute, rats, dermal >2000 mg/kg.
In rats significant effects on body weight and/or food consumption were observed after oral administration at dose levels of 100, 300 and 1,000 mg/kg bw. Adverse effects (abnormal gait and stance, decreased body tone, piloerection) were observed after dermal administration at 2000 mg/kg bwy, though these effects were not severe or irreversible.
In puppies treated at approximately 1x, 3x and 5x the maximum recommended therapeutic dose once monthly for 3 months, followed by a further 3 administrations at two week intervals no mortalities occurred, and no test article related changes were seen in clinical parameters, daily food consumption, body weight, hematology and urinalysis parameters or plasma chemistry values.
In a repeat-dose toxicity study dogs were treated at 40, 120 and 200 mg afoxolaner/kg bw (i.e. aprox. 8x, 20x, and 35x the max. recommended dose) administered orally three times at eight week time intervals. In dogs receiving doses of 120 and 200 mg/kg bw, vomiting was observed in the 24 hours following treatment. Some dogs also showed diarrhea. Female dogs in the treatment groups had lower food consumption but no weight loss could be observed. Hematology, serum chemistry and physical examination parameters did not show dose dependent changes.
In dermal toxicity study in cats it appears that afoxolaner may cause adverse liver effects (centrilobular vacuolation, biliary hyperplasia and/or hepatocellular necrosis, only in females) in all dose groups including the lowest dose of 10 mg/kg bw. However, it is recognized that the metabolic system of cats is unique when compared e.g. with rats, dogs and human: cats have a deficient glucuronidation. For this reason the liver effects observed in the dermal study in cats are considered not relevant for user and/or target animal safety on dogs.
Acute Toxicity and Tolerance of Afoxolaner
LD50 acute, rats, p.o. >1000 mg/kg
LD50 acute, rats, dermal >2000 mg/kg.
In rats significant effects on body weight and/or food consumption were observed after oral administration at dose levels of 100, 300 and 1,000 mg/kg bw. Adverse effects (abnormal gait and stance, decreased body tone, piloerection) were observed after dermal administration at 2000 mg/kg bwy, though these effects were not severe or irreversible.
In puppies treated at approximately 1x, 3x and 5x the maximum recommended therapeutic dose once monthly for 3 months, followed by a further 3 administrations at two week intervals no mortalities occurred, and no test article related changes were seen in clinical parameters, daily food consumption, body weight, hematology and urinalysis parameters or plasma chemistry values.
In a repeat-dose toxicity study dogs were treated at 40, 120 and 200 mg afoxolaner/kg bw (i.e. aprox. 8x, 20x, and 35x the max. recommended dose) administered orally three times at eight week time intervals. In dogs receiving doses of 120 and 200 mg/kg bw, vomiting was observed in the 24 hours following treatment. Some dogs also showed diarrhea. Female dogs in the treatment groups had lower food consumption but no weight loss could be observed. Hematology, serum chemistry and physical examination parameters did not show dose dependent changes.
In dermal toxicity study in cats it appears that afoxolaner may cause adverse liver effects (centrilobular vacuolation, biliary hyperplasia and/or hepatocellular necrosis, only in females) in all dose groups including the lowest dose of 10 mg/kg bw. However, it is recognized that the metabolic system of cats is unique when compared e.g. with rats, dogs and human: cats have a deficient glucuronidation. For this reason the liver effects observed in the dermal study in cats are considered not relevant for user and/or target animal safety on dogs.
Toxic Symptoms, Side Effects, Adverse Drug Reactions (ADRs) caused by Afoxolaner
The most frequent ADRs to be expected are
Vomiting (~4%)
Dry skin (~3%)
Diarrhea (~3%)
Lethargy (~1.5%)
Eating disorders (anorexia) (~1.2%)
A potential administration error in dogs is administration to small dogs of tablets approved for larger animals.
In general dogs tolerate very well afoxolaner at the therapeutic dose range (3 to 6.8 mg/kg) apart from sporadic vomiting and diarrhea reported in a number of studies and more notably at higher dose rates: diarrhea and vomiting was observed at approximately 5x overdose (25 mg/kg bw) in Collies, and at higher doses (120 and 200 mg/kg bw) in Beagles.
The most frequent ADRs to be expected are
Vomiting (~4%)
Dry skin (~3%)
Diarrhea (~3%)
Lethargy (~1.5%)
Eating disorders (anorexia) (~1.2%)
A potential administration error in dogs is administration to small dogs of tablets approved for larger animals.
In general dogs tolerate very well afoxolaner at the therapeutic dose range (3 to 6.8 mg/kg) apart from sporadic vomiting and diarrhea reported in a number of studies and more notably at higher dose rates: diarrhea and vomiting was observed at approximately 5x overdose (25 mg/kg bw) in Collies, and at higher doses (120 and 200 mg/kg bw) in Beagles.
Antidote and Treatment of Afoxolaner Intoxication
There is no antidote for afoxolaner poisoning.
Treatment consists in preventing further exposure together with supportive and symptomatic measures.
After accidental ingestion stomach lavage as well as administration of active charcoal administration and laxatives may be advisable.
There is no antidote for afoxolaner poisoning.
Treatment consists in preventing further exposure together with supportive and symptomatic measures.
After accidental ingestion stomach lavage as well as administration of active charcoal administration and laxatives may be advisable.
Pharmacokinetics of Afoxolaner
Afoxolaner orally administered to dogs was rapidly absorbed into blood. Max. blood levels were reached 2 to 12 hours after administration. Mean half-life in blood ranged from 7.7 to 17.8 days. Bioavailability was estimated to be approx. 74%. Half-life was higher in Collies than in Beagles, but no serious adverse effects were observed after treatment of Collies at 25 mg/kg bw (i.e. ~10x the therapeutic dose).
Absorbed afoxolaner binds strongly (>99%) to blood proteins but it seems not to cause displacement of other drugs with high protein binding capacities.
In dogs afoxolaner is slowly broken down into various metabolites, the major ones being a hydroxylate and a glucuronide. Elimination of both the metabolites and the parent compound occurrs mainly via biliary excretion and to a lesser extent through urine.
Environmental Toxicity of Afoxolaner
Little to nothing has been published yet regarding the environmental toxicity of afoxolaner. Its use in dogs as recommended is unlikely to pose a risk for the environment, and for this reason no environmental studies have been carried out for the approval of its use on dogs.
Based on its mode of action it must be assumed that it is highly toxic to both aquatic and terrestrial arthropods (insects, ticks, spiders, crustaceans, etc.).
Afoxolaner orally administered to dogs was rapidly absorbed into blood. Max. blood levels were reached 2 to 12 hours after administration. Mean half-life in blood ranged from 7.7 to 17.8 days. Bioavailability was estimated to be approx. 74%. Half-life was higher in Collies than in Beagles, but no serious adverse effects were observed after treatment of Collies at 25 mg/kg bw (i.e. ~10x the therapeutic dose).
Absorbed afoxolaner binds strongly (>99%) to blood proteins but it seems not to cause displacement of other drugs with high protein binding capacities.
In dogs afoxolaner is slowly broken down into various metabolites, the major ones being a hydroxylate and a glucuronide. Elimination of both the metabolites and the parent compound occurrs mainly via biliary excretion and to a lesser extent through urine.
Environmental Toxicity of Afoxolaner
Little to nothing has been published yet regarding the environmental toxicity of afoxolaner. Its use in dogs as recommended is unlikely to pose a risk for the environment, and for this reason no environmental studies have been carried out for the approval of its use on dogs.
Based on its mode of action it must be assumed that it is highly toxic to both aquatic and terrestrial arthropods (insects, ticks, spiders, crustaceans, etc.).
