Safety of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate in dogs.

NexGard®PLUS (moxidectin, afoxolaner, and pyrantel pamoate), is an oral combination product for dogs indicated for the prevention of heartworm disease, the treatment and prevention of flea and tick infestations, and the treatment of gastro-intestinal nematode infections. The safety of this product in dogs was evaluated in three studies. Study #1 was a margin-of-safety study conducted in puppies, dosed six times at 28-day intervals at 1X, 3X, or 5X multiples of the maximum exposure dose (equivalent to 24 µg/kg moxidectin, 5 mg/kg afoxolaner, and 10 mg/kg pyrantel). In Study #2, the product was administered to ABCB1-deficient collie dogs at a 1X dose twice at a 28-day interval, and at a 3X or 5X dose once. Study #3 evaluated the safety of the product at 1X and 3X doses administered three times at 4-week intervals, to dogs harboring adult Dirofilaria immitis. In the three studies, the safety was evaluated on the basis of multiple clinical observations and physical examinations, including a complete assessment of toxicity to macrocyclic lactones, and on comprehensive clinical and anatomical pathology evaluations in Study #1. No clinically significant combination product-related effects were observed in any of the three studies. No signs of macrocyclic lactone toxicity were observed in the ABCB1-deficient collie dogs. Some mild and self-resolving instances of emesis or diarrhea were occasionally observed in the 3X and 5X dosed dogs. NexGard® PLUS was demonstrated to be safe following multiple administrations in puppies, in ABCB1-deficient collie dogs, and in microfilaremic dogs infected with adult D. immitis.

Preclinical and Clinical Characteristics of the Trichuricidal Drug Oxantel Pamoate and Clinical Development Plans: A Review.

Soil-transmitted helminths (Ascaris lumbricoides, hookworm and Trichuris trichiura) infect about one-fifth of the world's population. The currently available drugs are all highly efficacious against A. lumbricoides. However, they are only moderately efficacious against hookworm and poorly efficacious against T. trichiura. Oxantel, a tetrahydropyrimidine derivative discovered in the 1970s, has recently been brought back to our attention given its high efficacy against T. trichiura infections (estimated 76% cure rate and 85% egg reduction rate at a 20 mg/kg dose). This review summarizes the current knowledge on oxantel pamoate and its use against T. trichiura infections in humans. Oxantel pamoate acts locally in the human gastrointestinal tract and binds to the parasite's nicotinic acetylcholine receptor (nAChR), leading to a spastic paralysis of the worm and subsequent expulsion. The drug is metabolically stable, shows low permeability and low systemic bioavailability after oral use. Oxantel pamoate was found to be safe in humans, with only a few mild adverse events reported. Several clinical trials have investigated the efficacy of this drug against T. trichiura and suggest that oxantel pamoate is more efficacious against T. trichiura than the currently recommended drugs, which makes it a strong asset to the depleted drug armamentarium and could help delay or even prevent the development of resistance to existing drugs. We highlight existing data to support the use of oxantel pamoate against T. trichiura infections.

An ocular myasthenia gravis attack after oral pyrantel pamoate: An unusual case report.

RATIONALE: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction that can be triggered by anticholinergic agents. PATIENT CONCERNS: We present a 4-year-old female patient who was admitted to the outpatient clinic. She complained of drooped eyelids, which first appeared 2 days after taking a 200 mg dose of pyrantel pamoate. Past medical history is negative. DIAGNOSES AND TREATMENT: She was hospitalized with a diagnosis of ocular type MG, and pyridostigmine (40 mg/day) treatment was started. OUTCOMES: The patient recovered, and subsequently, the treatment dose was tapered. CONCLUSION: Pyrantel is an antihelminthic that acts as an agonist of nicotinic acetylcholine receptors (AChRs) of nematodes and exerts its therapeutic effects by depolarizing their muscle membranes. Consequently, there may be an association between pyrantel pamoate and MG.

Off-target effects of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel-pamoate, and albendazole plus oxantel-pamoate on the human gut microbiota.

Soil-transmitted helminths infect 1.5 billion people worldwide. Treatment with anthelminthics is the key intervention but interactions between anthelminthic agents and the gut microbiota have not yet been studied. In this study, the effects of four anthelminthic drugs and combinations (tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel-pamoate, and albendazole plus oxantel-pamoate) on the gut microbiota were assessed. From each hookworm infected adolescent, one stool sample was collected prior to treatment, 24 h post-treatment and 3 weeks post-treatment, and a total of 144 stool samples were analyzed. The gut bacterial composition was analyzed using 16S rRNA gene sequencing. Tribendimidine given alone or together with oxantel-pamoate, and the combination of albendazole and oxantel pamoate were not associated with any major changes in the taxonomic composition of the gut microbiota in this population, at both the short-term post-treatment (24 h) and long-term post-treatment (3 weeks) periods. A high abundance of the bacterial phylum Bacteroidetes was observed following administration of tribendimidine plus ivermectin 24 h after treatment, due predominantly to difference in abundance of the families Prevotellaceae and Candidatus homeothermaceae. This effect is transient and disappears three weeks after treatment. Higher abundance of Bacteroidetes predicts an increase in metabolic pathways involved in the synthesis of B vitamins. This study highlights a strong relationship between tribendimidine and ivermectin administration and the gut microbiota and additional studies assessing the functional aspects as well as potential health-associated outcomes of these interactions are required.

Combination deworming for the control of double-resistant cyathostomin parasites - short and long term consequences.

Equine cyathostomin are pervasive gastrointestinal parasites with wide-spread resistance to the benzimidazole and tetrahydropyrimidine drug classes worldwide. Combination deworming has been proposed as a more sustainable parasite control strategy. Simulation studies have found combination deworming to be effective in controlling drug resistant ovine trichostrongylid parasites. One equine study demonstrated an additive effect of a combination of oxibendazole and pyrantel pamoate against cyathostomins. However, this is the only equine study evaluating combination therapy, and the effects of repeated combination treatments administered over time remain unknown. The purpose of this study was to observe the efficacy of repeated oxibendazole/pyrantel pamoate combination therapy administered over one year against a cyathostomin population with resistance to benzimidazole and pyrantel products. Fecal egg counts were determined for the entire herd (N = 21) at the day of anthelmintic treatment and at two-week intervals for eight weeks post treatment. Starting efficacies of oxibendazole (OBZ, 10 mg/kg) and pyrantel pamoate (PYR, 6.6 mg base/kg) were 66.7% and 63.3%, respectively. Hereafter, the herd was treated four times with an oxibendazole/pyrantel pamoate combination, eight weeks apart, followed by repeating the single active treatments before concluding the study. While the first combination treatment exhibited an additive effect of the two active ingredients, this efficacy was not sustained over the course of the study. Mean fecal egg count reduction (FECR) was significantly greater for the first combination treatment (76.6%) than the second (42.6%, p = 0.0454), third (41.6%, p = 0.0318), and fourth (40.7%, p = 0.0372) combination treatments. The final single active mean FECRs were 42.3% for oxibendazole, and 42.7% for pyrantel pamoate. These efficacies were not significantly different from the initial single active efficacies (OBZ, p = 0.4421; PYR, p = 0.8361). These results suggest that combination therapy against double resistant equine cyathostomin populations is not sustainable, when using actives with markedly decreased starting efficacies.

Efficacy of nitazoxanide to treat natural Giardia infections in dogs.

BACKGROUND: Giardia parasites cause gastrointestinal disease in humans, dogs, and many other animals worldwide. The treatment of dogs for giardiasis requires further investigation to ascertain levels of drug efficacy and the possibility of adverse side effects. Nitazoxanide (NTZ) has shown good clinical anti-Giardia activity in humans, yet it has not been evaluated for the treatment of giardiasis in dogs. METHODS: Thirty-five dogs, naturally infected with Giardia were divided into five groups (n = 7): dogs in group NTZ1, NTZ2, and NTZ3 were treated with a single oral dose of 37.5 mg/kg, 75 mg/kg, and 150 mg/kg, respectively, of NTZ on days 0 and 14. The fourth group was treated with a commercially available regimen that includes a combination of pyrantel, praziquantel, and febantel (FEB) administered orally for three consecutive days. Additionally, an untreated control group was established. Giardia cysts from the stool of each dog were quantified on days -3, 0, 5, 7, 9, 11, 14, 18, 25, and 28. Biochemical parameters were evaluated in all dogs, before the first treatment and after concluding the experiment. RESULTS: Shedding of Giardia cysts was reduced in all treated groups when compared to untreated controls (P < 0.01). However, NTZ2, NTZ3, and FEB had a lower risk during the study. Furthermore, NTZ was also effective against another protozoan, Cryptosporidium spp. at doses of 75 mg/kg and 150 mg/kg, in contrast to the combination of febantel + pyrantel + praziquantel. Biochemical parameters of treated animals, namely, aspartate transaminase and alanine transaminase enzymes, remained within physiological ranges. CONCLUSIONS: Based on these results, the implementation of NTZ as a treatment for giardiasis in dogs is proposed. The administration of a single dose is an important advantage of NTZ because it reduces workload, particularly in animals placed in shelters and kennels, where handling of large numbers of animals is required, and personnel is frequently scarce.

Efficacy and safety of oxantel pamoate in school-aged children infected with Trichuris trichiura on Pemba Island, Tanzania: a parallel, randomised, controlled, dose-ranging study.

BACKGROUND: Commonly used drugs for preventive chemotherapy against soil-transmitted helminths (ie, albendazole and mebendazole) show low efficacy against Trichuris trichiura. Recent studies with oxantel pamoate revealed good cure rates and high egg-reduction rates against T trichiura. We aimed to assess the nature of the dose-response relation to determine the optimum dose. METHODS: We did a parallel, randomised, placebo-controlled, single-blind trial with oxantel pamoate in school-aged children (aged 6-14 years) infected with T trichiura on Pemba Island, Tanzania. Children were asked to provide two stool samples and children positive for T trichiura were eligible to participate in the trial. Children were excluded if they suffered from any systematic illness. Children were randomly assigned to six different oxantel pamoate doses (5-30 mg/kg) or a placebo. Randomisation was stratified by baseline infection intensity using random block sizes of seven and 14. The primary endpoints were cure rates and egg-reduction rates against T trichiura, both analysed by available case. Drug safety was assessed 2 h and 24 h after treatment. The trial is registered at www.isrctn.com, number ISRCTN86603231. FINDINGS: Between Oct 14, and Nov 28, 2014, we enrolled 480 participants and randomly assigned 350 children to the different oxantel pamoate doses or the placebo. 5 mg/kg oxantel pamoate was the minimum effective dose (10 of 46 children cured [cure rate 22%, 95% CI 11-36]; egg-reduction rate 85·0%, 64·5-92·9). An increased probability of being cured and reduced egg counts with escalating doses was recorded. At 25 mg/kg oxantel pamoate 27 of 45 children were cured (cure rate 60%, 95% CI 44-65) with an egg-reduction rate of 97·5% (94·4-98·9), and at 30 mg/kg 27 of 46 children were cured (59%, 43-73) with an egg-reduction rate of 98·8% (96·8-99·6). Oxantel pamoate was well tolerated across all treatment groups; only mild adverse events were reported by the participants 2 h (27 [10%]) and 24 h (12 [4%]) after treatment. INTERPRETATION: Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura. An optimum therapeutic dose range of 15-30 mg/kg oxantel pamoate was defined. With a weight independent dose of 500 mg oxantel pamoate 95% of children aged 7-14 years in sub-Saharan Africa would receive doses of 11·7-32·0 mg/kg. Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes. FUNDING: Swiss National Science Foundation.

Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, randomised controlled trial.

BACKGROUND: Existing anthelmintic drugs (eg, albendazole and mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. METHODS: In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6-14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 µg/kg); albendazole (400 mg) plus mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. FINDINGS: We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6-77·4]; egg reduction 99·2%, 98·7-99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0-36·0]; egg reduction 94·5%, 91·7-96·3) were significantly more effective against T trichiura than mebendazole alone (nine of 107 cured [8·4%, 3·1-13·8]; egg reduction 58·5%, 45·2-70·9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1-13·8; egg reduction 51·6%, 35·0-65·3) to mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for mebendazole. INTERPRETATION: Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura. Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. FUNDING: Medicor Foundation and Swiss National Science Foundation.

Glutathione and glutathione-related enzymes in rats exposed to dimethoate and/or pyrantel.

The study was undertaken to examine the effect of single and combined administration of dimethoate (an OP insecticide) and pyrantel embonate (an anthelmintic agent) on the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx) and glutathione reductase (GR) in rats. Dimethoate (Group I) was administered to rats at a dose of 1/10 LD50 for 5 consecutive days and pyrantel embonate (Group II) at a dose of 1/5 LD50 for 3 consecutive days. The animals of group III were given both of the mentioned above compounds in the same manner as group I and II, but pyrantel embonate was applied on day 3, 4, and 5 from the beginning of dimethoate intoxication. Material from 6 rats randomly selected from each group was obtained after 3, 6 and 12 hours and 2, 7 and 14 days following the last applied dose of the compounds under study. It was found that application of pyrantel embonate caused only slight changes in the analysed parameters i.e. GSH, GPx and GR. Dimethoate administration caused disturbances in the antioxidative system manifested as a decrease in GSH concentration in the liver (max.--37.7% after 6 hours) and an increase of GPx and GR activities in erythrocytes (max.--21.7% and 29.6% after 3 hours, respectively), compared to the control group. The profile of changes after combined intoxication was similar, but their intensity was higher compared to the group of animals exposed to dimethoate only. Based on current studies, it was concluded that both dimethoate and pyrantel embonate at the applied doses showed a pro-oxidative activity.

Oxantel pamoate-albendazole for Trichuris trichiura infection.

BACKGROUND: Infections with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) are widespread and often occur concomitantly. These parasitic-worm infections are typically treated with albendazole or mebendazole, but both drugs show low efficacy against T. trichiura. Albendazole is the drug of choice against hookworm. METHODS: In this double-blind trial conducted on Pemba Island, Tanzania, we randomly assigned children, 6 to 14 years of age, to receive one of four treatments: oxantel pamoate at a dose of 20 mg per kilogram of body weight, plus 400 mg of albendazole, administered on consecutive days; oxantel pamoate at a single dose of 20 mg per kilogram; albendazole at a single dose of 400 mg; or mebendazole at a single dose of 500 mg. We assessed the efficacy and safety profile of oxantel pamoate-albendazole when used in the treatment of T. trichiura infection (primary outcome) and concomitant soil-transmitted helminth infection (secondary outcome). Efficacy was determined by means of assessment of the cure rate and egg-reduction rate. Adverse events were assessed four times after treatment. RESULTS: Complete data were available for 458 children, of whom 450 were infected with T. trichiura, 443 with hookworm, and 293 with A. lumbricoides. The cure rate of T. trichiura infection was significantly higher with oxantel pamoate-albendazole than with mebendazole (31.2% vs. 11.8%, P=0.001), as was the egg-reduction rate (96.0% [95% confidence interval {CI}, 93.5 to 97.6] vs. 75.0% [95% CI, 64.2 to 82.0]). The cure rate with albendazole (2.6%) and the egg-reduction rate with albendazole (45.0%; 95% CI, 32.0 to 56.4) were significantly lower than the rates with mebendazole (P=0.02 for the comparison of cure rates). Oxantel pamoate had low efficacy against hookworm and A. lumbricoides. Adverse events (mainly mild) were reported by 30.9% of all children. CONCLUSIONS: Treatment with oxantel pamoate-albendazole resulted in higher cure and egg-reduction rates for T. trichiura infection than the rates with standard therapy. (Funded by the Medicor Foundation and the Swiss National Science Foundation; Current Controlled Trials number, ISRCTN54577342.).

Massive proteinuria: a possible side effect of pyrantel pamoate?

Drug-induced renal injury represents a frequent clinical entity. The most common drugs associated with acute tubular necrosis are aminoglycosides, amphotericin B, radiocontrast agents, and cyclosporine, but no data exist about the potential renal toxicity due to anthelmintics administration. Anthelmintics are commonly considered quite safe agents, and side effects such as gastrointestinal, neurologic, hematologic, or hepatic injury have been only rarely described. We report a 4-year-old boy with persistent massive proteinuria without any other symptoms/signs suggesting nephrotic syndrome (NS). The only relevant anamnestic data was the administration of pyrantel pamoate due to oxyuriasis 7 days before the proteinuria development. The patient was affected by NS diagnosed 6 months before and treated with a 12-week course of corticosteroids. During follow-up, carried out at 3 and 6 months after discharge, he did not show further episodes of proteinuria, and no clinical symptoms/signs suggesting a relapse of NS were ever detected. Considering that the proteinuria observed in our patient spontaneously disappeared after 10 days without any treatment, apart from the interruption of the anthelmintic therapy, we would like to alert pediatricians about the possible occurrence of anthelmintics-related renal complications especially among predisposed patients and to perform a watchful waiting not considering the presence of even massive proteinuria as a certain sign of NS relapse.

Field evaluation of the efficacy and the safety of a combination of oxantel/pyrantel/praziquantel in the treatment of naturally acquired gastrointestinal nematode and/or cestode infestations in dogs in Europe.

In five multicentre field trials, the efficacy and safety of a combination of oxantel/pyrantel/praziquantel (Dolpac), Vetoquinol SA) in the treatment of naturally acquired gastrointestinal nematode and/or cestode infestation in dogs was evaluated in northern and southern Europe. Forty-eight investigators from France, Belgium, Germany, Italy and Spain enrolled 329 dogs to be treated with the tested combination; 235 of these dogs complied with the inclusion criteria of the protocol and had a tested helminth identified on Day 0. A pooled analysis was performed on each of the following helminth species: Toxocara canis, Ancylostoma caninum, Toxascaris leonina, Trichuris vulpis, Uncinaria stenocephala, Taenia spp. and Dipylidium caninum, which were isolated on Day 0. The main efficacy criterion was the egg per gram (epg) percent reduction of the nematodes and the absence of proglottids and or eggs for the cestodes. After treatment, dogs were examined on Day 7, Day 14 and Day 21. The efficacy of the combination against Toxocara canis was 99.1%, 98.8% and 98.9% on Day 7, Day 14 and Day 21, respectively. At the same occasions the efficacy was, respectively, 99.2%, 99.2% and 99.3% against Ancylostoma caninum, 97.3%, 97.2% and 98.4% against Trichuris vulpis, 98.4%, 98.8% and 98.8% against Uncinaria stenocephala, 98.9%, 99.5% and 99.9% against Toxascaris leonina, 97.1%, 100% and 100% against Dipylidium caninum and 100% against Taenia spp.

Comparative effects of milbemycin oxime-based and febantel-pyrantel embonate-based anthelmintic tablets on Toxocara canis egg shedding in naturally infected pups.

The effect of two treatment programmes on egg shedding in dogs naturally infected with Toxocara canis, one based on a milbemycin oxime-praziquantel-lufenuron combination (SENTINEL) Spectrum; Group 1) and the other based on a febantel-pyrantel embonate-praziquantel combination (DRONTAL) Plus; Group 2), was compared in a study involving 104 suckling pups from three different kennels. The animals in Group 1 were treated at a minimum milbemycin oxime dose of 0.5 mg/kg bw starting at 2 weeks of age and subsequently every 4 weeks until reaching 26 weeks of age. The animals in Group 2 were treated every 2 weeks from week 2 until week 12 of age and then once at week 26 at a minimum febantel and pyrantel embonate dose of 15.0 and 14.4 mg/kg bw, respectively. Toxocara egg counts were determined fortnightly starting at 2 weeks of age and continuing until 26 weeks of age for every pup. Any adverse drug event was recorded during the trial. Both treatment programmes significantly reduced the zoonotic Toxocara egg shedding and were well tolerated by the pups. The pups in Group 1 showed lower average faecal egg counts and were found more frequently shedding no eggs than the pups in Group 2.

Bioequivalence of pyrantel pamoate dosage forms in healthy human subjects.

Drugs that are largely restricted to the gastro-intestinal tract (GIT) for their therapeutic efficacy and that are not substantially absorbed into the body are usually inadequately studied in terms of systemic bioavailability. The possibility of systemic effects requires that bioavailabilities be studied to ensure against enhanced toxicity resulting from formulation differences. Pyrantel pamoate falls into this category. High-performance liquid chromatography was employed in this study to determine plasma levels of pyrantel in nine healthy human subjects after administration of tablet and suspension dosage forms. Mean peak plasma concentrations of 37.56 +/- 9.37, 35.89 +/- 8.94, and 36.22 +/- 10.10 ng mL-1 were obtained following administration of 750 mg pyrantel pamoate in three different formulations. The mean tmax values were 2.02 +/- 0.12, 2.05 +/- 0.356, and 2.05 +/- 0.339 h respectively for the above dosage forms; the respective AUC0-9 values were 81.01 +/- 12.97, 94.59 +/- 17.18, and 101.47 +/- 19.59 h ng mL-1. There was no statistically significant difference between the bioavailabilities of the dosage forms tested. Large inter-subject variations were observed. One subject experienced abdominal discomfort and one experienced dizziness. It was not possible to clearly correlate individual variations in absorption with the observed adverse effect because the number of incidents was low (two out of 27 treatments).

[Embovin efficacy and tolerance in the treatment of patients with intestinal nematode infections]. / Effektivnost' i perenosimost' émbovina pri lechenii bol'nykh kishechnymi nematodozami.

The efficacy and tolerance of embovin, a new anthelminthic manufactured in Russia, was studied in 60 patients with nematodiases. The results evidence its high efficacy in ankylostomiasis (100%), enterobiasis (100%), and ascariasis (90 +/- 6.4%). The drug was well tolerated in all the cases. No adverse effects on the liver, pancreas, kidneys, as well as on the peripheral blood and urine composition were detected. This recommends embovin for wide use in medical practice.

Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs.

To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6-week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls.

[Experience with the use of nemocide (pyrantel pamoate) in nematodiases]. / Opyt primeneniia nemotsida (pirantelia pamoata) pri nematodozakh.

The clinical efficacy of and tolerance to the nemocide pyranthel pamoate produced by "IPCA" (India) and applied to nematodiasis treatment have been investigated. A high efficacy of the drug (94.4-100%) for ascariasis, enterobiasis and ancylostomiasis treatment has been established. The drug is well tolerated by adults and induces slight short-term alterations of hepatic functional activity in 5-10-year-old children.