moxidectin and Drug-Related-Side-Effects-and-Adverse-Reactions

Strongyloidiasis represents a major public health issue, particularly in resource-limited countries. Preliminary studies suggest that moxidectin might serve as an alternative to the only available treatment option, ivermectin. We aimed to evaluate the efficacy and safety of ascending doses of moxidectin in Strongyloides stercoralis-infected patients.. We did a randomised, parallel-group, single-blinded, placebo-controlled, dose-ranging, phase 2a trial in four villages in northern Laos. Eligible adults (aged 18-65 years) with S stercoralis infection intensities of at least 0·4 larvae per g of stool in at least two stool samples were randomly assigned (1:1:1:1:1:1:1) by use of computerised, stratified, block randomisation into seven treatment groups: 2 mg of moxidectin, 4 mg of moxidectin, 6 mg of moxidectin, 8 mg of moxidectin, 10 mg of moxidectin, 12 mg of moxidectin, or placebo. Participants and primary outcome assessors were masked to treatment allocation, but study site investigators were not. Participants received a single oral dose of their allocated dose of moxidectin in 2 mg tablets, or four placebo tablets. Three stool samples were collected at baseline and two stool samples were collected 28 days after treatment from each participant. A Baermann assay was used to quantify S stercoralis infection and Kato-Katz thick smears were used to qualitatively identify coinfections with additional helminths species. The primary endpoint was cure rate against S stercoralis and was analysed in an available case analysis set, defined as all randomly assigned participants with primary endpoint data. Predicted cure rates and associated CIs were estimated with hyperbolic E. Between Nov 27, 2019, and March 15, 2020, 785 adults were screened for trial eligibility. Of these, 223 participants were randomly assigned to treatment groups and 209 completed the study and were analysed for the primary outcome. 2 mg of moxidectin had a predicted cure rate of 75% (95% CI 59-87; 22 [73%] of 30 cured) against S stercoralis compared with a predicted cure rate of 14% (5-31; four [14%] of 29 cured) for placebo. With escalating doses, the probability of cure increased from 83% (95% CI 76-88; 26 [90%] of 29 cured) at 4 mg to 86% (79-90; 27 [84%] of 32 cured) at 6 mg, and to 87% (80-92; 24 [83%] of 29 cured) at 8 mg, levelling off at 88% (80-93; 29 [97%] of 30 cured) at 10 mg and 88% (80-93; 26 [87%] of 30 cured) at 12 mg. Moxidectin was well tolerated across all treatment groups, with no serious adverse events being recorded and all reported symptoms being classified as mild.. 4-12 mg of moxidectin showed promising tolerability and efficacy profiles in the treatment of S stercoralis infections in adults. Because 8 mg of moxidectin is used for the treatment of onchocerciasis and has been evaluated for other helminth infections, we recommend this dose for phase 2b and phase 3 trials of strongyloidiasis therapy.. Fondazione Adiuvare.

Topics: Adult; Animals; Anthelmintics; Drug-Related Side Effects and Adverse Reactions; Feces; Female; Humans; Laos; Macrolides; Male; Middle Aged; Single-Blind Method; Strongyloides stercoralis; Strongyloidiasis; Treatment Outcome

Notoedric mange (feline scabies) is a rare, but highly contagious disease of cats and kittens caused by Notoedres cati (N. cati), which can infest other animals and also humans. The study objective was to determine the efficacy and safety of 10 % imidacloprid/ 1 % moxidectin (Advocate®/Advantage® Multi spot-on for cats) against natural N. cati infestation in cats. Sixteen cats were randomly assigned to treatment group or negative control using pre-treatment mite counts. The treatment group received a single spot on treatment of the investigational veterinary product (IVP) according to label instructions. The control group stayed untreated. Five cats from the negative control were treated with the IVP at the end of the study and observed for 28 days to increase the treatment group. Skin scrapings and mite counts were performed 28 days post treatment (p.t.). Notoedric skin lesion assessments with clinical scoring were performed regularly. Five animals had to be removed prematurely from the study population due to different reasons. The number of viable N. cati mites in all treated animals 28 days p.t. was zero compared with 2.8 ± 3.0 in the negative control, being significantly lower for treated cats (p = 0.0019, Wilcoxon test). The resulting efficacy was 100 %. Clinical cure based on skin lesion assessment was achieved 28 days p.t. in 100 % of all treated animals completing 28 study days. The IVP was well tolerated and applied at the minimal therapeutic dose (10 mg imidacloprid/1 mg moxidectin/kg body weight) a high therapeutic efficacy in curing N. cati infestations and feline scabies clinical symptoms was recorded.

Topics: Acaricides; Administration, Topical; Animals; Cat Diseases; Cats; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Imidazoles; Macrolides; Mite Infestations; Neonicotinoids; Nitro Compounds; Parasite Load; Sarcoptidae; Skin; Treatment Outcome

The safety of ProHeart® 12 (PH 12; extended-release injectable suspension; 10% moxidectin in glyceryl tristearate microspheres) was evaluated in four studies using Beagle dogs and one study using ivermectin-sensitive Collies. The recommended dose is 0.5 mg/kg subcutaneously once yearly.. Study 1: safety margin was evaluated as 3 treatments of PH 12 (0× (control); 1× (recommended dose); 3× (3 times recommended dose) and 5× (5 times recommended dose) in 12 months via clinical observations, body weights, food consumption, injection site observations, physical examinations, moxidectin tissue assay, pharmacokinetics, and clinical and anatomic pathology. Study 2: safety in breeding-age males was demonstrated by semen testing at 14-day intervals from Day 7 to Day 91 post-treatment (0× or 3×). Study 3: reproductive safety in females was demonstrated by monitoring dams and litters following treatments (0× or 3×) administered during breeding, gestation, or lactation. Study 4: safety in dogs surgically implanted with adult heartworms was evaluated by clinical and laboratory monitoring following treatment with 0× or 3× administered 61 days post-implantation. Study 5: safety in ivermectin-sensitive dogs (120 µg/kg SC) was by clinical monitoring for 1 week after administering 1×, 3× or 5×.. Study 1: slight swelling clinically detectable at some 3× and 5× injection sites was characterized microscopically as granulomatous inflammation, like tissue responses to medical implants, interpreted as non-adverse. Pharmacokinetics were dose-proportional and there was little or no systemic accumulation. Residual moxidectin mean (range) at 1× injection sites after 1 year was 16.0% (0.045-37.6%) of the administered mass. Studies 2 and 3: no effects were identified in reproductive indices (females) or semen quality characteristics (males). Study 4: PH 12 produced marked reductions in circulating microfilariae and lower numbers of adult heartworms, but no adverse clinical signs were identified. Study 5: there were no abnormal clinical signs at 1×, 3× or 5× overdoses of PH 12 in ivermectin-sensitive dogs.. PH 12 has a > 5× safety margin in both normal and ivermectin-sensitive dogs, has no effects on canine reproduction, and is well tolerated in heartworm-positive dogs. The only treatment-related finding was non-adverse, granulomatous inflammation at the injection site.

Topics: Animals; Antinematodal Agents; Delayed-Action Preparations; Dog Diseases; Dogs; Drug-Related Side Effects and Adverse Reactions; Heartwater Disease; Injections; Macrolides; Suspensions; Treatment Outcome

A field trial was conducted to assess the safety and efficacy of oral administration of moxidectin in mice naturally infected with the fur mites Radfordia affinis. The natural infection was diagnosed in two colonies within a large academic institution by direct hair examination. Animals received moxidectin (1% Cydectin, FortDodge) at an oral dosage of approximately 2 mg/kg body weight by micropipette; administration was repeated after 15 days. Forty mice served as an untreated control group. Moxidectin treatment resulted in clinical improvement within a few days after initial treatment, and mites were eradicated from all infested animals at day 30. No side effects or signs of ill health were observed in any of the treated animals. To our knowledge, this is the first report of oral moxidectin for treatment of murine acariosis.

Topics: Administration, Oral; Animals; Drug-Related Side Effects and Adverse Reactions; Female; Insecticides; Macrolides; Male; Mice; Mice, Inbred Strains; Mite Infestations; Mites; Rodent Diseases; Time Factors