Moxicloprid 9 (Canada)

Company: Modern Veterinary Therapeutics

(imidacloprid and moxidectin topical solution)

Topical parasiticide for cats and kittens 8 weeks of age and older, weighing up to 4 kg and adult ferrets weighing up to 2 kg.

DIN 02523612

VETERINARY USE ONLY

Description

Each 0.4 mL tube contains 40 mg imidacloprid and 4 mg moxidectin, as a colorless to yellow solution. Imidacloprid is a chloronicotinyl nitroguanidine insecticide. The chemical composition of imidacloprid is 1-{(6-Chloro-3-pyridinyl)methyl}-N-nitro-2-imidazolidinimine. Moxidectin is a semisynthetic macrocyclic lactone endectocide derived from the actinomycete Streptomycetes cyaneogriseus noncyanogenus.

Moxicloprid 9 Indications

Cats:

Moxicloprid™ 9 is indicated in cats and kittens, 8 weeks of age and older, for the prevention of cardiovascular dirofilariasis (heartworm disease) caused by Dirofilaria immitis, and for the treatment and control of parasitic infestations caused by the adult stage of the common flea, (Ctenocephalides felis) and due to ear mites (Otodectes cynotis). Moxicloprid™ 9 is also indicated for the treatment and control of parasitic infections caused by the developing L4, the sexually immature adult and the adult stages of hookworms (Ancylostoma tubaeforme) and ascarids (Toxocara cati).

Ferrets:

Moxicloprid™ 9 is indicated in adult ferrets for the prevention of cardiovascular dirofilariasis (heartworm disease) caused by Dirofilaria immitis and for the treatment and control of parasitic infestations caused by the common flea (Ctenocephalides felis).

DOSAGE:

Cats: Apply the entire contents of one tube to the skin of cats and kittens 8 weeks of age and older, weighing up to 4 kg, once a month. This will deliver at least the recommended minimum dose of 9.7 mg of imidacloprid and 0.9 mg of moxidectin per kg of body weight.

Ferrets: Apply the entire contents of one tube to the skin of adult ferrets weighing up to 2.0 kg, once a month. This will deliver at least the recommended minimum dose of 20 mg of imidacloprid and 2 mg of moxidectin per kg of body weight. In heavy flea infestations, Moxicloprid™ 9 may be re-applied after a 2 week interval, one time. All subsequent applications should continue at once monthly intervals.

ADMINISTRATION:

1. Remove one unit dose tube from the package.

2. Administer the entire contents of a unit dose applicator tube of Moxicloprid™ 9 topically.

3. While holding the tube in an upright position, twist off the cap.

The animal should be standing for application. Part the hair on the neck at the base of the skull until the skin is visible. Place the tip of the tube on the skin and squeeze the tube twice to expel the entire contents directly on the skin. Do not get this product in your pet’s eyes or mouth. The product is bitter tasting and salivation may occur for a short time if the animal licks the product immediately after treatment. Treatment at the base of the skull will minimize the opportunity for the animal to lick the product. A wet “paint brush,” oily appearance of the hair,

or a slight powdery residue may be observed at the site of application for a short period of time in some animals following treatment. Until Moxicloprid™ 9 dries, keep pet off furniture and away from hardwood floors.

Contraindications

Do not administer orally. See the Animal Safety section.

CAUTIONS:

Use with caution in sick, debilitated, or underweight animals.

The safe use of Moxicloprid™ 9 in cats and ferrets used for breeding purposes, during pregnancy, or lactation has not been evaluated.

The safety of Moxicloprid™ 9 has not been assessed in heartworm positive ferrets.

The product’s efficacy has not been tested in ferrets weighing over 2 kg and therefore the duration of effect might be shorter in these animals.

Brief contact of the animal with water on one or two occasions between monthly treatments is unlikely to significantly reduce the efficacy of the product. However, frequent shampooing or immersion of the animal in water after treatment may reduce the efficacy of the product.

Warnings

Keep this product, and all drugs, out of the reach of children.

May be irritating to skin and eyes. If contact with eyes occurs, flush eyes copiously with water. If eye irritation persists, contact a physician. Wash hands after use. If contact with skin occurs, wash skin immediately with soap and water. If ingested, contact a physician immediately.

Adverse Reactions

Use of the product may result in transient pruritus in cats. Rarely, greasy fur, erythema and vomiting can occur. These signs disappear without further treatment. The product may, in rare cases, cause local hypersensitivity reactions. If the animal licks the application site after treatment, transient, self-limiting neurological signs such as ataxia, generalised tremors, ocular signs (dilated pupils, little pupillary reflex, nystagmus), abnormal respiration, salivation and vomiting may occur infrequently.

The product tastes bitter. Salivation may occasionally occur if the animal licks the application site immediately after treatment. This is not a sign of intoxication and disappears within some minutes without treatment. Correct application will minimise licking of the application site.

The product may in very rare cases cause, at the application site, a sensation resulting in transient behavioural changes such as lethargy, agitation, and inappetence.

In case of accidental oral uptake, symptomatic treatment should be performed by a veterinarian. There is no known specific antidote. The use of activated charcoal may be beneficial.

If you notice any serious effects or other effects not mentioned in the leaflet, please inform your veterinarian.

Post-market experience:

Although all adverse reactions are not reported, the following adverse reaction information is based on voluntary post-approval drug experience reporting from a similar product. It is generally recognized that this method of reporting results in significant under-reporting of adverse drug reactions. It should be noted that suspected adverse drug reactions listed here reflect reporting and not causality. The categories of adverse reactions are listed in decreasing order of frequency by body system:

Application site disorders: erythema, alopecia, scab, irritation, pruritus

Digestive tract disorders: hypersalivation, vomiting, diarrhea

Systemic disorders: lethargy, inappetence, hyperthermia, hypothermia, shaking, pale mucous membranes, malaise

Behavioural disorders: agitation, vocalization, disorientation

Neurological disorders: ataxia, tremor, twitching, mydriasis, paresis, nystagmus, hyperesthesia

Skin and appendage disorders: pruritus, erythema, alopecia, dermatitis, lesion, pyoderma

Animal Safety

SAFETY STUDIES IN CATS AND KITTENS:

In a clinical field safety study, an imidacloprid and moxidectin topical solution was used safely in cats concomitantly receiving other classes of veterinary pharmaceuticals including anticonvulsants, antimicrobials, and progestins. In cats treated with an imidacloprid and moxidectin topical solution, owner observations classified as non-normal included: behavioral changes (including fright, irritability, isolation, nervousness and/or restlessness), coughing, head shaking, salivation, vocalization, scratching, and somnolence. No other reactions were reported.

Tolerance in Kittens:

In a formal tolerance study, an imidacloprid and moxidectin topical solution was applied topically at 1, 3 and 5 times the recommended dosage in 8-9 week-old kittens, once every two weeks for 12 weeks, for a total of 6 consecutive treatments. A control group of kittens received dermal application of mineral oil at 5 times the recommended volume of the imidacloprid and moxidectin topical solution.

The most common clinical signs occurring in kittens during the pre-treatment period (Day - 14 to Day - 1) included soft/loose stools and/or diarrhea, vomition, and occasional mydriasis and eye discharge. The most common clinical signs occurring in kittens on the first three treatment days (Days 0, 14 and 28) included rough hair coat appearance at application site (all kittens, including controls), soft/loose stools and/or diarrhea, and occasional pruritus, mydriasis, depression, eye discharge and salivation; similar observations were made during each following 13-day post-treatment period. The most common clinical signs occurring in kittens on the last three treatment days (Days 42, 56 and 70) included rough hair coat appearance at application site (all kittens, including controls), and occasional soft/loose stools; similar observations were made during each 13-day post-treatment period. Clinical signs were distributed in the various treatment groups, including controls, without any pattern indicative of treatment relationship.

Due to the apparent ingestion of the drug shortly after the second dosing on day 14, one kitten treated at 5 times the recommended dosage reacted violently. Major clinical signs of moxidectin toxicosis including mydriasis, salivation, depression, unsteadiness and respiratory distress (slow or rapid, difficult breathing) were observed on several occasions, i.e. at 1, 2, 3, 4, 6, 8 and 12 hours after treatment administration. In addition, anorexia, vomiting and generalized tremors were observed on Day 15. Finally, additional signs of dehydration and nystagmus were observed on Day 16, at which time the animal was euthanized.

Collectively, the results of this study indicate that the topical administration of an imidacloprid and moxidectin topical solution to 8-9 week-old kittens, at 1X, 3X or 5X the recommended dosage, applied at 2-week intervals over a 12-week period does not pose serious safety concerns to kittens; however, oral administration must be avoided.

Tolerance in juvenile cats:

The topical administration of an imidacloprid and moxidectin topical solution at 10X the proposed dosage to 4-5 months old juvenile cats did not result in any significant local or systemic toxic changes in the parameters examined, i.e. clinical observations, dermal irritation at application site, physical examination, body weight, food consumption, haematology and clinical biochemistry.

Effect of inadvertent oral administration:

In a safety study designed to investigate the potential misuse of an imidacloprid and moxidectin topical solution by oral administration, 24 adult cats, 11 to 16 months of aged, were randomly allocated to two groups of 12 cats, each consisting of equal numbers of each sex. The test article at 1X (Group A) the unit dosage or control article (Group B, water), were administered by oesophageal feeding tube on study Days 0 (study duration = 14 days). No reactions of any kind were observed in the control cats. Three of 12 cats administered the drug had excess salivation within 1 hour after treatment; four vomited within 1-24 hours after treatment; one cat vomited twice, 5 and 7 days after treatment.

Safety in heartworm infected cats:

A controlled, laboratory study was conducted to evaluate the safety an imidacloprid and moxidectin topical solution administered topically at 1X or 5X the recommended dosage, to cats artificially infected with Dirofilaria immitis. Abnormal clinical signs noted during the post-treatment observation period included: salivation within 2 hours of treatment administration in 1 of 12 cats in the 1X group and in 7 of 12 cats in the 5X group; skin irritation in 2 of 12 cats in the 5X group (from 0 to 12 hours after the second dose in one cat and for 25 days after the second dose in another). The data generated in this trial indicate that the administration of an imidacloprid and moxidectin topical solution as per label recommendations should not pose serious safety concerns in heartworm-positive cats.

Clinical safety under field conditions of administration:

A controlled, double-blind, multi-centered, field study was conducted in four veterinary clinics/hospitals, in client-owned cats randomly assigned to two treatment groups: animals in Group 1 (principals) were treated with an imidacloprid and moxidectin topical solution, and animals in Group 2 (positive controls) were treated with a topical parasiticide approved for sale in Canada.

Treatments were administered once monthly, for three consecutive months, by pet owners according to instructions provided by the attending veterinarian.

Scoring of post-treatment clinical observations was defined as:

(1) Animal normal, no observation;

(2) Definitely no relationship between observation and treatment;

(3) Probably no relationship between observation and treatment;

(4) Probable relationship between observation and treatment;

(5) Definite relationship between observation and treatment.

Animals were found normal (score of 1) in 96.9% of the cases. No observations with scores of 4 and 5 were noted. Forty-two post-treatment observations with scores of 2 or 3 can be summarized as follows:

- Post-treatment behavioral changes including fright, irritability, isolation, nervousness and/or restlessness, were the most frequently reported observations: 15 incidences in 7 principals; the modified behavior was transient in duration.

- Cats may react rather vigorously following oral administration of an imidacloprid and moxidectin topical solution. In this study, owners described 13 post- treatment responses in 9 cats (11 incidences in 8 principals and 2 incidences in 1 control cat) that were consistent with oral exposure to an unpalatable substances; the observed signs included coughing, head shaking, bursts of hyperactivity (pacing, running, spinning), salivation and vocalization. All signs were transient in duration and resolved without intervention.

- In 9 observations involving 5 principals, owners described post-treatment attempts by cats to scratch or rub the application site. Most attempts (7 of 9) occurred within 30-60 minutes post-treatment and all were transient in duration. Neither owners nor attending veterinarians observed visible lesions at the application site of any cat participating in the study.

- Five incidences of post-treatment somnolence were described in 3 geriatric principals (13 to 15 years of age at the time of treatment). These cats experienced an extended period of sleep that began approximately 60-90 minutes after the first treatment and persisted for the next 30-40 hours, after which they returned to normal. Clinical signs of somnolence/lethargy did not recur in conjunction with the 2nd and 3rd treatments.

SAFETY STUDIES IN FERRETS:

An imidacloprid and moxidectin topical solution was administered to 9 month old ferrets (0.9 - 1.7 kg body weight) at 5 times the recommended dose (2 ml), every 2 weeks for 4 treatments. There were no adverse effects or undesirable clinical signs recorded. A transient increase in AST (Aspartate aminotransferase) was seen on Day 15. On day 46, AST levels were within the reference range.

Effect of inadvertent oral administration:

In a safety study designed to investigate the potential misuse of an imidacloprid and moxidectin topical solution by oral administration, 16 ferrets, 78 to 101 days of age (0.5 - 0.8 kg body weight), were randomly allocated to two groups of 8 ferrets, each consisting of equal numbers of each sex. The ferrets were treated orally with either 0.4 mL of test article (1X treatment group, actual dose range was 50-80 mg/kg imidacloprid and 5-8 mg/kg moxidectin) or 0.4 mL of tap water (negative control group) and monitored for 14 days. Mild, self-limiting adverse events were observed in 3 of 8 ferrets in the test article group and included emesis and loss of coordinated mobility (ataxia) immediately post- treatment. No reactions were observed in the control ferrets.

Storage

Store at temperatures between 15°C and 30°C.

How Supplied

Manufactured for:

Modern Veterinary Therapeutics, LLC, Miami, FL 33186 - USA

info@modernveterinarytherapeutics.com

Imported by:

Modern Veterinary Therapeutics Inc, 261065 Wagon Wheel Way, Bay 3, Balzac (Rocky View County), AB T4A 0T5

Revision date: 6 December 2021

CPN: 1354030.0