(imidacloprid + moxidectin) Topical
Solution
Advantage Multi is a once-a-month topical solution
for the prevention of heartworm disease, kills adult fleas, is indicated for
the treatment of flea infestations, as well as the treatment and control of
intestinal parasite infections in dogs and puppies that are at least 7 weeks
of age and that weigh at least 3 lbs.
Advantage Multi® for Dogs (10%
imidacloprid + 2.5% moxidectin) is a colorless to yellow ready-to-use
solution packaged in single dose applicator tubes for topical treatment of
dogs. The formulation and dosage schedule are designed to provide a minimum
of 4.5 mg/lb (10 mg/kg) imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin
based on body weight.
INDICATIONS:
Advantage Multi for Dogs is indicated for
the prevention of heartworm disease caused by Dirofilaria immitis.
Advantage Multi for Dogs kills adult fleas and is indicated for the
treatment of flea infestations (Ctenocephalides felis). Advantage Multi
for Dogs is also indicated for the treatment and control of the
following intestinal parasites:
|
Intestinal Parasite
|
Intestinal Stage
|
|
Adult
|
Immature Adult
|
Fourth Stage Larvae
|
|
Hookworm Species
|
Ancylostoma caninum
|
X
|
X
|
X
|
|
Uncinaria stenocephala
|
X
|
X
|
X
|
|
Roundworm Species
|
Toxocara canis
|
X
|
|
X
|
|
Species
|
Toxascaris leonina
|
X
|
|
|
|
Whipworm
|
Trichuris vulpis
|
X
|
|
|
CONTRAINDICATIONS:
Do not administer this product orally. (See
WARNINGS.)
Do not use this product (containing 2.5% moxidectin)
on cats.
|
WARNINGS
For the first 30 minutes after
application:
Ensure that dogs cannot lick the product
from application sites on themselves or other treated dogs, and
Separate treated dogs from one another
and from other pets to reduce the risk of accidental ingestion.
Ingestion of this product by dogs may
cause serious adverse reactions including depression, salivation,
dilated pupils, incoordination, panting, and generalized muscle
tremors.
In avermectin sensitive dogs,
the signs may be more severe and may include coma and death.
|
a Some dogs are more sensitive to
avermectins due to a mutation in the MDR1 gene. Dogs with this mutation may
develop signs of severe avermectin toxicity if they ingest this product. The
most common breeds associated with this mutation include Collies and Collie
crosses.
b Although there is no specific
antagonist for avermectin toxicity, even severely affected dogs have
completely recovered from avermectin toxicity with intensive veterinary
supportive care.
HUMAN WARNINGS:
Not for human use. Keep out of the reach of
children.
Children should not come in contact with
application sites for two (2) hours after application.
Causes eye irritation. Harmful if swallowed. Do not
get in eyes or on clothing. Avoid contact with skin. Wash hands
thoroughly with soap and warm water after handling. If contact with eyes
occurs hold eyelids open and flush with copious amounts of water for 15
minutes. If eye irritation develops or persists, contact a physician. If
swallowed, call poison control center or physician immediately for treatment
advice. Have person sip a glass of water if able to swallow. Do not induce
vomiting unless told to do so by the poison control center or physician.
People with known hypersensitivity to benzyl alcohol, moxidectin, or
imidacloprid should administer the product with caution. In case of allergic
reaction, contact a physician. If contact with skin or clothing occurs, take
off contaminated clothing. Wash skin immediately with plenty of soap and
water. Call a poison control center or physician for treatment advice. The
Material Safety Data Sheet (MSDS) provides additional occupational safety
information.
PRECAUTIONS:
Do not dispense dose applicator tubes without
complete safety and administration information.
Use with caution in sick, debilitated, or
underweight animals. The safety of Advantage Multi for Dogs has not
been established in breeding, pregnant, or lactating dogs. The safe use of
Advantage Multi for Dogs has not been established in puppies and
dogs less than 7 weeks of age or less than 3 lbs. body weight.
Prior to administration of Advantage Multi for
Dogs, dogs should be tested for existing heartworm infection. At the
discretion of the veterinarian, infected dogs should be treated with an
adulticide to remove adult heartworms. Advantage Multi for Dogs is
not effective against adult D. immitis. While the number of
circulating microfilariae may decrease following treatment, Advantage
Multi for Dogs is not effective for microfilariae clearance.
ADVERSE REACTIONS:
Field Studies: Following treatment with
Advantage Multi for Dogs or an active control, dog owners reported the
following post-treatment reactions:
|
OBSERVATION
|
Advantage Multi n=128
|
Active Control n=68
|
|
Pruritis
|
19 dogs (14.8%)
|
7 dogs (10.3%)
|
|
Residue
|
9 dogs (7.0%)
|
5 dogs (7.4%)
|
|
Medicinal Odor
|
5 dogs (3.9%)
|
None observed
|
|
Lethargy
|
1 dog (0.8%)
|
1 dog (1.5%)
|
|
Inappetence
|
1 dog (0.8%)
|
1 dog (1.5%)
|
|
Hyperactivity
|
1 dog (0.8%)
|
None observed
|
During a field study using 61 dogs with pre-existing
flea allergy dermatitis, one (1.6%) dog experienced localized pruritus
immediately after imidacloprid application, and one investigator noted
hyperkeratosis at the application site of one dog (1.6%).
Laboratory Effectiveness Studies: One dog in
a laboratory effectiveness study experienced weakness, depression, and
unsteadiness between 6 and 9 days after application with Advantage Multi
for Dogs. The signs resolved without intervention by day 10
post-application. The signs in this dog may have been related to peak serum
levels of moxidectin, which vary between dogs, and occur between 1 and 21
days after application of Advantage Multi for Dogs.
The following clinical observations also occurred in
laboratory effectiveness studies following application with Advantage
Multi for Dogs and may be directly attributed to the drug or may be
secondary to the intestinal parasite burden or other underlying conditions
in the dogs: diarrhea, bloody stools, vomiting, anorexia, lethargy,
coughing, ocular discharge and nasal discharge. Observations at the
application sites included damp, stiff or greasy hair, the appearance of a
white deposit on the hair, and mild erythema, which resolved without
treatment within 2 to 48 hours.
The following adverse events were reported in
humans: eye irritation, allergic reactions, skin irritation, skin tingling,
sore throat, and chemical odor. Adverse events reported in dogs topically
treated with imidacloprid + moxidectin for dogs included: vomiting,
diarrhea, bloody diarrhea, salivation, poor appetite, lethargy, weakness,
restlessness, agitation, disorientation, ataxia, muscle tremors, seizures,
panting, labored breathing, acute pulmonary edema, hives, rash, swollen face
and ears, pruritus, erythema, alopecia, hot spots, local discomfort, and
discoloration of the hair at the application site. Accidental oral ingestion
in dogs caused salivation, vomiting, muscle tremor, seizures, mydriasis,
ataxia, lethargy, disorientation, agitation, and poor appetite. Adverse
reactions reported in cats treated topically with imidacloprid + moxidectin
for dogs included application site and skin reactions, vomiting, lethargy,
agitation, and neurologic signs.
DOSAGE AND ADMINISTRATION:
The recommended minimum dose is 4.5 mg/lb (10 mg/kg)
imidacloprid and 1.1 mg/lb (2.5 mg/kg) moxidectin, once a month, by topical
administration.
Do not apply to irritated skin.
1. Remove one dose applicator tube (tube) from the
package. As specified in the following table, administer the entire contents
of the Advantage Multi® for Dogs tube that
correctly corresponds with the body weight of the dog.
|
Dog (lbs.)
|
Advantage Multi For Dogs
|
Volume (mL)
|
Imidacloprid (mg)
|
Moxidectin (mg)
|
|
3 - 9
|
Advantage Multi 9
|
0.4
|
40
|
10
|
|
9.1 - 20
|
Advantage Multi 20
|
1.0
|
100
|
25
|
|
20.1 - 55
|
Advantage Multi 55
|
2.5
|
250
|
62.5
|
|
55.1 - 88
|
Advantage Multi 88
|
4.0
|
400
|
100
|
|
88.1 - 110*
|
Advantage Multi 110
|
5.0
|
500
|
125
|
* Dogs over 110 lbs. should be treated with the
appropriate combination of Advantage Multi for Dogs tubes.
2. While holding the tube in an upright position,
remove the cap from the tube.
3. Turn the cap over and push the other end of
cap onto the tip of the tube.
4. Twist the cap to break the seal and then
remove cap from the tube.
5. The dog should be standing for application.
Part the hair on the back of the dog between the shoulder blades until
the skin is visible. For dogs weighing 20 lbs. or less, place the tip of
the tube on the skin and apply the entire contents directly on the
exposed skin at one spot between the shoulder blades. For dogs weighing
more than 20 lbs., place the tip of the tube on the skin and apply the
entire contents directly on the exposed skin at 3 or 4 spots on the top
of the backline from the base of the neck to the upper back in an area
inaccessible to licking. Do not apply an amount of solution at any one
location that could run off the side of the dog.
Do not let this product get in your dog’s mouth
or eyes. Do not allow the dog to lick any of the application sites
for 30 minutes. In households with multiple pets, keep each treated
dog separated from other treated dogs and other pets for 30 minutes
after application to prevent licking the application sites.
Stiff hair, a damp appearance of the hair,
pink skin, or a slight powdery residue may be observed at the
application site on some animals. This is temporary and does not affect
the safety and effectiveness of the product.
Shampooing 90 minutes after treatment does not reduce the effectiveness
of Advantage Multi for Dogs in the prevention of heartworm
disease.
Shampooing or water immersion 4 days after
treatment will not reduce the effectiveness of Advantage Multi for
Dogs in the treatment of flea infestations. However, shampooing as
often as once weekly may reduce the effectiveness of the product against
fleas.
Heartworm Prevention: For prevention of
heartworm disease, Advantage Multi for Dogs should be
administered at one-month intervals. Advantage Multi for Dogs
may be administered year-round or at a minimum should start one month
before the first expected exposure to mosquitoes and should continue at
monthly intervals until one month after the last exposure to mosquitoes.
If a dose is missed and a 30-day interval between doses is exceeded,
administer Advantage Multi for Dogs immediately and resume the
monthly dosing schedule. When replacing another heartworm preventative
product in a heartworm prevention program, the first treatment with
Advantage Multi for Dogs should be given within one month of the
last dose of the former medication.
Flea Treatment: For the treatment of flea
infestations, Advantage Multi for Dogs should be administered
at one-month intervals. If the dog is already infested with fleas when
the first dose of Advantage Multi for Dogs is administered,
adult fleas on the dog will be killed. However, reinfestation from the
emergence of pre-existing pupae in the environment may continue to occur
for six weeks or longer after treatment is initiated. Dogs treated with
imidacloprid, including those with pre-existing flea allergy dermatitis
have shown clinical improvement as a direct result of elimination of
fleas from the dog.
Treatment and Control of Intestinal Nematode
Infections: For the treatment and control of intestinal hookworm
infections caused by Ancylostoma caninum and Uncinaria
stenocephala (adults, immature adults and fourth stage larvae) and
roundworm infections caused by Toxocara canis (adults and fourth stage
larvae), and Toxascaris leonina (adults), and whipworm
infections caused by Trichuris vulpis (adults), Advantage
Multi for Dogs should be administered once as a single topical
dose.
ANIMAL SAFETY:
In a controlled, double-masked, field safety study, Advantage
Multi for Dogs was administered to 128 dogs of various breeds, 3
months to 15 years of age, weighing 4 to 157 pounds. Advantage Multi
for Dogs was used safely in dogs concomitantly receiving ACE
inhibitors, anticonvulsants, antihistamines, antimicrobials,
chondroprotectants, corticosteroids, immunotherapeutics, MAO inhibitors,
NSAIDs, ophthalmic medications, sympathomimetics, synthetic estrogens,
thyroid hormones, and urinary acidifiers. Owners reported the following
signs in their dogs after application of Advantage Multi for Dogs:
pruritus, flaky/greasy residue at the treatment site, medicinal odor,
lethargy, inappetence, and hyperactivity.
Safety Study in Puppies: Advantage
Multi for Dogs was applied topically at 1, 3 and 5X the recommended
dose to 7-week-old Beagle puppies once every 2 weeks for 6 treatments on
days 0, 14, 28, 42, 56, and 70. Loose stools and diarrhea were observed
in all groups, including the controls, throughout the study. Vomiting
was seen in one puppy from the 1X treatment group (day 57), in two
puppies from the 3X treatment group (days 1 and 79), and in one puppy
from the 5X treatment group (day 1). Two puppies each in the 1X, 3X, and
5X groups had decreased appetites within 24 hours post-dosing. One puppy
in the 1X treatment group had pruritus for one hour following the fifth
treatment. A puppy from the 5X treatment group displayed rapid,
difficult breathing from 4 to 8 hours following the second treatment.
Dermal Dose Tolerance Study: Advantage Multi for Dogs
was administered topically to 8-month-old Beagle dogs at 10X the
recommended dose once. One dog showed signs of treatment site irritation
after application. Two dogs vomited, one at 6 hours and one at 6 days
post-treatment. Increased RBC, hemoglobin, activated partial
thromboplastin, and direct bilirubin were observed in the treated group.
Dogs in the treated group did not gain as much weight as the control
group.
Safety Study in Heartworm-Positive Dogs:
Advantage Multi for Dogs was administered topically at 1 and 5X
the recommended dose every 14 days for 3 treatments to dogs with adult
heartworm infections and circulating microfilariae. At 5X, one dog was
observed vomiting three hours after the second treatment.
Hypersensitivity reactions were not seen in the 5X treatment group.
Microfilariae counts decreased with treatment.
Oral Safety Study in Beagles:
Advantage Multi for Dogs was administered once orally at the
recommended topical dose to 12 dogs. Six dogs vomited within 1 hour of
receiving the test article, 2 of these dogs vomited again at 2 hours,
and 1 dog vomited again up to 18 hours post-dosing. One dog exhibited
shaking (nervousness) 1 hour post-dosing. Another dog exhibited abnormal
neurological signs (circling, ataxia, generalized muscle tremors, and
dilated pupils with a slow pupillary light response) starting at 4 hours
post-dosing through 18 hours post-dosing. Without treatment, this dog
was neurologically normal at 24 hours and had a normal appetite by 48
hours post-dosing.
Dermal Safety Study in Ivermectin-Sensitive Collies:
Advantage Multi for Dogs was administered topically at 3 and 5X the
recommended dose every 28 days for 3 treatments to Collies which had
been pre-screened for avermectin sensitivity. No clinical abnormalities
were observed.
Oral Safety Study in Ivermectin-Sensitive Collies:
Advantage Multi for Dogs was administered orally to 5 pre-screened
ivermectin-sensitive Collies. The Collies were asymptomatic after
ingesting 10% of the minimum labeled dose. At 40% of the minimum
recommended topical dose, 4 of the dogs experienced neurological signs
indicative of avermectin toxicity including depression, ataxia,
mydriasis, salivation, muscle fasciculation, and coma, and were
euthanized.
STORAGE INFORMATION:
Store at temperatures between 4°C (39°F) and 25°C (77°F), avoiding
excess heat or cold.
CAUTION:
Federal (U.S.A.) Law restricts this drug to use by or on the order of
a licensed veterinarian.
Manufacturer:
Bayer Animal Health