Comfortis Chewable Tablets for Dogs

Company: Elanco US

(spinosad)

Chewable Tablets

COMFORTIS™-Dogs

Comfortis Chewable Tablets for Dogs Caution

Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Description

COMFORTIS (spinosad) is available in five sizes of chewable flavored tablets for oral administration to dogs and puppies according to their weight. Each chewable tablet is formulated to provide a minimum spinosad dosage of 13.5 mg/lb (30 mg/kg). Spinosad is a member of the spinosyns class of insecticides, which are non-antibacterial tetracyclic macrolides. Spinosad contains two major factors, spinosyn A and spinosyn D, derived from the naturally occurring bacterium, Saccharopolyspora spinosa. Spinosyn A and spinosyn D have the chemical compositions 2 - [(6 - deoxy - 2,3,4 - tri - O - methyl - α - L - mannopyranosyl)oxy] - 13 - [[5 - dimethylamino) - tetrahydro - 6 - methyl - 2H - pyran - 2 - yl]oxy] - 9 - ethyl - 2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b - tetradecahydro - 14 - methyl - 1H - as - Indaceno[3,2 - d]oxacyclododecin - 7, 15-dione and 2 - [(6 - deoxy - 2,3,4 - tri - O - methyl - α - L - mannopyranosyl)oxy] - 13 - [[5 - dimethylamino) - tetrahydro - 6 - methyl - 2H - pyran - 2 - yl] oxy] - 9 - ethyl - 2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b - tetradecahydro - 4,14 - dimethyl - 1H - as - Indaceno[3,2 - d] oxacyclododecin-7,15-dione, respectively.

Comfortis Chewable Tablets for Dogs Indications

COMFORTIS kills fleas and is indicated for the prevention and treatment of flea infestations (Ctenocephalides felis) for one month, on dogs and puppies 14 weeks of age and older and 5.0 pounds of body weight or greater.

Dosage and Administration

COMFORTIS is given orally once a month, at the recommended minimum dosage of 13.5 mg/lb (30 mg/kg).

Do not use the dosing schedule below when administering COMFORTIS to cats, as it can result in an underdosage.

Dosage Schedule:

* Dogs over 120 lbs should be administered the appropriate combination of tablets.

Administer COMFORTIS with food for maximum effectiveness.

COMFORTIS is a chewable tablet and is readily consumed by dogs when offered by the owner just prior to feeding. Alternatively, COMFORTIS may be offered in food or administered like other tablet medications. COMFORTIS should be administered at monthly intervals.

If vomiting occurs within an hour of administration, redose with another full dose. If a dose is missed, administer COMFORTIS with food and resume a monthly dosing schedule.

Treatment with COMFORTIS may begin at any time of the year, preferably starting one month before fleas become active and continuing monthly through the end of flea season. In areas where fleas are common year-round, monthly treatment with COMFORTIS should continue the entire year without interruption.

To minimize the likelihood of flea reinfestation, it is important to treat all animals within a household with an approved flea protection product.

Contraindications

There are no known contraindications for the use of COMFORTIS.

Warnings

Not for human use. Keep this and all drugs out of the reach of children.

Serious adverse reactions have been reported following concomitant extra-label use of ivermectin with COMFORTIS (see POST APPROVAL EXPERIENCE).

Precautions

COMFORTIS are for use in dogs and puppies 14 weeks of age and older (see ANIMAL SAFETY).

Use with caution in breeding females (see ANIMAL SAFETY). Use with caution in dogs with pre-existing epilepsy (see ADVERSE REACTIONS). The safe use of COMFORTIS in breeding males has not been evaluated.

Adverse Reactions

In a well-controlled US field study, which included a total of 470 dogs (330 dogs treated with COMFORTIS and 140 dogs treated with an active control), no serious adverse reactions were observed with COMFORTIS. All reactions were regarded as mild and did not result in any dog being removed from the study.

Over the 90-day study period, all observations of potential adverse reactions were recorded. Reactions that occurred at an incidence > 1% within any of the 3 months of observation are presented in the following table. The most frequently reported adverse reaction in dogs in the COMFORTIS and active control groups was vomiting. The occurrence of vomiting, most commonly within 48 hours after treatment, decreased with repeated doses of COMFORTIS.

Percentage of Dogs (%) with Adverse Reactions

^a This number (n=139) is less than the total number of dogs in the safety population for the active control group (n=140) because one dog joined the study late and was only dosed at Month 3.

In US and European field studies, no dogs experienced seizures when dosed with COMFORTIS at the therapeutic dose range of 13.5-27.3 mg/lb (30-60 mg/kg), including 4 dogs with pre-existing epilepsy. Four epileptic dogs that received higher than the maximum recommended dose of 27.3 mg/lb (60 mg/kg) experienced at least one seizure within the week following the second dose of COMFORTIS, but no seizures following the first and third doses. The cause of the seizures observed in the field studies could not be determined.

Post Approval Experience (June 2009):

The following adverse reactions are based on post-approval adverse drug event reporting. The adverse reactions are listed in decreasing order of frequency: vomiting, depression/lethargy, anorexia, ataxia, diarrhea, pruritus, trembling, hypersalivation and seizures.

Following concomitant extra-label use of ivermectin with COMFORTIS, some dogs have experienced the following clinical signs: trembling/twitching, salivation/drooling, seizures, ataxia, mydriasis, blindness and disorientation.

Post approval experience continues to support the safety of COMFORTIS when used concurrently with heartworm preventatives according to label directions.

For technical assistance or to report suspected adverse drug events, contact Elanco US Inc. at 1-888-545-5973. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae

Mode of Action:

The primary target of action of COMFORTIS in insects is an activation of nicotinic acetylcholine receptors (nAChRs). Spinosad does not interact with known insecticidal binding sites of other nicotinic or GABAergic insecticides such as neonicotinoids, fiproles, milbemycins, avermectins, and cyclodienes. Insects treated with spinosad show involuntary muscle contractions and tremors resulting from activation of motor neurons. Prolonged spinosad-induced hyperexcitation results in prostration, paralysis, and flea death. The selective toxicity of spinosad between insects and vertebrates may be conferred by the differential sensitivity of the insect versus vertebrate nAChRs.

Effectiveness

In a well-controlled laboratory study, COMFORTIS began to kill fleas 30 minutes after administration and demonstrated 100% effectiveness within 4 hours. COMFORTIS kills fleas before they can lay eggs. If a severe environmental infestation exists, fleas may persist for a period of time after dose administration due to the emergence of adult fleas from pupae already in the environment. In field studies conducted in households with existing flea infestations of varying severity, flea reductions of 98.0% to 99.8% were observed over the course of 3 monthly treatments with COMFORTIS. Dogs with signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis and pruritus as a direct result of eliminating the fleas.

Animal Safety:

COMFORTIS was tested in pure and mixed breeds of healthy dogs in well-controlled clinical and laboratory studies. No dogs were withdrawn from the field studies due to treatment-related adverse reactions.

In a dose tolerance study, COMFORTIS was administered orally to adult Beagle dogs at average doses of up to 100 mg/kg once daily for 10 consecutive days (16.7 times the maximum recommended monthly dose). Vomiting was seen in 5 of 6 treated dogs during the first 6 days of treatment, usually within 2.5 hours of dosing. Treated females lost weight early in the treatment period, but their weights were similar to control dogs by the end of the 24-day study. COMFORTIS was not associated with any clinically significant changes in hematology, blood coagulation or urinalysis parameters; however, mild elevations in ALT occurred in all dogs treated with COMFORTIS. By day 24, ALT values had returned to near baseline levels. Phospholipidosis (vacuolation) of the lymphoid tissue was seen in all dogs treated with COMFORTIS, the long-term effects of which are unknown.

In a margin of safety study, COMFORTIS was administered orally to 6-week-old Beagle puppies at average doses of 1.5, 4.4, and 7.4 times the maximum recommended dose at 28-day intervals over a 6-month period. Vomiting was observed across all groups, including the control. Increased vomiting was observed at elevated doses, usually within 1 hour following administration. Vomiting at all doses decreased over time and stabilized when puppies were 14 weeks of age. The average daily and total weight gains of treated dogs were smaller than control dogs and were dose dependent. COMFORTIS was not associated with clinically significant changes in hematology, clinical chemistry, coagulation or urinalysis parameters. Phospholipidosis (vacuolation) of the lymphoid tissue was seen in some dogs in the 4.4X group and all dogs in the 7.4X group. The long term effects of phospholipidosis are unknown. Treatment with COMFORTIS was not associated with any other clinically significant adverse clinical observations, gross necropsy or histopathological changes.

In a reproductive safety study, COMFORTIS was administered orally to female Beagles at 1.3 and 4.4 times the maximum recommended therapeutic dose every 28 days prior to mating, during gestation, and during a six-week lactation period. No treatment-related adverse effects were noted for conception rates in the dams, or for mortality, body temperature, necropsy, or histopathology findings for the dams or puppies. One dam from each treatment group experienced early pregnancy loss and one additional high dose dam aborted late term. The treated dams experienced more vomiting, especially at one hour post-dose, than the control dams. Puppies from dams treated at 1.3 times the maximum recommended therapeutic dose had lower body weights than puppies from control dams. Although puppy mortality between treated and control dams was not different, the puppies from the treated dams experienced more lethargy (4.4X group only), dehydration, weakness and felt cold to the touch (4.4X group only) than puppies from control dams.

A pilot study without a control group was conducted to analyze milk from three lactating dogs treated with an experimental formulation of spinosad at 1.5 times the maximum recommended dose administered at day 28 of gestation and 24 hours prior to parturition. The data demonstrated that spinosyns were excreted in the milk of these dogs. Mortality and morbidity were greatest in puppies from the dam with the highest spinosyns level in milk. The spinosad milk: reference plasma exposure ratio calculated from this study ranged from 2.2 to 3.5.

In well-controlled field studies, COMFORTIS was administered safely in conjunction with other frequently used veterinary products, such as vaccines, anthelmintics, antibiotics, steroids, flea and tick control products, anesthetics, NSAIDs, antihistamines, alternative/herbal remedies, shampoos, and prescription diets. Changes in hematology, clinical chemistry and urinalysis values were compared pre- and post-study and were unremarkable.

Storage Information:

Store at 20-25°C (68-77°F), excursions permitted between 15 to 30°C (59 to 86°F).

How Supplied

COMFORTIS is available in five tablet sizes for use in dogs: 140, 270, 560, 810 or 1620 mg. Each tablet size is available in color-coded packages of 6 tablets.

Approved by FDA under NADA # 141-277

Manufactured for:

Elanco US Inc., Greenfield, IN 46140

www.comfortis.com

Comfortis, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates.

© 2021 Elanco or its affiliates

CA4222

CA4223

CA4224

CA4225

CA4227

Revised: August 2020

PA103019X

CPN: 1131050.1