Animal NDC 58198-5451-4 Credelio
Lotilaner

Animal Product Information

Field Name	Field Value
Animal NDC Code	58198-5451-4
Proprietary Name	Credelio What is the Proprietary Name? The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.
Non-Proprietary Name	Lotilaner What is the Non-Proprietary Name? The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.
Labeler Name	Elanco Us Inc.
Product Type	Prescription Animal Drug
Usage Information	CREDELIO kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Amblyomma americanum (lone star tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (black-legged tick) and Rhipicephalus sanguineus (brown dog tick)] for one month in dogs and puppies 8 weeks of age and older, and weighing 4.4 pounds or greater.
Active Ingredient(s)	Lotilaner
Marketing Category	NADA - NEW ANIMAL DRUG APPLICATION What is the Marketing Category? Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.
FDA Application Number	NADA141494 What is the FDA Application Number? This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

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Credelio Animal Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Other

Chewable Tablets

For oral use In dogs

Caution:

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

Palatability: In the U.S. field study, which included 567 doses administered to 198 dogs, 80.4% of dogs voluntarily consumed CREDELIO when offered by hand or in an empty bowl, an additional 13.6% consumed CREDELIO when offered with food, and 6.0% required placement of the chewable tablet in the back of the dog's mouth.

Description:

CREDELIO (lotilaner) is a beef-flavored, chewable tablet for oral administration to dogs and puppies according to their weight. Each chewable tablet is formulated to provide a minimum lotilaner dosage of 9 mg/lb (20 mg/kg).

Lotilaner has the chemical composition of 5-[(5S)-4,5-dihydro-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-3-isoxazolyl]-3-methyl-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-2-thiophenecarboxamide.

Indications:

CREDELIO kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Amblyomma americanum (lone star tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (black-legged tick) and Rhipicephalus sanguineus (brown dog tick)] for one month in dogs and puppies 8 weeks of age and older, and weighing 4.4 pounds or greater.

Dosage And Administration:

CREDELIO is given orally once a month, at the minimum dosage of 9 mg/lb (20 mg/kg).

Dosage Schedule:

Body Weight	Lotilaner Per Chewable Tablet (mg)	Chewable Tablets Administered
4.4 to 6.0 lbs	56.25	One
6.1 to 12.0 lbs	112.5	One
12.1 to 25.0 lbs	225	One
25.1 to 50.0 lbs	450	One
50.1 to 100.0 lbs	900	One
Over 100.0 lbs	Administer the appropriate combination of chewable tablets

CREDELIO must be administered with food (see Clinical Pharmacology).

Treatment with CREDELIO can begin at any time of the year and can continue year-round without interruption.

Contraindications:

There are no known contraindications for the use of CREDELIO.

Warnings:

Not for human use. Keep this and all drugs out of the reach of children. Keep CREDELIO in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

Precautions:

Lotilaner is a member of the isoxazoline class. This class has been associated with neurologic adverse reactions including tremors, ataxia, and seizures. Seizures have been reported in dogs receiving isoxazoline class drugs, even in dogs without a history of seizures. Use with caution in dogs with a history of seizures or neurologic disorders.

The safe use of CREDELIO in breeding, pregnant or lactating dogs has not been evaluated.

Adverse Reactions:

In a well-controlled U.S. field study, which included 284 dogs (198 dogs treated with CREDELIO and 86 dogs treated with an oral active control), there were no serious adverse reactions.

Over the 90-day study period, all observations of potential adverse reactions were recorded. Reactions that occurred at an incidence of 1% or greater are presented in the following table.

Dogs with Adverse Reactions in the Field Study
*Two geriatric dogs developed mildly elevated BUN (34 to 54 mg/dL; reference range: 6 to 31 mg/dL) during the study. One of these dogs also developed polyuria and a mildly elevated potassium (6.5 mEq/L; reference range: 3.6 to 5.5 mEq/L) and phosphorous (6.4 mg/dL; reference range: 2.5 to 6.0 mg/dL). The other dog also developed a mildly elevated creatinine (1.7 to 2.0 mg/dL; reference range: 0.5 to 1.6 mg/dL) and weight loss.
Adverse Reaction (AR)	CREDELIO Group: Number (and Percent) of Dogs with the AR (n=198)	Active Control Group: Number (and Percent) of Dogs with the AR (n=86)
Weight Loss	3 (1.5%)	2 (2.3%)
Elevated Blood Urea Nitrogen (BUN)	2 (1.0%)*	0 (0.0%)
Polyuria	2 (1.0%)*	0 (0.0%)
Diarrhea	2 (1.0%)	2 (2.3%)

In addition, one dog experienced intermittent head tremors within 1.5 hours of administration of vaccines, an ear cleaning performed by the owner, and its first dose of CREDELIO. The head tremors resolved within 24 hours without treatment. The owner elected to withdraw the dog from the study.

In an Australian field study, one dog with a history of seizures experienced seizure activity (tremors and glazed eyes) six days after receiving CREDELIO. The dog recovered without treatment and completed the study. In the U.S. field study, two dogs with a history of seizures received CREDELIO and experienced no seizures throughout the study.

In three well-controlled European field studies and one U.S. laboratory study, seven dogs experienced episodes of vomiting and four dogs experienced episodes of diarrhea between 6 hours and 3 days after receiving CREDELIO.

To report suspected adverse events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), 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.

Clinical Pharmacology:

Following oral administration of 43 mg/kg (approximately 1X the maximum labeled dose), peak lotilaner concentrations were achieved between 6 hours and 3 days in dogs 2 months of age and between 1 and 7 days in dogs 10 months of age. Dogs 2 months of age had a shorter elimination half-life (average of 9.6 days) than at 10 months of age (average of 28.4 days). Due to reduced drug bioavailability in the fasted state, CREDELIO must be administered with a meal or within 30 minutes after feeding.

Mode Of Action:

Lotilaner is an ectoparasiticide belonging to the isoxazoline group. Lotilaner inhibits insect and acarine gamma-aminobutyric acid (GABA)-gated chloride channels. This inhibition blocks the transfer of chloride ions across cell membranes, which results in uncontrolled neuromuscular activity leading to death of insects and acarines. The selective toxicity of lotilaner between insects and acarines and mammals may be inferred by the differential sensitivity of the insects and acarines' GABA receptors versus mammalian GABA receptors.

Effectiveness:

In well-controlled European laboratory studies, CREDELIO began to kill fleas four hours after administration or infestation, with greater than 99% of fleas killed within eight hours after administration or infestation for 35 days. In a well-controlled U.S. laboratory study, CREDELIO demonstrated 100% effectiveness against adult fleas 12 hours after administration or infestation for 35 days.

In a 90-day well-controlled U.S. field study conducted in households with existing flea infestations of varying severity, the effectiveness of CREDELIO against fleas on Days 30, 60 and 90 compared to baseline was 99.5%,100% and 100%, respectively. Dogs with signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis and pruritus as a direct result of eliminating fleas.

In a well-controlled laboratory study, CREDELIO killed fleas before they could lay eggs, thus preventing subsequent flea infestations for 30 days after the start of treatment of existing flea infestations.

In well-controlled laboratory studies, CREDELIO demonstrated > 97% effectiveness against Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis and Rhipicephalus sanguineus ticks 48 hours after administration or infestation for 30 days. In a well-controlled European laboratory study, CREDELIO started killing Ixodes ricinus ticks within four hours after administration.

Animal Safety:

In a margin of safety study, CREDELIO was administered orally to 24 (8 dogs/group) 8-week-old Beagle puppies at doses of 43 mg/kg, 129 mg/kg, and 215 mg/kg (approximately 1, 3, and 5X the maximum labeled dose, respectively) every 28 days for eight consecutive doses. The 8 dogs in the control group (0X) were untreated. There were no clinically-relevant, treatment-related effects on clinical observations, physical and neurological examinations, body weights, food consumption, electrocardiograms, clinical pathology (hematology, clinical chemistries, coagulation profiles and urinalysis), gross pathology, histopathology, or organ weights. Blood concentrations of lotilaner confirmed systemic exposure of all treated dogs, although the exposure was less than dose proportional at 5X.

In a well-controlled field study, CREDELIO was used concurrently with other medications, such as vaccines, anthelmintics, antibiotics, steroids, NSAIDS, anesthetics, and antihistamines. No adverse reactions were observed from the concomitant use of CREDELIO with other medications.

Storage Information:

Kills fleas

Kills ticks

Monthly dose

Give with
food

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

Approved by FDA under NADA # 141-494

Elanco_TM

* The information on this page is for an ANIMAL PRODUCT, please review the complete disclaimer below.

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