Credelio® PLUS (lotilaner + milbemycin oxime)

Lotilaner is a potent inhibitor of gamma–aminobutyric acid (GABA)-gated chloride channels and to a lesser extent of glutamate-gated chloride ion channels of insects and ticks, resulting in rapid death of ticks and fleas. While having no inhibitory effect on dog GABACIs, even at the highest concentration. ³

Milbemycin oxime is a member of the macrocyclic lactones chemical class and acts on invertebrate neurotransmission by increasing nematode and insect membrane permeability to chloride ions via glutamate-gated chloride ion channels. This leads to hyperpolarisation of the neuromuscular membrane, flaccid paralysis and death of the parasite.

Content uniformity of whole and half tablets has not been established. Therefore, Credelio^® PLUS tablets are not scored and splitting of Credelio^® PLUS tablets is not recommended. A variety of tablet sizes have been developed to allow for accurate dosing according to a dog’s weight.

Yes, as long as the total dose administered is given in whole tablets and remains within the recommended dose range of 20-41 mg lotilaner/kg body weight and 0.75-1.53 mg milbemycin oxime/kg body weight.

Credelio^® PLUS should be administered with or after food.

Lotilaner is readily absorbed following oral administration and peak plasma concentration is reached within 3‒5 hours. Food enhances the absorption of lotilaner. The bioavailability of lotilaner in Credelio^® PLUS is approximately 75%. ¹

The presence of food helps ensure that peak blood levels and exposure are achieved which is necessary for initial and ongoing efficacy. In a study with lotilaner in Credelio^®, the bioavailability of lotilaner in dogs in a fasting state was only 24 percent. ²

Puppies should be weighed each month and dosed according to the dosing table based on their weight at the time of administration.

Isoxazolines are chiral molecules with two stereoisomers that are exact mirror images of each other in a 50/50 ratio within the racemic mixture. For lotilaner, one of the enantiomers is active against parasites, the mirror image is inactive. Additional purification steps are taken during the manufacture of the lotilaner in Credelio^® PLUS to remove the inactive form, as it is also done for Credelio^®. ²

Since the inactive portion has been removed, the patient does not need to metabolize and/or excrete the inactive enantiomer and purification also allows for smaller tablets.

The meat dry flavoring used in the manufacture of Credelio^® PLUS is made from pork liver, barley, wheat and soybeans. ⁵ The flavor profile is described as “meat.” ⁵

The flavoring used in Credelio^® PLUS contains ≤ 20 ppm gluten, meeting the Health Canada guidelines for “gluten-free.” For more information, see list of excipients.

Consult package expiry date.

Lotilaner is a member of the isoxazoline class. It has acaricidal and insecticidal activity and is indicated for tick and flea treatment.

Milbemycin oxime is a systemically active macrocyclic lactone isolated from the fermentation of Streptomyces hygroscopicus var. aureolacrimosus. 

Milbemycin oxime is an antiparasitic endectocide with activity against mites, larval and adult stages of nematodes as well as larvae (L3/L4) of Dirofilaria immitis. The activity of milbemycin oxime is related to its action on invertebrate neurotransmission. Milbemycin oxime, like avermectins and other milbemycins, increases nematode and insect membrane permeability to chloride ions via glutamate-gated chloride ion channels. This leads to hyperpolarisation of the neuromuscular membrane and flaccid paralysis and death of the parasite.¹

Yes, Credelio^® PLUS can be used as part of a treatment strategy for the control of flea allergy dermatitis (FAD).

Adult fleas cannot begin laying eggs until 24 to 36 hours after taking their first blood meal. In Credelio^® lotilaner has shown a sustained speed-of-kill of greater than 99 percent within eight hours and 100 percent within 12 hours throughout the month. ⁴

Credelio^® PLUS' product kills existing and newly emerged flea infestations on dogs before the female can lay eggs. Therefore, the product breaks the flea life cycle and prevents environmental flea contamination in areas to which the dog has access.

In a speed-of-kill study with Credelio^® lotilaner killed 100 percent of fleas on dogs within 12 hours. ⁴

Treatment with Credelio^® PLUS may begin at any time of the year for ectoparasite and gastrointestinal nematode control.

If used for heartworm prevention the first dosing should be no later than one month after the beginning of the heartworm infection season and should continue monthly until two months after the last possible exposure to mosquitoes.

No data exists to support this use therefore we are not able to recommend this practice.

If a dose is missed, administer Credelio^® PLUS with food and resume a monthly dosing schedule from that date on.

The safety of the veterinary medicinal product in breeding, pregnant and lactating dogs has not been investigated. ¹

Use only according to the benefit/risk assessment by the responsible veterinarian.

Do not give to puppies younger than 8 weeks of age or to dogs weighing less than 1.4 kg. ¹

Credelio® PLUS is currently only approved for use in dogs, it has not been approved for use in cats. We recommend instead to try Credelio® Cat, flea and tick control uniquely designed for cats.

The following adverse events have been reported in dogs after administration of lotilaner/milbemycin oxime¹:

• Few adverse events (AEs) were uncommonly (more than 1 but less than 10 animals in 1,000 animals treated) reported including:
  • Gastrointestinal signs (diarrhea, vomiting and colitis)
  • Anorexia
  • Lethargy
  • Hepatopathy
  • Pruritus
  • Changes in behavior
• These events were generally self-limiting and of short duration
• Frequency similar to what is seen with Credelio^®

There is no known contraindication for the use of a tapeworm treatment concurrently with Credelio^® Plus.

For dogs at risk of infection with tapeworms, Interceptor^® Plus provides broad spectrum deworming including efficacy for tapeworms while Credelio^® (lotilaner) provides efficacy against ticks and fleas.