Credelio Quattro (lotilaner, moxidectin, praziquantel, pyrantel) is the broadest-label oral canine parasiticide, covering fleas, ticks, heartworm, roundworms, hookworms, and three tapeworm species.

Credelio Quattro (lotilaner, moxidectin, praziquantel, and pyrantel chewable tablets) received FDA approval in October 2024 as the broadest-label oral parasiticide for dogs. Since launch, it has picked up two additional label claims: Lyme disease prevention (via killing Ixodes scapularis ticks) and longhorned tick (Haemaphysalis longicornis) coverage in October 2025, plus a conditional approval for New World screwworm treatment (Credelio Quattro-CA1) in December 2025. This article breaks down what each of the four active ingredients covers, what the label actually says, the safety profile including the isoxazoline class warning, and how Credelio Quattro compares to Simparica Trio and NexGard PLUS on parasite spectrum, tick speed, and intestinal worm coverage.

What Credelio Quattro is and what it covers

Credelio Quattro is a prescription monthly chewable tablet for dogs and puppies 8 weeks of age and older weighing at least 3.3 lb. It contains four active ingredients, each targeting a different parasite group:

Ingredient	Class	What it targets
Lotilaner	Isoxazoline (ectoparasiticide)	Fleas and ticks
Moxidectin	Macrocyclic lactone	Heartworm prevention (Dirofilaria immitis)
Praziquantel	Pyrazinoisoquinoline	Tapeworms (Dipylidium caninum, Taenia pisiformis, Echinococcus granulosus)
Pyrantel pamoate	Tetrahydropyrimidine	Roundworms (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala)

The combination covers six parasite categories in one dose: fleas, ticks, heartworm, roundworms, hookworms, and tapeworms. The tapeworm coverage (three species including Echinococcus granulosus) is the primary differentiator versus other oral combination products, which typically do not include a cestocide.

The FDA-approved label indications

Per the Elanco product label and FDA Freedom of Information summary (NADA 141-581, approved October 7, 2024; supplemented October 20, 2025):

Fleas: Kills adult fleas (Ctenocephalides felis) and treats and prevents flea infestations for one month.

Ticks: Treats and controls tick infestations from five species for one month:

Amblyomma americanum (lone star tick)
Dermacentor variabilis (American dog tick)
Ixodes scapularis (black-legged tick / deer tick)
Rhipicephalus sanguineus (brown dog tick)
Haemaphysalis longicornis (longhorned tick) — added October 2025

Lyme disease prevention: Prevents Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks — added October 2025.

Heartworm: Prevents heartworm disease caused by Dirofilaria immitis. In laboratory studies, Credelio Quattro was 100% effective against heartworm disease from the first monthly dose. Dogs should be tested for existing heartworm infection before starting, because the product is not effective against adult heartworms.

Intestinal worms: Treats and controls:

Roundworms: immature adult and adult Toxocara canis, adult Toxascaris leonina
Hookworms: fourth-stage larvae, immature adult, and adult Ancylostoma caninum, adult Uncinaria stenocephala
Tapeworms: Dipylidium caninum, Taenia pisiformis, Echinococcus granulosus

New World screwworm (Credelio Quattro-CA1): In December 2025, the FDA conditionally approved Credelio Quattro-CA1 for treatment of infestations caused by New World screwworm (Cochliomyia hominivorax) larvae in dogs. This conditional approval (valid for up to 5 years while additional effectiveness data are collected) was based on a study showing lotilaner achieved 100% efficacy against screwworm larvae within 24 hours. The same chewable tablet carries both the Credelio Quattro and Credelio Quattro-CA1 label claims.

What each ingredient actually does

Lotilaner is the isoxazoline ectoparasiticide. It works by blocking ligand-gated chloride channels (GABA and glutamate receptors) in the insect and tick nervous system, causing paralysis and death. It has selectivity for arthropod receptors over mammalian receptors, though the FDA has noted that neurologic adverse reactions can occur in a small number of dogs (see Safety section). Lotilaner is also the active ingredient in Credelio (flea/tick-only product).

Moxidectin is a macrocyclic lactone that interferes with parasite neurotransmission, paralyzing and killing heartworm larvae (Dirofilaria immitis) before they can mature. It is the same heartworm-prevention agent used in other combination products including Simparica Trio and NexGard PLUS.

Praziquantel is the tapeworm treatment. It damages the tapeworm's tegument (outer surface), causing paralysis and enabling the host's immune system to eliminate the worm. This is the ingredient that sets Credelio Quattro apart from other oral combination products, which do not include praziquantel and therefore do not cover tapeworms.

Pyrantel pamoate is a nematocide that blocks nerve transmission in roundworms and hookworms, causing spastic paralysis. It covers both Toxocara and Toxascaris roundworm species and two hookworm species.

Dosing: weight bands and tablet sizes

Credelio Quattro is available in five weight-based tablet strengths, each given as a single chew once monthly:

Dog weight	Lotilaner (mg)	Moxidectin (mg)	Praziquantel (mg)	Pyrantel (mg)
3.3–6 lb	56.25	0.056	14.25	14.25
6.1–12 lb	112.5	0.113	28.5	28.5
12.1–25 lb	225	0.225	57	57
25.1–50 lb	450	0.45	114	114
50.1–100 lb	900	0.9	228	228

Dogs over 100 lb receive a combination of tablets to reach the appropriate dose. The moxidectin dose delivered per kilogram ranges from 20–40 µg/kg, which is lower than the maximum moxidectin dose in Simparica Trio (48 µg/kg). A 2025 study in Parasites & Vectors found this lower moxidectin dose contributed to a wider safety margin, including in MDR1-gene-mutation (multidrug-sensitive) collies, where Credelio Quattro was tolerated at up to 5× the labeled dose with only mild, self-limiting effects.

Safety: isoxazoline class warning and what the data show

Because lotilaner is an isoxazoline, Credelio Quattro carries the FDA's class-wide isoxazoline safety warning. The FDA fact sheet notes that isoxazoline products "have been associated with neurologic adverse reactions, including muscle tremors, ataxia, and seizures" in some dogs, including dogs without a prior seizure history.

The label states:

"Lotilaner, an ingredient in Credelio Quattro, belongs to the isoxazoline class and has been associated with neurologic adverse reactions like tremors, ataxia, and seizures even in dogs without a history of seizures. Use with caution in dogs with a history of seizures or neurologic disorders."

Key safety points from the label and published studies:

Most common adverse reactions in clinical trials: vomiting and diarrhea.
Neurologic events (tremors, ataxia, seizures) are reported but uncommon. The FDA considers the products in this class "safe and effective" for most dogs, and the overall incidence of neurologic adverse events is low relative to the number of doses administered nationwide.
MDR1-sensitive breeds: A target animal safety study demonstrated that Credelio Quattro was tolerated at 5× the maximum labeled dose in MDR1-mutant collies, with no neurologic events reported. This is a differentiating safety point from some other combination products.
Heartworm-positive dogs: A 2025 study in Parasites & Vectors evaluated Credelio Quattro in dogs with adult D. immitis infections and circulating microfilariae. Three consecutive monthly doses at the labeled dose were well tolerated, with observations limited to occasional vomiting and abnormal stools that resolved without treatment.
Breeding, pregnant, and lactating dogs: Safe use has not been evaluated.
Dogs should be tested for heartworm infection before administration, as the product prevents heartworm disease but does not treat adult heartworms.

Credelio Quattro vs. Simparica Trio vs. NexGard PLUS

Three oral isoxazoline-based combination products now compete in the same category. Here is where they differ on label claims:

Feature	Credelio Quattro	Simparica Trio	NexGard PLUS
Isoxazoline	Lotilaner	Sarolaner	Afoxolaner
Heartworm prevention	Moxidectin	Moxidectin	Moxidectin
Roundworms	Pyrantel (2 species)	Pyrantel (2 species)	Pyrantel (2 species)
Hookworms	Pyrantel (2 species)	Pyrantel (2 species)	Pyrantel (3 species: A. caninum, A. braziliense, U. stenocephala)
Tapeworms	Praziquantel (3 species)	Prevents D. caninum by killing vector fleas (April 2025 label)	Not labeled
Tick species on label	5 (lone star, American dog, black-legged, brown dog, longhorned)	6 (lone star, Gulf Coast, American dog, black-legged, brown dog, Asian longhorned)	6 (black-legged, brown dog, American dog, lone star, Gulf Coast, longhorned)
Lyme prevention	Yes (via killing I. scapularis)	Yes (via killing I. scapularis)	Yes (via killing I. scapularis)
Minimum age	8 weeks	8 weeks	8 weeks
Minimum weight	3.3 lb	2.8 lb	4 lb

The tapeworm difference. Credelio Quattro is the only one of the three that includes praziquantel, giving it direct label claims for treating and controlling three tapeworm species (D. caninum, T. pisiformis, E. granulosus). Simparica Trio received an April 2025 label expansion for prevention of D. caninum by killing vector fleas — but this prevents new infections only and does not treat existing tapeworms or cover Taenia or Echinococcus species. NexGard PLUS has no tapeworm claim. For dogs in areas where Echinococcus granulosus is endemic, or dogs with active tapeworm infections, Credelio Quattro's praziquantel provides direct treatment that the others do not.

The tick difference. Credelio Quattro does not carry Gulf Coast tick (Amblyomma maculatum) on its label; both Simparica Trio and NexGard PLUS do. All three products cover the longhorned/Asian longhorned tick (H. longicornis). The practical impact depends on which tick species are active in your region.

Tick speed. Elanco-funded head-to-head studies found that lotilaner (in Credelio, not Credelio Quattro specifically) killed ticks faster than sarolaner (Simparica Trio) and afoxolaner (NexGard) based on time to statistical significance versus control. These speed claims are based on the standalone Credelio product, not the four-ingredient Credelio Quattro formulation.

When Credelio Quattro is not the right fit

Dogs with a history of seizures or neurologic disorders. While the isoxazoline class warning applies to all three products, a veterinarian should weigh the benefit against the individual dog's history.
Dogs needing Gulf Coast tick coverage specifically. Simparica Trio carries that species on label.
Puppies under 3.3 lb. Simparica Trio's minimum weight is 2.8 lb.
Pregnant, breeding, or lactating dogs. Safety has not been established for any of the three products.
Dogs not tested for heartworm. All three products require a heartworm test before starting, because administering microfilaricidal doses to heartworm-positive dogs without veterinary oversight can cause adverse reactions.

What to ask your veterinarian

"Does my dog need tapeworm coverage, or is a flea/tick/heartworm/intestinal worm product sufficient?"
"Which tick species are most common in our area, and does that affect which product you recommend?"
"My dog had a seizure two years ago — is an isoxazoline product appropriate?"
"Does this product interact with anything else my dog is taking?"

Missed or vomited doses

Per the Elanco label: if a monthly dose is missed, give a new dose immediately and resume monthly dosing. If the dog vomits within one hour of administration, give a replacement dose. Dogs should be tested for heartworm 6 months after a missed dose to rule out infection acquired during the gap.