Lotilaner, Moxidectin, Praziquantel, Pyrantel Pamoate: what the FDA reviewed for dog products

Credelio Quattro™-CA1 NADA 141-619, Original approval, December 17, 2025; sponsor Elanco US Inc.; species: Dogs; foi_id 17789; FDA PDF

Indication

Treatment of infestations caused by New World screwworm (Cochliomyia hominivorax) larvae (myiasis) in dogs and puppies 8 weeks and older weighing 3.3 lb or more (conditional approval).

Dose regimen

minimum 9 mg/lb (20 mg/kg) lotilaner, 0.009 mg/lb (0.02 mg/kg) moxidectin, 2.28 mg/lb (5 mg/kg) praziquantel, 2.28 mg/lb (5 mg/kg) pyrantel (as pamoate salt), Oral (flavored chewable tablet), Single dose for NWS myiasis (re-infestation may occur sooner than one month), Must be administered with food; readminister if vomiting within an hour; use with mechanical removal of larvae remaining in the wound

Credelio Quattro™/Credelio Quattro™-CA1 is given orally at the minimum dosage of 9 mg/lb (20 mg/kg) lotilaner, 0.009 mg/lb (0.02 mg/kg) moxidectin, 2.28 mg/lb (5 mg/kg) praziquantel, and 2.28 mg/lb (5 mg/kg) pyrantel (as pamoate salt). Credelio Quattro™/Credelio Quattro™-CA1 must be administered with food.

Effectiveness

Reasonable expectation of effectiveness (conditional approval) based on published literature: do Vale et al. 2023 (Parasit Vectors 16:86), an uncontrolled study of client-owned dogs in Brazil with naturally acquired C. hominivorax myiasis given a single oral dose of Credelio (lotilaner 23.9-40.9 mg/kg); larvae counted at 2, 6 and 24 h with mechanical removal at 24 h; extrapolated to Credelio Quattro-CA1 via same lotilaner dose and non-interference data; n = Eleven (no control group); primary endpoint: Larval expulsion rate, larvicidal effect and overall effectiveness at 2, 6 and 24 h post-treatment; result: Larval expulsion 80.5%, 93%, 93% at 2, 6, 24 h; overall effectiveness 100% at 24 h (all remaining larvae dead on removal); mean larvicidal effect 41.1% at 24 h (effect driven mainly by expulsion)

Eleven client-owned dogs with active myiasis caused by C. hominivorax larvae were enrolled based on lesion severity and larval burden. All animals received a single oral administration of Credelio™ at doses ranging from 23.9 to 40.9 mg/kg body weight, following the dose bands for the approved flea and tick indications. The study did not include a control group.

Adverse reactions

Extraction notes: Conditional approval (application 141-619, section 571 FD&C Act) of a Credelio Quattro presentation; no new studies. FDA limitations noted: limited population of 11 dogs in Brazil, no control group, mechanical removal confounds treatment effect. TAS: supported entirely by the Credelio Quattro NADA 141-581 studies (dose identical). No PK content.

Credelio Quattro™ NADA 141-581, Supplemental approval, May 21, 2025; sponsor Elanco US Inc.; species: Dogs; foi_id 16986; FDA PDF

Indication

Adds treatment and control of hookworm (fourth stage larvae, immature adult and adult Ancylostoma caninum) infections in dogs and puppies 8 weeks and older weighing 3.3 lb or more.

Dose regimen

minimum 9 mg/lb (20 mg/kg) lotilaner, 0.009 mg/lb (0.02 mg/kg) moxidectin, 2.28 mg/lb (5 mg/kg) praziquantel, 2.28 mg/lb (5 mg/kg) pyrantel (as pamoate salt), Oral (flavored chewable tablet), once a month, Dose unchanged from original approval; administered with food

Credelio Quattro™ is given orally once a month, at the minimum dosage of 9 mg/lb (20 mg/kg) lotilaner, 0.009 mg/lb (0.02 mg/kg) moxidectin, 2.28 mg/lb (5 mg/kg) praziquantel, and 2.28 mg/lb (5 mg/kg) pyrantel (as pamoate salt).

Effectiveness

Field study ELA221321: randomized, masked, multicenter (17 U.S. sites), active-controlled (sarolaner/moxidectin/pyrantel) study in 155 client-owned dogs with naturally occurring GI nematode infections; single owner-administered dose on Day 0 (Credelio Quattro within 30 min of a meal); fecal egg counts Day -1 and Day 10; n = One hundred and three Credelio Quattro and 52 active-control dogs evaluated for safety; seventy-two and 37 for effectiveness; primary endpoint: Fecal egg count (FEC) reduction from pre-treatment to Day 10 (effectiveness = >=95% reduction and significant pre/post difference) for parasites with >=10 evaluable cases; result: A. caninum FEC reduction 99.9% (Credelio Quattro, N=52; p<0.0001) and 99.9% (control, N=27); T. canis 98.7% (N=33) vs 96.6% (N=11). Laboratory studies: 99.0% (L4), 99.8% (immature adult), 99.8% (L4), 100% (immature adult), 100% and 99.9% (adult A. caninum).

One hundred and three dogs administered Credelio Quattro™ and 52 dogs administered the active control were evaluated for safety. Seventy- two dogs administered Credelio Quattro™ and 37 dogs administered the active control were included in the effectiveness evaluation.

Adverse reactions

Extraction notes: Five laboratory dose-confirmation studies (ELA210524, ELA210539, ELA210611, ELA210573, ELA220857; 8-10 dogs/group; necropsy worm counts) plus the supportive field study ELA221321. n_dogs spelled out because the summary writes 'One hundred and three' and 'Seventy-two' (hyphenated across a line break) in words. Field adverse reactions are counts without percentages (safety population 103 vs 52). TAS: 'The Center for Veterinary Medicine did not require target animal safety studies for this supplemental approval.' No PK content.

Credelio Quattro™ NADA 141-581, Original approval, October 07, 2024; sponsor Elanco US Inc.; species: Dogs; foi_id 15966; FDA PDF

Indication

Prevention of heartworm disease (Dirofilaria immitis); treatment and control of roundworm (immature adult and adult Toxocara canis, adult Toxascaris leonina), hookworm (adult Uncinaria stenocephala) and tapeworm (Dipylidium caninum, Taenia pisiformis, Echinococcus granulosus); kills adult fleas, treatment and prevention of flea infestations (C. felis) and treatment and control of tick infestations (A. americanum, D. variabilis, I. scapularis, R. sanguineus) for one month in dogs and puppies 8 weeks and older weighing 3.3 lb or more.

Dose regimen

minimum 9 mg/lb (20 mg/kg) lotilaner, 0.009 mg/lb (0.02 mg/kg) moxidectin, 2.28 mg/lb (5 mg/kg) praziquantel, 2.28 mg/lb (5 mg/kg) pyrantel (as pamoate salt), Oral (flavored chewable tablet), once a month, Administered with food (lotilaner bioavailability lower/more variable fasted; dose confirmation studies conducted fed); maximum moxidectin dose 0.04 mg/kg selected from avermectin-sensitive Collie safety data

Credelio Quattro™ is given orally once a month, at the minimum dosage of 9 mg/lb (20 mg/kg) lotilaner, 0.009 mg/lb (0.02 mg/kg) moxidectin, 2.28 mg/lb (5 mg/kg) praziquantel, and 2.28 mg/lb (5 mg/kg) pyrantel (as pamoate salt).

Pharmacokinetics

Target-animal safety

dose multiples 0X, 1X, 3X, 5X; duration Nine oral doses once every 28 days (Days 0-224) starting at approx. 8 weeks of age; necropsy Day 252; animals Thirty-two (16 male and 16 female), eight per group.

Objective: Evaluate the safety of Credelio Quattro™ following oral administration at one (1X), three (3X), and five times (5X) the maximum labeled dose administered nine times, once every 28 days, to beagle dogs starting approximately 8 weeks of age. Study Animals: Thirty-two beagle dogs (16 male and 16 female), 7.9 to 8.4 weeks of age, weighing between 2 kg to 2.9 kg.

Effectiveness

Field study ELA210049 (heartworm prevention): randomized, masked, multicenter (13 U.S. clinics, mainly heartworm-endemic), active-controlled (sarolaner/moxidectin/pyrantel) study in 372 client-owned dogs; owners dosed monthly for 11 consecutive months (Days 0-300), Credelio Quattro within 30 min of a meal; D. immitis antigen and microfilariae tests Days -1, 120, 240, 330; n = 191 Credelio Quattro / 181 active control evaluated for safety; 156 / 149 for effectiveness; primary endpoint: Success/failure of heartworm prevention by D. immitis antigen and microfilariae testing on Day 330 (failure = positive on either test, confirmed on repeat); result: 100% success: none of the 156 Credelio Quattro dogs tested positive for adult heartworms on Days 120, 240 or 330 (no statistical analysis required). Tablet acceptance: 50.7% from bowl/floor, 9.1% from hand, 28.4% with food, 11.8% pilled (N=552 doses).

One hundred ninety-one (191) dogs administered Credelio Quattro™ and 181 dogs administered the active control product were evaluated for safety. One hundred fifty-six (156) dogs administered Credelio Quattro™ and 149 dogs administered the active control were included in the effectiveness evaluation.

Adverse reactions

Extraction notes: Adverse reaction rows from Table II.7 of field study ELA210049; column order = Credelio Quattro (N=191) then active control (N=181); also pruritus 3 (1.6%) vs 1 (0.6%), alopecia 2 (1%) vs 4 (2.2%), seizure 1 (0.5%) vs 4 (2.2%), ataxia 1 (0.5%) vs 1 (0.6%), nystagmus 1 (0.5%) vs 0, anisocoria 1 (0.5%) vs 1 (0.6%). Results sentence verbatim: 'None of the 156 dogs in the effectiveness population that were treated with Credelio Quattro™ tested positive for adult heartworms on Days 120, 240, or 330.' PK values are from the margin-of-safety study Table III.2 (first 1X dose; rows flattened by PDF extraction, column order lotilaner/moxidectin/praziquantel/pyrantel); praziquantel AUClast 486 (291-814) and pyrantel AUClast 184 (128-263) h*ng/mL not extracted as separate rows. Additional TAS: heartworm-positive dog study ELA210157 (1X/3X x3 doses; vomiting in all 3X dogs; no hypersensitivity) and avermectin-sensitive Collie study ELA210751 (up to 5X x3 doses; no ataxia/seizures/mydriasis/tremors; dose-dependent salivation and vomiting). Foreign/pilot experience includes seizures in 2 dogs (3-way combination U.S. field study) and one euthanized pilot-study dog with duodenal ulcer. 15 laboratory dose-confirmation studies (heartworm, T. canis, T. leonina, U. stenocephala, E. granulosus, fleas, R. sanguineus) plus a second field study for GI nematodes are summarized but not extracted.

Credelio Quattro™ NADA 141-581, Supplemental approval, October 20, 2025; sponsor Elanco US Inc.; species: Dogs; foi_id 17690; FDA PDF

Indication

Adds treatment and control of Haemaphysalis longicornis (longhorned tick) infestations for one month in dogs and puppies 8 weeks and older weighing 3.3 lb or more, and prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks.

Dose regimen

minimum 9 mg/lb (20 mg/kg) lotilaner, 0.009 mg/lb (0.02 mg/kg) moxidectin, 2.28 mg/lb (5 mg/kg) praziquantel, 2.28 mg/lb (5 mg/kg) pyrantel (as pamoate salt), Oral (flavored chewable tablet), once a month, Dose unchanged from original approval; administered with food

Credelio Quattro™ is given orally once a month, at the minimum dosage of 9 mg/lb (20 mg/kg) lotilaner, 0.009 mg/lb (0.02 mg/kg) moxidectin, 2.28 mg/lb (5 mg/kg) praziquantel, and 2.28 mg/lb (5 mg/kg) pyrantel (as pamoate salt).

Effectiveness

Laboratory dose confirmation study ELA241006 (Waverly, NY; GCP): dogs ranked by tick count and randomly allocated in blocks to vehicle control (10) or Credelio Quattro (10) given once orally at 20.1-26.2 mg/kg lotilaner in the fed state; approx. 50 adult female H. longicornis applied Days -7, -1, 5, 12, 19, 30; live and dead tick counts 48 h after treatment/infestation on Days 2, 7, 14, 21, 32; n = Twenty (11 male and 9 female); primary endpoint: Percent reduction in LS mean live tick counts vs control (>=90% for control indication) and numerically higher LS mean dead ticks (treatment indication) 48 h after treatment or infestation; result: 100% reduction in live H. longicornis counts at 48 h through Day 32 (p<0.001 all days); dead tick LS means 11.7-17.9 (treated) vs 0.9-4.3 (control), p<=0.002

Study Animals: Twenty beagle dogs (11 male and 9 female) approximately 15 to 44 months of age, weighing 7.1 to 13.9 kg.

Adverse reactions

Extraction notes: Five laboratory studies, no field study. H. longicornis: ELA231042 (100% through Day 21), ELA231098 (100% Days 7-32), ELA241006 (100% Days 2-32; extracted). B. burgdorferi prevention: ELA230932 (9/10 treated dogs uninfected; one treated dog had a single positive SNAP 4Dx Plus with negative Quant C6 and PCR; 8/10 controls infected; p=0.0055) and ELA230933 (10/10 treated uninfected vs 9/9 controls infected; p<0.0001); 100% live I. scapularis reduction on Day 33 in both. TAS: 'FDA did not require target animal safety studies for this supplemental approval.' No PK content. Lab-study adverse reactions have 10 dogs per group.