Side Effects of NexGard

NexGard (afoxolaner) is an FDA-approved oral flea and tick preventative manufactured by Boehringer Ingelheim Animal Health USA Inc., given as a once-monthly beef-flavored chewable tablet. It was first approved by the FDA in 2013 under NADA 141-406. NexGard kills fleas by targeting their nervous system — the parasite must bite the dog to ingest afoxolaner, which then causes overstimulation of the pest’s nervous system, paralysis, and death. The FDA’s pivotal US field study, which included 615 treated dogs across 333 households over 90 days, found no serious adverse reactions. However, post-approval adverse drug experience reporting to FDA/CVM has identified a range of side effects, listed on the official DailyMed label in decreasing order of reporting frequency. In 2018, the FDA issued a class-wide neurological safety alert for all isoxazoline-class flea and tick products — including NexGard — which was updated in 2019 and 2021 and remains current. This guide addresses the 10 most important questions dog owners ask about NexGard side effects, using official FDA label data and verified veterinary sources.

• 1
  What are the common side effects of NexGard in dogs? From the official FDA/DailyMed label, post-approval adverse events listed in decreasing order of frequency: vomiting · pruritus (itching) · lethargy · diarrhea (with and without blood) · anorexia (loss of appetite) · seizure · hyperactivity/restlessness · panting · erythema (skin redness) · ataxia (stumbling) · dermatitis (rash, papules) · allergic reactions (hives, swelling) · tremors

  The full post-approval adverse event list for NexGard is published on the official NIH DailyMed label, which reports events submitted to FDA/CVM. The DailyMed label notes explicitly: “Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.” What this means in practice: these are reported events, not proven drug reactions in every case. In the controlled pre-approval US field study of 615 dogs over 90 days, no serious adverse reactions were observed. BestiePaws.com’s March 2026 review of FDA Freedom of Information documents cites Veterinary Partner (VIN) data showing vomiting in approximately 4% of dogs and diarrhea in approximately 2%. GoodRx’s veterinary guide (updated August 2025) describes side effects in dogs as rare, with vomiting and diarrhea being the most common, and notes that “the most serious risk of NexGard is seizures.” The NexGard product FAQ from Boehringer Ingelheim confirms that most adverse reactions are self-limiting and of short duration.
• 2
  How long do NexGard side effects last in dogs? Common GI side effects (vomiting, diarrhea, lethargy): usually a few hours to 2–3 days · Most mild effects resolve within 1 week · Side effects typically appear within the first 24 hours after administration · Diarrhea: typically 24–48 hours but can vary · If any side effect persists beyond 1 week or worsens: contact your veterinarian

  The duration of NexGard side effects depends on the individual dog’s health, sensitivity, and the specific symptom. Dial A Vet’s veterinary guidance confirms that side effects — when they occur — generally appear within the first few hours to days after administration, and most are self-limiting. GI symptoms like vomiting and diarrhea, which are the most commonly reported, typically resolve within 24–48 hours, per veterinary Q&A guidance. Hf-dog.com’s detailed side effect duration analysis confirms: mild vomiting, diarrhea, and lethargy should improve within one week; if any symptom persists beyond a week or worsens at any point, veterinary evaluation is warranted. For lethargy specifically, ryanclab.com notes that behavioral changes like tiredness typically improve within 24–48 hours. If a dog vomits within two hours of receiving the NexGard chewable, BestiePaws.com notes (per the official product label) that re-dosing is recommended because absorption may be incomplete. If vomiting occurs more than two hours after administration, re-dosing is not necessary as absorption is likely already complete at that point. Neurological side effects — tremors, ataxia, seizures — do not follow the same “mild and self-limiting” pattern; these require prompt veterinary evaluation regardless of when they appear.
• 3
  Is NexGard safe for dogs — what does the FDA say? FDA says: NexGard continues to be safe and effective for the majority of animals · FDA approved NexGard in 2013 (NADA 141-406) after extensive pre-market testing · FDA issued a neurological class alert for all isoxazolines (including NexGard) in 2018, updated through 2021 · FDA continues to require neurological warning language on all isoxazoline product labels · FDA’s overall position: safe and effective for most dogs; individual risk varies

  The FDA’s official position, stated directly in its Animal Drug Safety Communication, is: “The FDA carefully reviewed studies and other data on Bravecto, Credelio, NexGard, and Simparica prior to approval, and these products continue to be safe and effective for the majority of animals.” The agency simultaneously requires updated neurological warning language on all isoxazoline-class product labels — including NexGard — because neurological events have been observed consistently across the drug class in post-marketing surveillance. Vetster’s November 2025 review of afoxolaner notes that “the overall consensus is that isoxazolines are generally safe and effective when used as directed” and that research into the seizure link is ongoing. In February 2026, the FDA issued an Emergency Use Authorization for NexGard for treatment of New World Screwworm larvae — reaffirming the product’s safety profile while also republishing the isoxazoline class neurological warning. The important nuance: FDA’s pre-approval US field study (615 dogs, 90 days) found no serious adverse events. Post-approval adverse event reporting reflects real-world use across millions of dogs and does not establish causality. The balance of available evidence supports NexGard as safe for most dogs when prescribed by a veterinarian with the dog’s individual medical history in mind.
• 4
  Can NexGard cause seizures in dogs? Yes — seizures are the most serious reported side effect · Listed on the official FDA/DailyMed NexGard label · The FDA issued a class-wide neurological alert in 2018 (updated 2021) for all isoxazolines including NexGard · Seizures have been reported even in dogs WITHOUT a prior history of seizures · Dogs WITH a history of seizures or neurological disorders: use with caution; consult vet about alternatives · Estimated frequency: less than 0.1% in reported data

  Seizures are listed on the official NexGard label and are described by GoodRx’s veterinary authors as “the most serious risk of NexGard.” The FDA’s 2018 Animal Drug Safety Communication — issued for the entire isoxazoline class and still in effect — explicitly states: “Isoxazoline products have been associated with neurologic adverse reactions, including muscle tremors, ataxia, and seizures in some dogs and cats. Although most dogs and cats haven’t had neurologic adverse reactions, seizures may occur in animals without a prior history.” The FDA’s current fact sheet for pet owners (2023, updated) confirms this language. The NexGard DailyMed label documents real-world seizure cases in the US field study: one dog with a prior seizure history experienced seizures after the first and second doses and one week after the third dose. The FDA’s Emergency Use Authorization document for NexGard (February 2026) repeats the class caution: “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.” Ryanclab.com estimates that seizures occur in less than 0.1% of dogs taking the medication based on available reporting data. If your dog has any history of epilepsy, seizures, or neurological conditions, discuss this explicitly with your veterinarian before starting NexGard and ask about alternative flea and tick prevention options.
• 5
  What to expect after giving NexGard to my dog Most dogs: no side effects at all · NexGard is absorbed within 6 hours; starts killing fleas within 4–8 hours · Monitor your dog for the first 24 hours after any dose · Mild vomiting or soft stool in the first few hours: expected in a small percentage of dogs, usually self-resolving · If your dog throws up within 2 hours: re-dose per product label · If your dog throws up after 2 hours: re-dosing not needed — absorption is complete

  For the vast majority of dogs, NexGard administration is uneventful. The BestiePaws.com March 2026 detailed review — citing FDA Freedom of Information documents for NADA 141-406 — confirms that NexGard demonstrated more than 99% effectiveness against adult fleas at 8 hours post-administration, with flea killing beginning as early as 4 hours after the first dose. Tick effectiveness exceeded 97% against American dog ticks at 48 hours. The chewable can be given with or without food, though the product label notes that if vomiting occurs on an empty stomach, future doses should be given with food or a small treat. Dial A Vet’s veterinary guidance recommends monitoring during the first 24 hours after any dose — especially the first dose — because most side effects, if they occur, appear in this window. WebMD Pets’ NexGard product guide identifies the serious signs that require prompt attention: nonstop vomiting, complete loss of appetite, muscle tremors, difficulty walking, or seizures. These are distinct from the mild, transient GI upset that a small minority of dogs experience and that resolves on its own. NexGard’s afoxolaner has a relatively long half-life of 7.7–17.8 days (BestiePaws.com, citing FDA pharmacokinetic data), meaning the drug remains protective throughout the full 30-day dosing period.
• 6
  Why is NexGard causing itching in my dog? Pruritus (itching) is the second most commonly reported side effect of NexGard after vomiting, per the official FDA/DailyMed label · Likely explanation: a small number of dying fleas may cause increased biting/movement, triggering temporary itching · Alternatively: a mild skin sensitivity or allergic response to the drug itself · Mild, temporary itching in the first 24–48 hours is not unusual · Severe or worsening itching, hives, skin redness (erythema), or swelling: contact your veterinarian

  Pruritus — medical term for itching — appears second on the NexGard official FDA/DailyMed adverse event list, after vomiting, in post-approval reporting. There are two primary explanations for itching after NexGard administration. First, NexGard works by requiring fleas to bite the dog and ingest the drug before dying — meaning in the hours immediately after dosing, fleas may become hyperactive as they are affected by the drug before dying, causing temporary increased biting and skin irritation. Second, some dogs have individual skin sensitivity or mild allergic response to the afoxolaner compound itself. Dermatitis — including rash and papules — also appears on the NexGard label, though it is further down the reporting frequency list. The Boehringer Ingelheim NexGard FAQ confirms: “Most adverse reactions are self-limiting and of short duration.” Mild itching that resolves within 24–48 hours and does not worsen is generally not a cause for alarm. Itching that is severe, spreading, accompanied by skin redness, papules (raised bumps), hives (urticaria), or swelling — particularly of the face — requires veterinary evaluation, as these may indicate an allergic reaction that needs treatment. Antihistamines or veterinary anti-itch treatment may be appropriate; never administer any human medication without veterinary guidance.
• 7
  Why should you not give your dog NexGard — who should avoid it? Avoid NexGard or use with extra caution in: (1) Dogs with a history of seizures or epilepsy — use with caution; discuss alternatives with vet · (2) Dogs with a history of other neurological disorders · (3) Breeding, pregnant, or lactating dogs — safety not evaluated per the label · (4) Puppies under 8 weeks or under 4 lbs body weight — not approved for this group · (5) Dogs with known hypersensitivity to afoxolaner or any ingredient in NexGard

  The official NexGard DailyMed label and the FDA’s Emergency Use Authorization document (February 2026) both specify the primary caution category: dogs with a history of seizures or neurological disorders. The label states explicitly: “Use with caution in dogs with a history of seizures or neurological disorders.” GoodRx’s veterinary guide reinforces this: “If your dog has a history of seizures, speak with your veterinarian about other options for flea and tick control.” The label also states: “The safe use of NexGard in breeding, pregnant, or lactating dogs has not been evaluated,” which means the safety data simply does not exist for these populations — this is not necessarily a contraindication but a data gap that should be discussed with a veterinarian before use. Approved only for puppies 8 weeks of age and older weighing at least 4 pounds (1.8 kilograms) — do not use in younger or lighter puppies. There are no known absolute contraindications listed on the current label, according to the FDA Emergency Use Authorization document, but the above cautions represent situations where the risk-benefit discussion with your veterinarian is especially important. Dogs on other medications should also have potential interactions reviewed before starting NexGard, per Dial A Vet’s guidance on drug interactions.
• 8
  Does NexGard kill ticks immediately? Not immediately — ticks must bite your dog first to ingest afoxolaner · Black-legged tick and American dog tick: over 94–97% killed within 48 hours post-infestation · NexGard does not repel ticks — they must make contact and bite · NexGard PLUS (with moxidectin and pyrantel) covers a broader range including the longhorned tick and Gulf Coast tick · NexGard kills fleas faster: killing begins as early as 4 hours; 99% dead by 8 hours

  NexGard’s mechanism requires the parasite to bite the dog and ingest afoxolaner through the dog’s blood — it is not a repellent and does not prevent contact or attachment. BestiePaws.com’s March 2026 review, citing FDA FOI data for NADA 141-406, confirms that flea killing begins as early as 4 hours after the first dose, with more than 99% effectiveness against adult fleas at 8 hours. Tick killing is slower because ticks feed more slowly than fleas. Per the DailyMed label: more than 97% effectiveness against American dog ticks at 48 hours post-infestation; black-legged tick effectiveness exceeded 94% at the same timeframe. Because ticks are not killed immediately, they may still be found on dogs shortly after NexGard is given — this is expected and does not mean the product is not working. The critical implication for tick-borne disease prevention: the FDA-approved labeling confirms NexGard is indicated for the prevention of Borrelia burgdorferi (Lyme disease) infections specifically as a result of killing the carrier black-legged ticks before disease transmission can occur, since tick-to-dog transmission of Lyme disease typically requires 24–48 hours of attachment. NexGard PLUS (approved July 2025, per the DailyMed label revision) extends coverage to include the longhorned tick (Haemaphysalis longicornis) and Gulf Coast tick (Amblyomma maculatum) in addition to the four tick species covered by standard NexGard.
• 9
  What are the side effects of NexGard PLUS? NexGard PLUS (afoxolaner + moxidectin + pyrantel) side effects: same isoxazoline class warnings apply (seizures, tremors, ataxia) · Additional ingredients add: moxidectin (macrocyclic lactone class — caution in MDR1/ABCB1 gene mutation dogs, especially Collies and herding breeds) · pyrantel (nematocide — GI side effects possible) · One dog in clinical trials showed muscle tremors, nausea, and depression for one day after the first dose

  NexGard PLUS combines afoxolaner with moxidectin (for heartworm prevention and additional parasite coverage) and pyrantel (for roundworms and hookworms), and its label was revised in July 2025 per the DailyMed NexGard PLUS entry. The same isoxazoline class neurological warnings apply to NexGard PLUS as to standard NexGard, because afoxolaner is present in both. The NexGard PLUS clinical study documentation, which references a Boehringer Ingelheim 2023/2025 package insert, notes that one dog in the NexGard PLUS group experienced muscle tremors along with nausea and depression for one day after the first dose — after which these were not repeated. Moxidectin, the additional ingredient, is in the macrocyclic lactone class and works by interfering with chloride channel-mediated neurotransmission in parasites. Moxidectin carries a specific caution for herding breeds (Collies, Shetland Sheepdogs, Australian Shepherds, Border Collies, and related breeds) that may carry the MDR1/ABCB1 gene mutation, which causes these dogs to accumulate macrocyclic lactones to potentially toxic levels. Owners of herding breeds should specifically discuss the MDR1 gene test and NexGard PLUS suitability with their veterinarian before administering. Pyrantel acts as a neuromuscular blocking agent in parasites and may cause mild GI side effects in some dogs.
• 10
  What is the FDA’s neurological warning for NexGard and isoxazolines? FDA issued a formal Animal Drug Safety Communication in September 2018 (updated 2019 and 2021) for all isoxazoline-class products including NexGard · Warning: muscle tremors, ataxia (stumbling), and seizures associated with isoxazoline products in post-market reporting · Seizures can occur in animals without prior history · FDA required all isoxazoline manufacturers to update labels with neurological warning language · FDA’s position: products remain safe and effective for the majority of animals; the warning exists to enable informed individual decisions

  The FDA’s September 2018 Animal Drug Safety Communication — which applies to NexGard, Bravecto, Credelio, and Simparica — was one of the most significant veterinary drug safety communications in recent years. It requires all isoxazoline manufacturers to include specific neurological warning language on their labels, because neurological adverse events had been observed consistently across the entire isoxazoline drug class in post-marketing surveillance, not just in one product. The FDA’s 2023 Fact Sheet for Pet Owners and Veterinarians (the most current publicly available FDA guidance) states: “Isoxazoline products have been associated with neurologic adverse reactions, including muscle tremors, ataxia, and seizures in some dogs and cats. Although most dogs and cats haven’t had neurologic adverse reactions, seizures may occur in animals without a prior history.” This language was republished verbatim in the FDA’s February 2026 Emergency Use Authorization fact sheet for NexGard. The FDA’s key guidance for decision-making: “Veterinarians should use their specialized training to review their patients’ medical histories and determine, in consultation with pet owners, whether a product in the isoxazoline class is appropriate for the pet.” This places the decision in the hands of the veterinarian and informed owner together — not as a blanket restriction but as an individual risk-benefit assessment for each dog.

Sources: FDA/NIH DailyMed (NexGard afoxolaner NADA 141-406; post-approval adverse events in decreasing frequency: vomiting, pruritus, lethargy, diarrhea with/without blood, anorexia, seizure, hyperactivity, panting, erythema, ataxia, dermatitis, allergic reactions, tremors; no serious AEs in 615-dog 90-day US field study; re-dose if vomit within 2hr; not in dogs under 8 weeks or under 4 lbs); FDA Animal Drug Safety Communication Sept 2018 (updated 2019, 2021; isoxazoline class alert; Bravecto/Credelio/NexGard/Simparica; muscle tremors, ataxia, seizures; seizures without prior history; label update required); FDA Fact Sheet for Pet Owners and Veterinarians 2023 (isoxazoline neurologic AEs; most dogs haven’t had; seizures without prior history; FDA continues to consider safe and effective for majority); FDA Emergency Use Authorization NexGard Feb 2026 (fda.gov/media/191166; New World Screwworm EUA; isoxazoline class warning reaffirmed; no known contraindications stated; seizures in dogs without prior history; caution seizure/neurologic history; safe use in breeding/pregnant/lactating not evaluated); NexGard PLUS DailyMed label Rev. 07/2025 (Boehringer Ingelheim 2025; afoxolaner + moxidectin + pyrantel; muscle tremors nausea depression one day Day 0 one dog; moxidectin chloride channel mechanism; pyrantel neuromuscular blocking); GoodRx/Dr. Rhiannon Koehler DVM MPH Aug 2025 (most serious risk seizures; vomiting/diarrhea rare; history of seizures = alternative options; FDA approved 2013); BestiePaws.com Mar 2026 (FDA FOI NADA 141-406; vomiting ~4%; diarrhea ~2%; VIN Veterinary Partner; flea killing 4hr; 99% at 8hr; 97% American dog tick 48hr; 94% black-legged tick; half-life 7.7-17.8 days; re-dose <2hr; 615 dogs 333 households); WebMD Pets Oct 2024 (isoxazoline neurologic SE overdose/incorrect; nonstop vomiting/complete loss of appetite = serious; seek vet immediately); Vetster Nov 2025 (afoxolaner isoxazoline; FDA neurologic alert; seizures even without prior history; research ongoing; overall consensus generally safe and effective); Dial A Vet (side effects first 24 hours; mild GI self-limiting; drug interaction consult); hf-dog.com (few hours to several days; vomiting/diarrhea improve within 1 week; persist or worsen = vet); ryanclab.com Jul 2025 (seizures less than 0.1%; behavioral changes 24-48hr; FDA approved 2013; absorbed by liver); nexgard.com.au FAQ (absorbed within 6 hours; fleas killed within 8 hours; most AEs self-limiting short duration; caution epilepsy seizure history)

Sources: FDA DailyMed NADA 141-406 (615-dog study; no serious AEs); FDA Animal Drug Safety Communication Sept 2018, updated 2021; FDA Fact Sheet 2023 (isoxazoline neurologic alert); BestiePaws.com Mar 2026 (FDA FOI; efficacy data; VIN rates); GoodRx DVM Aug 2025 (most serious risk = seizures); ryanclab.com Jul 2025 (less than 0.1% seizures)

Sources: FDA DailyMed NexGard label NADA 141-406 (full adverse event list in decreasing frequency; US field study 615 dogs; seizure history cases; re-dose within 2hr; not under 8 weeks/4lbs; breeding/pregnant/lactating not evaluated); FDA Animal Drug Safety Communication Sept 2018 (updated 2021; isoxazoline class; muscle tremors/ataxia/seizures; no prior history; require label update); FDA Fact Sheet for Pet Owners and Veterinarians 2023 (isoxazoline; most dogs haven’t had AEs; seizures without prior history; safe and effective majority); FDA Emergency Use Authorization NexGard Feb 2026 (fda.gov/media/191166; isoxazoline warning; no known contraindications; caution seizure/neurologic; safe use breeding/pregnant not evaluated); NexGard PLUS DailyMed Rev. 07/2025 (afoxolaner+moxidectin+pyrantel; Jul 2025 revision; 6 tick species including longhorned/Gulf Coast; muscle tremors Day 0 one dog; MDR1 herding breed moxidectin caution); GoodRx/Dr. Rhiannon Koehler DVM MPH Aug 2025 (most serious risk seizures; rare vomiting/diarrhea; seizure history = alternatives); BestiePaws.com Mar 2026 (vomiting 4%; diarrhea 2%; VIN data; re-dose within 2hr per label; efficacy data); WebMD Pets Oct 2024 (nonstop vomiting/complete loss appetite = serious; neurologic if overdose/incorrect; seek vet immediately); Vetster Nov 2025 (FDA alert; seizures without prior history; research ongoing; generally safe effective); ryanclab.com Jul 2025 (lethargy 24-48hr; seizures less than 0.1%; FDA approved 2013)

Use the links below for official FDA labeling, veterinary guidance, and adverse event reporting. If your dog is showing serious symptoms, call your vet or emergency animal hospital immediately — do not wait to research online.