10+ Side Effects of NexGard® PLUS in Dogs
⚠️ Key Takeaways (Quick Answers)
| Question | Answer |
|---|---|
| Is NexGard PLUS generally safe for dogs? | Yes, in most dogs. Mild side effects are common; serious ones are rare. |
| What are the most common side effects? | Diarrhea, vomiting, lethargy, itching. |
| Are neurological effects a real concern? | Yes. Seizures, tremors, and ataxia are documented even in dogs with no prior issues. |
| Is NexGard PLUS safe for dogs with seizure history? | Use with extreme caution. Some vets advise against it. |
| Can puppies take NexGard PLUS? | Yes, if they are ≥8 weeks old and ≥4 lbs. |
| Does it interact with other meds? | No known drug interactions, but always tell your vet. |
| Can side effects happen long after dosing? | Yes, delayed neurological events have been reported. |
| What should I do if I notice side effects? | Contact your vet immediately. Don’t try to self-treat. |
💩 Why Does My Dog Get Diarrhea After NexGard PLUS?
Diarrhea is the most commonly reported side effect, often appearing within 48 hours of ingestion. It may contain mucus or blood but usually resolves on its own.
💡 Tip: Keep your dog hydrated. If stools persist beyond 48–72 hours or become black/tarry, see your vet ASAP.
| Symptom | Frequency | Duration | Severity |
|---|---|---|---|
| 💩 Diarrhea | 6.7% | <48 hours | Mild |
🤮 Vomiting: A Short-Lived Reaction or a Red Flag?
Vomiting occurs in roughly 4.5% of dogs post-dose. It’s usually short-lived and resolves without medical treatment, especially after the first few doses. If vomiting occurs within 2 hours, your dog may not have absorbed the full dose.
💡 Tip: Ask your vet whether a repeat dose is needed if vomiting occurs quickly after administration.
| Symptom | Frequency | Typical Onset | Re-dose Needed? |
|---|---|---|---|
| 🤮 Vomiting | 4.5% | <24 hours | Sometimes |
😴 Why is My Dog Lethargic After NexGard PLUS?
Lethargy reflects a systemic response that can feel like “doggy jet lag.” Dogs may nap more or seem disinterested in play.
| Symptom | Frequency | Onset | Duration | Severity |
|---|---|---|---|---|
| 😴 Lethargy | 2.2% | Hours | 1–2 days | Mild |
🐾 Why Does My Dog Itch After Taking NexGard PLUS?
Itching is likely a transient dermatologic response or related to dying fleas. It tends to subside as flea populations drop off.
| Symptom | Frequency | Severity | Treatment Needed |
|---|---|---|---|
| 🐾 Itching | 2.2% | Mild-Moderate | Rarely |
⚡ What’s the Real Risk of Neurological Side Effects?
This is where things get serious. NexGard PLUS contains afoxolaner, part of the isoxazoline class. While effective, this class has a known risk for neurological symptoms—even in dogs with no prior history of seizures.
| Neuro Symptom | Notes |
|---|---|
| 🧠 Seizures | Documented in clinical trials and post-market reports. Can be life-threatening. |
| 💥 Tremors | Involuntary shaking or twitching, sometimes accompanied by nausea or depression. |
| 🤸 Ataxia | Loss of coordination or wobbly walking—should be considered a red flag. |
| 🚨 Restlessness | Often overlooked, but could signal neurological overstimulation. |
🧪 Can NexGard PLUS Affect Lab Results?
Yes. In post-approval data, dogs showed elevated liver enzymes, changes in kidney markers, and anemia.
| Lab Marker Affected | Implication |
|---|---|
| ALT/AST ↑ | Possible liver stress |
| BUN/Creatinine ↑ | Potential renal overload |
| Anemia or Low RBC | Reduced oxygen capacity |
🐶 Is It Safe for Puppies and Small Breeds?
Yes, but only if they’re ≥8 weeks old and at least 4 pounds. Smaller or younger puppies haven’t been studied in detail. Always weigh risk vs. reward.
| Factor | Requirement |
|---|---|
| Age 🍼 | 8 weeks min |
| Weight ⚖️ | 4 lbs min |
🧬 Are Certain Breeds More Sensitive?
Yes. Collies and breeds with MDR1 gene mutations may be more susceptible, particularly to moxidectin (another ingredient). This can cause GI or neurologic symptoms at lower doses.
| Breed Concern | Reaction Type | Caution Level |
|---|---|---|
| Collies | GI, neuro signs | High |
| Aussies | Possible MDR1 + | Moderate |
❗ How to Respond to Side Effects Immediately
| Symptom Type | Home Action | Vet Visit Required? |
|---|---|---|
| GI Upset (Mild) | Bland diet, water, monitor closely | If >72 hrs or blood |
| Neurological | Stop use, keep dog calm, urgent vet care | YES IMMEDIATELY |
| Skin Issues | Bath with hypoallergenic shampoo | If persistent |
📞 How to Report a Side Effect
| Agency / Company | Contact Info |
|---|---|
| Boehringer Ingelheim (Maker) | 1-888-637-4251 / nexgardforpets.com |
| FDA (U.S.) | 1-888-FDA-VETS / ReportAnimalAE |
FAQs
💬 “My dog had diarrhea a few hours after taking NexGard PLUS. Should I be worried?”
🧠 Expert Response:
Mild diarrhea is one of the most frequently observed reactions—reported in about 6.7% of dogs in clinical studies. It often occurs within 24–48 hours post-dose and usually resolves without intervention. The GI upset may be due to the parasite die-off or the body adjusting to the active ingredients, especially moxidectin and pyrantel.
| 🚩 Symptom | 💡 Onset Time | ⏱️ Duration | 🔍 Significance | 🛠️ Suggested Action |
|---|---|---|---|---|
| Diarrhea 💩 | 4–24 hrs | 1–3 days | Usually mild/transient | Monitor hydration, bland diet |
⚠️ Watch for: black stools, visible blood, extreme lethargy, or vomiting with diarrhea—these warrant a vet visit.
💬 “My dog seemed really sleepy after taking it. Is that normal?”
🧠 Expert Response:
Yes, lethargy or drowsiness can occur, typically within the first 12–24 hours. It may be linked to systemic metabolic changes or the immune system responding to parasitic breakdown. This side effect tends to diminish after the first few doses.
| 😴 Symptom | ⏱️ Onset | 🔁 Recurrence | ✅ Usual Outcome |
|---|---|---|---|
| Fatigue or Sleepiness 💤 | Same day as dose | Rare with repeated use | Full recovery in 24–48 hrs |
🧪 Pro tip: If lethargy persists beyond 48 hours or is accompanied by tremors, disorientation, or vomiting, consult your vet.
💬 “My dog had a seizure after the third dose. She’s never had one before.”
🧠 Expert Response:
That’s a serious neurological event. Afoxolaner (in NexGard PLUS) is part of the isoxazoline drug class, which can cross the blood-brain barrier and, in rare cases, interact with mammalian GABA receptors, triggering seizures—even in dogs with no seizure history.
| ⚠️ Neuro Reaction | 🧬 Mechanism | 🔍 Common in? | 🚑 Action Required |
|---|---|---|---|
| Seizure 💥 | GABA interference | Dogs w/ & w/o seizure hx | Immediate vet visit |
🚫 Do not give further doses without explicit vet clearance. Some dogs may require switching to a non-isoxazoline-based preventive.
💬 “Why does my dog scratch more right after taking the chew?”
🧠 Expert Response:
This is commonly referred to as a “flea kill reaction.” As NexGard PLUS kills fleas, they may temporarily increase movement or bite more aggressively before dying. This causes increased itchiness for a brief period post-dose.
| 🐛 Itching Episode | 📆 Timeline | ⏳ Duration | 🩺 Typical Cause |
|---|---|---|---|
| Post-dose scratching 🐾 | Within 12 hours | <48 hours | Fleas reacting to afoxolaner |
If itching persists beyond a few days or worsens, it could signal a skin sensitivity or allergic response. In that case, consult your vet.
💬 “I noticed panting and restlessness a few hours later. Is this neurological?”
🧠 Expert Response:
Possibly. Panting, restlessness, or agitation can be early signs of neurological stimulation or anxiety-like responses caused by CNS engagement from the isoxazoline. These symptoms may also stem from mild nausea or discomfort.
| 🔄 Symptom | 🧠 Category | 🕐 When it Appears | 🩺 Risk Level |
|---|---|---|---|
| Panting 😤 | Neurological / GI | 2–8 hours post-dose | Mild to moderate |
| Pacing/Agitation 🚶♂️ | CNS stimulation | Same window | Monitor, may resolve |
If combined with disorientation, pupil dilation, or tremors, contact a vet immediately.
💬 “Are there breed-specific risks with NexGard PLUS?”
🧠 Expert Response:
Yes, particularly in Collies, Australian Shepherds, and Shelties that may carry the MDR1 gene mutation. This mutation impairs drug excretion from the brain, increasing susceptibility to neurotoxicity—especially from moxidectin.
| 🧬 Breed Risk Table | 🧪 MDR1 Mutation Link | 🚫 Recommended Precaution |
|---|---|---|
| Collies, Aussies, Shelties | High sensitivity | Genetic testing; vet advice |
Dogs with known or suspected MDR1 gene mutation should be given alternatives unless cleared by a veterinarian familiar with their genetics.
💬 “Can I give NexGard PLUS with other medications like Rimadyl or vaccines?”
🧠 Expert Response:
Yes, in controlled studies, NexGard PLUS was co-administered safely with NSAIDs (like Rimadyl), antibiotics, vaccines, steroids, antihistamines, and sedatives. No significant interactions were reported.
| 💊 Drug Class | ✔️ Compatibility with NexGard PLUS |
|---|---|
| NSAIDs (e.g., Rimadyl) | ✅ Yes |
| Antibiotics | ✅ Yes |
| Vaccines | ✅ Yes |
| Steroids | ✅ Yes |
Always inform your vet of any ongoing meds or supplements to monitor for unanticipated interactions.
💬 “Can the side effects happen after multiple doses, not just the first one?”
🧠 Expert Response:
Absolutely. While many side effects occur within the first dose or two, some dogs may experience delayed onset reactions. Sensitization over time or cumulative neurotoxic burden can trigger events weeks or months after starting the medication.
| ⏰ Reaction Timing | 📌 Typical Cause | 🧪 Common in? |
|---|---|---|
| First dose | Acute hypersensitivity | Most mild cases |
| 2nd–4th dose | Cumulative effect | Neuro-sensitive dogs |
| After months | Delayed neurologic | Often misattributed |
If a pet becomes symptomatic after months of no issues, NexGard PLUS should still be considered a possible trigger—discuss with your vet before ruling it out.
💬 “Should I stop using NexGard PLUS after a mild side effect?”
🧠 Expert Response:
That depends on the type, severity, and duration of the reaction. Mild, transient effects like soft stool or reduced appetite that resolve within 1–2 days typically do not require discontinuation. However, any worsening or recurring symptom, or neurologic signs, should be taken seriously.
| 🟢 Mild Reactions | 🟡 Moderate | 🔴 Severe (Neuro) |
|---|---|---|
| Monitor at home 🏠 | Vet consult 📞 | Discontinue + Emergency 🏥 |
Always document symptoms and timelines. This helps your vet determine whether to continue, adjust, or switch therapies.
💬 “My dog started scratching again two weeks after taking NexGard PLUS. Does that mean it’s not working?”
Absolutely not. NexGard PLUS kills fleas quickly—usually within 4–8 hours of attachment—but it doesn’t repel them. That means fleas can still jump on your dog from the environment (e.g., carpet, yard, other pets) and cause itching before they die. Itching two weeks post-dose typically indicates environmental reinfestation, not product failure.
| 🐛 Cause of Itch | 📌 Description | ✅ NexGard’s Role | 📣 What to Do |
|---|---|---|---|
| Flea re-exposure | New fleas jump on and bite | Kills them after bite | Treat the environment 🏠 (bedding, carpet, yard) |
| Allergic reaction | Sensitivity to flea saliva | Doesn’t prevent bites | Add antihistamine therapy if allergic |
💡 Pro Tip: Use environmental control (e.g., vacuuming, flea sprays, yard treatments) in conjunction with NexGard PLUS to break the flea life cycle completely.
💬 “Can I switch from NexGard PLUS to a topical flea treatment if side effects appear?”
Yes, you can—but timing and transition matter. NexGard PLUS is systemic and remains in your dog’s bloodstream for up to a month. You should avoid overlapping medications unless directed by your vet, especially if neurological or gastrointestinal side effects have occurred.
| 🔄 Switching Consideration | ⏱️ Recommended Wait Time | 🧠 Risk If Ignored |
|---|---|---|
| From oral to topical 🐾 | Wait 30 days | Overmedication, compounding side effects |
🧠 Important: Before switching, identify which component caused the issue. If the problem was due to moxidectin (heartworm prevention), switching to another oral flea treatment won’t help; you’ll still need a separate heartworm med.
💬 “My dog had mild tremors but they stopped. Is it safe to continue NexGard PLUS?”
Only with extreme caution. Even if the tremors resolved, their presence indicates your dog may be sensitive to afoxolaner’s neurological effects. Repeating the dose could lead to more severe symptoms, such as full-body seizures or prolonged disorientation.
| ⚠️ Observation | 📊 Severity Indicator | 🧪 Next Steps |
|---|---|---|
| Tremors (resolved) 🫨 | Moderate warning sign | Discontinue and report to vet 🩺 |
| No seizure but uncoordinated 🌀 | Red flag symptom | Seek neuro eval, switch product |
🧠 Clinical Insight: The nervous system can become sensitized over time, so a small tremor today doesn’t mean a larger reaction won’t happen tomorrow. Safer alternatives are available, especially for sensitive breeds or neurologically fragile pets.
💬 “Are the neurological risks really worth it for flea and worm protection?”
That’s a valid concern—and it depends entirely on your dog’s medical history, age, breed, and environment. For healthy dogs with no history of seizures, NexGard PLUS offers broad-spectrum protection in a convenient, palatable chew. However, in dogs with underlying neurological conditions or certain genetic predispositions (e.g., MDR1 mutation), the risk-to-benefit ratio shifts.
| ✅ Ideal Candidates | ⚠️ Caution Advised | 🚫 Avoid If… |
|---|---|---|
| Healthy adult dogs 🐕 | Senior dogs, toy breeds, MDR1 suspect breeds | Dog has history of seizures or neuro episodes 🚫 |
💬 Tip: If your dog’s parasite risk is low (indoor-only, northern climate), and they have neurological vulnerabilities, it may be safer to use separate products with non-isoxazoline ingredients.
💬 “Why does my dog act weird after chewing the tablet—like he’s zoned out or scared?”
You’re observing what could be early-stage neurological overstimulation. Afoxolaner works by disrupting parasite nerve transmission—but it may also affect GABA channels in dogs, leading to behaviors like zoning out, head shaking, circling, or fear posturing.
| 🧠 Behavior Type | 🧬 Likely Cause | ⏱️ When It Appears | 🚑 What to Do |
|---|---|---|---|
| Disorientation, fear, staring 🫣 | CNS hypersensitivity | Minutes to hours post-dose | Discontinue and monitor |
| Circling, pacing, restlessness 🌀 | Early neurologic signs | Usually within 12 hrs | Contact vet ASAP |
⚠️ Important: These aren’t “normal” side effects and should never be brushed off. Document and report them to the manufacturer and FDA.
💬 “How do I know if NexGard PLUS is safe for long-term use?”
Look at cumulative response—not just single-dose reaction. Many side effects from isoxazoline compounds are dose-dependent, meaning repeated use may amplify risk even in dogs that initially tolerated the product well.
| 🗓️ Month | 🧪 What to Monitor | 🚨 Red Flags |
|---|---|---|
| 1st Dose | Watch for vomiting, tremors, disorientation | Any neuro symptoms = Stop |
| 2nd–4th | Behavioral changes, GI disruption | Increased intensity |
| After 6+ | Bloodwork for liver/kidney stress | Elevated ALT, BUN, creatinine |
🧬 Pro Tip: If you plan to use NexGard PLUS long term, request annual or biannual bloodwork to check organ function and adjust the plan as needed.
💬 “Is there a blood test to see if NexGard PLUS harmed my dog’s liver or kidneys?”
Yes, but standard panels might not show early-stage damage. For a complete picture, ask your vet for liver panel (ALT, ALP, AST, bilirubin) and renal panel (BUN, creatinine, SDMA).
| 🔬 Test Type | 🧫 What It Detects | 🧪 Sensitivity |
|---|---|---|
| Liver Enzymes 🧪 | Inflammation or stress | Moderate |
| SDMA 🧠 | Early kidney dysfunction | High |
| Bile Acids 🧬 | Hepatic function pre/post meal | Best for subtle liver issues |
💡 Recommendation: Do a full panel before starting a long-term preventive if your dog has a history of vomiting, behavior changes, or is a senior.
💬 “Is it true that NexGard PLUS can cause aggression or behavioral changes in dogs?”
Yes, behavioral alterations—though uncommon—have been observed. These can include sudden anxiety, irritability, pacing, or uncharacteristic vocalizations, especially in neurologically sensitive dogs. Such changes may result from central nervous system overstimulation, a possible consequence of isoxazoline compounds like afoxolaner.
| 🧠 Behavior Change | 🧬 Potential Mechanism | 🐕 Common In | ⚠️ Action to Take |
|---|---|---|---|
| Sudden aggression 😠 | CNS overstimulation (GABA disruption) | High-strung or neurologically predisposed dogs | Discontinue use; vet consultation |
| Pacing or agitation 🚶♀️ | Neurological excitation | Any breed | Monitor & document episodes |
| Vocalization / Whining 🗣️ | Anxiety or GI discomfort | Small/toy breeds | Consider alternative therapy |
Pro Insight: If your normally calm dog becomes reactive post-dose, it’s not a coincidence—log behavioral timestamps and report to your vet and the manufacturer.
💬 “Why does my dog lick her paws excessively after taking NexGard PLUS?”
This can be a subtle dermatologic or neurologic symptom. It may indicate tingling, irritation, or altered nerve sensation—which can occur during drug metabolism or due to mild allergic responses. It’s especially common in dogs who are prone to contact allergies or obsessive behaviors.
| 👅 Symptom | 🧠 Possible Cause | 🕒 Timeline | 🛠️ Recommended Step |
|---|---|---|---|
| Excessive paw licking 🐾 | Neurological hypersensitivity or skin irritation | Within 1–3 days post-dose | Rule out GI upset or allergic cause; vet follow-up |
💡 Vet Tip: If licking persists beyond 72 hours or is accompanied by red, hot, or inflamed skin, a dermatologic or neurologic exam may be warranted.
💬 “Can NexGard PLUS cause a false positive on heartworm tests?”
No. NexGard PLUS prevents heartworm infection but does not interfere with diagnostic testing. However, if given to a dog with an existing heartworm infection (particularly adult worms), it won’t treat the mature parasites, which may continue to cause damage or test positive.
| 💉 Test Type | 🧪 What It Detects | 🧬 NexGard PLUS Interaction |
|---|---|---|
| Antigen Test | Adult female heartworms | No interference ❌ |
| Microfilaria Test | Larval stage in blood | No suppression ❌ |
⚠️ Reminder: Dogs must be tested negative for heartworm prior to starting NexGard PLUS to prevent reactions from larval kill-off and ensure effectiveness.
💬 “Is it dangerous if my dog accidentally gets two doses of NexGard PLUS?”
It depends on the size, breed, and health status. NexGard PLUS has a wide safety margin, but in sensitive individuals (like MDR1-mutant Collies, young puppies, or dogs with liver compromise), overdosing could trigger significant reactions, including vomiting, tremors, or lethargy.
| 🐶 Factor | ⚠️ Risk Level | 🧪 What to Monitor |
|---|---|---|
| Large healthy dog 🐕 | Low | Mild GI upset, if anything |
| Toy/sensitive breed 🧸 | Moderate | Lethargy, drooling, tremors possible |
| Neurologically at-risk 🧠 | High | Immediate veterinary attention needed |
☎️ Action: Contact your veterinarian or an animal poison control hotline if double dosing occurs—especially in high-risk breeds.
💬 “My vet says it’s fine, but I’m seeing so many warnings online. Who should I trust?”
Both perspectives can be valid—context is everything. Vets rely on clinical trials, post-market data, and firsthand experience, but pet parents often notice subtle, breed-specific or long-term effects that might not be captured in broad studies. Online warnings often arise from real cases, but lack vet interpretation or diagnosis.
| 🔍 Source | ✅ Strength | ❗ Limitation |
|---|---|---|
| Veterinary advice 🩺 | Based on broad clinical experience | May under-recognize outlier effects |
| Online reviews 💬 | Highlight rare, real-world reactions | Not always clinically verified |
💬 Final Word: Discuss your concerns openly with your vet, bring specific case examples, and don’t be afraid to ask for alternatives if your gut says “this isn’t right.”
💬 “Can NexGard PLUS cause long-term organ damage?”
Direct organ damage is rare, but elevated liver enzymes and kidney stress have been observed in post-market surveillance. These are often subclinical, meaning no visible symptoms, but can be detected via routine lab panels.
| 🧪 Organ System | 🧬 Potential Markers Affected | 🧭 Frequency | 📋 Recommendation |
|---|---|---|---|
| Liver 🧬 | ALT, AST, ALP | Occasional | Test every 6–12 months |
| Kidneys 🧪 | BUN, Creatinine, SDMA | Rare | Especially in seniors/ill dogs |
💡 Tip: If your dog has pre-existing organ issues or is a senior, it’s wise to do baseline labs before starting any oral systemic parasite prevention.
