Long-Term Side Effects of Apoquel

🧠 Key Takeaways: Straight Answers at a Glance

❓ Question✅ Short Answer
Does Apoquel weaken my dog’s immune system over time?Yes, by design. It tempers inflammation but may reduce local immune defenses.
Is there a link between Apoquel and cancer?No proven link to new cancers, but caution is essential in dogs with existing tumors.
Can it make infections more likely?Definitely—especially in the skin, ears, and urinary tract.
What’s the deal with warts and skin bumps?Benign lumps like papillomas and histiocytomas may appear or persist longer.
Is it safe for life-long use?Generally, yes—but only with regular checkups, lab work, and individualized risk assessments.
Does it interfere with vaccines?Possibly. In young dogs or during primary vaccination series, response may be reduced.
Can it cause rare problems like autoimmune disease or kidney issues?Rarely, but isolated case reports do suggest these risks after years of use or overdose.

📉 Why “Mild” Immune Suppression Still Matters

Although Apoquel is selective, it doesn’t discriminate perfectly. By blocking JAK1, it affects multiple cytokines essential for front-line immune response at skin and mucosal surfaces.

🧬 Barrier Defense Trade-Offs

Affected Area 🐕Why It’s Vulnerable ⚠️Common Complication 💥
SkinLess IL-31 and IL-6 → delayed neutrophil responsePyoderma, yeast dermatitis
EarsMoist, inflamed environment + reduced local defenseOtitis externa (chronic ear infections)
BladderReduced immune surveillance in mucosaRecurrent UTIs
Hair folliclesLocal immunosuppressionDemodicosis (mange flare-ups) 🐜

💡 Clinical Tip: Any dog developing more than two infections per year while on Apoquel warrants deeper evaluation or dose adjustment.


⚠️ Is Cancer a Risk—or Just a Rumor?

This is where nuance matters. Apoquel doesn’t cause cancer per se, but it may interfere with the body’s natural ability to detect and destroy early abnormal cells, especially in dogs with subclinical or preexisting malignancy.

🎯 How Immune Modulation Could Alter Cancer Surveillance

Immune Function 🔬What Apoquel Impacts 💊Why It Matters 🧠
T-cell activationIL-2 inhibition = fewer cytotoxic T-cellsReduced detection of mutated cells
Inflammation at tumor sitesSuppressed IL-6, IL-13Tumor may grow undetected
Antigen presentationBlunted skin cytokine activityEarly warning system weakens

🩺 What To Do:

  • Avoid in dogs with any known or suspected cancer unless advised by a veterinary oncologist.
  • Screen new masses early. Skin lumps can seem harmless but evolve if unchecked.

🐾 Papillomas, Warts, and “Just Skin Things”?

Oclacitinib is associated with increased reports of papillomas, especially in young or immunocompromised dogs. These viral growths usually regress—but not always.

📋 Wart Watch: What to Know

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Observation 👁️Likely Cause 📉Response 🔧
Small, smooth wartDelayed immune response to papillomavirusMonitor; most resolve in weeks
Cluster of bumpsSystemic immune compromiseConsult vet; may need removal
Rapidly growing lesionNot typical wart behaviorBiopsy immediately 🧪

💡 Pro Insight: Consider adding immune-boosting support, like omega-3s, mushrooms (AHCC), or canine-specific beta-glucans during therapy.


🧪 What Happens to Bloodwork Over Time?

Apoquel’s impact on blood values is usually mild, but that doesn’t mean it’s nonexistent. Some dogs develop subclinical leukopenia or changes in liver/lipid profiles.

📊 Long-Term Monitoring Priorities

Parameter 🧾What May Change 📉When to Act 🛑
Neutrophils/EosinophilsMay drop below baselineIf persistent or very low, reduce dose
GlobulinsMild decline possibleWatch for concurrent infections
Cholesterol/LipaseCan increaseRule out pancreatitis if symptomatic

🧬 Advanced Protocol: Dogs on Apoquel >12 months should get annual CBC + biochemistry panels, minimum. Increase frequency if comorbidities exist.


💉 Apoquel + Vaccines = Lower Response? Sometimes.

Especially in puppies or unprimed immune systems, Apoquel may blunt antibody responses to inactivated vaccines like rabies or leptospirosis. Live vaccines (like parvo or distemper) appear unaffected.

📋 Vaccine Compatibility Matrix

Vaccine Type 💉Safety on Apoquel ✅Timing Tip ⏱️
Killed (rabies, lepto)May underperformDelay Apoquel 5–7 days around vax date
Live (parvo, distemper)UnaffectedAdminister normally
Boosters in adult dogsLikely safeConsider titer testing for assurance

🧠 Recommendation: For young dogs starting Apoquel early, complete core vaccines first if possible. Always document titer status in long-term therapy cases.


😱 Rare But Real: Autoimmune and Toxic Reactions

Though incredibly rare, case reports have linked long-term Apoquel use to autoimmune polyendocrinopathy and even kidney injury in overdose scenarios.

🧾 Documented Rare Events

Event 🚨Details 🧬Outcome 🔄
Autoimmune polyglandular syndromeAddison’s + hypothyroidism after 7 yearsHormone therapy; Apoquel discontinued
Acute kidney injury (AKI)After ingesting 50x doseResolved with fluids and hospitalization
Seizures or mania-like behaviorVery rare, anecdotalNot officially linked; monitor closely

📍 Emergency Tip: Any dog showing unusual behavior, lethargy, collapse, or sudden weight change on Apoquel should be immediately evaluated—don’t wait.


🧰 Clinical Management Toolbox: Keep Dogs Safe on Long-Term Apoquel

✔️ DO:

  • Baseline labs and derm diagnosis before starting
  • Recheck blood every 6–12 months
  • Educate owners to watch for subtle signs of infection
  • Examine all new lumps early
  • Pause Apoquel during serious infections or active cancer treatment

DON’T:

  • Combine with steroids or cyclosporine without strict supervision
  • Start in dogs <12 months or <3kg
  • Use long-term without routine vet check-ins
  • Ignore persistent diarrhea, coughing, or fatigue—it may not be the allergy
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📎 FAQs


💬 Comment: “Why does my dog still get ear infections on Apoquel?”
Answer: Apoquel manages the itch, not the microbiome. Chronic ear infections often stem from deeper issues — like anatomical ear structure, yeast overgrowth, or secondary bacterial colonization — that Apoquel doesn’t directly target.

📌 Why Ears Stay Problematic Despite Itch Control

Cause 🎯Underlying Mechanism 🔬Strategy to Break the Cycle 🔧
Residual inflammationApoquel helps systemically but ears are semi-isolatedUse otic corticosteroids or tacrolimus drops locally
Biofilm formationChronic bacterial colonies resist treatmentCulture + sensitivity testing is vital
Unresolved allergiesApoquel controls symptoms, not the allergenConsider food or environmental allergy testing
Moisture-retaining ear canalsEspecially in floppy-eared breedsRegular drying solutions or vet-formulated cleansers

🧠 Expert Tip: Apoquel reduces scratching around the ears, but recurrent otitis often needs its own direct, localized management — ideally guided by ear cytology at each visit.


💬 Comment: “Is Apoquel safe for senior dogs?”
Answer: With structured monitoring, yes. Older dogs often benefit from relief without the systemic burden of steroids. But age brings nuances — like slower metabolism, more comorbidities, and a heightened risk for neoplasia.

📊 Key Considerations for Geriatric Dogs on Apoquel

Factor 🧬Why It Matters 👵Clinical Protocol 🩺
Liver/kidney functionDrug clearance may slow downMonitor ALT, ALP, BUN/creatinine every 6–12 months
Tumor surveillanceCancer risk rises with age, regardless of medsFull-body palpation at each visit; biopsy early
Drug interactionsSeniors are more likely to be on multiple medsUse veterinary drug interaction tools (Plumb’s, VIN)
Muscle mass lossReduced metabolism alters dose-per-kg effectStart with lowest effective dose and reassess quarterly

🩺 Caution: Apoquel isn’t contraindicated in seniors, but individual risk stratification is essential. Think more about the dog’s biologic age, not just years.


💬 Comment: “My dog’s Apoquel dose isn’t working anymore. What now?”
Answer: This can indicate either disease progression, emerging infections, or allergen shifts. Apoquel resistance isn’t a real pharmacological concept, but symptom relapse is very real — and usually fixable.

🔍 Top Reasons for Apoquel “Failure”

Possible Cause 🧩What to Investigate 🔍Adjustments to Consider 🔄
Secondary skin infectionCheck for pustules, crusts, malodorAdd antibiotics or antifungal shampoos
Seasonal/environmental triggersDid the relapse align with spring, summer?Add Cytopoint or antihistamines temporarily
New dietary issueAny new treats or protein sources?Restart a strict elimination diet
Age-related immune shiftImmune profiles change over timeReevaluate all medications and diagnostics

🧠 Veterinary Insight: Don’t just increase the Apoquel dose. Look at why the itch has changed. Often, the underlying cause is evolving — not the drug’s efficacy.

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💬 Comment: “Can Apoquel affect my dog’s behavior?”
Answer: Rarely, yes. While not listed as a common side effect, there are isolated reports of restlessness, pacing, or mild irritability — often transient and dose-dependent.

🎭 Behavioral Side Effects Snapshot

Behavior Observed 🧠Potential Mechanism 🧬Management Advice 🧰
Increased pacing or anxietyCentral nervous system sensitivity in select individualsMonitor closely; reduce dose temporarily
Disinhibited play or hyperactivityRapid itch relief may unmask underlying energyUse structured activity to channel behavior
LethargyCan occasionally occur early in therapyTypically resolves in <72 hrs; monitor hydration, appetite
Moody or withdrawn behaviorAnecdotal, not provenRule out pain, organ issues before blaming drug

📋 Note: If behavior changes persist, perform a full systemic workup to rule out metabolic or neurologic disease before attributing it solely to Apoquel.


💬 Comment: “What’s safer long term: Apoquel or Cytopoint?”
Answer: Cytopoint generally has fewer systemic effects, as it’s a monoclonal antibody rather than a small molecule immunomodulator. But safety must be weighed against response variability, cost, and ease of administration.

⚖️ Apoquel vs. Cytopoint — Long-Term Comparison Chart

Attribute 🔍Apoquel 💊Cytopoint 💉
Onset of ActionFast (within 4 hours)Slower (1–3 days)
DurationDailyMonthly injection
Safety in Immunocompromised DogsCaution requiredGenerally preferred
Infection riskSlightly higherVery low
ConvenienceOral pill dailyVet-administered shot
Efficacy for all allergy typesExcellent for mostBest for IL-31–driven itch
Cost-effectivenessCheaper short-termPotentially cheaper long-term

💡 Pro Tip: Some dogs thrive on combination therapy—especially during seasonal flares. Start with one, and layer carefully if needed under vet supervision.


💬 Comment: “Are there alternatives if Apoquel isn’t right for my dog?”
Answer: Yes. A number of options exist, from biologics to supplements to immunotherapy, depending on your dog’s allergy profile and medical history.

🧾 Apoquel Alternatives Worth Exploring

Category 🧬Example Options ✅When to Use 🕒
BiologicsCytopointGood for IL-31–driven itch without immune suppression
Allergy Testing + ImmunotherapyCustom allergen shotsIdeal for long-term allergen desensitization
Fatty Acid SupplementsOmega-3s, fish oilSupportive; improves barrier function
Topical therapiesAntimicrobial/anti-itch shampoosEssential for local flare control
Steroids (short-term only)Prednisone, dexamethasoneUse cautiously in acute crises only
Novel dietsHydrolyzed or novel proteinsAddress potential food allergies

🧠 Strategy Insight: Allergy management works best when multimodal. Think of Apoquel as a strong anchor—not a solo act. Build a support system around it.


💬 Comment: “Why did my dog develop a lump while on Apoquel?”
Answer: Apoquel isn’t directly oncogenic, but its influence on immune signaling can delay the body’s response to benign or early-stage skin growths. Most reported lumps are non-cancerous—think papillomas or histiocytomas—but they still require prompt evaluation.

📍 Lumps & Bumps on Apoquel: What We Know

Lump Type 🧪Characteristics 🔎Clinical Relevance ⚠️Vet Recommendation 🩺
Papilloma (wart)Pink, cauliflower-like, often near mouthViral; may regress slowlyMonitor size, remove if ulcerated
HistiocytomaSmooth, raised, red; rapid onsetBenign immune-cell tumorOften resolves, but biopsy if persistent
LipomaSoft, movable, under skinFatty growth; common with ageRegular measurement and body scoring
Mast Cell TumorRed, inflamed, itchy massMalignant potentialFine needle aspirate ASAP

🧠 Expert Insight: In dogs on immunomodulators, benign masses may regress more slowly, but vigilance is key—any change in size, shape, or texture warrants cytology.


💬 Comment: “Can Apoquel cause weight gain?”
Answer: Not directly. Unlike corticosteroids, Apoquel doesn’t increase appetite or alter glucose metabolism. However, symptom relief often restores appetite and energy, which can look like weight gain if caloric intake isn’t adjusted.

⚖️ Post-Apoquel Weight Shifts: What’s Really Happening?

Observation 📊Possible Cause 🔍What to Do 🧰
Increased appetiteDog feels better → normal hunger returnsMonitor feeding volume
Reduced activityAllergic dogs may still avoid playEncourage gentle exercise
Fluid retention (rare)Not typical of ApoquelRule out endocrine/metabolic issues
Muscle loss with agingAlters fat-to-lean ratio visuallyConsider senior wellness plan

🍖 Clinical Note: If weight changes exceed 10% in under 3 months, reassess total daily caloric intake, consider baseline thyroid or metabolic screening, and adjust treats accordingly.


💬 Comment: “How does Apoquel compare to antihistamines?”
Answer: Apoquel is significantly more targeted and potent. Antihistamines may work for mild cases but have limited efficacy in true allergic dermatitis, which involves cytokines—not just histamine.

🧪 Mechanism Comparison: Apoquel vs. Antihistamines

Feature 🔬Apoquel 💊Antihistamines 🌼
Target MoleculeJAK1 cytokine pathwaysHistamine (H1 receptors)
Effectiveness in CADHigh (especially IL-31 driven)Low to moderate
Onset of ReliefRapid: within 4 hoursVariable: often >1 day
Side EffectsMinimal; rare GI upset or mild leukopeniaSedation, dry mouth, paradoxical agitation
Use in CombinationsExcellent synergy with Cytopoint or diet therapyAdditive benefit mild, if any

📚 Pro Perspective: Antihistamines can serve as adjuncts in mild cases or seasonal flares—but rarely suffice as monotherapy for moderate to severe allergic dermatitis.


💬 Comment: “Does Apoquel work for food allergies?”
Answer: Apoquel suppresses symptoms of allergic skin disease regardless of the trigger—but it doesn’t address the root cause of food allergies. That’s where elimination diets come in.

🥩 Food Allergy vs. Environmental: How Apoquel Interacts

Parameter 📋Food Allergy 🍗Environmental Allergy 🌿
Primary driverProtein or carb antigensPollen, dust, mites
GI involvement?Often (vomiting, soft stool)Rare
Effect of ApoquelItch relief onlyItch + inflammation reduction
Long-term solutionDiet trial, ingredient eliminationAllergen avoidance or immunotherapy
Diagnostic tool8-12 week hydrolyzed or novel protein dietIntradermal or serum IgE testing

🥚 Practical Tip: If itching returns after stopping Apoquel, consider that diet may be the missing link—especially if GI symptoms or perianal licking is present.


💬 Comment: “Is it okay to combine Apoquel with other drugs or supplements?”
Answer: In most cases, yes—with professional oversight. Apoquel has a favorable interaction profile, but caution is needed with other immunosuppressants or in patients with polypharmacy.

💊 Combining Apoquel: What’s Safe vs. What Needs Scrutiny

Medication/Supplement 🧴Interaction Risk ⚠️Expert Advice 🩺
CytopointLowSafe; synergistic
Omega-3sNoneEnhances skin barrier support
Antibiotics/AntifungalsNoneCommonly used together
PrednisoneCautionShort-term use okay; long-term combo = high risk
CyclosporineHighAvoid concurrent long-term use
CBD/HerbalUnknownLimited data; monitor closely
VaccinesPossibly blunted responseDelay Apoquel 5–7 days around vaccine date when possible

📌 Rule of Thumb: Always flag immunosuppressive stacking (Apoquel + steroids + cyclosporine). Monitor CBC and chemistry every 6 months if combining therapies long-term.


💬 Comment: “Why did my dog get a UTI while on Apoquel?”
Answer: Apoquel alters cytokine signaling, especially those involved in immune surveillance at barrier sites like the bladder wall. This immunomodulation may subtly reduce local defenses, allowing opportunistic bacteria to colonize the urinary tract more easily — especially in females, seniors, or dogs with prior infections.

🚽 UTI Risk and Apoquel: Understanding the Link

Factor 🦠Role in UTI Development 🧬Clinical Strategy 💡
IL-6 suppressionIL-6 recruits neutrophils to fight urinary pathogensMonitor urine for bacteria if clinical signs appear
Reduced epithelial immunityDecreased local cytokine activity in bladder mucosaEncourage hydration to flush the system
Pre-existing anatomical issuesEctopic ureters, recessed vulva, bladder stonesRule out structural abnormalities via imaging
Subclinical infectionsMay worsen under immune modulationRecommend routine urine cultures for high-risk dogs

📍 Practical Insight: Apoquel doesn’t “cause” UTIs, but it can tip the balance in dogs already predisposed. Adding probiotics or D-mannose may support bladder health.


💬 Comment: “Can Apoquel affect my dog’s vaccine response?”
Answer: Yes, selectively. Apoquel doesn’t destroy immunity, but it may blunt the body’s ability to mount a robust antibody response — especially if the dog is young, immunologically naïve, or on the drug at the time of first-time vaccinations.

💉 Apoquel and Vaccination: What to Know

Vaccine Type 🧪Apoquel Impact 🧬Veterinary Recommendation 🐾
Killed (inactivated)Slightly reduced seroconversion possibleDelay Apoquel if giving first-time rabies/parvo
Modified-live vaccines (MLV)Minimal interactionSafe in adults with prior exposure
Booster dosesGenerally well toleratedProceed as scheduled, monitor response
Puppy seriesBlunted immune priming riskPostpone Apoquel until series complete if possible

📌 Vet Tip: For young puppies or immunocompromised dogs, time Apoquel dosing around vaccinations. For adults, maintain good records and check titers if unsure.


💬 Comment: “Is Apoquel safe for dogs with liver or kidney disease?”
Answer: Apoquel is metabolized in the liver and excreted via both urine and bile. While it isn’t hepatotoxic or nephrotoxic by design, dogs with compromised liver or renal function may handle the drug differently — necessitating tighter dose control and ongoing monitoring.

🧬 Organ Function and Apoquel Metabolism

Organ 🏥Role in Processing 💊Adjustment Needed? 🔍
LiverCytochrome P450 metabolism (CYP3A4 suspected)Start low; test ALT/ALP every 3–6 months
KidneysExcretes metabolites via urineNo change unless severe azotemia present
Bile ductsSecondary excretion routeMonitor bile acids if on other hepatobiliary meds
GI tractNo direct irritationGive with food to reduce vomiting risk

🧪 Clinical Protocol: For dogs with elevated liver enzymes or creatinine, consider switching to Cytopoint or lowering Apoquel dose with frequent rechecks.


💬 Comment: “My dog started Apoquel and now has skin infections. Coincidence?”
Answer: Not likely. Oclacitinib affects cytokines critical for local immune defense — especially IL-31 and IL-2 — reducing the skin’s ability to control microbial populations. This opens the door to bacterial and yeast overgrowth, particularly in already barrier-compromised skin.

🧫 Infection Risks with Apoquel: Skin-Specific Breakdown

Pathogen 🧴Common Presentation 🐕Why It Flourishes 🔍Treatment Protocol 🩺
Staphylococcus pseudintermediusPustules, crusts, hotspotsReduced neutrophil activity in epidermisOral/topical antibiotics + medicated baths
Malassezia pachydermatisGreasy skin, odor, darkened areasYeast overgrowth in moist environmentsAntifungal wipes or ketoconazole
Demodex canisPatchy alopecia, scalingSuppressed T-cell-mediated clearanceIvermectin/moxidectin (off-label), contraindicate Apoquel in active cases

📍 Important Note: Repeated infections should prompt a skin cytology, not just automatic refills. Consider cycling Apoquel or pausing during antimicrobial therapy.


💬 Comment: “Can Apoquel lead to cancer?”
Answer: Current data shows no conclusive causal link between Apoquel and cancer development. However, it may theoretically reduce immune surveillance of abnormal cells. Therefore, it’s contraindicated in dogs with known malignancies or those at high risk.

📊 Apoquel & Neoplasia: What the Science Says

Evidence Source 📚Key Findings 🧬Clinical Interpretation 🧠
Retrospective cohort studiesNo significant increase in new cancer cases vs. control groupApoquel is not inherently carcinogenic
FDA post-marketing dataReports of papillomas, MCTs, lymphomasTemporal association ≠ causation
Veterinary dermatology consensusPapillomas most common, usually benignRoutine mass checks recommended
Label warnings“May exacerbate neoplastic conditions”Avoid in dogs with cancer or precancerous diagnoses

🧠 Clinical Judgment: Don’t avoid Apoquel out of fear — but do avoid it in dogs with existing tumors or rapidly developing masses. Otherwise, combine with regular skin/mass exams every 6 months.

2 Responses

  1. My 12-year-old, 12-pound Yorkie has been on Apoquel for most of his life due to chronic itching. The cost of the medication over the years has been astronomical. Recently, a new veterinarian recommended a diet of boiled chicken and rice after he became ill. Since starting this diet, he hasn’t been itching at all, so I stopped the Apoquel—and he’s still itch-free.

    I know a long-term diet of just chicken and rice isn’t nutritionally complete, but neither is long-term use of Apoquel ideal. I’m unsure whether it’s safe for him to continue on this limited diet, and I’m concerned about the potential health risks of feeding him only chicken and rice.

    1. First off, it’s incredible that you’ve found relief from lifelong itching without Apoquel—especially after years of expense and limited results. That’s a huge discovery, and it likely points to an undiagnosed dietary sensitivity or food intolerance that was triggering the immune system.

      That said, a diet of only boiled chicken and white rice is not nutritionally complete and can result in long-term deficiencies, especially in a 12-year-old dog whose metabolism and organ function require very specific support. The goal now is to identify the ingredient(s) your dog was previously reacting to and transition to a complete, balanced hypoallergenic or elimination diet.

      📉 Why Chicken and Rice Isn’t a Long-Term Solution

      🍗 Nutrient 🥄 Chicken & Rice Diet 🚨 Deficiency Risk
      Calcium Missing (unless bones or supplements added) Bone loss, muscle tremors, weak joints
      Essential Fatty Acids (Omega-3 & 6) Minimal—especially without fish oils Dry skin, inflammation, cognitive decline
      Vitamins A, D, E, K Absent—rice and lean meat lack these Vision loss, immune dysfunction, poor healing
      Zinc, Selenium, Manganese Trace amounts, not adequate for dogs Skin problems, poor coat quality, fatigue

      🧠 Critical Insight: Chicken and rice diets are often used temporarily during digestive illness or food allergy trials. They are intentionally “bland” to reduce inflammation—but they should not exceed 2–3 weeks without supplementation or veterinary nutrition guidance.

      🧪 What Likely Happened?

      Your Yorkie may have had a **chronic food allergy** or intolerance (likely to an additive, protein source, or grain filler in commercial food), and the chicken/rice combo removed the irritant. This doesn’t mean chicken and rice is ideal—it just means it’s less inflammatory for him right now.

      ✅ What To Do Next: Safe Reintroduction or Full Hypoallergenic Diet

      📋 Step 🔍 Action 💡 Why It Matters
      1 Work with your vet to identify common allergens (e.g., beef, dairy, wheat, soy, preservatives) Targeted elimination avoids random guessing or flare-ups
      2 Introduce a complete limited-ingredient diet (e.g., hydrolyzed or novel protein like rabbit or venison) Ensures full nutrition while still reducing allergenic load
      3 If staying on home-cooked meals, add a vet-formulated supplement like Balance IT or The Honest Kitchen base mix Fills in calcium, fats, and micronutrients absent in chicken/rice
      4 Reintroduce previous proteins/ingredients one at a time every 10–14 days Helps pinpoint the true cause of the reaction

      💬 Bonus Tip: Since he’s a senior, focus on joint support too—consider adding omega-3s from wild salmon oil and a small amount of pumpkin or chia seeds for fiber and inflammation control (pending vet approval).

      Want help building a custom transition plan or finding the best commercially available limited-ingredient food that mimics your chicken/rice success? Drop your pup’s full history and we’ll build one tailored to age, weight, and allergy profile. 🐾🍲🧠

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