What Are the Side Effects of Palladia?

The most common side effects of Palladia (toceranib phosphate) are gastrointestinal. Diarrhea, reduced or absent appetite, weight loss, vomiting, and blood in the stool are all listed as common on the drug's label. Lethargy and lameness or muscle soreness are also frequent.

Beyond what you can see at home, Palladia commonly affects things detected only on testing: low white blood cell counts, low platelets, raised liver enzymes, reduced albumin, high blood pressure, and protein loss in the urine. This is why ongoing monitoring is part of the treatment rather than an optional extra.

Most of these effects are mild and manageable. A minority of dogs experience severe versions of the same problems, and rarely, serious gastrointestinal complications including ulceration and perforation occur — the label describes a narrow margin of safety and these have occasionally been fatal.

Two things make the biggest practical difference. Know the thresholds at which to stop the drug and call — more than two episodes of vomiting or diarrhea in 24 hours, loss of appetite, fresh blood in the stool for more than two days, or unexplained bruising. And know that dose reductions and treatment breaks are built into how this drug is designed to be used. Pausing is normal management, not failure.

Key points

• Gastrointestinal effects are the most common — diarrhea, appetite loss, vomiting, weight loss, and blood in the stool.
• Lameness, stiffness, or muscle soreness occurs frequently and is often mistaken for arthritis or the cancer progressing.
• Some effects are invisible at home — neutropenia, thrombocytopenia, raised liver enzymes, low albumin, hypertension, and proteinuria — which is why bloodwork, blood pressure, and urine testing are scheduled.
• Most side effects are mild. A smaller proportion of dogs experience severe vomiting, diarrhea, dehydration, gastrointestinal bleeding or ulceration, fever, or sepsis.
• The label dose is widely considered higher than necessary. Research at lower doses found substantially reduced rates of appetite loss, vomiting, lethargy, and neutropenia while maintaining drug levels sufficient to work.
• Dose reductions and interruptions of up to two weeks are part of the label, and are the normal way side effects are managed.
• Anti-inflammatories raise the risk of ulceration and perforation when combined with Palladia.
• These are hazardous drug tablets. Wear gloves, wash hands, never crush or split them, and keep them away from children and pregnant women.

Detailed explanation

Why the side effects happen

Palladia blocks signalling receptors — KIT, VEGFR2, and PDGFR — that tumors depend on. Healthy tissues use these same pathways, particularly the lining of the gut and the cells that maintain blood vessels. That overlap is where the side effects come from.

This is different from conventional chemotherapy, which damages any rapidly dividing cell. It explains why the effects here skew heavily toward the digestive tract and why they tend to be ongoing and low-grade rather than arriving in a wave after each dose.

The common side effects

The European product information lists these as occurring in more than 10% of treated dogs:

• Diarrhea, often intermittent
• Reduced or absent appetite
• Weight loss
• Vomiting
• Blood in the stool, ranging from streaks to hemorrhagic diarrhea
• Lethargy
• Lameness or musculoskeletal problems
• Dehydration
• Skin inflammation and itchiness
• Neutropenia — low white blood cells
• Thrombocytopenia — low platelets
• Raised liver enzymes (ALT)
• Reduced albumin and reduced red cell volume

The US label summarizes the most common as diarrhea, decreased or lost appetite, lameness, weight loss, and blood in the stool.

Lameness deserves particular attention because it is so easily misattributed. A dog on Palladia who becomes stiff, sore, or reluctant to walk may be experiencing a drug effect rather than arthritis or bone metastasis. It is worth reporting rather than assuming.

How severe are they, usually?

Most are mild. In a study of dogs treated at doses slightly below the label dose, the great majority of events were the lowest severity grade — around half the dogs had mild diarrhea, roughly a third had mild vomiting, a third had mild appetite loss, and a third had mild lethargy. Only three dogs lost weight, all mildly.

A smaller proportion of dogs experience severe versions of the same effects. The European product information lists severe vomiting, diarrhea, appetite loss, lethargy, dehydration, skin necrosis, fever, gastrointestinal bleeding and ulcers, nausea, sepsis, and weight loss as occurring in between 1% and 10% of dogs.

The serious, uncommon complications

Palladia is described on its label as having a narrow margin of safety, and serious gastrointestinal complications including perforation have occurred, occasionally fatally.

The warning signs are worth memorizing:

• Vomiting blood, or vomit resembling coffee grounds
• Black, tarry stool, or substantial fresh blood
• A tense, painful abdomen, or a dog that resents being touched there
• Collapse, marked weakness, or pale gums
• Fever, particularly with lethargy — possible infection while white cell counts are low

Any of these warrants emergency assessment rather than a next-day appointment.

The side effects you cannot see

A significant part of this drug's risk profile is invisible at home, which is the entire reason for the monitoring schedule.

• Neutropenia and thrombocytopenia — low white cells raise infection risk; low platelets raise bleeding risk. Detected on a blood count.
• Liver enzyme elevations — common and usually manageable, sometimes requiring a pause.
• High blood pressure — a recognized effect of drugs that target blood vessel receptors, checked with a cuff at appointments.
• Proteinuria — protein leaking into the urine, detected on urinalysis, and a reason for dose adjustment if it develops.
• Low albumin, which can contribute to fluid accumulation.

Monitoring is typically frequent for the first several weeks and then spaced out once a dog is stable. Skipping these appointments removes the main safeguard the treatment has, and it is worth budgeting for the monitoring alongside the drug itself.

The dose question

This is the single most useful thing an owner can understand about Palladia's side effects.

The original label dose was set as the maximum tolerated dose. Subsequent research found that somewhat lower doses achieve drug levels sufficient to block the target receptors while producing substantially fewer adverse effects — with rates of appetite loss, vomiting, lethargy, and neutropenia all markedly lower than in the original field study. The authors concluded that this lower dose range should be considered for future use.

Current veterinary guidance reflects this, noting that most clinicians consider the label dosage higher than necessary and associated with more side effects. Many oncologists now start below it, and some use a Monday/Wednesday/Friday schedule rather than strict alternate days.

If your dog is struggling, dose reduction is a legitimate and evidence-supported conversation. The label itself provides for stepwise dose reductions and for treatment interruptions of up to two weeks to manage adverse reactions. This is built into how the drug is meant to be used.

Managing the common problems at home

Diarrhea. Report it rather than waiting it out, particularly if there is blood or if it lasts more than a day. Your veterinarian may recommend a bland diet, a probiotic, or specific anti-diarrheal medication. Ask for these to be dispensed in advance so you have them when needed.

Appetite loss. Treat this seriously and early — it is one of the most common reasons families stop treatment, and it is usually manageable. Anti-nausea medication and appetite stimulants both have a role. If nausea might be underlying the appetite loss, nausea gets treated first.

Weight loss. Weigh your dog regularly rather than relying on impression. Most practices will let you use their scale between appointments, and a trend is more informative than any single number.

Lethargy. Mild flatness may be tolerable; marked lethargy, especially with fever, is not, and needs same-day attention.

The stop thresholds

Veterinary guidance is specific about when to pause the drug pending advice. Stop giving Palladia and contact your veterinarian if your dog has:

• More than two episodes of vomiting in 24 hours
• More than two episodes of diarrhea in 24 hours
• Loss of appetite
• Fresh blood in the stool for more than two days
• Unexplained bruising

Expect a dose reduction once your dog has returned to normal. Ask for these thresholds in writing when the drug is first dispensed — they are precisely what nobody recalls under pressure on a weekend.

Drug interactions

Anti-inflammatories. NSAIDs should be used with caution alongside Palladia because the combination increases the risk of gastrointestinal ulceration or perforation. If your dog is seen by an emergency clinic or a different practice — for a limp, a dental, anything — make sure they know your dog is on this drug before an anti-inflammatory is prescribed.

Other medications. Several drugs affect how Palladia is metabolized. Tell your veterinary team about everything your dog receives, including supplements, and check before adding anything new.

Safety for your household

Palladia tablets are classed as a hazardous drug:

• Wear gloves when handling the tablets, and wash your hands afterward
• Never split or crush the tablets
• Do not handle them in kitchens or food preparation areas
• Wear gloves when cleaning up your dog's waste
• Keep the medication well away from children
• Anyone pregnant, trying to conceive, breastfeeding, or immunocompromised should not handle the drug or the treated dog's waste
• If a person accidentally swallows a tablet, seek medical advice immediately and show the treating doctor the package insert

Keeping perspective

Side effects are common with this drug, and the list above is long. But most are mild, most are manageable, and most dogs continue on treatment with adjustments rather than stopping.

What distinguishes dogs who do well is usually not luck. It is early reporting of problems, a willingness to reduce the dose rather than push through, monitoring appointments kept, and having medications on hand before they are needed.

If your dog is having a hard time, say so before the next scheduled appointment. There is nearly always something to adjust.

When to contact a veterinarian

Stop the medication and call your veterinarian if your dog:

• Vomits more than twice in 24 hours
• Has more than two episodes of diarrhea in 24 hours
• Stops eating
• Has fresh blood in the stool for more than two days
• Develops unexplained bruising

Seek emergency care immediately if your dog:

• Is vomiting blood or material resembling coffee grounds
• Is passing black tarry stool, or substantial fresh blood
• Has a tense, painful abdomen
• Is collapsed, very weak, or has pale gums
• Has a fever, especially with lethargy
• Cannot keep water down
• Has difficulty breathing, facial swelling, or hives

Contact your veterinarian within a day if your dog:

• Has mild but persistent diarrhea or a reduced appetite
• Is losing weight
• Has become lame, stiff, or sore
• Is unusually tired or flat
• Has developed skin irritation or itchiness
• Is due for monitoring bloodwork, blood pressure, or a urine test

Questions to ask your veterinarian

• What dose are you starting at, and is it below the label dose?
• What side effects should I expect in the first few weeks?
• At exactly what point should I stop the drug and call you? Can you write that down?
• Can I have anti-nausea, anti-diarrheal, and appetite medications to keep at home?
• What monitoring does my dog need, how often, and what does it cost?
• What are you checking blood pressure and urine protein for?
• If side effects become a problem, would you reduce the dose or pause treatment first?
• Is my dog on anything that interacts with this, particularly an anti-inflammatory?
• Is my dog's lameness a side effect, arthritis, or the cancer?
• What handling precautions do I need at home?
• How will we decide whether the benefit is still worth the side effects?

Sources

American Animal Hospital Association. (2026). 2026 AAHA oncology guidelines for dogs and cats: Therapeutic modalities — chemotherapy. https://www.aaha.org/resources/2026-aaha-oncology-guidelines-for-dogs-and-cats/section-5-therapeutic-interventions/therapeutic-modalities-chemotherapy/

Christensen, J., Johnson, K., Ettinger, S., Garrett, L., Gordon, I., Ireifej, S., Love, A., & Wisecup, M. (2026). AAHA oncology guidelines for dogs and cats. Journal of the American Animal Hospital Association, 62(1), 1–37. https://doi.org/10.5326/JAAHA-MS-7549

European Medicines Agency. (2016). Palladia (toceranib) — summary of product characteristics. https://ec.europa.eu/health/documents/community-register/2016/20160308134417/anx_134417_en.pdf

Bernabe, L. F., Portela, R., Nguyen, S., et al. (2013). Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose. BMC Veterinary Research, 9, 190. https://pmc.ncbi.nlm.nih.gov/articles/PMC3850926/

London, C. A., Malpas, P. B., Wood-Follis, S. L., et al. (2009). Multi-center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clinical Cancer Research, 15(11), 3856–3865. https://doi.org/10.1158/1078-0432.CCR-08-1860

VCA Animal Hospitals. (n.d.). Toceranib phosphate. https://vcahospitals.com/know-your-pet/toceranib-phosphate

Veterinary Information Network. (n.d.). Toceranib phosphate (Palladia). Veterinary Partner. https://veterinarypartner.vin.com/default.aspx?pid=19239&catId=102894&id=4952879

Zoetis. (n.d.). Palladia (toceranib phosphate) tablets — prescribing information. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae09ae83-0812-4ddc-92e3-730f7a1ae449

Zoetis. (n.d.). Palladia (toceranib phosphate) tablets — client information sheet. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/medguide.cfm?setid=ba468d7a-0353-4a45-97fd-a336abcf8a99

This article is for educational purposes only and is not a substitute for veterinary care. It describes side effects in general terms and deliberately does not include doses. Never change your dog's dose or stop a prescribed medication permanently without consulting your veterinarian. If your dog is vomiting blood, passing black tarry stool, has a painful abdomen, is collapsed or very weak, or has a fever while taking Palladia, seek emergency veterinary care immediately.