TOCERANIB PHOSPHATE

(for veterinary information only)

BRAND NAME: PALLADIA

AVAILABLE in
10 mg, 15 mg and 50 mg
TABLETS

BACKGROUND

This medication was developed to address the mast cell tumor in dogs. Normal mast cells line the body’s interfaces with the outside world (skin, respiratory tract, etc.) and become bound by antibodies directed against invading parasites. When a mast cell coated with antibodies meets a parasitic protein, a reaction occurs whereby the mast cell “degranulates” which means it releases its stored inflammatory proteins. These inflammatory mediators help destroy the invader.

When mast cells become tumorous, they degranulate spontaneously creating inappropriate tissue inflammation. When mast cell tumors are malignant, they can spread through the body creating a highly inflammatory form of cancer. Mast cells tumor malignancy is commonly graded 1, 2, or 3, with 3 being the most highly invasive and malignant form.

Toceranib phosphate was developed for use against grade 2 and grade 3 mast cell tumors. Toceranib phosphate is what is called a “tyrosine kinase inhibitor.” It has two actions against the mast cell tumor: first it kills the tumor cells directly and second, it interferes with the tumor’s blood supply.

Since its release and success against the mast cell tumor, much research has been conducted using toceranib phosphate against an assortment of other tumors, particularly those not generally amenable to other types of chemotherapy agents. Tumors that have found to show a notable response to this medication include:

• Squamous Cell Carcinoma
• Metastatic Osteosarcoma
• Vaccine Associated Fibrosarcoma
• Anal Sac Adenocarcinoma
• Thyroid Carcinoma
• Transitional Cell Carcinoma
• Malignant Melanoma

Research is continuing to determine new uses for this relatively unique medical approach to cancer.

HOW THIS MEDICATION IS USED

Toceranib phosphate is a tablet usually given every other day. Monitoring blood tests are periodically recommended.

SIDE EFFECTS

The most common side effects of toceranib phosphate include:

• Diarrhea
• Appetite loss
• Lameness
• Weight loss
• Bloody stool (either black and tarry or with fresh blood)

Notify your veterinarian if any of the above occurs. In fact, the drug should be temporarily discontinued in the event of more than 2 episodes of vomiting or diarrhea in a 24 hour period, appetite loss, more than 2 days of fresh blood in stool, or unexplained bruising. Report any such episodes to your veterinarian and expect a dose reduction after the pet has returned to normal.

Blood test monitoring may reveal anemia (deficiency of red blood cells), drop in neutrophil (a type of white blood cell) count, increase in renal toxin build up (azotemia), elevated blood phosphate, or drop in blood albumin level. Any of these changes warrant temporary discontinuation of the medication.

Since the commercial release of toceranib phosphate, three other conditions have emerged as potential side effects: renal (kidney) protein loss, liver disease, and pancreatitis. The first two issues listed are reportedly manageable with medication allowing for reinstitution of toceranib phosphate at a lower dose. Pancreatitis is also treatable but recurrence may be severe enough not to warrant risk with continued use of toceranib phosphate.

Some dogs have depigmentation of their nose or fur during treatment with toceranib phosphate.

INTERACTIONS WITH OTHER DRUGS

Use of toceranib phosphate with non-steroidal anti-inflammatory drugs can increase the risk of intestinal bleeding. That said, it is not unusual to combine toceranib phosphate with piroxicam, a non-steroidal anti-inflammatory agent that has anti-tumor properties. In this situation, medications are given on alternating days and the combination seems to be well tolerated.

Concurrent use with calcitriol, the active form of vitamin D, appears to enhance the activity of toceranib phosphate. Exploiting this enhancement is currently being studied.

Concurrent use with antifungal medications such as: ketoconazole, itraconazole, or fluconazole may increase toceranib phosphate concentrations in the body. This is a theoretical issue at this point but worth consideration.

There is some feeling that 4-7 days of antacids, carafate, and anti-inflammatory medication prior to starting toceranib phosphate can minimize the potential for side effects.

CONCERNS AND CAUTIONS

• Toceranib phosphate should not be considered a substitute for surgery.
• Toceranib phosphate is typically administered every other day. The dose is frequently altered based on the response.
• It is important to wash your hands after handling this medication. Do not break the tablets as they have a special coating.
• If the dog spits out the tablet or the tablet gets wet in any way, use gloves to handle the tablet.
• Wear protective gloves when handling the stool, vomit, or urine of a dog using toceranib phosphate. Seal the waste in double plastic bag before placing it in the trash so as to minimize exposure of other people to the trash. Any laundry items contaminated with stool, vomit or urine of a dog on toceranib phosphate should be washed separately.
• Feline use is still in early stages of investigation but appears promising.
• There are some concerns of embolic disease (abnormal blood clotting) with toceranib phosphate. If surgery is planned, it is best to wait at least 3 days from the last dose of toceranib phosphate before surgery to minimize complications.
• Expect blood pressure to be monitored regularly during toceranib phosphate use.
• Safety of toceranib phosphate has not been evaluated in dogs under age 2 years nor in dogs under 11 lbs.

The manufacturer of toceranib phosphate (Zoetis, formerly Pfizer Animal Health) has created this client information sheet/product insert and recommends that it accompany each prescription:

https://www.zoetisus.com/content/_assets/docs/vmips/package-inserts/palladia.pdf

Short version (to help us comply with "Lizzie's Law")

Page posted: 7/17/2011
Page last updated: 5/14/2023