Palladia (toceranic phosphate) is an antiproliferative and antiandiogenic agent used to treat Patnaik grade II or III, cutaneous mast cell tumors in dogs. It uses toceranic phosphate to combat the effects of these recurrent tumors and works on both tumors with and without regional lymph node involvement. Palladia can also be used as an alternative to chemotherapy for other various types of tumors, including melanomas, thyroid carcinomas, and more.
Palladia is available in 10 mg, 15 mg, and 50 mg tabs to ensure that adjusting your dog’s dosage based on their weight is a simple manner. Each dosage is available for purchase by the tab or in a container of 30 tabs.
Always provide Client Information Sheet with prescription. Administer an initial dosage of 3.25 mg/kg (1.48 mg/lb) body weight, orally every other day. Dose reductions of 0.5 mg/kg (to a minimum dose of 2.2 mg/kg (1.0 mg/lb) every other day and dose interruptions (cessation of Palladia for up to two weeks) may be utilized, if needed, to manage adverse reactions. Adjust dose based on approximately weekly veterinary assessments for the first 6 weeks and approximately every 6 weeks, thereafter. Palladia may be administered with or without food. Do not split tablets.
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Store at controlled room temperature 20° to 25° C (68° to 77° F). Keep away from children and pets.
Do not use in dogs used for breeding, or for pregnant or lactating bitches.
Palladia may cause vascular dysfunction which can lead to edema and thromboembolism, including pulmonary thromboembolism. Discontinue drug until clinical signs and clinical pathology have normalized. To assurevasculature homeostasis, wait at least 3 days after stopping drug before performing surgery.
NOT FOR USE IN HUMANS. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.Children should not come in contact with Palladia. Keep children away from feces, urine, or vomit of treated dogs.To avoid exposure to drug, wash hands with soap and water after administering Palladia and wear protective gloves to prevent direct contact with feces, urine, vomit, and broken or moistened Palladia tablets. Place all waste materials in a plastic bag and seal before general disposal. If eyes are accidentally exposed to the drug, rinse eyes with water immediately. In case of accidental ingestion by a person, seek medical advice immediately, show the package insert or label to the physician. Gastrointestinal discomfort such as vomiting or diarrhea may occur if this drug is accidentally ingested.
Pregnant women, women who may become pregnant, or nursing mothers should pay special attention to these handling precautions. (See handling instructions above.) Palladia, like other drugs in its class, prevents the formation of new blood vessels in tumors. In a similar manner, Palladia may affect blood vessel formation in the developing fetus and may harm an unborn baby (cause birth defects). For pregnant women, accidental ingestion of Palladia may have adverse effects on pregnancy.
A US clinical field study of Palladia in 151 client-owned dogs found the following side effects:
Palladia is an oral receptor tyrosine kinase (RTK) inhibitor that blocks the activity of multiple receptors on cancer cells and blood vessels. The active ingredient in Palladia is toceranib. It is approved for use in dogs with recurrent, cutaneous mast cell tumors (Patnaik grade II or III) with or without regional lymph node involvement.
Palladia is a antineoplastic agent belonging to the receptor tyrosine kinase (RTK) inhibitor class of drugs.
Kinases are enzymes that catalyze the transfer of phosphate groups from ATP. Receptor tyrosine kinases (RTKs) are tyrosine kinases on the cell surface that are activated through binding of growth factors. Receptor tyrosine kinsases play a role in signaling pathways that govern normal cellular processes such as proliferation, migration, metabolism, and differentiation. Examples of RTKs include: platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), stem cell factor receptor (Kit). In normal cells, RTK activity is tightly controlled. In some cancerous conditions, abnormalities such as mutations can lead to abnormal activation of RTKs resulting in increased cellular proliferation and growth, prevention of apoptosis (cellular death) as well as increased angiogenesis and metastasis. The result of RTK dysfunction is phosphorylation of the kinase in the absence of an appropriate signal and constitutive signaling and abnormal promotion of cell growth and survival. These conditions promote tumor development, growth and progression.
Toceranib phosphate is a small molecule that has both direct antitumor and antiangiogenic activity. In non-clinical pharmacology studies, toceranib selectively inhibited the tyrosine kinase activity of several members of the split kinase receptor tyrosine kinase (RTK) family, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Toceranib inhibited the activity of Flk-1/KDR tyrosine kinase (vascular endothelial growth factor receptor, VEGFR2), platelet-derived growth factor receptor (PDGFR), and stem cell factor receptor (Kit) in both biochemical and cellular assays. Toceranib has been shown to exert an antiproliferative effect on endothelial cells in vitro. Toceranib treatment can induce cell cycle arrest and subsequent apoptosis in tumor cell lines expressing activating mutations in the split kinase RTK, c-Kit. Canine mast cell tumor growth is frequently driven by activating mutations in c-Kit.
Palladia is indicated for the treatment of Patnaik Grade II or III, recurrent, cutaneous mast cell tumors (MCT) with or without regional lymph node involvement in dogs.
Always provide Client Information Sheet with prescription. Administer an initial dosage of 3.25 mg/kg (1.48 mg/lb) body weight, orally every other day. Dose reductions of 0.5 mg/kg (to a minimum dose of 2.2 mg/kg (1.0 mg/lb) every other day) and dose interruptions (cessation of Palladia for up to two weeks) may be utilized, if needed, to manage adverse reactions. Adjust dose based on approximately weekly veterinary assessments for the first 6 weeks and approximately every 6 weeks, thereafter. Palladia may be administered with or without food. Do not split tablets.
During the clinical efficacy study, Palladia was administered concomitantly with other medications such as antimicrobials, H-2 receptor blockers, antihistamines, anti-emetics, non-steroidal anti-inflammatory drugs, locally-acting anti-ulcer medications, opiate gastro-intestinal motility modifiers, opioids, vaccines, anthelmintics, antiparasitics, and topical/ophthalmic/otic corticosteroid preparations. During the open-label phase only, 5 dogs received a brief course of short-acting corticosteroids. Specifically the most common concomitant treatments in the blinded and open label phase: Metronidazole, diphenhydramine, famotidine, metoclopramide, fluids, amoxicillin-clavulanic acid, cephalexin, ampicillin, enrofloxacin, sucralfate, omeprazole, carprofen, cimetidine, dolasetron mesylate, loperamide, ranitidine. A statistically higher number of Palladia treated dogs received metronidazole.