Products
Toceranib is commercially available in the form of film-coated tablets (Palladia). It is approved exclusively as a veterinary drug in many countries and has been since 2010.
Structure and properties
Toceranib (C22H25FN4O2, Mr = 396.5 g/mol) is present in drugs as the phosphate salt toceranib phosphate, a crystalline, yellow-orange powder. It has structural and functional similarity to sunitinib.
Effects
Toceranib (ATCvet QL01XE91) is antineoplastic and antiangiogenic. It is an inhibitor of tyrosine kinase, particularly the split-kinase-type receptor tyrosine kinase. Tyrosine kinases are enzymes found in mast cell tumors, where they are involved in the growth and spread of cancer cells and in the formation of blood vessels.
Mechanism of action
Toceranib selectively blocks the activity of several tyrosine kinases involved in tumor growth, new blood vessel formation (angiogenesis), and metastasis. The effect is based on competitive inhibition of ATP, preventing phosphorylation of tyrosine and subsequent signal transduction.
Indications
For the treatment of inoperable recurrent cutaneous mast cell tumors in dogs.
Dosage
According to the SmPC. Toceranib is administered orally, with or without food. It is given only every other day to avoid or reduce potential side effects. Do not split, crush, or break the tablets.
Contraindications
Toceranib is contraindicated in hypersensitivity and bleeding in the gastrointestinal tract. It should not be used during pregnancy, lactation, or in breeding animals because it is antiangiogenic. This increases the risk of malformations and death in the offspring. Toceranib is also suspected of causing fertility problems in humans and of being harmful to fertility. Therefore, it is imperative that the user avoid skin contact with wet or broken tablets, as well as with vomit, feces, urine, and saliva of the treated animal, and always wear protective gloves when handling. Pregnant women should not administer toceranib. For complete precautions, see the drug label.
Interactions
To date, there are no known interactions with other drugs. However, toceranib should not be given concomitantly with NSAIDs because they further increase the risk for gastrointestinal bleeding.
Adverse effects
Possible adverse effects include diarrhea, vomiting, loss of appetite, weight loss, increased eating, gastrointestinal bleeding, listlessness, fatigue, weakness, muscle cramps and pain, limb pain, pruritus, difficulty walking (lameness), and blood count changes. Deaths due to bleeding in the digestive tract have been reported. If adverse effects occur, the dose may need to be reduced or therapy discontinued.
