Tocerapet-10 — Toceranib Phosphate 10 mg, 40 Tablets

Tocerapet-10 is formulated as tablets for oral administration in dogs. Each tablet contains a controlled therapeutic dose:

• Active Ingredient: Toceranib phosphate — 10 mg equivalent to free toceranib.
• Excipients: Lactose monohydrate, microcrystalline cellulose (binders/fillers), sodium starch glycolate (disintegrant), magnesium stearate, colloidal anhydrous silica (lubricants and glidants).
• Film Coating: Protective coating formulated to facilitate ease of swallowing and prevent premature tablet degradation prior to gastric entry.

Pharmacodynamics: Toceranib is a small-molecule, multi-target receptor tyrosine kinase (RTK) inhibitor. It selectively inhibits both wild-type and mutated forms of the c-Kit receptor tyrosine kinase, which is frequently dysregulated in canine mast cell tumors. Additionally, toceranib inhibits VEGFR-2 and PDGFR-beta receptors. Inhibition of c-Kit leads to cell cycle arrest and induction of apoptosis in malignant mast cells. Blockade of VEGFR and PDGFR suppresses endothelial cell proliferation and tumor microvascularization, leading to tumor hypoxia and tumor regression.

Pharmacokinetics: Following oral administration in dogs, toceranib is rapidly absorbed from the gastrointestinal tract, reaching peak plasma concentration (Cmax) in approximately 6 to 8 hours. Bioavailability is approximately 77% and is not significantly impacted by food co-administration. Plasma protein binding in canine blood exceeds 91%. Toceranib displays wide tissue distribution. It undergoes hepatic metabolism to form an N-oxide metabolite. Excretion occurs predominantly via feces (approx. 92%) with a minimal renal contribution. The terminal elimination half-life (T1/2) in dogs is approximately 16 to 18 hours, supporting alternate-day dosing regimens.

Tocerapet-10 mg is indicated for use in dogs with the following oncological conditions:

• 🔹 Canine Mast Cell Tumors (MCT): Treatment of recurrent, refractory, or unresectable Patnaik grade II or grade III cutaneous and subcutaneous mast cell tumors (with or without c-Kit mutation status).
• 🔹 Other Canine Solid Tumors (Off-Label Veterinary Use): Under direction of a veterinary oncologist, used in managing neuroendocrine carcinomas, anal sac adenocarcinomas, thyroid carcinomas, squamous cell carcinomas, and osteosarcomas.

Tocerapet-10 is strictly for use in dogs only (For use in dogs only). Dosing and treatment protocols must be established by a qualified veterinarian. Tablets must be administered orally whole and must not be split, crushed, or broken. Can be administered with or without a small amount of food.

• Recommended Initial Dose: 3.25 mg/kg body weight administered orally every other day (every 48 hours). If needed, veterinarians may reduce the dose to 2.75 mg/kg every other day to manage mild toxicity.
• Administration Schedule: Treatment is maintained continuously on an alternate-day schedule until disease progression, complete response, or unacceptable adverse effects occur.
• Dose Modifications for Toxicity: If moderate-to-severe gastrointestinal signs (vomiting, diarrhea) or hematologic abnormalities (neutropenia) occur, temporarily suspend treatment for 1–2 weeks until clinical recovery, then resume at a reduced dose (2.75 mg/kg).
• Missed Dose: If a scheduled dose is missed, do not administer a double dose. Resume administration with the next scheduled dose on the appropriate day.

Tocerapet-10 is contraindicated in animals under the following conditions:

• ⛔ Species Restrictions: Strictly prohibited in cats or other non-canine animal species. Administer exclusively to dogs.
• ⛔ Hypersensitivity: Hypersensitivity to toceranib phosphate or any excipient in the tablet.
• ⛔ Pregnancy, Lactation, and Breeding: Do not use in pregnant or lactating bitches, or in male or female dogs intended for breeding.
• ⛔ Age and Body Weight: Do not use in dogs less than 2 years of age or weighing less than 3 kg (due to inability to accurately dose smaller patients).
• ⛔ Active Gastrointestinal Ulceration: Dogs with active GI bleeding, ulceration, or severe pre-existing enteropathy.

Toceranib is extensively bound to plasma proteins and metabolized in the liver, requiring careful consideration of drug interactions:

• ⚠️ Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Concomitant use with NSAIDs (meloxicam, carprofen, firocoxib) significantly increases the risk of severe gastrointestinal ulceration and perforation. Concomitant use requires extreme caution and gastroprotective coverage.
• ⚠️ Highly Protein-Bound Drugs: Co-administration with other highly protein-bound medications (e.g., phenobarbital, furosemide) may alter free toceranib plasma levels.
• ⚠️ CYP450 Inhibitors/Inducers: Medications altering hepatic CYP enzyme pathways (ketoconazole, erythromycin) may increase toceranib plasma concentration and potential toxicity.

The administration of Tocerapet-10 in pregnant, lactating, or breeding animals is strictly contraindicated:

• Embryofetal Toxicity: Toceranib causes fetal loss, teratogenicity, and severe embryofetal harm.
• Breeding Precautions: Animals undergoing toceranib therapy must be excluded from breeding programs. Breeding bitches must not be mated during therapy and for at least 3 months following the final dose.
• Lactation: Toceranib is excreted in milk and presents severe toxicity risks to nursing puppies. Discontinue nursing if therapy is initiated.

The most common and clinically significant adverse reactions associated with Tocerapet-10 in dogs include:

• 🔴 Gastrointestinal Toxicity (Most Common): Anorexia, vomiting, diarrhea (sometimes hemorrhagic/melena), weight loss, and gastrointestinal ulceration.
• 🟡 Hematologic Abnormalities: Neutropenia, anemia, thrombocytopenia (increased risk of bruising or bleeding).
• 🟠 Dermatologic and Musculoskeletal Effects: Coat depigmentation, alopecia, lameness, muscle pain, and cramping.
• 🟢 General and Systemic Effects: Lethargy, depression, hypertension, and proteinuria (requiring routine renal monitoring).

Toceranib overdose represents a severe toxicity event in dogs:

• Symptoms: Exceeding recommended doses leads to severe toxicity characterized by profuse bloody diarrhea, intractable vomiting, severe bone marrow suppression (profound neutropenia), GI ulceration, seizures, and acute renal failure.
• Management: There is no specific antidote. Immediately discontinue Tocerapet-10. Initiate aggressive supportive therapy: intravenous fluid therapy, gastroprotectants (misoprostol, omeprazole, sucralfate), systemic hemostatics, broad-spectrum antibiotics, and blood component transfusions if indicated.

Storage instructions to maintain product efficacy and human safety:

• 🌡️ Temperature Control: Store in original packaging in a dry place protected from light at controlled room temperatures between 15 °C and 25 °C.
• 👶 Human Safety Warning: Keep out of reach of children and domestic pets. Dog owners must wash hands thoroughly with soap and water after handling tablets. Pregnant women must strictly avoid contact with this product.
• ⏳ Expiration Date: Stamped on the package. Do not use after the expiration date (Exp. Date). Dispose of unused product according to hazardous veterinary waste guidelines.

Authentic Tocerapet-10 (10 x 1 x 4 Tablets) manufactured by Vivaldis Animal Health features distinct packaging and security elements:

• 🛡️ Color Panel Layout: The outer carton displays a clean dual-tone design: top white section with vertical gold-brown stripes on the left, and a broad vibrant blue bottom panel.
• 🔒 Vivaldis Branding: The top right corner displays the «VIVALDIS Animal Health» logo with a light blue stylized «V» emblem containing a dot. The left side of the blue bottom panel contains a circular white badge featuring a dog head silhouette.
• 🔍 Veterinary Usage & Quantity Notice: The right side of the blue panel explicitly states in white font: «For use in dogs only» and «Net Quantity: 10 x 1 x 4 tablets».
• 🔢 Product Labeling & Side Markings: The brand name «TOCERAPET-10» is printed in white lettering inside a blue box with a white outline. The prescription icon «Rx» and full name «Toceranib phosphate tablets» are printed directly above. The side panel contains details on Composition, Storage, and warning blocks («CYTOTOXIC DRUG», «SCHEDULE H PRESCRIPTION DRUG»). Side flaps display printed details for Batch No., Manufacturing Date (Mfg. Date), and Expiry Date (Exp. Date).