Tocerapet 10 — Toceranib 10 mg Tablets, 4 Tablets · Toceranib Phosphate

Tocerapet-10 is supplied as film-coated oral tablets specifically designed for canine administration.

Qualitative and Quantitative Composition per Tablet:

• • Active Ingredient: Toceranib phosphate equivalent to toceranib free base — 10 mg.
• • Inactive Excipients: Lactose monohydrate (diluent), microcrystalline cellulose (structural stabilizer), magnesium stearate (lubricant), colloidal anhydrous silica (glidant), and film-coating agents (hypromellose, polyethylene glycol, titanium dioxide).

Packaging and Presentation: Tablets are sealed in push-through blister packs constructed from aluminium foil and polymer backing, providing high barrier protection against moisture and light. Each blister contains 4 tablets (packaged as 1 x 4 tablets). Blisters are enclosed in an outer cardboard carton along with the official veterinary package insert. The carton features the Vivaldis Animal Health corporate logo, a canine silhouette icon, product branding, and net quantity declarations.

Pharmacodynamics:
Toceranib is a small-molecule receptor tyrosine kinase (RTK) inhibitor. It selectively inhibits split-kinase family RTKs involved in tumor growth, pathological angiogenesis, and metastatic progression. Key molecular targets include the stem cell factor receptor (c-KIT, frequently mutated in canine mast cell tumors), vascular endothelial growth factor receptors (VEGFR-2 and VEGFR-3), and platelet-derived growth factor receptor (PDGFR-β). Inhibition of c-KIT signaling halts cell proliferation and induces apoptosis in mutant mast cells. Concurrently, VEGFR and PDGFR blockade deprives the tumor microenvironment of blood supply, causing ischemia and tumor regression.

Pharmacokinetics:

• • Absorption: Rapidly absorbed following oral administration in dogs, reaching peak plasma concentrations ($C_{max}$) within 2 to 4 hours post-dose. Absolute oral bioavailability in dogs is approximately 77%. Food intake does not significantly alter total systemic exposure but helps smooth peak concentration spikes.
• • Distribution: Exhibits an extensive volume of distribution and high plasma protein binding (exceeding 91%), primarily to serum albumins.
• • Metabolism: Extensively metabolized by the hepatic cytochrome P450 enzymatic system into multiple metabolites, with toceranib-N-oxide being the primary pharmacologically active metabolite.
• • Elimination: The terminal elimination half-life ($T_{1/2}$) ranges from 16 to 18 hours, supporting an every-other-day (EOD) dosing schedule. Excretion occurs primarily via the feces (approximately 80%) and secondarily through renal pathways in urine (approximately 20%).

Tocerapet-10 is indicated for veterinary clinical use in dogs for the following conditions:

• • Cutaneous and Subcutaneous Mast Cell Tumors: Treatment of recurrent, unresectable, or metastatic Patnaik Grade II or III mast cell tumors in dogs, including cases with confirmed c-KIT mutations.
• • Unresectable Solid Neoplasms: Adjunctive targeted therapy for other canine malignancies (e.g., anal sac apocrine gland adenocarcinoma, thyroid carcinoma, soft tissue sarcomas, osteosarcoma) as prescribed by a veterinary oncologist following appropriate diagnostic staging.

Prescription, dose calculation, and treatment management with Tocerapet-10 must be performed exclusively by a licensed veterinarian experienced in veterinary oncology.

Method of Administration:
Administer tablets orally, whole, with or without food. Splitting, crushing, chewing, or breaking the tablets is strictly prohibited, as it compromises the protective film coating, increases human exposure risk to cytotoxic substances, and alters drug absorption kinetics.

Dosing Regimen:
The recommended starting therapeutic dose of toceranib is 3.25 mg per kg of canine body weight administered orally every other day (EOD). Veterinarians achieve precise dosing by combining various tablet strengths (10 mg, 15 mg, 50 mg).

Monitoring and Dose Adjustments: If severe toxicity occurs (e.g., severe diarrhea, vomiting, grade 3-4 neutropenia), dosing should be temporarily suspended until resolution, then resumed at a reduced dose level (typically 2.75 mg/kg EOD).

Administration of Tocerapet-10 is strictly contraindicated in the following clinical scenarios:

• • Human Use Prohibition: The product is formulated exclusively for canine patients and must never be administered to humans.
• • Hypersensitivity: Known hypersensitivity or allergic reactions to toceranib phosphate or any inactive tablet excipient.
• • Breeding & Reproductive Status: Contraindicated in pregnant or lactating bitches, as well as breeding male and female dogs, due to established teratogenic and embryotoxic risks.
• • Age and Weight Limits: Dogs under 2 years of age or weighing less than 3 kg (safety and efficacy have not been established in this population).
• • Gastrointestinal Pathology: Presence of active gastrointestinal ulceration, bleeding disorders, or severe GI erosions.

Careful evaluation of concurrent medications is required when prescribing Tocerapet-10:

• • Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Concurrent use of toceranib with NSAIDs (such as carprofen, meloxicam, or firocoxib) significantly increases the risk of severe gastrointestinal ulceration, perforation, and bleeding. If co-administration is necessary, aggressive gastroprotective therapy (e.g., proton pump inhibitors) is mandatory.
• • CYP450 Enzyme Modulators: Medications that inhibit or induce hepatic cytochrome P450 enzymes may alter systemic toceranib concentrations, requiring dosage titration.
• • Highly Protein-Bound Drugs: Co-administration requires caution due to potential competitive binding for plasma protein sites.

Pregnancy and Lactation:
Tocerapet-10 is strictly contraindicated in pregnant or nursing bitches. Toceranib crosses the placental barrier and is secreted into milk, causing severe fetal malformations, growth retardation, and neonatal mortality.

Handler Safety Precautions:
Pregnant women, women attempting conception, and nursing mothers must avoid direct handling of tablets (do not touch broken or whole tablets without gloves) and practice rigorous hygiene when cleaning feces or urine from treated dogs, as excreta may contain trace active drug residues.

Therapy with Tocerapet-10 requires scheduled monitoring through complete blood counts, serum chemistry panels, and urinalysis.

Potential Adverse Reactions in Dogs:

• • Gastrointestinal Tract (Very Common): Decreased appetite (anorexia), vomiting, diarrhea (ranging from mild to bloody/watery), melena, oral mucosal ulceration, and gastric ulcers.
• • Hematologic Abnormalities: Neutropenia, thrombocytopenia, and anemia of varying severity grades.
• • Renal and Vascular Disorders: Proteinuria (renal protein loss), systemic arterial hypertension, peripheral edema.
• • Dermatologic Changes: Coat color depigmentation, skin lightening, nasal depigmentation, dry paw pads, and transient alopecia.

Symptoms of Overdose:
Accidental or intentional ingestion exceeding therapeutic dosages results in profound toxicity: intractable vomiting, hemorrhagic diarrhea, severe cachexia, profound myelosuppression (severe neutropenia), dehydration, and heightened susceptibility to sepsis.

Management of Overdose:
No specific antidote exists for toceranib. Immediate drug withdrawal, aggressive intravenous fluid therapy for electrolyte and fluid balance, parenteral nutrition, antiemetics, gastroprotectants, and broad-spectrum antibiotics for neutropenic support are mandatory.

Storage Requirements for Tocerapet-10:

• 🌡️ Temperature Range: Store in a dry place at controlled room temperature between 20 °C and 25 °C (68 °F to 77 °F); temporary excursions permitted between 15 °C and 30 °C.
• ☀️ Environmental Protection: Keep in original, tightly closed packaging to protect from moisture and direct sunlight.
• 👶 Safety Precautions: Store in a securely locked cabinet out of reach of children and domestic pets.
• ⏳ Shelf Life: Stated on the outer carton and blister foil. Do not use past the expiration date. Dispensed strictly on veterinary prescription.

To verify product authenticity and prevent counterfeit exposure, original Tocerapet-10 manufactured by Vivaldis Animal Health features specific security elements:

• ✅ Vivaldis Corporate Trademark: The official "VIVALDIS Animal Health" brand mark featuring a distinctive blue stylized "Y" symbol located in the upper right corner of the carton face.
• ✅ Dosage Badge Design: Product branding "TOCERAPET-10" rendered in bold white text set inside a solid blue rectangular badge positioned directly above vertical orange accent stripes.
• ✅ Canine Iconography: A clear white silhouette icon depicting a dog's head enclosed inside a blue circular emblem in the lower left corner.
• ✅ Specification and Pack Text: Prominent black typography stating "For use in dogs only" and the pack count declaration "Net Quantity: 1 x 4 tablets".