Grapiprant
Grapiprant is a non-steroidal, non-cyclooxygenase (COX) inhibiting anti-inflammatory drug belonging to the piprant class. It specifically blocks the **EP4 receptor**, which is the primary mediator of prostaglandin E2 (PGE2) elicited pain and inflammation. > **Clinical Pearl:** Because it does not inhibit COX enzymes, grapiprant theoretically spares the production of beneficial prostaglandins involved in gastrointestinal, renal, and platelet homeostasis, potentially offering a safer profile for long-term osteoarthritis management.
Mechanism: Grapiprant is a highly selective **EP4 receptor antagonist**. Arachidonic acid → COX enzymes → PGE2 → binds to **EP4 receptors** (mediating pain/inflammation). By blocking the EP4 receptor, grapiprant inhibits PGE2-mediated vasodilation, vascular permeability, and sensory nerve sensitization without disrupting the synthesis of PGE2 or other prostanoids.
Dosing by species
- Management of mild to moderate pain caused by osteoarthritis · 2 mg/kg · PO · sid · As directed by veterinarian · For dogs >9 months of age and >3.6 kg.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Hypersensitivity to grapiprant
- Concurrent use with other NSAIDs or corticosteroids
- Breeding, pregnant, or lactating dogs
- Dogs under 9 months of age or weighing less than 3.6 kg
- Dogs under 9 months of age
- Dogs weighing less than 3.6 kg
- Cats (not authorized for use)
- Known hypersensitivity to grapiprant
Adverse effects
- Vomiting
- Diarrhea
- Anorexia
- Lethargy
- Decreased serum albumin
- Soft-formed faeces
- Diarrhoea
- Inappetence
- Mild decreases in serum albumin and total protein
- Haematemesis (very rare)
- Haemorrhagic diarrhoea (very rare)
Drug interactions
- Other NSAIDs · Increased risk of gastrointestinal toxicity · major
- Corticosteroids · Increased risk of gastrointestinal ulceration · major
- Highly protein-bound drugs · Potential competition for protein binding sites · moderate
- Other NSAIDs (e.g., meloxicam, carprofen) · Increased risk of gastrointestinal toxicity and adverse effects. Concurrent use should be avoided. · major
- Corticosteroids (e.g., prednisolone, dexamethasone) · Increased risk of gastrointestinal ulceration and adverse effects. Concurrent use should be avoided. · major
Monitoring
- Clinical response (pain scoring)
- Fecal consistency
- Appetite
- Baseline and periodic CBC, serum biochemistry (especially albumin, BUN, creatinine, liver enzymes)
- Clinical response to pain management
- Signs of gastrointestinal upset or ulceration (vomiting, diarrhoea, melaena)
- Serum albumin and total protein levels
- Baseline and periodic renal and hepatic panels, especially in older or compromised patients
Overdose
Overdoses up to 15x the recommended dose for 9 months resulted in mild, transient GI signs (vomiting, soft feces) and mild decreases in total protein and albumin. No specific antidote exists; treat symptomatically with GI protectants and supportive care.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.