Spinosad: veterinary dose and monograph

At a glance

Drug class

Antiparasitic

Also known as

Comfortis, Trifexis (component)

Species with doses

Dogs and Cats

General dose range

30–60 mg/kg PO monthly — check the species tables for the indication

Routes

PO

Last reviewed

1 October 2026

Indications

• Monthly adult flea control / prevention (dogs and, where licensed, cats)
• Flea-allergy dermatitis management
• Owners preferring an oral, water-resistant alternative to spot-ons
• (Trifexis combination adds milbemycin for heartworm/intestinal worms)

Spinosad dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

Dogs

• Flea control (monthly, with food): Papich 5e: 30 mg/kg PO once monthly. Plumb’s p.1073 (Comfortis label): 30–60 mg/kg (minimum 30) PO once monthly with food. Re-dose if vomiting within 1 h. Caution with high-dose ivermectin (interaction).

Cats

• Flea control (where licensed): Papich 5e: 50–100 mg/kg PO once monthly (approved dose in some countries 50 mg/kg). Give with food.

Contraindications

Concurrent high (extra-label) doses of ivermectin/macrocyclic lactones (neurotoxicity risk via P-gp inhibition) — routine heartworm-preventive doses are generally considered safe, but avoid demodicosis-level ivermectin dosing with spinosad. History of seizures (use cautiously). Give with food. Known hypersensitivity.

Species-specific warnings

Dogs: Avoid concurrent high-dose ivermectin/macrocyclic-lactone protocols (P-gp inhibition → neurotoxicity), particularly in MDR1-mutant breeds.

Adverse effects

• Vomiting (the most common effect, especially first dose — give with food)
• Lethargy, decreased appetite, diarrhoea
• Rare: tremor/ataxia/seizure (more likely with concurrent high-dose ivermectin)

Drug interactions

• High-dose ivermectin / macrocyclic lactones (extra-label, e.g. demodicosis protocols): spinosad inhibits P-gp → increased CNS exposure and neurotoxicity (tremor, seizures) — avoid the combination
• Routine monthly heartworm-preventive macrocyclic-lactone doses: generally considered compatible
• No major other systemic interactions

Pregnancy and lactation

Considered safe in breeding, pregnant and lactating dogs at label doses (per product data).

Monitoring

• Flea control over the month; vomiting (especially first dose)
• Review concurrent ivermectin/macrocyclic-lactone use (avoid high doses)
• Neurologic signs if interaction risk

Toxicity and overdose

Wide margin; the dominant adverse effect is vomiting (give with food). Neurotoxicity is uncommon and chiefly associated with concurrent high-dose ivermectin (P-gp inhibition). Overdose may increase GI signs and, with the ivermectin interaction, CNS signs.

Management: No specific antidote. Supportive care; anti-emetic for vomiting. For neurotoxicity (especially with concurrent high-dose ivermectin): supportive/intensive care, control seizures with benzodiazepines, consider intravenous lipid emulsion. Re-dose flea product only per label if vomiting was early.

Clinical pearls

• A palatable, water-resistant monthly oral flea killer — great for dogs that swim/bathe or owners who dislike spot-ons
• ALWAYS give with food (absorption) and re-dose if the pet vomits within an hour
• Do NOT pair with high-dose (demodicosis-level) ivermectin — spinosad inhibits P-gp and can precipitate neurotoxicity; routine heartworm-preventive doses are fine
• Vomiting is the usual nuisance effect — feeding with the dose minimises it

Mechanism of action

Spinosyns activate insect nicotinic acetylcholine receptors at a novel (allosteric) site and also affect GABA-gated channels, causing involuntary muscle contractions, paralysis and rapid death of fleas. The receptor target differs from neonicotinoids/other classes (low cross-resistance). It inhibits mammalian P-glycoprotein, which is the basis of the high-dose ivermectin interaction.

Formulations and products

• Chewable tablet 30–60 mg/kg (Comfortis) — weight bands
• Comfortis (Elanco) — Spinosad chewable (weight bands), Chewable tablet
• Trifexis (Elanco) — Spinosad + Milbemycin oxime, Chewable (combination)

Storage

Chewables: 15–30 °C, dry, keep in original packaging away from pets (palatable — risk of accidental over-ingestion).

Before you use this dose

Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

Other antiparasitics

• Rafoxanide
• Ronidazole
• Sarolaner
• Selamectin
• Toltrazuril
• Triclabendazole

Frequently asked questions