Spinosad
Spinosyn A and Spinosyn D
Also known as: Comfortis · Natroba · Extinosad · Trifexis · Spinosyn A & B · XDE-105 · Spinosyn D
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Prevention or treatment of fleas infestations | 30-60 mg/kg (minimum dosage of 30 mg/kg) PO once monthly with food. | PO | q30d | 1 month | 🌎 NA |
| Flea infestation | 45-70 mg/kg | PO | q28d | — | 🌍 EU |
- Prevention or treatment of fleas infestations: Must be given with food for optimal absorption.
- Flea infestation: Give with or immediately after food.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Flea infestation | 50-75 mg/kg | PO | q28d | — | 🌍 EU |
- Flea infestation: Give with or immediately after food.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Spinosad is a systemic, oral macrocyclic lactone insecticide derived from the naturally occurring soil bacterium Saccharopolyspora spinosa. It is primarily indicated for the prevention and treatment of flea (Ctenocephalides felis) infestations in dogs.
Key Clinical Advantages:
- Rapid Onset: Begins killing fleas within 30 minutes, with complete flea death in 4 hours, effectively breaking the flea life cycle by killing adults before they can lay eggs.
- Waterproof: Because it is administered systemically (orally), its efficacy is completely unaffected by swimming, bathing, or dermatologic shampoos.
Clinical Pearls: While primarily a flea adulticide, pilot studies have shown high efficacy in killing adult brown dog ticks (R. sanguineus*) within 24 hours at higher off-label doses, though it is not officially labeled for tick control.
- Note on Feline Use: While this specific monograph notes it is not approved for cats, a feline-specific formulation of Comfortis was subsequently approved by the FDA. Always refer to current product labeling for feline dosing.
Mechanism of action
Spinosad targets the insect nervous system through a unique mechanism distinct from other parasiticides:
- Primary Pathway: Acts as an agonist at the nicotinic acetylcholine D-alpha receptors → causes motor neuron activation → leads to involuntary muscle contractions and tremors → prolonged exposure results in paralysis and rapid flea death.
- Secondary Pathway: Opens GABA-gated chloride channels in insects, similar to the mechanism of other macrocyclic lactones, further contributing to neuromuscular paralysis.
Because mammalian nicotinic receptors are structurally different from insect receptors, spinosad exhibits a high margin of safety in dogs.
Safety & warnings
Contraindications
- Cats (per this specific monograph's label status)
- Dogs with known pork or soy allergies (chewable tablets contain pork proteins and hydrolyzed soy)
- Dogs and cats weighing < 1.2 kg
- Dogs and cats < 14 weeks of age
- Dogs with MDR1 mutation (relative contraindication due to increased risk of adverse effects)
Adverse effects
- Vomiting (most common)
- Depression/lethargy
- Diarrhea
- Pruritus
- Trembling
- Hypersalivation
- Seizures (rare)
- Vomiting (occasional)
- Lethargy (rare)
- Diarrhoea (rare)
- Anorexia (rare)
- Ataxia (rare)
Precautions
Use with caution in breeding females and dogs with pre-existing epilepsy, as higher than labeled dosages may decrease the seizure threshold. Safe use in breeding males has not been evaluated. The chewable tablets contain pork proteins and hydrolyzed soy; use cautiously in dogs with severe food allergies to these ingredients.
Drug interactions
Concurrent use with high extra-label doses of ivermectin (e.g., for demodicosis) increases the risk of neurotoxicity. However, spinosad is safe to use with standard low-dose heartworm preventatives.
Increased risk of severe neurological toxicity. Do not use in combination.
Competition for P-glycoprotein efflux pump, potentially increasing digoxin levels.
Competition for P-glycoprotein efflux pump, potentially increasing doxorubicin toxicity.
Monitoring
- Flea control efficacy
- Adverse gastrointestinal or neurologic effects
- Efficacy of flea control
- Gastrointestinal tolerance (vomiting)
- Adverse neurological signs
Pharmacokinetics
Half-life
Absorption
Peak plasma levels for spinosyn A and D occur in about 2 and 3 hours, respectively, when administered with food.
Distribution
Extensively bound to canine plasma proteins.
Metabolism
Undergoes hepatic metabolism.
Elimination
Excreted in milk at levels approximately 2.5X of that found in plasma.
Overdose
Spinosad has a wide margin of safety. The oral LD50 in mice is >5000 mg/kg. In canine dose tolerance studies (up to 16.7X the normal dose for 10 days), the primary sign was routine vomiting. No significant changes in hematology or coagulation were noted, though mild elevations in ALT and phospholipidosis (vacuolation) of lymphoid tissue occurred.
Available products
Formulations
- Chewable tablets
- Topical suspension (human)
- 90 mg chewable tablet
- 140 mg chewable tablet
- 270 mg chewable tablet
- 425 mg chewable tablet
- 665 mg chewable tablet
- 1040 mg chewable tablet
- 1620 mg chewable tablet
Veterinary
- Spinosad Chewable Tablets: 140 mg, 270 mg, 560 mg, 810 mg, 1620 mg (Comfortis)
- Comfortis chewable tablets (90 mg, 140 mg, 270 mg, 425 mg, 665 mg, 1040 mg, 1620 mg)
- Trifexis chewable tablets (spinosad + milbemycin oxime)
Human-labeled
- Spinosad 0.9% topical suspension in 120 mL (Natroba)
Regulatory status
POM-V
POM-V
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Chewable tablets should be stored at 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).
Client information
Administration Guidelines
- Give with a full meal: Food is required for the medication to be properly absorbed into your dog's system.
- Vomiting: If your dog vomits within one hour of taking the tablet, you should give another full dose to ensure they are protected.
- Missed Doses: If you forget a dose, give it with food as soon as you remember, and then resume your normal once-a-month schedule from that new date.
Important Note: These chewable tablets are beef-flavored but actually contain pork proteins and hydrolyzed soy. If your dog has a known food allergy to pork or soy, please inform your veterinarian.
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.