Restlessness or agitation after Milbemycin Oxime + Spinosad (Trifexis) in dogs

1,101 reports to the FDA describe restlessness or agitation in dogs given Milbemycin Oxime + Spinosad. That is 0.8% of all reports for this medicine, compared with 1.6% across reports for all dog medicines, so it is reported less often than average with this medicine.

1,101Reports

28%Marked serious

61%Recovered

5.0%Died or euthanised

Same dayTypical onset

How soon it started

Same day

429 51%

1–2 days

71 8.4%

3–7 days

17 2.0%

1–4 weeks

53 6.3%

Over a month

276 33%

How the animals did

Recovered

553 50%

Recovered with lasting effects

121 11%

Still unwell when reported

133 12%

Died

28 2.5%

Euthanised

27 2.5%

Not known

239 22%

Problems reported at the same time

363 33%

317 29%

284 26%

263 24%

250 23%

208 19%

159 14%

118 11%

Age of the animals

Under 1 year

153

1–3 years

381

4–7 years

301

8–11 years

160

12+ years

About this medicine

Milbemycin Oxime prevents heartworm and controls some intestinal worms (monthly). Spinosad kills fleas; monthly chewable.

Products with this combination include Trifexis. The FDA hides brand names in its public data, so these reports cover every product with the same active ingredients.

Some herding breeds (for example Collies) carry the MDR1 gene variant and can be more sensitive to this drug class at high doses.

Questions owners ask

Can Milbemycin Oxime + Spinosad cause restlessness or agitation in dogs?: 1,101 reports link the two, but a report alone does not prove the medicine was the cause: other illnesses, other medicines or coincidence can be involved. Your vet can judge it for your animal.
How soon after a dose was it reported?: In half of the reports with dates, it started within the same day of the first dose.
What should I do?: Don't give another dose until you've spoken to your vet, and keep the packaging so you can tell them the product and dose. Your vet can also report it to the FDA (or you can, through the manufacturer or FDA form 1932a).

Restlessness or agitation with similar medicines

Restlessness or agitation after Ivermectin + Pyrantel (Heartgard Plus) 1,021 reports · 0.7% of its reports
Restlessness or agitation after Moxidectin (ProHeart 6) 508 reports · 1.0% of its reports
Restlessness or agitation after Milbemycin Oxime + Praziquantel (Interceptor Plus) 222 reports · 0.7% of its reports
Restlessness or agitation after Milbemycin Oxime (Interceptor) 250 reports · 0.8% of its reports
Restlessness or agitation after Selamectin (Revolution) 561 reports · 1.9% of its reports
Restlessness or agitation after Ivermectin (Heartgard) 213 reports · 1.8% of its reports
Restlessness or agitation after Ivermectin + Praziquantel + Pyrantel (Iverhart Max) 82 reports · 1.0% of its reports
Restlessness or agitation after Moxidectin + Pyrantel + Sarolaner (Simparica Trio) 20 reports · 1.7% of its reports

All reported side effects of Milbemycin Oxime + Spinosad in dogs · Medicines most reported with restlessness or agitation