Elevated temperature after Milbemycin Oxime + Spinosad (Trifexis) in dogs

The FDA has received 409 reports of elevated temperature in dogs after Milbemycin Oxime + Spinosad. That is 0.3% of all reports for this medicine, compared with 0.2% across reports for all dog medicines, so it is reported unusually often with this medicine.

409Reports

42%Marked serious

53%Recovered

5.9%Died or euthanised

Same dayTypical onset

How soon it started

Same day

167 52%

1–2 days

44 14%

3–7 days

10 3.1%

1–4 weeks

16 5.0%

Over a month

86 27%

How the animals did

Recovered

175 43%

Recovered with lasting effects

43 11%

Still unwell when reported

57 14%

Died

11 2.7%

Euthanised

13 3.2%

Not known

110 27%

Problems reported at the same time

250 61%

164 40%

143 35%

134 33%

68 17%

56 14%

44 11%

44 11%

Age of the animals

Under 1 year

1–3 years

149

4–7 years

8–11 years

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 elevated temperature in dogs?: 409 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).

Elevated temperature with similar medicines

Elevated temperature after Ivermectin + Pyrantel (Heartgard Plus) 126 reports · 0.1% of its reports
Elevated temperature after Moxidectin (ProHeart 6) 224 reports · 0.4% of its reports
Elevated temperature after Milbemycin Oxime + Praziquantel (Interceptor Plus) 75 reports · 0.2% of its reports
Elevated temperature after Ivermectin (Heartgard) 27 reports · 0.2% of its reports

All reported side effects of Milbemycin Oxime + Spinosad in dogs · Medicines most reported with elevated temperature