Milbemycin/Spinosad (Trifexis) for Dogs

Medically Reviewed by Joshua Conrad, PharmD on October 09, 2024
Written by Kathleen Claussen, DVM
5 min read

Milbemycin/spinosad (Trifexis) is a combination medicine to kill fleas, prevent heartworms, and control intestinal parasites (roundworms, hookworms, and whipworms) in dogs and puppies. It is FDA-approved for dogs and puppies at least 8 weeks old and weighing at least 5 pounds (2.2 kg).  Milbemycin/spinosad does not kill ticks.  Even though milbemycin and spinosad can be separately used in cats, the combination medicine is not for use in cats.

Milbemycin is classified as a macrolide antiparasitic for monthly prevention of heartworms and control of intestinal parasites. Milbemycin can be prescribed “extra-label” or “off-label” in dogs for some skin mites.  “Extra-label” or “off-label” means that there is evidence of safe and effective use but the FDA has not approved that use. 

Spinosad is classified as a macrocyclic lactone oral flea adulticide for the prevention and treatment of fleas in dogs and puppies.

Milbemycin/spinosad is generally well tolerated in dogs. Spinosad starts to kill fleas within 30 minutes and is complete within 4 hours.  

Milbemycin/spinosad is available by prescription from your veterinarian or from a veterinary pharmacy.  It is available as a beef flavored chewable tablet in various sizes.

Milbemycin/spinosad is given by mouth. Dogs and puppies should be at least 8 weeks old and weigh at least 5 pounds (2.2 kg). Give milbemycin/spinosad every 30 days (monthly) without stopping for best results.

Milbemycin/spinosad must be given with a small amount of food or immediately after the pet eats. Make sure the entire chewable tablet is eaten. If the dog or puppy vomits within 1 hour after taking the medicine, give them another dose.

Always follow your veterinarian’s directions for giving medicines to animals. Remember to tell your veterinarian about any medicines, vitamins, supplements, or herbal therapies you are giving your dog. Talk to your veterinarian before stopping any pet medicines.  

Combination milbemycin/spinosad should not be given to cats or kittens. 

  • Milbemycin/spinosad is FDA-approved for use in dogs and puppies.
  • Milbemycin/spinosad is well-tolerated by dogs, including puppies.
  • Milbemycin/spinosad starts to kill fleas in 30 minutes.
  • You only have to give one chewable tablet every 30 days.

You and your veterinarian should monitor your dog for improvement of their condition as well as for side effects of the medicine. Signs of improvement include fewer live adult fleas, less itching, and less scratching. If milbemycin/spinosad is used for mites, follow-up skin tests may be done by your veterinarian. If milbemycin/spinosad is used for intestinal parasites, follow-up fecal (stool) tests may be checked.

Before giving milbemycin/spinosad, a heartworm test must be negative.  The heartworm test should be repeated yearly or if there are missed doses of milbemycin/spinosad.

Do not use milbemycin/spinosad in animals that are allergic to it. Use with caution in dogs with pork or soy allergies. Do not use milbemycin/spinosad in dogs that weigh less than 5 pounds or are less than 8 weeks old. Do not use in dogs with heartworm disease. Use with caution in animals that have a history of seizures (epilepsy). Use milbemycin/spinosad with caution in breeding, pregnant, or nursing dogs. 

Milbemycin/spinosad is usually well-tolerated in animals. Side effects include:

  • Vomiting
  • Diarrhea or loose stool
  • Decreased appetite
  • Depression
  • Tiredness or fatigue
  • Scratching or itching
  • Excessive drooling

While there is a low risk of serious side effects with milbemycin/spinosad, they can happen. Serious side effects include:

  • Seizures or tremors 
  • Weakness
  • Difficulty walking

If you think that your pet is having a serious side effect or may have been overdosed, call your veterinary clinic immediately. If it is outside of regular office hours, you can contact a local emergency veterinary hospital or an animal poison control center. 

You can reach the ASPCA Animal Poison Control Center at 888-426-4435 or the Pet Poison Helpline at 855-764-7661.

Using multiple medicines can sometimes change how your pet’s medicines work or increase your pet’s risk for serious side effects. Always tell your veterinarian about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements that your pet is using.

Some medicines that may interact with milbemycin are benzodiazepines such as alprazolam (Xanax) or diazepam (Valium), “azole” antifungals such as itraconazole or ketoconazole, cyclosporine, diltiazem, and erythromycin.  

Some medicines that may interact with spinosad are cyclosporine, ivermectin (especially extra-high doses), ketoconazole, and loperamide.

This may not be a complete list of medicines that can interact with milbemycin/spinosad. Always check with your veterinarian.

  • Keep milbemycin/spinosad out of reach of children.
  • Wash your hands after giving milbemycin/spinosad to your dog.
  • Do not handle milbemycin/spinosad if you are allergic to it.

Milbemycin/spinosad is well tolerated by animals and the risk of an overdose is low. If you are concerned your dog is having an adverse reaction or if you suspect your dog has taken more milbemycin/spinosad than prescribed, call your veterinarian or veterinary emergency clinic immediately.

If you realize that your dog has missed a dose, give the dose when you remember and then continue with the rest of the medicine at the correct dosing schedule. Do not double the dose of the medicine.  

If more than eight weeks have passed since the last dose, start the monthly milbemycin/spinosad again.  Your dog will need to have a heartworm test performed in 6 months to determine if there is heartworm disease. It takes 6 months from the bite of an infected mosquito until a dog may test positive for heartworm disease.

Store milbemycin/spinosad in the original foil packet at room temperature.  Protect it from light.  Be careful about disposal of any extra or expired doses as they can be toxic to wildlife.