NexGard kills fleas and ticks by circulating through your dog’s bloodstream after being eaten as a flavored chew. The active ingredient, afoxolaner, belongs to a class of drugs called isoxazolines. When a flea or tick bites your dog and begins feeding, it ingests afoxolaner along with the blood, which overstimulates the parasite’s nervous system and kills it. One chew protects your dog for a full month.
What Happens Inside the Parasite
Afoxolaner targets a specific type of channel in the flea or tick’s nervous system: GABA-gated chloride channels. These channels normally help regulate nerve signals, acting like a brake on nerve activity. Afoxolaner blocks them with extremely high potency, measured in nanomolar concentrations. Without that braking system, nerve cells in the parasite fire uncontrollably, leading to hyperexcitation, paralysis, and death.
What makes this mechanism particularly effective is that afoxolaner binds to a different site on these channels than older insecticides like the cyclodienes. That means parasites that have developed resistance to those older chemicals are still fully vulnerable to afoxolaner. Lab studies confirmed this by testing it against both normal and resistant strains of insects, finding comparable potency against both.
Importantly, the channels afoxolaner targets in insects and arachnids are structurally different from the equivalent channels in mammals. That selectivity is why the drug kills parasites at doses that are safe for dogs.
Parasites Must Bite to Be Affected
NexGard is not a repellent. It doesn’t prevent fleas or ticks from landing on your dog or even from latching on. The parasite has to bite and begin feeding to be exposed to afoxolaner circulating in your dog’s blood. For ticks, this means a tick will attach before it starts dying.
That said, the process works faster than you might expect. Ticks typically spend their first hours on a host just securing their attachment, not yet taking a full blood meal. But even during that early phase, small fluid exchanges occur between the tick and the host. Research published in Parasites & Vectors found that the amount of afoxolaner a tick encounters during this limited early fluid exchange is enough to initiate the killing process, well before the tick begins feeding heavily (which usually starts around 24 hours after attachment).
How Quickly It Kills Fleas and Ticks
NexGard works fast against fleas. In clinical studies, it achieved 100% flea kill within 6 hours of treatment. Even at the 2-hour mark, fleas collected alive from treated dogs had a 99.7% mortality rate shortly after, meaning the drug had already delivered a lethal dose even in that short window. This speed matters because it kills fleas before they can lay eggs, which helps break the flea life cycle in your home.
Ticks take a bit longer. In FDA efficacy trials, NexGard was over 97% effective against American dog ticks when measured 48 hours after infestation. That 48-hour window reflects the tick’s slower feeding behavior compared to fleas.
Why One Chew Lasts a Month
After your dog eats a NexGard chew, afoxolaner absorbs quickly into the bloodstream and then clears slowly. The terminal half-life (the time it takes for blood levels to drop by half) averages about 15.5 days. That combination of fast absorption and slow elimination is what makes monthly dosing work: blood levels rise quickly enough to start killing parasites within hours and stay high enough to remain effective for 30 days.
By the time a month has passed, levels have dropped enough that a new dose is needed to maintain protection. Missing a dose or stretching the interval leaves a gap where parasites can feed and survive.
Which Parasites It Covers
The original NexGard formula is FDA-approved to kill adult fleas and to treat and control American dog tick infestations. It’s cleared for dogs and puppies 8 weeks of age and older, weighing 4 pounds or more. NexGard PLUS, a newer version, adds protection against heartworm, roundworms, and hookworms by including two additional active ingredients alongside afoxolaner.
NexGard comes in weight-based chew sizes so each dog gets the right dose. The tiers cover dogs from 4 pounds up to 132 pounds, and dogs over 132 pounds take an appropriate combination of chews. Your vet selects the correct size based on your dog’s current weight.
Safety and Side Effects
The FDA considers isoxazoline products, including NexGard, safe and effective for dogs. However, the agency issued an alert noting that drugs in this class have been associated with neurological side effects in some animals, including muscle tremors, loss of coordination, and seizures. These reactions can occur even in dogs with no prior seizure history, though most dogs never experience them.
Dogs with a known seizure disorder may be at higher risk, which is something to discuss with your vet before starting treatment. Vomiting, diarrhea, and decreased appetite are among the more commonly reported mild side effects.