Combining Flea Treatments and All-In-One Meds: What You Need to Know Is It OK to Cross The Streams?

Combining Flea Treatments and All-In-One Meds: What You Need to Know
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Mixing medication without proper supervision is always a bad idea, even when it comes to your pet's flea and tick medications. Here are a few things you should know before experimenting.

We all want to protect our pets from fleas and ticks and our homes from flea infestations. There are many great products out there right now, like Advantix and Frontline Plus, that make doing so easy, like spot-on treatments that kill adult fleas and ticks and stop the growth of new fleas. But what if a medication no longer seems to be working well, or you want extra protection for your pet—is it safe to add a second flea and tick medication? Every pet is different. The right product(s) for one pet might not be right for another pet, which is why having guidelines is important in making the best choices for your best friend. Some pets might do well with Advantage Multi for cats, and others with Nexgard. Below are some tips to help you protect your pets.  

How to Find the Right Combination

Always read product labels, particularly the drug interaction sections, if you intend to combine products, and check with your vet before combining products. Products that only treat fleas are generally safe to combine with products that only treat ticks. But similar to how some people can have different reactions to combinations of medication—pets can react differently to combinations of medications. Your pet might have special medical conditions that only a veterinarian would know. Again, consult your veterinarian before combining medications.

Combinations to Know: Oral Flea Treatments

Either Capstar or Comfortis can be combined individually with a variety of other flea and tick medications, including one of the following: K9 Advantix II, Frontline Plus for Dogs, Advantage II for Dogs, Revolution for dogs, Pet Armor for Dogs, Advantage Multi, Frontline Top Spot for Dogs, Sentinel, or Farnam Bio Spot for Dogs. Capstar will knock out a flea infestation quickly and is over the counter. Comfortis requires a prescription and works to kill adult fleas for a month. It’s not usually recommended to use more than one oral flea medication at the same time. However, Comfortis and Capstar can be combined. Another exception is Sentinel, which doesn’t kill adult fleas, so it can be combined individually with either Comfortis or Capstar.

Combinations to Know: Flea Collars

Some flea collars, like Preventic, are generally safe to combine individually with one of the following: Frontline Plus, Revolution, Pet Armor, Frontline Top Spot or Farnam Bio Spot, K9 Advantix II, Advantage II, Trifexis, Interceptor, Certifect, or Advantage Multi. When used in conjunction with one of the above medications, Preventic collars have been shown to be effective for flea and tick prevention, particularly tick prevention. A good time to use a collar like Preventic with your normal preventative is if you're going for a deep woods hike with your dog. You can remove the collar after the hike! Talk to your vet before combining a Seresto flea collar with any other medications.

Combinations to Know: Heartworm Medication

If you’re concerned about combining heartworm medication with flea and tick products, Heartgard is a good choice, as it doesn’t target fleas or ticks. This means that it can usually be safely combined with other flea and tick medications. However, Heartgard is not safe to combine with a flea and tick medication if that second medication also contains heartworm medication.

Combinations Not to Use

Here are some examples of common medications that should never be combined: Frontline Plus should not be combined with Advantage II; Advantage Multi should not be combined with Revolution; with the exception of Capstar or the Preventic collar, Advantage Multi should not be combined with other medications. Frontline products should not be used in conjunction with Advantage or Advantix products. Your pet shouldn’t receive a flea bath if it has recently been introduced to another flea or tick treatment (for example, if your pet was treated with a spot-on in the past month). If your pet is given a flea bath, they shouldn’t receive another medication for a few days after—Capstar is a more flexible, reliable alternative to flea baths. Flea and tick treatments that are applied to the surrounding environment—either outdoors or in your home, usually won't conflict with medications given directly to your pet. Just try to be mindful of where you're aiming the treatment (don’t spray your pet)!

Should you use all-in-one medications? 

All-in-one flea, tick, and worm monthly preventative medicines claim to offer convenient and complete protection for dogs from multiple parasites. These medications usually contain an adulticide that kills adult fleas, along with medications to eliminate and/or prevent common worms. But are these medications really the best possible solutions, or should you stay away from them? 

Advantages and Disadvantages 

There are some clear advantages of using these medications, such as:

  • Easy to administer
  • Comprehensive protection from parasites
  • Less chance of missing doses and lapses in protection
  • No need to buy multiple products

However, there are also some disadvantages that dog parents should be aware of.

  • Exposure to multiple chemicals and pesticides
  • Increases risk of reaction to an ingredient
  • Possibility of developing resistance to an ingredient
  • Possibility of reactions with other medications
  • Lack of protection from some parasites

Now the last point might have you thinking, “Wait a minute, am I not using these so my dog is protected from all parasites.” Unfortunately, none of these medications offer protection against all parasites. Only a few of them cover whipworms or ear mites, and even fewer cover tapeworms and lungworms. We’ll discuss that more in detail. 


Safety is obviously the first concern that comes to mind when using these products because if they claim to kill so many parasites, there must be some strong ingredients in them. Thankfully, all of these products pass stringent safety tests by the FDA, but they do contain more chemicals than the usual preventative. Needless to say, all of the chemicals are approved for veterinary use, but some dog parents prefer not to expose their dogs to too many chemicals. 

Interactions with medications are another safety aspect to consider. Can the multiple ingredients in these preventative medicines react between themselves and/or other medicines and cause adverse effects? You must understand that every commercial or natural product ever made has the potential to cause idiosyncratic reactions in your dog, which can even prove fatal at times. 

However, these products pass stringent safety tests, so intra-reactions between the ingredients are far from the norm. Think of it this way - peanuts can kill those who are allergic, but the rest of us can eat peanuts safely. As far as reaction to other medicines is concerned, that’s something you should always discuss with your veterinary doctor, especially if your dog takes any medicines regularly. You should also discuss the possibility of any long-term effects with the vet.

Available Products

Let’s discuss some of the all-in-one products available for dogs. We must emphasize that these are prescription-only products and should not be administered without the guidance of a veterinary doctor or professional. Also, none of these medications are effective against adult heartworms. 

Heartworm treatment is extremely elaborate, expensive, and painful for dogs, so preventive medicines are the best way to deal with them. Also, you should get your dog checked for adult heartworm infestation before you start these preventaives. In fact, dog parents should always take their dogs for an annual checkup for heartworms. Now, let’s see what these all-in-one medicines are all about. 

NexGard PLUS

NexGard PLUS is manufactured by the same company that makes Heartgard, and the dosage is simple and convenient - you only need one chewable tablet per month. The active ingredients are - 

  • Afoxolaner (75 mg) -  This compound disrupts the nervous system of fleas and ticks and kills adult fleas before they can lay eggs.
  • Moxidectin (360 mcg) -  This ingredient targets the heartworm eggs and immature stages and prevents some intestinal parasites.
  • Pyrantel (150 mg) -  Pyrantel combats hookworms and roundworms.

NexGard PLUS targets four species of ticks, including black-legged ticks, brown dog ticks, American dog ticks, and lone star ticks. It is also effective against three species of hookworms and two species of roundworms that can cause intestinal problems and anemia in infected dogs.

The product is suitable for puppies as young as 8 weeks. NexGard PLUS should be used with caution in dogs with a history of seizures or neurological disorders, so you should always discuss that with a veterinarian.

Simparica Trio

Simparica Trio chewable tablets combine Sarolaner, moxidectin, and pyrantel and prevent heartworm disease, kill adult fleas before they can lay eggs, kill 5 types of ticks, and prevent flea infestations. It also treats and controls roundworms and hookworms and can be used for dogs and puppies 8 weeks of age and older. The chewable tablets can be taken with or without food. 

The formula contains 

  • 3 mg Sarolaner
  • 0.06 mg Moxidectin
  • 12.5 mg Pyrantel

Simparica Trio should be used with caution in dogs with a history of seizures. Sarolaner, a member of the isoxazoline class, has been associated with neurologic adverse reactions in dogs with or without a history of neurologic disorders. Also, the safe use of Simparica Trio has not been evaluated in breeding, pregnant, or lactating dogs. The most frequently reported adverse reactions in clinical trials were vomiting and diarrhea.


Trifexis can kill fleas and prevent flea infestations as well as heartworm disease. However, like other preventative medicines, it does not cure heartworm diseases. It also treats and controls adult hookworm, roundworm, and whipworm infections. The active ingredients are - 

  • Spinosad: 270 mg
  • Milbemycin Oxime: 4.5 mg

Trifexis is for dogs and puppies aged 8 weeks and older, weighing 5 pounds or more. Side effects are rare when used as prescribed, but some dogs may experience GI distress, skin irritation, vomiting, diarrhea, lethargy, lack of appetite, itching, and reddening of the skin. Also, allergic reactions may include facial swelling, hives, scratching, sudden diarrhea, vomiting, shock, seizures, pale gums, cold limbs, or coma. The chances of vomiting are more likely in puppies under 14 weeks of age.

There are some more precautions that dog parents should take while using Trifexis. High doses of ivermectin alongside Trifexis can lead to serious side effects. Also, less than three monthly doses after mosquito exposure may not provide complete heartworm prevention. As with other preventatives, dogs should be tested for existing heartworm infection before Trifexis administration. The medicine's safety in breeding males is not evaluated, and caution is advised when used for breeding females. Pet parents should observe the dog for an hour after administration. If vomiting occurs, parents should administer another dose.


Sentinel is another monthly oral preventive prescription that protects against heartworms, adult roundworms, adult hookworms, and whipworms, and prevents flea egg development. But it doesn’t kill adult fleas. Dog parents would have to use an adulticide product for flea control. The medicine is suitable for dogs and puppies aged four weeks and older, weighing two pounds or greater. The product contains 5.75 mg of Milbemycin Oxime and 115 mg of Lufenuron. There can be some side effects, such as:

  • Vomiting
  • Depression/lethargy
  • Pruritus (itching)
  • Urticaria (hives)
  • Diarrhea
  • Anorexia
  • Skin congestion
  • Ataxia (loss of coordination)
  • Convulsions
  • Hypersalivation
  • Weakness

Sentinel Spectrum

Sentinel Spectrum is a monthly oral preventive prescription that guards dogs against heartworms, adult roundworms, adult hookworms, and whipworms and prevents flea egg development. The active ingredients are - 

  • 23 mg Milbemycin Oxime
  • 460 mg Lufenuron
  • 228 mg Praziquantel

The medicine is suitable for dogs and puppies six weeks of age and older, weighing at least two pounds. The possibility of side effects include:

  • Vomiting
  • Depression/lethargy
  • Pruritus (itching)
  • Urticaria (hives)
  • Diarrhea
  • Anorexia
  • Skin congestion
  • Ataxia (loss of coordination)
  • Convulsions
  • Salivation
  • Weakness

If a dog is treated with fewer than 6 monthly doses after the last exposure to mosquitoes, it may not provide complete heartworm prevention. Mild hypersensitivity reactions may occur in some cases, and the medicine’s safety is not evaluated in breeding dogs or lactating females. 

Advantage Multi

Advantage Multi can treat various symptoms caused by parasites. It also treats circulating microfilariae in heartworm-positive dogs but doesn’t affect adult heartworms. The medicine kills and prevents adult fleas and controls flea infestations (Ctenocephalides felis). It also treats and controls sarcoptic mange caused by Sarcoptes Scabiei Varcanis. The medicine also takes care of common intestinal parasites, including roundworms, hookworms, and whipworms. The composition includes 400 mg of Imidacloprid and 100 mg of Moxidectin. There can be possible side effects, such as:

  • Localized pruritus (itchiness)
  • Hematochezia (bloody stools)
  • Diarrhea
  • Vomiting
  • Lethargy
  • Inappetence
  • Pyoderma (skin infection)

Pet parents should use the medicine with caution in sick, debilitated, or underweight animals. Also, safety is not established in breeding, pregnant, or lactating dogs. The medicine is not suitable for puppies and dogs less than 7 weeks of age or less than 3 lbs. body weight. The safety of the preventative is also not evaluated when administered on the same day as an adulticide.

Some Final Tips

Using more than the recommended dosage of any individual medication is never advisable. This is not limited to prescription flea and tick medications. In fact, over-the-counter medications can present greater risks when more than the recommended quantity is given to your pet. In particularly bad flea or tick infestations, certain products recommended for monthly use might be used every three weeks under the advice and supervision of your vet. Aside from any of the above exceptions, it is not recommended to combine medications that are designed to target the same problems (in essence, “doubling up” on certain types of products). For example, it is not safe to use more than one spot-on flea and tick medication during the time that the product is still active, more than one oral flea and tick medication, or more than one product that contains heartworm medication at the same time. Consult your veterinarian if you’re not sure about a medication choice.

Will I Overmedicate My Pet if I Mix Flea Meds?

We can't say it enough. Read and follow the package instructions for any and all medications you give your pet. Even over-the-counter products can be dangerous if misused or combined with the wrong products (the label should mention potential drug interactions), so read those labels and always ask your vet if you have any questions.

Don’t Play Pharmacist

When it comes to flea and tick medicine, pet owners are often looking for a quick fix. In reality, it can take three months or more to completely rid your pet of a flea’s full life cycle. (Capstar is a good, quick way to knock out an adult infestation should one occur, but it won't deal with the complete flea life cycle). Don’t let human impatience harm your pet. Allow the medication to completely work its way into your pet’s system before sounding the alarm. Whatever you do, don’t take dosage matters into your own hands. Overmedicating your animal or not following weight /dosage guidelines can really harm your pet. If your pet is battling a serious case of flea infestation consider adding Capstar or a flea collar. Collars will help kickstart the healing process by moving fleas away from the head and neck and down to the rear of the body. It is not a total fix, but it should provide some relief. Read this article to learn more about how flea and tick products can be combined. Again, always check with your vet if you have questions about which products to use and combine for your pet.

How PetPlus Can Help

When it comes to protecting your dog from fleas and ticks, PetPlus is the best way to provide them with the medications they need. Everything from topicals like K9 Advantix II and Frontline Plus to collars like Seresto is right at your fingertips, and with savings, you are going to love -- some as high as 65% off!

Frequently Asked Questions

Can you combine flea treatments?

It is generally not recommended to combine different flea treatments unless specifically advised to do so by a veterinarian. Flea treatments come in a variety of forms, such as spot-on treatments, shampoos, oral medications, and sprays, and each may contain different active ingredients. When different flea treatments are combined, there is a risk of over-treating the animal, which can be harmful. Additionally, some active ingredients in flea treatments may interact with each other, which can also be harmful. Only a veterinary doctor can tell you what combinations to use. For example, Dr. Diane, with 30 years of experience in small animal practice, says that topical pyrethrin-based insecticides like Advantage or Advantix can be used alongside Simparica. Pyrethroids (found in Advantage or Advantix) act on sodium channels, whereas isoxazoline (in Simparica) affects GABA-gated chloride channels, so no significant interactions are expected between the two types of insecticides. However, care must be taken not to overdose Simparica. Overdose can cause tremors in puppies less than 6 months old. If the problem persists, treatment of the environment may be necessary. Fleas spend 90% of their time off the pet, and flea bites on humans indicate the need for environmental treatment. Permethrin-type spray can be used on carpets, and the puppy's bedding should be washed. Ensure everything is dry before allowing the puppy back into the house.

What happens if I give my dog two flea treatments?

Giving your dog two topical flea treatments simultaneously can be dangerous. As mentioned, different flea treatments can contain different active ingredients, and when these are combined, there is a risk of over-treating your dog. Over-treating can lead to a number of adverse reactions. Some dogs may experience redness, itching, or rash on their skin as a result of the increased concentration of active ingredients. Certain active ingredients in flea treatments can cause neurological side effects such as tremors, seizures, or even death. Additionally, if you're applying two different spot-on treatments, one of the active ingredients might be neutralized or inactivated by the other, making it less effective. However, a veterinarian can tell you if you can use two treatments together. Dr. Kara has over 20 years of experience as a veterinarian. She says you can give your dog two flea treatments by combining Frontline containing Fipronil for quick adult flea elimination with a pill like Nitenpyram (Capstar) to swiftly kill adults. It shouldn't pose a problem as there are no contraindications for using both products simultaneously. However, Capstar's effects only last about 24 hours, and while Fipronil spray kills adult fleas, it doesn't affect the eggs they lay before dying. Therefore, you may continue to notice fleas as eggs hatch and larvae mature into adults despite treatment. In such cases, she advises against using another topical treatment immediately, especially in combination with Frontline or Advantage II, as it might cause problems. After approximately two weeks, a different topical can be used safely since the residual Frontline spray would have diminished sufficiently to avoid potential issues.

How close together can you do flea treatments?

The recommended time frame for administering flea treatments can vary depending on the specific product you are using. Some flea treatments are intended for monthly use, while others may be used every three months. Read the product label carefully and follow the instructions for use. In general, it is generally not recommended to administer flea treatments more frequently than once per month, as this can increase the risk of over-treating your pet. Dr. Clayton Greenway says that fleas on the dog represent only 10% of the total flea problem. 90% of fleas exist in juvenile forms, such as larvae and eggs found around the home. Effective treatment involves addressing both adult fleas on the dog and juvenile forms in the environment, and multiple applications over time are necessary for comprehensive flea control. However, that should be done at the prescribed intervals and not too close to each other. Veterinarians usually advise monthly applications for three months. The first application kills adult fleas on the dog, the second one targets adult fleas that develop from larvae and eggs in the home, and the third application ensures the success of flea eradication. Kimberly Dolim, a cat owner since 1985, is more satisfied with Comfortis than topical ones. Comfortis is priced similarly to Frontline or Advantage but requires only monthly administration. She breaks the tablet into small pieces and mixes it into her cat's food, which effectively kills adult fleas that bite the cat, as well as any larval fleas that mature and bite. She uses food-grade diatomaceous earth to address the remaining eggs, particularly in the carpeted areas. If you are using a monthly treatment and are still seeing fleas on your pet, it may be a sign that the treatment is not working effectively or that there is a high infestation level in your environment. In these cases, it is best to consult with your veterinarian to determine the best course of action.

What happens if you give flea medicine too close together?

Dr. Liz Bales, VMD, says it's not recommended to reapply a topical flea treatment too early, even if you're still finding fleas on your pet, as it could result in an overdose. Since there's a wide array of flea and tick medications available for dogs and cats, you should adhere to the instructions provided by your vet for a specific topical flea medication. These medications typically contain one or two active ingredients, and different brands use distinct active ingredients that function in varied ways to prevent fleas. If you've already administered a second dose earlier than instructed, monitor your pet closely for signs of overdose and promptly seek assistance from your veterinarian or a vet emergency professional. They can evaluate the potential toxicity level and provide appropriate guidance. Dr. Danielle Wassink, DVM, says that it's not a good idea to use topical medicines too close to the next dose because it could result in an overdose. The medication usually maintains its killing power in the later stage but possibly works at a slower rate. She suggests using other medications between monthly treatments if necessary. Capstar is a fast-acting option that kills fleas rapidly and does not interact with topical medicines easily. Capstar is also not long-lasting and is quickly metabolized by the pet's system so it can be used as a supplement to regular flea control if immediate flea eradication is required.

Can I use flea treatment again after 2 weeks?

The recommended time frame for administering flea treatment can vary depending on the specific product you are using. Some flea treatments are intended for monthly use, while others may be used every three months. If you are using a monthly treatment and you notice fleas on your pet after two weeks, it may be a sign that the treatment is not working effectively or that there is a high infestation level in your environment. In these cases, it is best to consult with your veterinarian to determine the best course of action. Dr. Melanie, BVSC MS, says that if the flea preventive applied initially doesn't work within two weeks, consider reapplying the flea treatment early or switching to another brand. She recommends using Advantix or a chewable prescription product from your vet, such as Bravecto, Nexgard, Simparica, or Credelio. Capstar (Nitenpyram) is a one-time pill that starts killing adult fleas in 30 minutes and is safe to use with a topical treatment. She says you should use a monthly preventive on all pets for at least 3 consecutive months to break the flea life cycle and recommends year-round use of preventive treatments.

More Flea and Tick Control Advice

The Flea Life Cycle: How to Kill Fleas in the YardFlea and Tick Season: When to Use What TreatmentHow Do Flea Collars Work?Oral Flea Control: Flea Pills For Dogs And Cats

This information is for informational purposes only and is not meant as a substitute for the professional advice of, or diagnosis, or treatment by, your veterinarian with respect to your pet. It has, however, been verified by a licensed veterinarian for accuracy.
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