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Shortage of Immiticide for Heartworm Treatment

Image of mosquito

If you can’t get Immiticide, what can you do for heartworm-positive dogs  instead?

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Merial Runs Out of Immiticide for Heartworm Treatment

News item by Mary Straus, published in the Whole Dog Journal, October 2011.

The supply of Immiticide (melarsomine dihydrochloride), the only drug approved to treat heartworm infections in dogs, has been low since December 2009, but now it’s completely gone. Merial confirmed that it was officially out of the drug on August 9, 2011. The current situation is due to a new and separate manufacturing challenge related to technical issues with the company who provides the finished product, according to a Merial spokesperson. Merial said the company is working hard to make the drug available again, but cannot speculate when that might happen.

With Immiticide unavailable, the American Heartworm Society (AHS) has issued guidelines for treating heartworm-positive dogs to try to mitigate the damage that heartworms cause while in the body and the danger they present when they die. Briefly, here is what the AHS advises:

  1. Verify all positive antigen tests with a second antigen test from a different manufacturer.
  2. Give monthly heartworm preventive medication to prevent further infection. If the dog tests positive for microfilariae, pretreat with corticosteroids prior to giving the first dose of heartworm preventive medication and keep the dog under veterinary observation for at least 8 hours afterwards, due to the risk of anaphylactic shock from the rapid die-off of the microfilariae.
  3. Treat dogs with doxycycline at the rate of 10 milligrams per kilogram of body weight twice a day for four weeks (give half as much if a dog cannot tolerate the higher dose). Repeat this dose quarterly (one month on, two months off) for as long as the dog is infected with heartworms. This will reduce the possibility of the infection being passed to other dogs through mosquitoes, shorten the lifespan of the adult worms, and lessen the chance of adverse side effects from worm death.
  4. Restrict all activity and limit all exercise, as the danger from adult heartworms increases with physical activity.
  5. Dogs with symptoms from the heartworms should receive medical treatment to alleviate respiratory distress. Surgical removal of the worms should be considered if cardiac function is affected.
  6. When Immiticide becomes available, proceed with treatment if the dog still tests positive for heartworms.

I’d like to offer a few additional suggestions, based on what I’ve learned about this disease over the years.

While the AHS does not suggest any particular heartworm preventive medication, I recommend using Heartgard (ivermectin) or generic equivalent. Of the four drugs currently used to prevent heartworms, ivermectin has the strongest effect against adult worms. It also has a weaker effect against microfilariae, and so is unlikely to cause an adverse reaction, making pretreatment and observation less critical.

I also suggest giving weekly heartworm-preventive doses of ivermectin to most infected dogs. Be sure to use Heartgard, not Heartgard Plus or any other combination product, when giving weekly. Studies have shown that weekly ivermectin used along with pulsed doxycycline can reduce the number of adult heartworms by more than 78 percent over 36 weeks.

Do not combine Comfortis or Trifexis (also called Vethical AcuGuard and ComboGuard), both of which contain spinosad to control fleas, with weekly doses of ivermectin, as spinosad increases the risks of neurological side effects. Ivermectin should not be given more often than monthly to dogs with the MDR1 gene mutation making them more sensitive to certain drugs. Commonly affected breeds include the Australian Shepherd (standard and mini), Collie, Long-Haired Whippet, and Silken Windhound. See Dogs with a Drug Problem for more information, including a complete list of affected breeds, and an inexpensive test to identify affected dogs.

As we discussed in “Update on Doxycycline and Heartworm Disease” (WDJ August 2009) and “Shortage of Immiticide for Heartworm Treatment” (April 2010), doxycycline is given to kill wolbachia, a symbiotic parasite that lives within heartworms. Destroying wolbachia weakens heartworms, makes them unable to reproduce viable offspring, reduces their adverse effects on the body, and decreases the likelihood of adverse reaction from their death. Doxycycline must be pulsed (given periodically) to keep wolbachia from repopulating. Studies that combined doxycycline with ivermectin for 36 weeks gave doxycycline during weeks 1 to 6, 10 to 11, 16 to 17, 22 to 25, and 28 to 33, but the schedule suggested by the AHS may be equally effective. Giving doxycycline with food can reduce gastric upset.

If Immiticide becomes available while your dog still tests positive for heartworms, you’ll have to decide whether treatment is warranted. Remember that the worms are doing damage as long as they are in the body, and danger of pulmonary embolism from their death also remains as long as any worms are present. Dogs showing symptoms of heartworm infection, those with heavy infections, and those who have been infected for a long time are most likely to benefit from Immiticide treatment, as are very active dogs, since the need for activity restriction would be shorter. Young heartworms are killed more quickly by the combination of ivermectin and doxycycline, so if the infection was caught early, later treatment with Immiticide is less likely to be needed. Keep in mind that dogs may test positive for heartworms for up to six months following the death of all worms.

If Immiticide treatment is not done, continue to give doxycycline quarterly until your dog tests negative for heartworms. Give ivermectin weekly to monthly while your dog remains infected.

For those considering natural heartworm treatment, remember that natural does not necessarily mean either safe or effective. These products are untested and usually contain toxic ingredients, such as wormwood (Artemisia absinthinium) and black walnut (Juglans nigra). The biggest danger of heartworm treatment is from the death of the worms, which can cause pulmonary embolism no matter how the worms die. There’s no reason to believe that alternative treatments are safer than conventional therapy, particularly if you do not give doxycycline as well.

Update: A study published in 2015 showed that Advantage Multi (topical heartworm preventive medication using moxidectin) eliminated adult worms in 8 of 11 heartworm-infected dogs in just six months. It appears to work even better than Heartgard (ivermectin) against adult worms, as well as being safe to give to heartworm-infected dogs (will not cause anaphylaxis by killing too many microfilariae at once). In addition, Advantage Multi has been found to kill older heartworm larvae that are unaffected by ivermectin or Immiticide (see next Update below). Advantage Multi is also effective against fleas. More info:
Evaluation of the Adulticidal Efficacy of Imidacloprid 10 %/Moxidectin 2.5 % (w/v) Spot-on (Advocate®, Advantage® Multi) against Dirofilaria repens in Experimentally Infected Dogs.

Update: A combination of Advantage Multi heartworm preventive medication given monthly plus Doxycycline given for 30 days initially (10 mg/kg twice a day) has been found to kill immature worms that were three to five months old at the time treatment was started. This is significant because prior to this study, there was no known treatment that would kill these immature worms (other heartworm preventive medications generally kill larva that are up to about two months old, while Immiticide is effective only against adult worms six months of age or older). This information can be used to treat dogs who have missed heartworm preventive medication for up to five months. It may also indicate that Advantage Multi could be a good choice to use for the first few months of any heartworm treatment, since it would eliminate these older larvae before they become adult worms (when combined with doxycycline). See Experimental Dirofilaria immitis infection in dogs: effects of doxycycline and Advantage Multi® administration on immature adult parasites for more information.

Update September 2011: The FDA is allowing Merial to import limited quantities of Immiticide their European supplier while Merial works out the problems with its U.S. manufacturing. See FDA Announces Availability of a Limited Supply of Immiticide and FDA Addresses Continued Shortage of Drug Used to Treat Heartworm Infection in Dogs (dated December 3, 2013), for more information.

Update October 2011: Veterinarians at the University of Florida announced that they are now offering a minimally invasive method of extracting heartworms through the jugular vein using specialized instruments. See UF veterinarians offer alternative treatment for severe heartworm cases or call the UF Small Animal Hospital at (352) 392-2235 for more information.

Update February 2017: The FDA approved Diroban (melarsomine dihydrochloride), a generic version of Immiticide.

More information:

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Shortage of Immiticide for Heartworm Treatment

News item written by Mary Straus, published in the Whole Dog Journal, April 2010

On December 1, 2009, Merial published an open letter to veterinarians, announcing a shortage of Immiticide (melarsomine dihydrochloride), the only drug licensed for use in treating heartworm infestations in dogs. The shortage is due to a manufacturing site transfer. The company expressed hope that the shortage will not last beyond the first quarter of this year. [As of August, 2011, Immiticide is not available.]

An apparently unrelated problem is responsible for Merial's announced shortage of Heartgard (ivermectin) tablets, which may be unavailable until 2011. Heartgard prevents canine heartworm disease by eliminating the "tissue stage" of heartworm larvae for a month after infection.

Fortunately, Heartgard chewables and other ivermectin products (including products made by other manufacturers) remain available, so a shortage of the tablets is not cause for concern. The Immiticide shortage, however, has alarmed veterinarians and shelters (who see a lot of heartworm-positive dogs) across the country.

To repeat: Immiticide is the only drug licensed or used to treat adult heartworms in dogs, and Merial is the only company who makes this product. Because of the shortage, veterinarians can no longer order Immiticide from distributors, in order to prevent stockpiling.

Instead, with veterinarians who have a heartworm-positive patient must contact Merial directly and provide details of their patient's case. For now, Merial is selling the drug on a case-by-case basis, providing the drug only to the more severe cases, those dogs with clinical signs of heartworm disease. Dogs who test positive but have no clinical sign of disease will have to wait.

Safe, effective alternative

Fortunately, there is an alternative therapy for heartworm. As we discussed in Update on Doxycycline and Heartworm Disease (WDJ August 2009), a combination of ivermectin (the active ingredient in Heartgard) and doxycycline (an antibiotic) weakens and sterilizes adult heartworms, eventually killing them. The time this take depends on the age of the worms; the older the worms, the longer they take to die.

In addition, giving doxycycline and ivermectin prior to treatment with Immiticide lowers the risk of adverse reaction to worm death, making the treatment much safer. It also lessens the negative effects of the worms themselves, primarily due to doxycycline’s effect on Wolbachia, a symbiotic parasite of the heartworms (see Update: Wolbachia).

The American Heartworm Society (AHS) recently updated its guidelines for treatment of heartworm infection in dogs. It says, “Studies have shown that heartworm-positive dogs pretreated with ivermectin and doxycycline prior to receiving melarsomine [Immiticide] injections had less pulmonary pathology associated with the death of the heartworms. If doxycycline is incorporated into a heartworm treatment protocol it should be given before administration of melarsomine so the Wolbachia organisms and their metabolites are reduced or absent when the worms die and fragment. Doxycycline administered at 10mg/kg BID [twice a day] for four weeks has been shown to eliminate over 90% of the Wolbachia organisms and the levels remain low for three to four months.”

For dogs who are not treated with Immiticide, the guidelines say, “the use of a monthly ivermectin-based heartworm preventive along with doxycycline could be considered. It has been reported that ivermectin and doxycycline administered periodically over 36 weeks resulted in a 78% reduction in adult worm numbers. Moreover, microfilariae from dogs treated with doxycycline that were ingested by mosquitoes developed into third-stage larvae that appeared to be normal in appearance and motility, but these larvae were not able to develop into adult worms, thus negating the risk of selecting for resistant strains. The administration of doxycycline at 10 mg/kg BID for a 4 week period every three to four months should eliminate most Wolbachia organisms and not allow them to repopulate.”

While the AHS still recommends monthly use of heartworm preventatives in combination with doxycycline during treatment for heartworms, the studies reported above used standard heartworm preventative doses of ivermectin given weekly during the 36-week treatment period. They also pulsed doxycycline throughout the treatment period rather than just giving it every three to four months.

Based on the above, it may be best to give Heartgard (not Heartgard Plus) weekly until treatment with Immiticide is begun, or until the dog no longer tests positive for heartworms, if Immiticide treatment is not used. Giving Heartgard weekly (rather than monthly or every two weeks) is less important for dogs who will be treated with Immiticide than those relying on ivermectin and doxycycline alone to get rid of heartworms. (Note that weekly Heartgard is not recommended for dogs with the MDR1 gene mutation that causes sensitivity to ivermectin. See Dogs with a Drug Problem for more information.)

Doxycycline should be given at the dosage level listed above for four weeks prior to starting Immiticide treatment. If treatment has not been completed within three to four months, doxycycline should be given again for four weeks. If Immiticide treatment is not done, treatment with doxycycline should be repeated every three to four months until the dog no longer tests positive for heartworms.

Ivermectin and doxycycline may seem a safer (though slower) alternative to Immiticide, even when the shortage is over. But heartworms cause damage as long as they are in the dog's body, and the danger from the dying worms, while reduced by the use of doxycycline, exists as long as the worms are present.

Immiticide following one month of treatment with doxycycline and ivermectin is still the treatment of choice for most dogs with heartworm disease. If Immiticide treatment is not available or affordable, or if you have a dog with early-stage heartworm disease and a low worm burden, then long-term use of ivermectin with doxycycline is a reasonable alternative.

Update August, 2011: Merial announced that Immiticide is completely unavailable. See above for how to treat dogs with heartworm disease during this period.

Update February 2017: The FDA approved Diroban (melarsomine dihydrochloride), a generic version of Immiticide.

More information:

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You can contact me if you have any comments, but I regret to say that I can no longer respond to questions about individual dogs. See my Contact page for more information. My name is Mary Straus and you can email me at either or

   


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