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Update on Doxycycline and Heartworm Disease

A safer and more effective alternative to to slow-kill method of heartworm treatment.

News item written by Mary Straus, published in the Whole Dog Journal, August 2009.

In August 2006, we reported on the finding that heartworms harbor a symbiotic organism called Wolbachia, and that treatment with doxycycline to destroy the Wolbachia could reduce the chance of adverse reactions during heartworm treatment.

According to studies published in late 2008, treatment with a combination of weekly ivermectin (Heartgard) and intermittent doxycycline helps rid the body of adult worms, reduces the effects of the worms, and stops the heartworms from being infectious to other dogs (via mosquitoes). The effects of the combined treatment are more pronounced than with either drug alone, making the treatment a more effective and safer alternative or adjunct to Immiticide (melarsomine dihydrochloride, now also available in a generic form called Diroban).

“Preliminary observations suggest that administration of doxycycline and ivermectin for several months prior to (or without) melarsomine [Immiticide] will eliminate adult heartworms with less potential for severe thromboembolism than melarsomine alone,” one study concluded.

This study followed dogs treated with weekly ivermectin at standard monthly heartworm preventative doses (6 mcg/kg), and with doxycycline at 10 mg/kg daily for weeks 1-6, 10-11, 16-17, 22-25, and 28-33 (the study lasted 36 weeks). Antigen test scores gradually decreased, reflecting a reduction in the number of adult worms (antigen test scores did not change for dogs treated with either ivermectin or doxycycline alone).

After 36 weeks, adult worms had been reduced by 78.3 percent in dogs treated with both medications. In addition, all microfilariae were gone by week 9, meaning that the adult worms had ceased reproducing. Mosquitoes that fed on the dogs treated with doxycycline produced heartworm larvae that were not infective to other dogs.

An Italian study found that dogs treated with the same combination of doxycycline and ivermectin had less perivascular inflammation. Dogs who also received Immiticide showed no thrombi in their lungs (pulmonary thromboembolism, or blood clots in the lungs, are the major life-threatening adverse effect of worm death). A third study with the same protocols concluded, “Results indicate that the combination of these two drugs causes adult worm death.”

These studies clearly indicate that treatment with a combination of weekly ivermectin and daily doxycycline given intermittently will sterilize the heartworms, prevent the dog from being infectious to other dogs, speed up the death of the worms prior to (or in place of) Immiticide treatment, limit inflammation and damage caused by the worms' presence, and reduce the chance of serious adverse reaction from Immiticide treatment.

Weekly doses of the Heartgard should be safe for all but those dogs with the mutant MDR1 gene that affects collies and related breeds, making them more sensitive to ivermectin and a number of other drugs. See Dogs with a Drug Problem for more information.

Update: A study done 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.

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