Respectfully submitted by: Sarah Iannacone Third year pharmacy student working with Dr. Drew Olson at Essential Pharmacy Compounding (EPC).
With Doxirobe hard to get many veterinary clinics have been searching for other ways to help treat periodontitis in their patients. With a quick search through VIN you can see there are many options that vets have tried. Here at Essential Pharmacy Compounding we want to make sure you are aware of the stability of products when compounded. One thing to keep in mind is that doxycycline hyclate, one salt form of doxycycline as well as the API formulation, is not stable in an aqueous environment for longer than a few days (~72 hours). In order to extend stability calcium chloride must be added in to form an insoluble salt that will remain active in the aqueous formulation1. Aqueous formulations include oral solutions, suspensions, gels, ointments and others that contain water.
When ordering a compounded doxycycline product from a compounding pharmacy ask about the salt form of doxycycline being used (hyclate, monohydrate, calcium) and what is being added into the compound to ensure stability of the medication if it comes pre-mixed. You don’t want to run into the problem of ordering in a medication and upon receiving the shipment from the compounding pharmacy the medication is no longer stable or active.
The tetracycline antibiotics (doxycycline, minocycline) have antimicrobial activity as well as matrix metalloproteinase (MMPs) inhibition2. This second action of tetracyclines is what differs from other antibiotics in periodontal disease. MMPs are enzymes that are involved in the breakdown of extracellular matrix. In a study on human adult chronic periodontitis patient’s gingival crevicular fluid MMP-8 concentrations were found to be lower in the treatment group (doxycycline 20 mg PO BID) compared to placebo3. Because minocycline is part of the tetracycline drug class this is an option for treatment for canine periodontal disease. There is already a minocycline dental product that is FDA approved for humans that has indications for periodontitis, Arestin4. However, in animals there is no such product on the market and we still worry about the stability of minocycline in an aqueous environment since it is part of the tetracycline class.
In a study done in 2011 using 2% Clindamycin Hydrochloride oral gel in dogs with Stage 2 periodontal disease it was found that pocket depth, bleeding sites and gingival index scores improved significantly at 90 days compared to just cleaning alone. The type of improvement in pocket depth was found to be higher (>0.5mm) compared to just cleaning alone. This study used the FDA approved formulation Clindoral™5. As of current, there are no head-to-head, randomized, double-blinded clinically controlled trials done comparing doxycycline and clindamycin oral gels to each other for the use in periodontitis.
To obtain the action of the tetracycline antibiotic’s MMP inhibition and still use an oral gel to fill the pockets one may want to consider the dual use of an oral sub-antimicrobial doxycycline in addition to Clindoral™.
Have a great day!
- Remington J, Beringer P. Remington. Philadelphia: Lippincott Williams & Wilkins; 2006.
- Plumb D. Plumb’s Veterinary Drug Handbook. 8th ed. Stockholm: PharmaVet Inc.; :365-369.
- Choi D, Moon I, Choi B et al. Effects of sub-antimicrobial dose doxycycline therapy on crevicular fluid MMP-8, and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic periodontitis. J Periodontal Res. 2004;39(1):20-26.
- Online.factsandcomparisons.com. Facts & Comparisons® eAnswers. 2015. Available at: http://online.factsandcomparisons.com/MonoDisp.aspx?monoID=fandc-hcp14976&quick=194559%7c5&search=194559%7c5&isstemmed=True&NDCmapping=-1&fromTop=true#firstMatch. Accessed June 19, 2015.
- Trilogicpharma.com. CLINDORAL. 2015. Available at: http://www.trilogicpharma.com/Clindoral%20IFU%20legal%20size_HA.htm. Accessed June 22, 2015.