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By Tricia Heitman, PharmD, PCCA Clinical Compounding Pharmacist

The PCCA Clinical Services department is a team of researchers, listeners and learners. Like many, we learn from the published medical literature and practice experience, but also through working with compounding pharmacists on the patient challenges that doctors present to them for potential solutions. Working with compounders on recommendations to their dentists is another facet of the patient needs we work to address. Dentists oftentimes request compounded medication that will be used in their office procedures. Since the FDA does not allow office-use compounding for human patients, compounding pharmacists must have a patient-specific prescription from the dentist and provide patient-specific labeling. While this may be a challenge, it is also an opportunity to get to know physicians and their patients’ needs, and compounders are always up for a challenge too. Solving difficult problems is what you do every day, and that is what makes compounding so important in health care. To help you meet the needs of patients in your community, here are some common requests from dentists as well as compounding options to consider.

Compounding for Common Dental Procedures

Some dentists are seeking options for numbing the oral mucosa of patients prior to certain invasive procedures. Combining anesthetics, such as lidocaine, prilocaine and tetracaine, can be a potential way to provide quick-acting as well as long-lasting pain control.1,2,3,4

Dry-socket pastes are another common request made by dentists. A dry socket, also called alveolar osteitis, can occur three or four days after a tooth extraction. If the blood clot that is formed after the extraction is either dislodged or dissolved, underlying bone and nerves are exposed, causing pain and leaving the area vulnerable to infection. Combining healing agents such as phenytoin with an anesthetic and an antibiotic into a long-lasting, mucoadhesive gel can provide a complete treatment for the patient’s needs.5,6

Another common compound that dentists prescribe is a mixture of metronidazole 45.5%, ciprofloxacin HCl 45.5% and minocycline 9% as a dental paste, also referred to as 3 Mix MP. This paste is used for non-instrumentation endodontic treatment of necrotic primary molars in children. Research shows that this treatment allows for less invasive root canal treatment for children ages 3–8, which may be performed in one office visit in most cases.7,8,9,10

Burning Mouth Syndrome, Oral Mucositis & Oral Lichen Planus

Painful dental conditions including burning mouth syndrome, oral mucositis and oral lichen planus are also issues that compounders are asked to provide solutions for. In burning mouth syndrome, one option is a combination of an anesthetic, such as lidocaine, and an active ingredient for neuropathic pain, such as amitriptyline or gabapentin. 11,12,13

Oral mucositis, most often caused by radiation or chemotherapy, is another common compounding request from dentists and oncologists. If the mucositis is painful or complicated by fungal infection, a commonly used treatment option is Stanford mouthwash. Our Research and Development department conducted an in vitro study on a modified version of this mouthwash, and the promising results were published in the International Journal of Pharmaceutical Compounding.14 This formulation was modified by using MucoLox ™, a mucoadhesive base, to improve active ingredient contact time with the mucosa. PCCA also has a corresponding formula in our database that has been tested for stability through the use of a method-validated, stability-indicating assay to achieve a beyond-use date of 180 days.

Painful oral lichen planus is another difficult-to-treat dental condition. It commonly causes swollen mucosa, white patches or open sores in the mouth. Lichen planus is an autoimmune disorder that may be treated with tacrolimus, a calcineurin-inhibiting immunosuppressive agent. 15,16 One option that compounding pharmacies can provide for dentists and their patients are tacrolimus mouthwashes.

Herpes Simplex Virus Type 1

Herpes simplex virus type 1 (HSV-1) is yet one more dilemma for dentists. This condition is chronic and appears as a vesicular rash most commonly on the lips but can occur inside the mouth and on the face. HSV-1 is also an occupational hazard for the dental team, as it can affect the skin (herpetic whitlow) and the cornea (ophthalmic keratitis) if direct contact with a lesion occurs.17 Compounding pharmacists can provide customized preparations with combinations of ingredients to help with HSV-1 outbreaks in infected individuals. By combining a sunscreen with anesthetic agents such as lidocaine and antivirals like acyclovir — or even the antiseptic agent benzalkonium chloride — compounders can offer dentists a unique solution for patients with this condition.18,19,20

Xerostomia

Xerostomia, or dry mouth, can be caused by a variety of factors, such as increased age, Sjögren’s syndrome, diabetes, thyroid dysfunction, dehydration, certain medications or cancer treatments. Even the best over-the-counter saliva substitutes typically offer only a short window of relief. Compounding options that combine a variety of moisturizing agents can extend this window and offer an alternative for patients who want longer-lasting relief.21

One of the most troublesome results of xerostomia for patients is the increase in dental infection and dental caries. Sweet-tasting xylitol could be useful in breaking down the biofilm barrier of bacteria inside the mouth if it exists.22,23 An electrolyte troche that dissolves in the mouth might be another option as well. Ultimately, combining both a saliva substitute and a salivary stimulant may offer the best possible outcome for these patients.

Halitosis

Halitosis can understandably be one of the most embarrassing of all dental conditions. Mouth odor can be caused by bacterial infections, xerostomia, tobacco use, poor oral hygiene, medications and certain disease states. Halitosis is also associated with periodontal disease, also called gingivitis.24 Gingivitis occurs when the bacterial overgrowth causes inflammation in the gums (gingiva). Treatment of these conditions often targets the symptoms and is therefore not a complete success due to the complexity of the condition. Combining antioxidants such as coenzyme Q10 with biofilm reducers such as xylitol in an oral, mucoadhesive base like PCCA’s MucoLox could be a great option.22,23,25,26

Solving dental treatment dilemmas and providing more complete therapeutic treatment options for dentists will set your pharmacy apart in the field of dentistry. PCCA members with Clinical Services support can contact our clinical compounding pharmacists to help with this. They can also access a list of PCCA dental compounding formulas that are commonly requested in this area. Dental pain, mucosal conditions, xerostomia and periodontal disease are just the beginning of the many conditions you can offer options for. There are many opportunities to make a difference in the health of patients and become the dental problem-solver in your community.

Patricia Heitman, PharmD, is a Clinical Compounding Pharmacist at PCCA. She is a graduate of the University of Houston College of Pharmacy and served as a PCCA PharmD Resident for one year post-graduation, which included a teaching position at her alma mater. She has been a full-time PCCA Clinical Compounding Pharmacist since completing her residency in 2000, answering compounding-related calls daily from pharmacists in the United States and Canada. She lectures frequently at PCCA International Seminars and symposiums. Her passions include pediatric compounding—especially options for patients with autism—as well as women’s health, gastrointestinal health and pain management.

A version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

References

1. Lee, H.-S. (2016). Recent advances in topical anesthesia. Journal of Dental Anesthesia and Pain Medicine, 16(4), 237–244. https://doi.org/10.17245%2Fjdapm.2016.16.4.237

2. Mayor-Subirana, G., Yagüe-García, J., Valmaseda-Castellón, E., Arnabat-Domínguez, J., Berini-Aytés, L., & Gay-Escoda, C. (2014). Anesthetic efficacy of Oraqix® versus Hurricaine® and placebo for pain control during non-surgical periodontal treatment. Medicina Oral, Patologia Oral y Cirugia Bucal, 19(2), e192–201. https://doi.org/10.4317/medoral.19202

3. Nayak, R., & Sudha, P. (2006). Evaluation of three topical anaesthetic agents against pain: A clinical study. Indian Journal of Dental Research, 17(4), 155–160. https://doi.org/10.4103/0970-9290.29871

4. Daneshkazemi, A., Abrisham, S. M., Daneshkazemi, P., & Davoudi, A. (2016). The efficacy of eutectic mixture of local anesthetics as a topical anesthetic agent used for dental procedures: A brief review. Anesthesia Essays and Researches, 10(3), 383–387. https://doi.org/10.4103/0259-1162.172342

5. Rashidi Maybodi, F., Haerian-Ardakani, A., Nabi-Maybodi, M., & Nasrabadi N. (2016). Effect of 1% phenytoin muco-adhesive paste on improvement of periodontal status in patients with chronic periodontitis: A randomized blinded controlled clinical study. Journal of Dentistry , 17(Suppl. 3), 256–261.

6. Das, S. J., & Olsen, I. (2001). Up-regulation of keratinocyte growth factor and receptor: A possible mechanism of action of phenytoin in wound healing. Biochemical and Biophysical Research Communications, 282(4), 875–881. https://doi.org/10.1006/bbrc.2001.4621

7. Sato, I., Ando-Kurihara, N., Kota, K., Iwaku, M., & Hoshino, E. (1996). Sterilization of infected root-canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocycline in situ. International Endodontic Journal, 29 (2), 118–124. https://doi.org/10.1111/j.1365-2591.1996.tb01172.x

8. Windley, W., III, Teixeira, F., Levin, L., Sigurdsson, A., & Trope, M. (2005). Disinfection of immature teeth with a triple antibiotic paste. Journal of Endodontics, 31(6), 439–443. https://doi.org/10.1097/01.don.0000148143.80283.ea

9. Vijayaraghavan, R., Mathian, V. M., Sundaram, A. M., Karunakaran, R., & Vinodh, S. (2012). Triple antibiotic paste in root canal therapy. Journal of Pharmacy and Bioallied Sciences, 4(Suppl. 2), S230–S233. http://doi.org/10.4103/0975-7406.100214

10. Nakornchai, S., Banditsing, P., & Visetratana, N. (2010). Clinical evaluation of 3Mix and Vitapex® as treatment options for pulpally involved primary molars. International Journal of Paediatric Dentistry, 20(3), 214–221. https://doi.org/10.1111/j.1365-263x.2010.01044.x

11. Treldal, C., Petersen, J., Mogensen, S., Therkildsen, C., Jacobsen, J., Andersen, O., & Pedersen A. M. L. (2020). Characterization of burning mouth syndrome profiles based on response to a local anaesthetic lozenge. Oral Diseases, 26(3), 656–669. https://doi.org/10.1111/odi.13267

12. Fenelon, M., Quinque, E., Arrive, E., Catros, S., & Fricain, J. C. (2017). Pain-relieving effects of clonazepam and amitriptyline in burning mouth syndrome: A retrospective study.International Journal of Oral & Maxillofacial Surgery, 46(11), 1505–1511. https://doi.org/10.1016/j.ijom.2017.03.032

13. Suga, T., Takenoshita, M., Watanabe, T., Tu, T. T., Mikuzuki, L., Hong, C., Miura, K., Yoshikawa, T., Nagamine, T., & Toyofuku A. (2019). Therapeutic dose of amitriptyline for older patients with burning mouth syndrome. Neuropsychiatric Disease and Treatment, 15, 3599–3607. https://doi.org/10.2147/NDT.S235669

14. Song, G., Banov, D., & Bassani, A. S. (2018). Effects of compounded Stanford modified oral rinse (MucoLox) on the survival and migration of oral keratinocytes and fibroblasts: Implications for wound healing. International Journal of Pharmaceutical Compounding, 22 (1), 60–65. https://ijpc.com/Abstracts/Abstract.cfm?ABS=4434

15. Olivier, V., Lacour, J.-P., Mousnier, A., Garraffo, R., Monteil, R. A., & Ortonne, J. P. (2002). Treatment of chronic erosive oral lichen planus with low concentrations of topical tacrolimus: An open prospective study. Archives of Dermatology, 138(10), 1335–1338. https://doi.org/10.1001/archderm.138.10.1335

16. Chamani, G., Rad, M., Zarei, M. R., Lotfi, S., Sadeghi, M., & Ahmadi, Z. (2015). Efficacy of tacrolimus and clobetasol in the treatment of oral lichen planus: A systematic review and meta-analysis. International Journal of Dermatology, 54(9), 996–1004. https://doi.org/10.1111/ijd.12925

17. Lewis. M. A. O. (2004). Herpes simplex virus: An occupational hazard in dentistry. International Dental Journal, 54(2), 103–111. https://doi.org/10.1111/j.1875-595x.2004.tb00263.x .

18. Ichihashi, M., Nagai, H., & Matsunaga, K. (2004). Sunlight is an important causative factor of recurrent herpes simplex. Cutis, 74(Suppl. 5), 14–18.

19. Wood, A., & Payne, D. (1998). The action of three antiseptics/disinfectants against enveloped and non-enveloped viruses. Journal of Hospital Infection, 38(4), 283–295. https://doi.org/10.1016%2FS0195-6701(98)90077-9

20. Armstrong, J. A., & Froelich, E. J. (1964). Inactivation of viruses by benzalkonium chloride. Applied Microbiology, 12(2), 132–137.

21. Navarro Morante, A., Wolff, A., Bautista Mendoza, G. R., & López-Jornet, P. (2017). Natural products for the management of xerostomia: A randomized, double-blinded, placebo-controlled clinical trial. Journal of Oral Pathology & Medicine, 46(2), 154–160. https://doi.org/10.1111/jop.12487

22. Nayak, P. A., Nayak, U. A., & Khandelwal, V. (2014). The effect of xylitol on dental caries and oral flora. Clinical, Cosmetic and Investigational Dentistry, 6, 89–94. https://doi.org/10.2147/CCIDE.S55761

23. Loimaranta, V., Mazurel, D., Deng, D., & Söderling, E. (2020). Xylitol and erythritol inhibit real-time biofilm formation of Streptococcus mutans. BMC Microbiology, 20. https://doi.org/10.1186/s12866-020-01867-8

24. De Geest, S., Laleman, I., Teughels, W., Dekeyser, C., & Quirynen, M. (2016). Periodontal diseases as a source of halitosis: A review of the evidence and treatment approaches for dentists and dental hygienists. Periodontology 2000, 71(1), 213–227. https://doi.org/10.1111/prd.12111

25. Dommisch, H., Kuzmanova, D., Jönsson, D., Grant, M., & Chapple, I. (2018). Effect of micronutrient malnutrition on periodontal disease and periodontal therapy. Periodontology 2000, 78(1), 129–153. https://doi.org/10.1111/prd.12233

26. Prakash, S., Sunitha, J., & Hans, M. (2010). Role of coenzyme Q(10) as an antioxidant and bioenergizer in periodontal diseases. Indian Journal of Pharmacology, 42(6), 334–337. https://doi.org/10.4103/0253-7613.71884

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.



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