Anti-Fungal Therapy
Topical Therapy for Nail Infections
Yeast and bacterial infections of the nails are usually the result of microscopic damage to the nail plates. The nails will have either a white, thin discoloration at the tip of the nail that starts to extend toward the cuticle, or may have a greenish-black color to the nail. A mixture of 4% thymol in alcohol used twice daily until the affected area has grown out is excellent for this condition.1 Thymol is an antibacterial and antifungal, and alcohol also reduces moisture in skin folds and cuticles.
For treatment of onychomycosis, penetration of the topical antifungal agent through the nail plate from the surface of the nail and diffusion of the systemic antifungal drug through the nail bed may increase the total amount of antifungal activity at the site of infection. Results from an initial study in patients with onychomycosis suggest that this approach can enhance the overall efficacy of therapy. Using a combination of antifungal drugs in this manner may potentially reduce the duration of therapy and allow a reduction in dose of the oral agent, which may reduce systemic adverse effects. Physicians may also consider combining topical antifungal therapy with topical urea. Urea degrades protein, including keratin -- a major component of the nail plate. Potentially, urea can soften the nail plate, making it more porous and penetrable to topical antifungal drugs.2 Urea ointment (40 to 55%) can be applied to the nail twice daily for two weeks. Then, topical formulations such as clotrimazole 2% and ibuprofen 2% in DMSO USP (“apply to affected nails BID for 6 weeks”)3 or butenafine 2% and tea tree oil 5% cream can be applied to the affected nail.
A randomized, double-blind, placebo-controlled study examined the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% Melaleuca alternifolia (tea tree) oil incorporated into a cream base to manage toenail onychomycosis. Sixty outpatients (39 M, 21 F) aged 18-80 years (mean 29.6) with 6 to 36 months duration of disease were randomized to two groups (40 active therapy and 20 placebo). After 16 weeks, 80% of patients using medicated cream were cured, as opposed to none in the placebo group. Four patients in the active treatment group experienced subjective mild inflammation without discontinuing treatment. During follow-up, no relapse occurred in cured patients and no improvement was seen in medication-resistant and placebo participants.4
1 Audrey Kunin, M.D. http://www.AAAskindoctor.com/nailfungus.html (accessed September 16, 2008)
2 http://www.medscape.com/viewarticle/452687_8 (accessed September 16, 2008)
3 Timothy J. Scott, DPM, FACFAS, Clarion, PA
4 Trop Med Int Health. 1999 Apr;4(4):284-7.
Fungal infections of the feet are commonly associated with dry, cracked skin surrounding the plantar surface and heel fissures. Hyperkeratosis can have various etiologies, and chronic conditions are often quite difficult to treat. Moccasin tinea pedis is typically resistant to topical antifungal therapy when used as sole therapy, because the scale on the plantar surface of the foot impedes or limits the absorption of the antifungal agent. However, one study showed a 100% cure rate was achieved in 12 patients with confirmed moccasin tinea pedis who were treated with topical 40% urea cream and antifungal cream concomitantly for 2 to 3 weeks.
Cutis 2004 May;73(5):355-7
Click here to access the PubMed abstract
Arthritis/Inflammation
The following article concludes: "Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions."
BMJ. 1998 Jan 31;316(7128):333-8
Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.
Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ.
University of Oxford, Oxford Radcliffe Hospital, Headington.
Click here to access the PubMed abstract of this article.
Free full text article available at bmj.com: http://bmj.bmjjournals.com/cgi/content/full/316/7128/333
The following article reports "The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure."
Pharm Res. 1996 Jan;13(1):168-72
Percutaneous absorption of ketoprofen from different anatomical sites in man.
Shah AK, Wei G, Lanman RC, Bhargava VO, Weir SJ.
Pfizer Inc., Central Research Division, Groton, Connecticut 06340, USA.
Click here to access the PubMed abstract of this article.
Athlete's Foot
Various synergistic combinations are used for antifungal therapy. Research points to the practicality "of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties."
J Med Microbiol 2000 Sep;49(9):831-40
Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species.
Pina-Vaz C, Sansonetty F, Rodrigues AG, Martinez-De-Oliveira J, Fonseca AF, Mardh PA.
Department of Microbiology, Porto School of Medicine, University of Porto, Portugal
Click here to access the PubMed abstract of this article.
Diabetic Neuropathy
Neuropathic pain includes a variety of conditions such as diabetic neuropathy, phantom limb pain, reflex sympathetic dystrophy (RSD or Complex Regional Pain Syndrome), and pain caused by blunt trauma or crushing injuries. Symptoms of neuropathic pain may not be evident for weeks to months after the injury. Optimal treatment may involve not only the use of traditional analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, but may also include medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA antagonists. "Combination therapy is frequently the only effective approach for managing the complex array of chemical mediators and other contributors to the individual pain experience."1
"As topical formulations are developed, they provide hope for more effective drug combinations, with fewer systemic adverse drug effects and drug-drug interactions."1 For example, research has shown that topically applied ketoprofen provides a high local concentration of drug below the site of application but decreases systemic exposure and significantly reduces the risk of gastrointestinal upset or bleeding. When properly compounded into an appropriate base, tissue concentrations of ketoprofen were found to be 100-fold greater below the application site (knee) compared to systemic concentrations.2 Sever disease is the most common cause of heel pain in pre-pubertal children. A case report described the use of topical ketoprofen 10% gel as an adjunct to physical therapy to relieve pain and inflammation.3
1 Advanced Studies in Medicine 2003 July;3(7A):S639
2 Pharmaceutical Research (1996) 13: 1; 168-172
3 Phys Ther. 2006 Mar;86(3):424-33
Neuropathy Foot Cream
The following testimonial appeared in the December 1999 issue of Neuropathy News, a patient newsletter:
"My local [compounding pharmacist] has created a cream to help alleviate the pain of foot neuropathy. It reduces the burning and sharp, needle-like pain. All you need is a very thin coat. The directions call for using it four times a day, but I find it particularly helpful at night. [The formulation contains] 2% amitriptyline and 2% baclofen in a transdermal gel."
"Compounding pharmacists have the unique training and ability to create medications that address the individual needs of patients. One of the most helpful products they use are transdermal gels that allow for the passage of medication directly through the tissue into the area of pain. Many of the medications typically prescribed for neuropathy patients such as amitriptyline, lidocaine, mexilitene, ketamine and [gabapentin] can cause significant side effects when taken orally. Transdermal gel minimizes systemic side effects and maximizes local pain relief. Compounding pharmacists have many resources that offer relief from neuropathic pain."
In Diabetes Interviews, January 2000, Neil A. Burrell, DPM, CDE, of Beaumont, Texas, writes "We have a very high success rate using amitriptyline and baclofen mixed in a gel component. This compound is applied to the feet three times per day, and offers immediate relief... [For] recalcitrant neuropathic pain, many times we use a combination of tramadol, gabapentin and amitriptyline."
At our compounding pharmacy, we work together with physicians and patients to prepare formulations containing the medications and doses that are most appropriate to meet each patient's specific needs. Let us know how we can be of service.
Arginine Transdermal
Diabetes Care, January 2004; 27(1):284-5
Improvement of Temperature and Flow in Feet of Subjects with Diabetes With Use of a Transdermal Preparation of L-Arginine - A pilot study
Eric T. Fossel, PHD
Strategic Science and Technologies, Wellesley, Massachusetts
PubMed PMID: 14694013 No abstract available.
Topical doxepin could be an alternative and relatively safe treatment in alleviating neuropathic pain in the diabetic patient, especially when the use of systemic treatment is contraindicated. In the following case study, the soles of the patient's feet were treated with topical doxepin 5% twice daily for four weeks. The patient responded dramatically with loss of the severe burning sensation and no side effects reported.
Wounds 15(8):272-276, 2003. © 2003 Health Management Publications, Inc.
Burning Feet Due to Diabetic Neuropathy
Amna Al-Muhairi, MD, Tania J. Phillips, MD, FRCPC
The print version of this article was originally certified for CME credit. For accreditation details, contact the publisher. Tanya J. Phillips, MD, FRCPC, Boston University School of Medicine, Department of Dermatology, 609 Albany Street, J-106, Boston, MA 02118; Phone: 617/638-5540, Fax: 617/638-5552
Molluscum Contagiosum
Resistant warts and molluscum contagiosum have been treated successfully with compounded topical medications, avoiding discomfort associated with freezing, scraping, electrocautery and laser therapy.
The following study found that 5% KOH aqueous solution proved to be as effective and less irritating when compared to the 10% KOH solution. This trial also emphasizes the effectiveness of topical KOH in the treatment of molluscum contagiosum, sparing affected children from more aggressive physical modalities of treatment.
Pediatr Dermatol 2000 Nov-Dec;17(6):495
Evaluation of the effectiveness of 5% potassium hydroxide for the treatment of molluscum contagiosum.
Romiti R, Ribeiro AP, Romiti N.
Department of Dermatology, University of Sao Paulo, Sao Paulo, Brazil.
Click here to access the PubMed abstract of this article.
Nail Removal
Although surgical excision is the most popular method for removing nails, the use of concentrated urea plasters applied under occlusion may be superior. The use of urea plasters has inherent advantages - they are inexpensive, several nails can be treated in one session, and the procedure is essentially painless. Various synergistic combinations and topical medications with penetrant enhancers can be compounded for antifungal therapy. Topical medications usually have a lower adverse drug-reaction profile than systemic medications.
Cutis. 1980 Jun;25(6):609-12
Urea ointment in the nonsurgical avulsion of nail dystrophies--a reappraisal.
South DA, Farber EM.
Click here to access the PubMed abstract of this article.
Cutis. 1980 Apr;25(4):397, 405
Combination urea and salicyclic acid ointment nail avulsion in nondystrophic nails: a follow-up observation.
Buselmeier TJ.
Click here to access the PubMed abstract of this article.
JAMA 1979 Apr 13;241(15):1559, 1563
Urea plasters alternative to surgery for nail removal.
Montgomery BJ.
PMID: 430701 (No abstract available)
Clin Exp Dermatol 1982 May;7(3):273-6
The treatment of fungus and yeast infections of nails by the method of "chemical removal".
White MI, Clayton YM.
PMID: 7105479 (No abstract available)
Onychomycosis
Management of onychomycosis, a fungal infection of the fingernails and toenails, usually consists of systemic antifungal medications, topical therapy (e.g., urea ointment, desiccating solutions, keratolytics, vital dyes), or surgical intervention (e.g., nail plate avulsion, laser therapy). Topical prescription antifungal preparations, containing the active ingredient of your choice, may be less likely to cause the serious systemic side effects that can occur with oral antifungal therapy and can provide a more economical alternative, as lower doses are needed when the medication is applied topically at the site. Penetrant enhancers can be included in the preparation to improve the effectiveness of topical antifungals.
Trop Med Int Health 1999 Apr;4(4):284-7
Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream.
Syed TA, Qureshi ZA, Ali SM, Ahmad S, Ahmad SA
Department of Dermatology, University of California, San Francisco, USA. tasyed@itsa.ucsf.edu
Click here to access the PubMed abstract of this article.
Plantar Warts
Phys Ther. 2002 Dec;82(12):1184-91
Treatment of plantar verrucae using 2% sodium salicylate iontophoresis.
Soroko YT, Repking MC, Clemment JA, Mitchell PL, Berg L.
Marshfield Clinic-Wausau Center, 2727 Plaza Dr, Wausau, WI 54401-4192, USA.
Click here to access the PubMed abstract of this article.
Wound Care
Wounds and pressure sores may heal more quickly if treated with topical phenytoin. Medications which improve capillary blood flow can be added to a compounded medication to enhance circulation at the wound margins and promote healing of the injured area.
Topical Phenytoin for Wound Healing
The stimulatory effect of orally administered phenytoin on gingival tissue prompted its assessment in wound healing. Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. Phenytoin has been used topically in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns.
Rhodes et al compared the healing of stage II decubitus ulcers with topically applied phenytoin and two other standard topical treatment procedures in 47 patients in a long-term care setting. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications. The mean time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within 2 to 7 days in all subjects, compared to 6 to 21 days in the standard treatment groups. The phenytoin-treated group showed no detectable serum phenytoin concentrations.
Anstead et al. described a patient with a massive grade IV pressure ulcer that was unresponsive to conventional treatment, yet responded rapidly to treatment with topical phenytoin. Song and Cheng reported phenytoin improved wound breaking strength in normal and radiation-impaired wounds. The results of their study indicated that topical phenytoin accelerated normal and irradiation-impaired wound healing by increasing the number of wound macrophages and improving the macrophage function. Pendse et al evaluated the effectiveness of topical phenytoin in healing chronic skin ulcers in a controlled trial of 75 inpatients. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. They concluded: "topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing."
The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite and a conventional topical antibiotic dressing (Soframycin) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean pain scores were lower and mean time to complete healing (complete epithelialization) was best in the phenytoin-treated group (6.2 +/- 1.6 days). Topical phenytoin compared very favorably with, and in some aspects was superior to, occlusive dressings.
The efficacy of topical phenytoin in the treatment of diabetic foot ulcers was evaluated in a controlled inpatient study. Fifty patients were treated with topical phenytoin, and 50 patients received dry sterile occlusive dressings. Both groups improved, but the ulcers treated with topical phenytoin healed more rapidly. Mean time to complete healing was 21 days with phenytoin and 45 days with control.
No study reported any significant adverse effects secondary to topical phenytoin therapy.
Ann Pharmacother 2001 Jun;35(6):675-81
Biochem Pharmacol 1999 May 15;57(10):1085-94
Ann Pharmacother 1996 Jul-Aug;30(7-8):768-75
Int J Dermatol 1993 Mar;32(3):214-7
Chung Hua I Hsueh Tsa Chih 1997 Jan;77(1):54-7
Burns 1993 Aug;19(4):306-10
Diabetes Care 1991 Oct;14(10):909-11
Iontophoresis & Phonophoresis
Iontophoresis facilitates delivery of medications into the tissues beneath the skin by electronic transport of ionized drugs in solution. Acetic acid iontophoresis is effective in the treatment of heel pain. Iontophoresis of dexamethasone for plantar fasciitis should be considered when more immediate results are needed. Iontophoresis has also been used to successfully treat plantar hyperhidrosis.
Phonophoresis is a technique that combines topical drug therapy with ultrasound to achieve therapeutic drug concentrations in muscle and other tissues beneath the skin. Ultrasound gels can be formulated to contain medications such as anti-inflammatories and/or anesthetics.
J Am Podiatr Med Assoc. 1999 May;89(5):251-7
Management of heel pain syndrome with acetic acid iontophoresis.
Japour CJ, Vohra R, Vohra PK, Garfunkel L, Chin N.
Department of Surgery, Veterans Affairs Medical Center, Brooklyn, NY 11209, USA.
Click here to access the PubMed abstract of this article.
Am J Sports Med 1997 May-Jun;25(3):312-6
Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study.
Gudeman SD, Eisele SA, Heidt RS Jr, Colosimo AJ, Stroupe AL.
Specialty Centers for Orthopaedic & Rehabilitative Excellence, Indianapolis, Indiana, USA.
Click here to access the PubMed abstract of this article.
Warts
Cantharidin in a collodion vehicle has been used by dermatologists as a treatment for molluscum contagiosum and warts since the 1950s. Cantharidin lost FDA approval in 1962 because its manufacturers failed to submit data attesting to cantharidin's efficacy. However, in 1999, the FDA included cantharidin on its "Bulk Substances List" of drugs which although not available as commercial products, were approved for compounding on a customized basis for individual patients.
Because of cantharidin's potential for toxicity, the FDA has proposed that cantharidin should be limited to "topical use in the professional office setting only." Severe blistering can result from improper use, and ingestion, especially by children, can be fatal. Treatment of mucous membranes is contraindicated and placement of cantharidin near the eyes and eyelids should be avoided to prevent scleral erosion.
Caution: The treatment of plantar warts with cantharidin is NOT recommended and may have a higher rate of significant complications including lymphangitis and refractory lymphedema.
Arch Dermatol. 2001;137:1357-1360
Click here to access the PubMed abstract
J Am Acad Dermatol. 2000;43:503-507
Click here to access the PubMed abstract
Squaric Acid Dibutylester (SADBE) for Cutaneous Warts in Children
Warts are a common pediatric skin infection and clearance may be enhanced by contact sensitizers, such as squaric acid dibutylester (SADBE). Contact immunotherapy with SADBE is relatively safe and an effective alternative in the management of multiple and resistant cutaneous warts in children.
J Am Acad Dermatol. 2000 May;42(5 Pt 1):803-8
Click here to access the PubMed abstract
Pediatr Dermatol. 2000 Jul-Aug;17(4):315-8
Click here to access the PubMed abstract J Am Acad Dermatol. 1999
Oct;41(4):595-9
Click here to access the PubMed abstract
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