Onychomycosis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]
Overview
The mainstay of treatment for onychomycosis is antifungal therapy
Treatment
Treatment of onychomycosis is challenging because the infection is embedded within the nail and is difficult to reach. As a result full removal of symptoms is very slow and may take a year or more. Mild onychomycosis sometimes responds to a combination of topical antifungal medication, sometimes applied as special medicinal nail lacquer, and periodic filing of the nail surface. For advanced onychomycosis, especially if more than one nail is infected, systemic medication (pills) is preferred.
Pharmacotherapy
Most treatments are either systemic antifungal medications such as terbinafine and itraconazole, or topical such as nail paints containing ciclopirox or amorolfine. There is also evidence for combining systemic and topical treatments.[1]
For superficial white onychomycosis systemic rather than topical antifungal therapy is advised.[2]
Chronic Pharmacotherapies
Relative effectiveness of treatments
In July 2007 a meta-study reported on clinical trials for topical treatments of fungal nail infections. The study included 6 randomised controlled trials dating up to March 2005.[3] The main findings are:
- There is some evidence that ciclopiroxolamine and butenafine are both effective but both need to be applied daily for prolonged periods (at least 1 year).
- There is evidence that topical ciclopiroxolamine has poor cure rates and that amorolfine might be substantially more effective.
- Further research into the effectiveness of antifungal agents for nail infections is required.
A 2002 study compared the efficacy and safety of terbinafine in comparison with placebo, itraconazole and griseofulvin in treating fungal infections of the nails.[4] The main findings were that for reduced fungus terbinafine was found to be significantly better than itraconazole and griseofulvin, and terbinafine was better tolerated than itraconazole.
- A small study in 2004 showed that ciclopirox nail paint was more effective when combined with topical urea cream.[5]
- A study of 504 patients in 2007 found that aggressive debridement of the nail combined with oral terbinafine significantly reduced symptom frequency over terbinafine alone.[6]
- A 2007 randomised clinical trial with 249 patients show that a combination of amorolfine nail lacquer and oral terbinafine enhances clinical efficacy and is more cost-effective than terbinafine alone.[7]
Most drug development activities are focused on:
- the discovery of new antifungals
- novel delivery methods to promote access of existing antifungal drugs into the infected nail plate
Active clinical trials investigating Onychomycosis:[8]
Some phase III clinical trials revolving around onychomycosis are shown below.
- A medicinal nail lacquer, NM100060 from NexMed,[9] contains terbinafine as the active ingredient and a permeation enhancer which facilitates the delivery of the drug into the nail bed where the fungus resides. Commercial sale of the product is expected to begin no earlier than in 2010.[10]
- A comparison of delivery methods for Itraconzole.[11]
- Safety and tolerability of topical Terbinafine.[12]
Some phase II clinical trials revolving around onychomycosis are show below.
- A topical treatment, AN-2690, is being developed by Schering-Plough Corp and Anacor Pharmaceuticals. It is active against Trichophyton species.[13]
- Posaconazole, taken orally.[14]
- A topical treatment, NB-002, is being developed by NanoBio Corporation.[15] It has completed Phase II trails.[16]
A non-pharmalogical approach with encouraging preliminary results is ultraviolet germicidal irradiation which has been shown to deactivate dermatophytes both in vitro and ex vivo.[17]
Natural remedies As with many diseases, there are also some scientifically unverified folk or alternative medicine remedies.
- Australian tea tree oil.[18][19] In a study at the University of Rochester tea tree oil applied twice daily in conjunction with debridement was found to be an appropriate initial treatment strategy, equally effective to topical use of clotrimazole[20].
- Grapefruit seed extract as a natural antimicrobial is not demonstrated. Its effectiveness is scientifically unverified. Multiple studies indicate that the universal antimicrobial activity is due to contamination with synthetic preservatives that were unlikely to be made from the seeds of the grapefruit.[21][22][23][24][25]
- Another procedure is to apply two drops of distilled white vinegar to the nail base, or, additionally, nail plate and under the nail, two or three times daily for approximately six months or until the fungus is gone. This treatment is very effective, due to the vinegar's acidity, if followed consistently.
New developments
- A medicinal nail lacquer, NM100060 from NexMed is in Phase III clinical trials[26]. It contains terbinafine as the active ingredient and a permeation enhancer which facilitates the delivery of the drug into the nail bed where the fungus resides. Commercial sale of the product is expected to begin no earlier than in 2008. [27]
- A topical treatment, AN-2690, is being developed by Schering-Plough Corp. It is active against Trichophyton species. Phase II and IIb trials are underway. [13]
Active clinical trials investigating Onychomycosis: [4].
Primary Prevention
- Avoid walking barefoot in public areas such as showers, communal changing rooms.
- Keeping feet clean and dry.
- Avoid sharing shoes and socks
Antimicrobial Regimen
- Onychomycosis
- Fingernail Treatment Options
- Preferred regimen: Terbinafine 250 mg PO q24h (children <20 kg: 67.5 mg/day, 20–40 kg: 125 mg/day, >40 kg: 250 mg/day) for 6 weeks OR Itraconazole 200 mg PO q24h for 3 months OR Itraconazole 200 mg PO bid for 1 week/month for 2 months OR Fluconazole 150–300 mg PO q week for 3–6 months
- Toenail Treatment Options
- Preferred regimen: Terbinafine 250 mg PO q24h (children <20 kg: 67.5 mg/day, 20–40 kg:125 mg/day, >40 kg: 250 mg/day) for 12 weeks OR Itraconazole 200 mg PO q24h for 3 months OR Itraconazole 200 mg bid for 1 week/month for 3–4 months OR Fluconazole 150–300 mg PO q week for 6–12 months
References
- ↑ Rodgers P, Bassler M (2001). "Treating onychomycosis". Am Fam Physician. 63 (4): 663–72, 677–8. PMID 11237081.
- ↑ Baran R, Faergemann J, Hay RJ (2007). "Superficial white onychomycosis--a syndrome with different fungal causes and paths of infection". J. Am. Acad. Dermatol. 57 (5): 879–82. doi:10.1016/j.jaad.2007.05.026. PMID 17610995.
- ↑ Crawford F, Hollis S (2007). "Topical treatments for fungal infections of the skin and nails of the foot". Cochrane Database Syst Rev (3): CD001434. doi:10.1002/14651858.CD001434.pub2. PMID 17636672.
- ↑ Haugh M, Helou S, Boissel JP, Cribier BJ (2002). "Terbinafine in fungal infections of the nails: a meta-analysis of randomized clinical trials". Br. J. Dermatol. 147 (1): 118–21. PMID 12100193.
- ↑ Mitchel L. Zoler (April 1, 2004). "Boosts drug entry into nails: urea, ciclopirox combo tested for onychomycosis.(Focus on Skin Disorders)". Internal Medical News. p. 69.
- ↑ Potter LP, Mathias SD, Raut M, Kianifard F, Landsman A, Tavakkol A (2007). "The impact of aggressive debridement used as an adjunct therapy with terbinafine on perceptions of patients undergoing treatment for toenail onychomycosis". The Journal of dermatological treatment. 18 (1): 46–52. PMID 17373090.
- ↑ Baran R, Sigurgeirsson B, Berker DD; et al. (2007). "A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement". British Journal of Dermatology. 157: 149. doi:10.1111/j.1365-2133.2007.07974.x. PMID 17553051.
- ↑ clinicaltrials.gov
- ↑ Clinical trial number NCT00459537 at ClinicalTrials.gov
- ↑ NEXMED Medicines of the Future
- ↑ Clinical trial number NCT00356915 at ClinicalTrials.gov
- ↑ Clinical trial number NCT00443820 at ClinicalTrials.gov and Clinical trial number NCT00443898 at ClinicalTrials.gov
- ↑ 13.0 13.1 Barak O, Loo DS (2007). "AN-2690, a novel antifungal for the topical treatment of onychomycosis". Curr Opin Investig Drugs. 8 (8): 662–8. PMID 17668368.
- ↑ Clinical trial number NCT00491764 at ClinicalTrials.gov
- ↑ Clinical trial number NCT00356915 at ClinicalTrials.gov
- ↑ NanoBio - Onychomycosis
- ↑ PMID 18410410
- ↑ Buck DS, Nidorf DM, Addino JG (1994). "Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole". J Fam Pract. 38 (6): 601–5. PMID 8195735.
- ↑ Nenoff P, Haustein UF, Brandt W (1996). "Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro". Skin Pharmacol. 9 (6): 388–94. PMID 9055360.
- ↑ [1].
- ↑ von Woedtke T, Schlüter B, Pflegel P, Lindequist U, Jülich WD (1999). "Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained". Pharmazie. 54 (6): 452–6. PMID 10399191.
- ↑ Sakamoto S, Sato K, Maitani T, Yamada T (1996). "[Analysis of components in natural food additive "grapefruit seed extract" by HPLC and LC/MS]". Eisei Shikenjo hōkoku. Bulletin of National Institute of Hygienic Sciences (in Japanese) (114): 38–42. PMID 9037863.
- ↑ Takeoka G, Dao L, Wong RY, Lundin R, Mahoney N (2001). "Identification of benzethonium chloride in commercial grapefruit seed extracts". J. Agric. Food Chem. 49 (7): 3316–20. PMID 11453769.
- ↑ Takeoka GR, Dao LT, Wong RY, Harden LA (2005). "Identification of benzalkonium chloride in commercial grapefruit seed extracts". J. Agric. Food Chem. 53 (19): 7630–6. doi:10.1021/jf0514064. PMID 16159196.
- ↑ Ganzera M, Aberham A, Stuppner H (2006). "Development and validation of an HPLC/UV/MS method for simultaneous determination of 18 preservatives in grapefruit seed extract". J. Agric. Food Chem. 54 (11): 3768–72. doi:10.1021/jf060543d. PMID 16719494.
- ↑ Clinical trial number NCT00459537 at ClinicalTrials.gov
- ↑ [2]