Onychomycosis Treatment & the Antifungal Drug Chart (Chart Pages 1 & 2 printed; 3rd page available online) April 2010 Recent Guidelines: General Overview – Onychomycosis4,5,6,7,8 Oral treatment Canadian : • Onychomycosis is a fungal infection of the nails most • Terbinafine LAMISIL 250mg PO once daily is the Bugs and drugs 2006 commonly caused by dermatophytes. Less often Candida drug of choice (cure rate >50-80%, however relapse is http://www.bugsanddrugs.ca/ and molds may affect the nail. common). Terbinafine is more effective than 12 American : • Onychomycosis is recognized by thickening of the distal itraconazole and able to maintain cure for a longer 13 IDSA Candida guidelines 2009 end of the nail associated with some loosening of the nail duration (2 year follow-up). Terbinafine also has less http://www.journals.uchicago.ed plate from the nail bed. The nail plate shows butter yellow risk for potential drug interactions. u/doi/pdf/10.1086/596757 coloured, vertical bands starting at the distal end of the nail. • Alternate treatments UK Guideline 2003 • Both toenails and finger nails may be affected, but o Itraconazole SPORANOX pulse therapy is an http://bad.org.uk/Portals/_Bad/ dermatophyte infections of fingers seldom occur in the alternative if terbinafine contraindicated. Guidelines/Clinical%20Guidel absence of toenail infections. o Fluconazole DIFLUCAN is less effective but is ines/Onychomycosis.pdf 1 • Fungal infections of the foot are not life-threatening but useful in patients unable to take the above. Review Articles: can cause discomfort and become unsightly. For some, 2009 NEJM: Fungal nail disease they predispose to recurrent cellulitis of the legs. Duration & approach to treatment 14,15 http://content.nejm.org/cgi/reprint/360/ 20/2108.pdf 2 Case discussion • Duration of treatment for terbinafine and itraconazole: Ötoenail 12-16 weeks; fingernail 6 weeks. Cochrane:Topical fungal • Mr. T., a 69 yr old man reports that his big toenail has treatments of the skin & foot some yellow “streaks” and looks different. He has a • Weekly topical terbinafine cream application after 2007 history of recurring tinea pedis. completion of oral treatment may be tried to prevent http://mrw.interscience.wiley.com/ • He has diabetes and is on metformin BID and a small dose reinfection (expert opinion). The cream is applied cochrane/clsysrev/articles/CD001 between toes and around nail margin. 434/pdf_fs.html 3 of Humulin N at bedtime. He started swimming a year ago to improve his health after he had a “mild” heart attack. • Alternate treatments Other Resources: Itraconazole pulse therapy (ie. 200mg po BID for 1 Images of skin diseases, includes other • Upon examination, you notice a yellowish discoloration o dermatologic links: www.dermnet.com mainly under the distal end of a thickened toenail. week per month) may decrease costs, side effects when compared to fixed dose (ie. 200mg po daily). Risk factors for onychomycosis9 Patient Resources: Cure rates are similar with pulsed vs. continuous • Risk factors include: age (increased risk with older age), BMJ Clinical Evidence treatments. {Continuous daily dosing is more 10 16 http://clinicalevidence.bmj.com/ceweb/ gender – males 2.4x at risk than females , history of effective than pulse therapy for terbinafine.} conditions/skd/1715/fungal-toenail- tinea pedis or known infected family members. infections-standard- o Fluconazole 150mg po once weekly (x 6-12 months 17,18 ce_patient_leaflet.pdf • Medical conditions that increase risk of infection include for toenail; x ≥3 months for fingernail). diabetes, immunodeficiency, psoriasis or genetic factors. • To monitor for treatment success, mark the nail at Highlights: • Other contributory factors include: poor peripheral completion of oral treatment. This can be done by 1) Not all abnormal nails are circulation, nail trauma, occlusive shoes, smoking, sports filing a line in the nail at the proximal part of known fungal, treat only if culture activities or other activities involving bare feet. infection and marking with a permanent marker. Ask positive for dermatophyte the patient to return if mark and affected toenail do not When to consider treatment grow out or if infection moves proximal past the 2) To minimize potential for false negative, culture nail clipping • Patients with diabetes and/or additional risk factors for marked line. and deep scrapings cellulitis (i.e. prior cellulitis, venous insufficiency, edema). Onychomycosis may be a predictor of foot Cautions including contraindications 11 3) Treat with terbinafine for 12- ulcer in a diabetic patient . and side effects 16 weeks (drug of choice for • Patient experiencing nail pain or discomfort. • A meta-analysis19 found the risk of severe liver injury toenail onychomycosis) • Cosmetic improvement desired. or asymptomatic elevations of serum transaminases with all treatments to be <2%. Liver enzymes should 4) Mark nail at end of treatment Diagnosis to monitor treatment success be done at baseline and after 4-6 weeks with terbinafine Nail clippings, scrapings under the nail and deep nail • and monthly for itraconazole. RxFiles Related: samples are essential to confirm diagnosis of dermatophyte • Itraconazole is contraindicated in patients with heart infection. This is recommended before starting treatment! Antifungal chart: failure or ventricular dysfunction and in patients using http://www.rxfiles.ca/rxfiles/uploads/docu • If negative for dermatophytes, assess for possible psoriasis, drugs metabolized by CYP 3A4 (see Antifungal Chart). ments/members/cht-antifungal.pdf lichen planus, nail trauma, onycholysis (e.g. distance runners), Topical Steroid Chart: changes due to aging or gel nails, & yellow-nail syndrome. http://www.rxfiles.ca/rxfiles/uploads/docu ments/members/CHT- Other Fungal Infections: Clinical Pearls from the Antifungal Chart (chart, next page &/or online) SteroidClassPotencyCOLOR.pdf Common skin infections Oral candidiasis OTC Chart: Fungal Infections • Nystatin only effective for Candida infections (e.g. diaper • The nystatin dose for oral candidiasis (adult) is usually http://www.rxfiles.ca/rxfiles/uploads/docu rash, intertrigo, vulvovaginal infection). 5ml QID to ensure enough liquid to cover area in mouth ments/members/CHT-OTCs.pdf RxFiles Academic Detailing • Combination products that contain steroids and/or nystatin Vulvovaginal candidiasis (uncomplicated) Saskatoon City Hospital should not be used for dermatophyte infections (e.g. ® • 1-3 days with a topical azole as effective as 6-7 days for Saskatoon, SK Canada Viaderm : nystatin, neomycin, gramicidin & treatment but allow ~3 days for symptom resolution. triamcinolone; Lotriderm:clotrimazole + betamethasone). see www.RxFiles.ca • 7 day topical azole treatment recommended in pregnancy 20 Select drug interactions with antifungals Case Discussion (continued): • Terbinafine has minimal significant drug interactions and is a good • Nail clipping and scraping was cultured and came back positive after antifungal option for patients on multiple drug regimens. As an 4 weeks. Due to patient’s diabetes, potential risk for cellulitis and inhibitor of CYP 2D6, it does still have some potential for drug history of tinea pedis, it was decided to recommend pharmacological interactions including increasing the levels and effect of TCAs, beta- treatment. blockers and antipsychotics. (See also Antifungal Treatment Chart.) • The option of treating, including the benefits, risks and costs were • Itraconazole is a strong CYP 3A4 inhibitor resulting in many discussed. Since he had diabetes, he was deemed to derive frequent and significant drug interactions. The majority of drug substantial benefit. interactions result in increased levels of drugs that may: prolong QT • Terbinafine 250mg once daily x 12 weeks was initiated interval (i.e. amiodarone, quinidine, erythromycin), increase side • Mr T. returned 3 months later after completing a course of treatment effects (digoxin-nausea, vomiting; nifedipine-hypotension, dizziness; and noticed an improvement in his toe appearance. However, it still simvastatin/lovastatin-rhabdomyolysis; repaglinide, pioglitazone?- did not look “normal”. He was reassured that he did not require hypoglycemia) or increase toxicity (i.e. cyclosporine, tacrolimus) additional treatment at this time. The nail was marked at the margin o Strong CYP 3A4 inducers (i.e. phenytoin, grapefruit juice) proximal to the infection and patient counseled to return if the and antacids may decrease itraconazole levels. infection moved past the mark or failed to grow out in the coming • Fluconazole has less potential for major drug interactions than 12-18 months. He was instructed to trim & file the nail as it grew. itraconazole because of its renal elimination and lesser effects as an enzyme inhibitor. (Agent is 3rd line in onychomycosis due to limited efficacy.) Prevention topics to discuss with patient… Penlac • Treatment of tinea pedis Is ciclopirox nail lacquer an option? 21 • Proper footwear e.g. wear sandals/slippers in communal areas such as • Penetration into the nail is limited and use is of minimal value. It is swimming pools, locker rooms, gyms, mosque, etc. slightly more effective when compared to placebo22; no additive 23 • Avoid going barefoot where possible benefit when combined with oral terbinafine • Proper nail hygiene – trim nails short & straight across • Recurrence is common on discontinuation. • Avoid using same nail clippers or files on both diseased and normal nails; • Consider cost of solution: