Fungal Nail Infections
Fungal Nail Infections
References
- Onychomycosis: a review — Journal of the European Academy of Dermatology and Venereology (Gupta AK, Stec N, Summerbell RC, et al.). J Eur Acad Dermatol Venereol 2020;34(9):1972-1990
- Onychomycosis: clinical overview and diagnosis — Journal of the American Academy of Dermatology (Lipner SR, Scher RK). J Am Acad Dermatol 2019;80(4):835-851
- S1 guideline onychomycosis — Journal der Deutschen Dermatologischen Gesellschaft, German Society of Dermatology (Nenoff P, Reinel D, Mayser P, et al.). J Dtsch Dermatol Ges 2023;21(6):678-692
- Onychomycosis: treatment and prevention of recurrence — Journal of the American Academy of Dermatology (Lipner SR, Scher RK). J Am Acad Dermatol 2019;80(4):853-867
- Oral antifungal medication for toenail onychomycosis — Cochrane Database of Systematic Reviews (Kreijkamp-Kaspers S, Hawke K, Guo L, et al.). Cochrane Database Syst Rev 2017;7:CD010031
- Antifungal selection for the treatment of onychomycosis: patient considerations and outcomes — Infection and Drug Resistance (Axler E, Lipner SR). Infect Drug Resist 2024;17:819-843
- Retrospective analysis of laboratory abnormalities in patients prescribed terbinafine for onychomycosis — Journal of the American Academy of Dermatology (Wang Y, Geizhals S, Lipner SR). J Am Acad Dermatol 2021;84(2):497-499
- British Association of Dermatologists' guidelines for the management of onychomycosis 2014 — British Journal of Dermatology, British Association of Dermatologists (Ameen M, Lear JT, Madan V, et al.). Br J Dermatol 2014;171(5):937-958
Clinical Snapshot
Onychomycosis (a fungal nail infection) is a chronic condition of the nail plate and nail bed, most often affecting the toenails — particularly the great toenail — and typically caused by dermatophyte fungi (chiefly Trichophyton rubrum), with yeasts such as Candida and nondermatophyte moulds accounting for a smaller share of cases.[1] It rarely resolves on its own, needs many months of treatment even when it responds well, and can progress to involve additional nails or spread to household contacts if left untreated. Because a large share of dystrophic-looking nails referred as "possible fungus" are not actually fungal — the differential includes nail psoriasis, lichen planus, trauma, and even subungual melanoma — confirming the diagnosis mycologically before starting any antifungal is the single most important step in management, not an optional add-on.[2]
Recognize the Condition
Typical findings
Toenail involvement is more common than fingernail involvement, and the great or second toe is most often affected. Look for discoloration (white, yellow, or brown), white streaks or patches, thickening of the nail plate, separation of the nail from the nail bed (onycholysis), and crumbling at the nail edges. Symptoms are often purely cosmetic, though pain, difficulty trimming the nail, and pressure discomfort in footwear can occur once the nail is thickened.
The 5 subtypes of onychomycosis
Distal lateral subungual (DLSO)
The most common subtype. Nail thickening with onycholysis; white-yellow or brownish discoloration; the nail may crumble at its outer corners.
Superficial white (SWO)
Chalky white patches on the top surface of the nail plate that can be scraped away. The fungus invades the plate directly from above without generally involving the nail bed; the entire plate can become roughened and crumbly if extensive. Mechanical debridement of the affected surface improves topical drug penetration.
Proximal subungual (PSO)
Uncommon. White discoloration starting at the proximal nail fold (cuticle) that migrates distally as the fungus penetrates newly formed nail plate. Seen most often in immunosuppressed patients and can be a marker of advanced HIV disease.
Endonyx (EO)
Uncommon. A milky patch with indentations and some splitting; the plate is infected but does not separate from the nail bed.
Total dystrophic (TDO)
Uncommon. Complete crumbling, thickened, yellow destruction of the nail — usually the end stage of another subtype.
Risk Factors
- Age 18 years or older, with risk climbing further well past 65.
- Occlusive or tight-fitting footwear.
- Use of public showers, pool decks, or other repeated barefoot exposure to shared wet environments.
- A concurrent foot condition — tinea pedis, nail trauma, poor nail care, bunions — or a personal history of onychomycosis.
- A concurrent dermatologic condition, such as hyperhidrosis or psoriasis.
- A concurrent medical condition — diabetes mellitus, peripheral vascular disease, hyperthyroidism, or immunodeficiency, including transplant recipients — diabetes in particular raises both the likelihood of infection and the stakes of treating it.
- Smoking and obesity.
- A household contact with a known fungal infection.
Red Flags & Refer
Most onychomycosis is a nonurgent, cosmetically predominant problem — but escalate promptly for any of the following:
- Signs of secondary bacterial infection or cellulitis around the nail — new pain, spreading redness, warmth, swelling, or purulent drainage — rather than the slow, painless changes typical of fungal nail disease alone.
- Significant peripheral vascular disease or a diabetic foot at elevated ulceration/amputation risk — these patients need a more cautious risk-benefit calculation before starting oral therapy or attempting any debridement/avulsion, and often benefit from podiatry involvement alongside antifungal treatment rather than pharmacotherapy alone.
- Symptoms of hepatotoxicity in a patient taking an oral antifungal — fatigue, jaundice, anorexia, nausea, vomiting, dark urine, or pale stools — stop the drug and obtain liver function tests immediately rather than waiting for the next scheduled visit.
- A single-nail finding that does not fit typical onychomycosis — a longitudinal pigmented band, a nodule with ulceration or bleeding under the nail, or rapidly progressive nail destruction — these can represent subungual melanoma or squamous cell carcinoma and need urgent dermatology referral rather than empiric antifungal treatment.[2]
- Infection that persists despite a genuinely completed, adherent treatment course with reinfection excluded — refer rather than repeating the same regimen indefinitely.
Assessment & Diagnosis
Differential diagnosis — conditions that mimic onychomycosis
| Condition | Clinical features |
|---|---|
| Nail psoriasis | Symmetrical nail involvement; pitting, onycholysis, subungual hyperkeratosis (white debris under the nail bed), brown-red or pink patches or spots, nail crumbling, white lines on the plate. Associated with psoriatic arthritis. |
| Lichen planus of the nail | Vertical grooving and ridging with progressive nail thinning and atrophy. Can also affect the cuticles, skin (itchy papules), oral mucosa, and genitals. |
| Onycholysis (nontraumatic causes) | Separation of the nail plate from the nail bed from trauma, an underlying tumour, phototoxicity, contact dermatitis, nail psoriasis, or nail lichen planus rather than fungal invasion. |
| Onychogryphosis | Thickened, yellow-brown, curved (claw-like) nail, often in older adults with vascular insufficiency. |
| Onychocryptosis (ingrown nail) | Nail plate curls into the cuticle causing inflammation, discomfort, and secondary infection; usually from trauma, poorly fitted shoes, or improper trimming. |
| Onychomadesis | Complete separation and shedding of the nail plate from the nail bed; can follow infections (hand-foot-and-mouth disease, varicella), trauma, chemotherapy, lichen planus, or Kawasaki disease, and is itself a risk factor for later onychomycosis. |
| Trachyonychia | Rough, brittle nail plate with red or dark coloration and vertical ridging, sometimes splitting; can follow alopecia areata or nail psoriasis. |
| Yellow nail syndrome | Slow-growing, yellow-green, thickened, curved nails; associated with defective lymphatic drainage and pulmonary disease. |
| Subungual or nail-matrix melanoma | A vertical pigmented band in the nail matrix, or a red-brown-black nodule under the nail plate with ulceration or bleeding — always a red flag requiring urgent referral, never presumed to be fungal. |
| Squamous cell carcinoma of the nail | The most common malignant nail disorder; nail bed erosion, ulceration, discharge, bleeding, and nail loss. Risk factors include immunosuppression, chronic sun exposure, HPV, and nail trauma. |
History and examination
- Identify which nails are affected — toenails more often than fingernails, and the great or second toe most commonly — and whether there is a history of nail trauma or another foot condition contributing to the presentation.
- Examine for discoloration, white streaks or patches, and thickening or crumbling of the nail plate, and check surrounding skin for tinea pedis.
Severity grading (guides the topical-versus-systemic decision)
Multiply the area of nail plate involved (scored 0-5) by the proximity of the infection to the nail matrix (scored 1-5), then add 10 points if nail streaks or nail-plate hyperkeratosis over 2 mm are present.[3]
| Score component | Range |
|---|---|
| Area of nail plate involved | 0-5 points |
| Proximity of infection to the nail matrix | 1-5 points |
| Nail streaks or hyperkeratosis over 2 mm present | Add 10 points |
Total score: 0-5 = mild; 6-15 = moderate; 16-35 = severe — this grading, not personal preference alone, should drive the topical-versus-systemic choice made in Choose Initial Treatment.
Do not start antifungal therapy — oral or prescription topical — for a dystrophic nail without first confirming a fungal cause. A large share of dystrophic-looking nails referred as possible fungal infection turn out to be psoriasis, lichen planus, trauma, or another nonfungal cause, and treating the wrong diagnosis wastes months of therapy, cost, and — for oral agents — real hepatic and drug-interaction exposure for no benefit.[2]
Diagnostic methods
- Direct microscopy (KOH preparation): nail-bed scrapings dissolved in potassium hydroxide and examined under a microscope. Inexpensive with fast in-office results (15-60 minutes) but low sensitivity — a negative result does not reliably exclude infection.
- Fungal culture: nail clippings grown on agar. Identifies the causative organism and subtype with high accuracy but takes 3-4 weeks and also has a meaningful false-negative rate.
- Histopathology (periodic acid-Schiff or hematoxylin-eosin stain): the most sensitive laboratory technique and useful for distinguishing onychomycosis from its mimics, but cannot identify the subtype and is more expensive.
- PCR: identifies the subtype in under 48 hours with high sensitivity, but has a meaningful false-positive rate and is expensive.
- Nail dermoscopy (onychoscopy): an in-office, noninvasive tool that helps distinguish onychomycosis from traumatic onycholysis, melanonychia, and nail psoriasis.
The practical standard is a combination of KOH microscopy plus fungal culture. If KOH is positive but culture is negative, repeat the culture rather than accepting the negative result, given culture's high false-negative rate.[2]
Treatment Targets
- Achieve mycological cure — a negative KOH and/or fungal culture at the end of therapy.
- Achieve clinical cure — a visually normal nail, recognizing this lags well behind mycological cure as the nail grows out.
- Prevent spread to other nails, skin, or household contacts.
- Prevent complications such as secondary bacterial infection and cellulitis, particularly in patients with diabetes or peripheral vascular disease.
- Avoid unnecessary treatment — mild, asymptomatic disease in a patient who does not want treatment is a legitimate, direct choice, not a failure to treat.
Choose Initial Treatment
Step 1 — confirm the diagnosis before treating anything
Obtain KOH microscopy and/or fungal culture before starting any oral or prescription topical antifungal — do not treat a dystrophic nail empirically. A large share of dystrophic nails are not fungal at all, and confirming the diagnosis first avoids wasting months of therapy, cost, and real drug-interaction/hepatotoxicity exposure on the wrong problem.[2]
Step 2 — match topical or systemic therapy to severity and candidacy
Topical therapy, preferred for mild-to-moderate disease: under 50% of the nail plate affected, nail-plate thickness under 2 mm, and no nail matrix involvement.
Systemic (oral) therapy, preferred for moderate-to-severe disease, nail matrix involvement, more than 3 nails affected, or combined finger-and-toe disease — oral therapy has a materially higher cure rate than topical monotherapy in this group.[4]
Combine oral plus topical therapy in patients age 65 or older, those with diabetes, peripheral vascular disease, or immunosuppression, and anyone who has already failed monotherapy.
Step 3 — choose the specific oral agent by likely organism
Oral terbinafine, 1st line for dermatophyte onychomycosis, which accounts for the great majority of cases — terbinafine is more effective than pulsed itraconazole for dermatophyte disease and carries a meaningfully smaller drug-interaction burden than the oral azoles, which matters most in patients already taking multiple medications.[5]
Oral itraconazole, 1st line — use when a nondermatophyte mould or a yeast such as Candida is confirmed or strongly suspected, since itraconazole's broader spectrum covers these organisms better than terbinafine. Screen the patient's full medication list for CYP3A4 interactions before starting — this is one of the most pharmacist-relevant steps in onychomycosis care.[6]
Avoid ketoconazole for onychomycosis — it lacks supporting efficacy data and carries a disproportionate hepatotoxicity risk relative to terbinafine or itraconazole.
Fluconazole — reserve for patients who cannot tolerate or have a contraindication to both terbinafine and itraconazole; it is an off-label, lower-efficacy alternative, not an equal first choice.
Step 4 — decide whether to treat at all
Do not default to treatment for mild, asymptomatic disease in a patient who does not want it — many months of therapy, cost, and, for oral agents, hepatotoxicity/interaction risk are a real trade-off against a modest cosmetic benefit, and declining treatment is a legitimate, direct choice to document, not a gap in care.
Favor treating — and favor systemic therapy specifically — in a patient with diabetes, immunosuppression, prior cellulitis, venous insufficiency, nail pain, or a clear wish to improve the nail's cosmetic appearance.
Non-Pharmacologic Treatment
- Wear footwear and socks that minimize humidity — moisture-wicking socks and breathable, non-occlusive shoes.
- Dry feet and the spaces between toes thoroughly after washing.
- Avoid going barefoot in shared wet environments — public showers, pool decks, gym locker rooms, nail salons.
- Keep nails clean and trimmed short to reduce trauma; avoid sharing nail clippers, towels, sheets, or footwear.
- Wash affected socks and clothing separately, at a high temperature.
- Discard old, heavily infected footwear, or disinfect footwear and socks before reusing them.
- Wear rubber gloves to protect fingernails during prolonged water immersion (dishwashing, cleaning).
- Apply emollients to cracked skin to reduce entry points for fungus.
- Optimize control of contributing chronic conditions, particularly diabetes and peripheral vascular disease.
- Treat any concurrent tinea pedis in the patient, and offer testing/treatment to household contacts, since untreated tinea pedis is both a reservoir for reinfection and a portal of entry for secondary bacterial infection.
- For superficial white onychomycosis specifically, gentle mechanical debridement/scraping of the affected surface improves topical drug penetration.
Device-based and procedural adjuncts
Nail drilling (mechanical debridement), iontophoresis, photodynamic therapy, laser, microwave, and nonthermal plasma therapy have all been studied as adjuncts or alternatives to standard pharmacotherapy. None has demonstrated a clear advantage over oral or topical antifungal therapy, evidence remains limited, and further study is needed before recommending any of them in place of standard treatment.
Surgical or chemical nail avulsion (partial or total nail removal) is generally discouraged — it is painful, and the regrowing nail can become ingrown or reinfected. It is specifically hazardous in patients with diabetes, where it raises the risk of infection and gangrene; involve podiatry rather than pursuing avulsion routinely in this group.
Pharmacologic Treatment Options
Topical therapy track
Best candidate
Mild-to-moderate disease — under 50% of the nail plate affected, nail-plate thickness under 2 mm, no nail matrix involvement — or any severity in a patient who cannot safely take an oral antifungal, understanding cure rates will be lower than with systemic therapy.
Systemic (oral) therapy track
Best candidate
Moderate-to-severe disease, nail matrix involvement, more than 3 nails affected, or combined finger-and-toe disease, in a patient medically appropriate for an oral antifungal.
Combination (oral + topical) track
Best candidate
Age 65 or older, diabetes, peripheral vascular disease, immunosuppression, or prior monotherapy failure.
| Drug / intervention | Role | Dose / use | Important adverse effects | Teaching points |
|---|---|---|---|---|
| Terbinafine (oral) Preferred | 1st-line oral agent for dermatophyte onychomycosis (most cases) | 250 mg PO once daily — 6 weeks for fingernails, 12 weeks for toenails | GI upset, headache, transient taste/smell disturbance; rare hepatotoxicity | More effective than pulsed itraconazole for dermatophyte disease with a smaller drug-interaction burden than the azoles. Obtain baseline liver function tests before starting. |
| Itraconazole (oral, pulse) Preferred | 1st-line for yeast/nondermatophyte mould OM; alternative for dermatophyte OM | 200 mg PO twice daily for 1 week per month — 2 pulses for fingernails, 3 pulses for toenails | GI upset, headache; rare hepatotoxicity, heart failure | Potent CYP3A4 inhibitor with an extensive interaction list — screen the full medication list before dispensing. Pulse dosing preferred over continuous dosing given a lower cumulative interaction/side-effect burden. |
| Fluconazole (oral) Alternative | Reserve for intolerance/contraindication to terbinafine and itraconazole | 150 mg PO once weekly until the nail grows out | GI upset, headache; rare hepatotoxicity | Off-label for onychomycosis and less effective than terbinafine or itraconazole — not an equal first choice. |
| Ketoconazole (oral) Avoid | Not recommended for onychomycosis | Not used for onychomycosis | Hepatotoxicity risk exceeds that of other oral agents used for OM | Lacks supporting efficacy data for onychomycosis — do not use. |
| Efinaconazole 10% solution Preferred | 1st-line topical agent for mild-to-moderate toenail OM | 1 drop (2 drops for the great toenail) applied once daily; up to 48 weeks | Application-site erythema, vesicles; rare allergic contact dermatitis | No debridement needed and no lacquer buildup — penetrates the intact nail directly. |
| Ciclopirox 8% nail lacquer Alternative | Topical option for mild-to-moderate OM, especially in poor oral-therapy candidates | Apply once daily; remove weekly with acetone and file/trim loose nail; 24 weeks for fingernails, 48 weeks for toenails | Periungual erythema, local burning/irritation, nail colour change | Weekly acetone-removal regimen is easy to under-adhere to — set expectations up front. Adding this to oral terbinafine has not been shown to improve complete-cure rates over terbinafine alone. |
| Propylene glycol / urea / lactic acid solution Special situation | Nonprescription option for mild distal disease or when prescription therapy is not wanted or accessible | Apply a thin layer to the affected nail and under its free edge once daily; up to 24 weeks | Transient irritation; nail whitening is common | Available without a prescription; cure rates are modest and lower than prescription topical or oral therapy — set expectations accordingly. |
Special Populations
Pregnancy
Onychomycosis is a chronic, nonurgent condition needing many months of treatment — the preferred approach in pregnancy is to delay treatment until after delivery, since controlled safety data in pregnancy are limited for every available agent.[4]
If treatment cannot wait, prefer topical therapy over oral therapy — topical antifungals have minimal systemic absorption and are theoretically low-risk, though human pregnancy safety data remain sparse; use only when the benefit clearly outweighs the uncertainty.
Avoid oral fluconazole in pregnancy — it carries a risk of spontaneous abortion and major malformation. Avoid oral itraconazole — animal studies show fetal teratogenic effects. Oral terbinafine is not currently recommended in pregnancy for this indication, though a more recent systematic review did not identify a significant signal of risk; treat only if a prescriber judges it necessary and cannot wait, pending further confirmatory study.
Breastfeeding
Topical ciclopirox and efinaconazole have limited breastfeeding safety data — use only if benefit outweighs risk. Avoid oral fluconazole, itraconazole, and terbinafine during breastfeeding given limited safety data and known accumulation in breast milk with prolonged courses; this differs from the well-established safety of a short 2-3 week course of fluconazole used for other indications, which is not the same exposure as many weeks of therapy for onychomycosis.
Pediatrics
Onychomycosis is substantially less common in children than adults, mainly because of faster nail growth, less nail trauma, and better peripheral circulation. Confirm the diagnosis mycologically before treating, the same as in adults. Topical therapy is preferred in children since it needs no dose adjustment or laboratory monitoring and has minimal adverse effects — though no topical or oral onychomycosis therapy currently carries a Canadian pediatric indication, so all pediatric use is off-label. Systemic agents (terbinafine, itraconazole) can be used off-label with the same caution around hepatotoxicity and drug interactions as in adults, using the weight-based pediatric dosing in Drug Tables; avoid fluconazole, which is not well studied in this population.
Older adults
Onychomycosis becomes more common with age, and older patients more often have the comorbidities (diabetes, peripheral vascular disease) and polypharmacy that make treatment selection more complex. Favor combination oral-plus-topical therapy, and weigh itraconazole's substantial CYP3A4 interaction burden carefully against this population's typically longer medication list before choosing it over terbinafine.
Hepatic impairment
Pre-existing liver disease raises the stakes of oral antifungal hepatotoxicity — obtain baseline liver function tests and favor topical therapy where severity allows it; if oral therapy is genuinely needed, use it with closer monitoring and a lower threshold to stop at the first sign of hepatotoxicity.
Renal impairment
Dosage adjustment may be needed for some oral antifungals in significant renal impairment — confirm current product-specific guidance before prescribing.
Monitoring & Follow-Up
Resolution of the fungal infection itself takes months, and it can take up to 18 months for the nail's appearance to normalize, especially with poor circulation — some nails never look fully normal even after a true mycological cure. Set this expectation explicitly at the start of treatment.
Baseline and on-treatment liver monitoring for oral antifungals
Obtain baseline liver function tests (ALT, AST) before starting any oral antifungal for onychomycosis.[7]
Repeat liver function tests at 4-6 weeks in patients with an elevated hepatotoxicity risk — pre-existing liver disease, concomitant hepatotoxic medications, heavy alcohol use, or age over 65.[7]
Routine on-treatment liver monitoring is not required for an otherwise healthy patient on standard continuous terbinafine or pulsed itraconazole — clinically significant transaminase elevations on terbinafine are uncommon and are usually asymptomatic and self-limiting — but discuss the small residual risk with every patient and set a low threshold to check labs if any hepatotoxicity symptom develops.[7]
Treatment Failure / Next Step
- Confirm the diagnosis was actually fungal in the first place — repeat KOH microscopy and fungal culture (or add histopathology/PCR if available) rather than assuming the same drug just needs more time; misdiagnosis is a leading cause of apparent treatment failure.
- Confirm adherence to the full prescribed dose and duration, and confirm the nonpharmacologic measures (footwear/sock hygiene, treating concurrent tinea pedis in the patient and household contacts) were actually followed.
- If the diagnosis, adherence, and nonpharmacologic measures are all confirmed but response remains inadequate at the expected endpoint, consider switching drug class — for example, moving from terbinafine to itraconazole if a nondermatophyte mould or yeast is now confirmed, or adding topical therapy to an oral regimen that has been only partially effective.
- For a partial responder, consider extending the treatment duration or repeating a full course under specialist guidance rather than an indefinite open-ended course.
- If infection still persists despite all of the above — confirmed diagnosis, confirmed adherence, optimized nonpharmacologic measures, and an appropriate drug switch or combination trial — refer to dermatology or podiatry. At this point, also revisit with the patient whether continued treatment is still worth pursuing given the real relapse and reinfection rates, rather than defaulting to another course.
Common Errors to Avoid
- Starting an oral or prescription topical antifungal for a dystrophic nail without confirmatory KOH microscopy and/or fungal culture first.
- Using ketoconazole for onychomycosis — it lacks supporting efficacy data and carries a disproportionate hepatotoxicity risk.
- Relying on topical monotherapy for matrix-involved or extensive disease and being surprised when cure rates are low — set expectations by candidacy, not by convenience.
- Telling a patient the nail will look normal as soon as the prescribed course ends — mycological cure comes first, and visible nail-appearance improvement can take many more months, up to about 18, after that.
- Skipping counselling on footwear, sock, and shared-surface hygiene — this is a major driver of the high relapse and reinfection rate, not an optional afterthought.
- Forgetting to treat concurrent tinea pedis in the patient, and to offer testing/treatment to household contacts, leaving an active fungal reservoir in place.
- Assuming any single discoloured, thickened nail is fungal without considering subungual melanoma or squamous cell carcinoma, especially with a pigmented band, ulceration, or bleeding.
- Adding ciclopirox lacquer to oral terbinafine expecting a meaningfully higher complete-cure rate — the combination has not been shown to outperform terbinafine alone.
- Not screening for itraconazole's extensive CYP3A4 drug-interaction list before dispensing, especially in older patients on multiple medications.
- Recommending surgical nail avulsion routinely — it is painful, the regrowing nail can become ingrown or reinfected, and it is specifically hazardous in patients with diabetes given infection and gangrene risk.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses unless a separate pediatric line is given, and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.
Allylamine antifungals
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Terbinafine | Adults, continuous (preferred): 250 mg PO once daily Children 10 to under 20 kg: 62.5 mg PO once daily Children 20-40 kg: 125 mg PO once daily Children over 40 kg: 250 mg PO once daily Duration, fingernails: 6 weeks Duration, toenails: 12 weeks Alternative pulse regimen 1 (adults): 250 mg PO once daily for 4 weeks, then 4 weeks off, then repeat Alternative pulse regimen 2 (adults): 500 mg PO once daily for 1 week, then 3 weeks off, repeated for 3 cycles total | GI upset, headache, transient taste or smell disturbance, rash; rare hepatotoxicity, severe cutaneous reactions, blood dyscrasias | Cimetidine decreases and rifampin increases terbinafine clearance. Terbinafine inhibits CYP2D6, raising levels of cyclosporine, tamoxifen's active metabolite, atomoxetine, bupropion, fluoxetine, paroxetine, tramadol, and tricyclic antidepressants (monitor for toxicity); may reduce the therapeutic effect of codeine. | 1st-line oral agent for dermatophyte onychomycosis — more effective than pulsed itraconazole for dermatophyte disease, with fewer significant interactions than the oral azoles. Obtain baseline liver function tests; repeat at 4-6 weeks in patients with elevated hepatotoxicity risk. |
Azole antifungals
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Itraconazole | Adults, continuous: 200 mg PO once daily Duration (continuous), fingernails: 6 weeks Duration (continuous), toenails: 12 weeks Adults, pulse (preferred): 200 mg PO twice daily for 1 week per month Duration (pulse), fingernails: 2 pulses (8 weeks total) Duration (pulse), toenails: 3 pulses (12 weeks total) Children under 20 kg, pulse: 5 mg/kg PO once daily for 1 week per month Children 20 to under 40 kg, pulse: 100 mg PO once daily for 1 week per month Children 40-50 kg, pulse: 200 mg PO once daily for 1 week per month Children over 50 kg, pulse: 200 mg PO twice daily for 1 week per month | GI upset, headache; rare hearing loss/tinnitus, minor rash/pruritus/urticaria; rare serious or fatal hepatotoxicity, heart failure, Stevens-Johnson syndrome | Potent CYP3A4 inhibitor — avoid, or use with extreme caution and dose adjustment, with alfuzosin, atorvastatin/lovastatin/simvastatin, calcium channel blockers, clarithromycin, cyclosporine, digoxin, dronedarone, eplerenone, ergot derivatives, erythromycin, phosphodiesterase-5 inhibitors, pimozide, quinidine, rivaroxaban, salmeterol, solifenacin, tacrolimus, tamsulosin, and warfarin. H2-receptor antagonists and proton pump inhibitors reduce itraconazole absorption by raising gastric pH. | 1st-line for onychomycosis caused by yeasts or nondermatophyte moulds given its broader spectrum; an alternative to terbinafine for dermatophyte disease. Pulse dosing is preferred over continuous dosing given a lower cumulative interaction/side-effect burden for similar efficacy. Obtain baseline and 4-6 week liver function tests. |
| Fluconazole | Adults: 150 mg PO once weekly until the nail grows out Children: 3-6 mg/kg PO once weekly Duration, fingernails: 3-6 months Duration, toenails: 6-12 months | Nausea, headache, pruritus, facial edema; rare hepatotoxic reactions | Inhibits CYP2C9, CYP2C19, and CYP3A4 — decreases clopidogrel's active metabolite and raises QT-prolongation risk with dronedarone, fluoroquinolones, macrolides, methadone, pimozide, and ziprasidone; increases levels of (monitor for toxicity) alfuzosin, atorvastatin, benzodiazepines, calcium channel blockers, clarithromycin, colchicine, cyclosporine, erythromycin, fentanyl, lovastatin, midazolam, phenytoin, phosphodiesterase-5 inhibitors, simvastatin, solifenacin, sulfonylureas, tacrolimus, and warfarin. | Off-label and lower-efficacy alternative — reserve for patients who cannot tolerate or have a contraindication to terbinafine and itraconazole. |
| Ketoconazole | Use in onychomycosis: Not recommended — do not use | Hepatotoxicity disproportionate to other oral antifungals used for onychomycosis; adrenal suppression at higher exposure | Potent CYP3A4 inhibitor with an interaction profile similar to itraconazole | Not recommended for onychomycosis — insufficient supporting efficacy data and a hepatotoxicity risk that outweighs benefit relative to terbinafine or itraconazole. Listed here to state explicitly that it should not be used for this indication, not as a treatment option. |
Topical antifungals (prescription)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Efinaconazole 10% topical solution | Application: 1 drop once daily to the affected nail, nail bed, undersurface of the nail plate, and surrounding skin (2 drops for the great toenail) Duration, toenails: Up to 48 weeks | Nail discoloration, application-site erythema, vesicles; rare allergic contact dermatitis | Minimal systemic absorption; no clinically established interactions | 1st-line topical agent for mild-to-moderate toenail onychomycosis; fingernail evidence is more limited. No debridement needed — penetrates the intact nail plate directly, and does not build up with repeated daily application. |
| Ciclopirox 8% nail lacquer | Application: Once daily (preferably at bedtime) to the affected nail, nail bed, undersurface of the nail plate, and surrounding skin; remove weekly with acetone and file/trim loose nail material Duration, fingernails: Up to 24 weeks Duration, toenails: Up to 48 weeks | Periungual erythema, localized burning or irritation, nail colour/shape change | Minimal systemic absorption; no clinically established interactions | Alternative topical option for mild-to-moderate onychomycosis, useful for a patient who is a poor candidate for oral therapy. Weekly acetone removal plus filing/trimming of loose nail material is part of the regimen — counsel on this explicitly, since adherence commonly lapses. Adding this to oral terbinafine has not been shown to improve complete-cure rates over terbinafine alone. Flammable — keep away from open flame. |
Nonprescription topical option
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Propylene glycol / urea / lactic acid solution | Application: Apply a thin layer to the affected nail and under its free edge once daily; allow to dry a few minutes before covering Duration: Up to 24 weeks | Transient application-site irritation; nail whitening/opacity is common; rare nail loosening or detachment | Minimal systemic absorption; no clinically established interactions | Nonprescription option, most appropriate for mild distal disease or a patient who prefers to avoid, or cannot access, prescription therapy. Wash excess solution from unaffected skin, including the hands, after each application. Cure rates are modest and lower than prescription topical or oral therapy — set expectations accordingly. |
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.