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Medication for Onychomycosis

Treatment of onychomycosis depends on the clinical type of the disease, the number of affected nails, and the severity of the case. Most doctors agree that a systemic treatment by oral medications is always required in proximal subungual onychomycosis and in distal lateral subungual onychomycosis involving the lunula region.

White superficial onychomycosis and distal lateral subungual onychomycosis limited to the distal nail can sometimes be treated with topical agents.

A combination of systemic and topical treatment increases the cure rate. Because the rate of recurrence remains high, even with newer agents, the decision to treat should be made with a clear understanding of the cost and risks involved, as well as the risk of recurrence.

Photodynamic therapy and lasers represent the most advanced treatment options.

Topical antifungals

The use of topical agents is limited to cases involving less than half of the distal nail plate or for patients unable to tolerate systemic treatment. Agents include:

  • amorolfine (approved in other countries, but not approve3d by the FDA in the U.S.),
  • ciclopirox olamine 8% nail lacquer solution, and
  • bifonazole/urea (available outside the United States).

Topical treatments alone are generally unable to cure onychomycosis because of insufficient nail plate penetration. Ciclopirox and amorolfine solutions have been reported to penetrate through all nail layers but have low efficacy when used as monotherapy. They may be useful as adjunctive therapy in combination with oral therapy or as prophylaxis to prevent recurrence in patients successfully treated with systemic agents.

Oral therapy

The newer generation of oral antifungal agents (itraconazole and terbinafine) has replaced older therapies in the treatment of onychomycosis. They offer shorter treatment regimens, higher cure rates, and fewer adverse effects.

Fluconazole (not approved by the US Food and Drug Administration for treatment of onychomycosis) offers an alternative to itraconazole and terbinafine. Derivatives of fluconazole may be available soon. The efficacy of the newer antifungal agents lies in their ability to penetrate the nail plate within days of starting therapy. Evidence shows better efficacy with terbinafine than with other oral agents.

To decrease the adverse effects and duration of oral therapy, topical treatments and nail avulsion may be combined with oral antifungal management.

Terbinafine (Lamisil)
Inhibits squalene epoxidase, which decreases ergosterol synthesis, causing fungal cell death. The optimal duration of treatment has not been established. The medication is typically used until symptoms improve.

Standard Dosing

Toenails: 250 mg PO qd for 12 weeks
Fingernails: 250 mg PO qd for 6 weeks
Pulse therapy: 500 mg PO qd for 1 wk/mo for 4 mo (toenails) or 2 mo (fingernails); 250 mg qd for 1 wk q3mo for 4 cycles has also been used

Itraconazole (Sporanox)
Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Standard Dosing
Toenails: 200 mg PO qd for 12 weeks or 200 mg PO bid for 1 week, then 3 weeks without treatment; repeat for 3 pulses
Fingernails: 200 mg PO bid for 1 wk, then 3 wk without treatment, then 200 mg PO bid for 1 additional wk for 2 pulses

Fluconazole (Diflucan)
Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Treatment should continue until infection resolves.

Standard Dosing
Toenails: 150-300 mg PO qwk
Fingernails: 150-300 mg PO qwk

Ciclopirox (Penlac)
Interferes with synthesis of DNA, RNA, and protein by inhibiting transport of essential elements in fungal cells.

Standard Dosing
Apply evenly over entire nail plate and 5 mm of surrounding skin qhs or 8h before washing; if possible, apply to nail bed, hyponychium, and undersurface of nail plate when free of nail bed; do not remove product on daily basis; apply daily over previous coat and remove with alcohol q7d; repeat cycle throughout duration of therapy.

Counter Indications and Risks of Side Effects

All of the oral medications are known to have side effects. This is not an all-inclusive list:

  • Generally not recommended for children, diabetics, patients with liver and kidney problems, pregnant and breastfeeding women, people older than 60 years of age, patients using other medications.
  • Chemical irritation and changes in ocular lens or retina may develop in cases with hepatobiliary dysfunction, neutropenia, and Stevens-Johnson syndrome.
  • Many interactions with other medications and increase in toxicity have been described in the medical literature. Following conditions may occur: rashes, edema, hypoglycemia, increased levels of cyclosporine plasma and digoxin, rhabdomyolysis, cardiac rhythm abnormalities (possibly death). Coadministration may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants and cyclosporine.

Onychomycosis caused by molds, particularly Fusarium species, are often not responsive to systemic therapy.

Recurrence (relapse or reinfection) of onychomycosis is very common, with reported rates ranging from 30-53%.


Surgical approaches to onychomycosis treatment include mechanical, chemical, or surgical nail avulsion.

  • Chemical removal by using a 40-50% urea compound is painless and useful in patients with very thick nails.
  • Removal of the nail plate should be considered an adjunctive treatment in patients undergoing oral therapy.
  • A combination of oral, topical, and surgical therapy can increase efficacy and reduce cost.


Onychomycosis is often accompanied by skin infections. Skin injury adjacent to the nail may allow harmful microorganisms to colonize, thereby increasing the risk of infectious complications. Reports of complications in elderly persons and persons with diabetes include cellulitis, osteomyelitis, sepsis, and tissue necrosis.

Special Concerns

HIV disease: Onychomycosis in patients who are immunocompromised is associated with increased severity and morbidity. Lesions may appear atypical and require more aggressive management compared with the healthy population. Proximal subungual (ie, proximal subungual onychomycosis) involvement is much more prevalent in patients with HIV infection than in those without HIV infection. In this population, white superficial onychomycosis is more commonly caused by T rubrum, rather than T mentagrophytes.

Diabetes: The diabetic foot may lead to serious complications associated with onychomycosis. Peripheral neuropathy and sensory loss may lead to increased trauma without pain in patients with diabetes. Bacterial colonization and vascular insufficiency may exacerbate the problem and may lead to serious sequelae. A clinical guideline summary from the American College of Foot and Ankle Surgeons, Diabetic foot disorders: a clinical practice guideline, may be helpful.

Elderly age: Onychomycosis in elderly people is complicated by diseases (eg, poor vision, arthritis) that prevent optimal foot care. Nail changes are much more common in elderly persons and often involve the fingernails and the toenails. The potential for drug-drug interactions is more evident and must be addressed before initiating oral therapy.

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