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Oral Antifungals at a Glance
  • Indicated for extensive fungal skin infections, tinea pedis, onychomycosis, and tinea capitis.
  • Preventive therapy for the immunosuppressed.
  • Major classes of antifungal medications used in outpatient settings are the allylamines (terbinafine), triazoles (itraconazole, fluconazole) and imidazoles (ketoconazole), griseofulvin, polyenes (nystatin, amphotericin B), and ciclopirox olamine.
  • Speciation of fungal infections can be important in defining length of treatment and choosing the appropriate medication.

Oral antifungal agents are widely and frequently used for the treatment of fungal infections of the skin, nails, and mucous membranes.1 This chapter summarizes the four most widely used oral antifungal agents in dermatology: (1) terbinafine, (2) itraconazole, (3) fluconazole, and (4) griseofulvin.

Terbinafine hydrochloride is a topical and oral antimycotic agent that belongs to the family of compounds known as the allylamines. Naftifine, a topical antifungal agent, also belongs to this class. All allylamine derivatives possess a tertiary allylamine, a structural component crucial for antifungal activity (Fig. 232-1).2 In vitro, terbinafine is highly active against dermatophytes but less active against molds, dimorphic fungi, and yeasts.2

Figure 232-1

Structures of selected oral antifungal agents.

Mechanism of Action

Terbinafine inhibits the enzyme squalene epoxidase in the fungal cell membrane, thereby blocking the biosynthesis of ergosterol (Fig. 232-2).3 Squalene epoxidase, a complex, microsomal noncytochrome P450 enzyme, catalyzes the first enzymatic step of ergosterol synthesis: the conversion of squalene into squalene epoxide. Consequently, terbinafine causes an abnormal intracellular accumulation of squalene and a deficiency in ergosterol.4 In-vitro accumulation of squalene accounts for the drug's fungicidal activity by weakening the cell membrane, while deficiency of ergosterol is associated with the drug's fungistatic activity, as ergosterol is a component of fungal membranes required for normal growth.4

Figure 232-2

Sites of action of terbinafine and the azole antifungals.


Terbinafine is well absorbed from the gastrointestinal tract, mostly in chylomicrons. The distribution half-life is 1.5 hours, and the elimination half-life is 22 hours.5 Terbinafine is highly lipophilic and keratophilic in nature and, therefore, is widely distributed upon absorption throughout skin and adipose tissue. Terbinafine is extensively biotransformed by the liver through oxidation by CYP2D6. More than 80% of the drug is excreted in urine; the rest is eliminated with feces.6


The US Food and Drug Administration has approved terbinafine tablets for the treatment of onychomycosis due to dermatophytes. Terbinafine oral granules are approved for the treatment of tinea capitis in patients over 4 years old. Terbinafine also has clinically proven efficacy for select cases of tinea corporis, tinea pedis, or tinea cruris that are widespread, severe, or resistant to topical treatment (...

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