Which medications in the drug class Antifungal agents are used in the treatment of Tinea Capitis?

Updated: Feb 21, 2020
  • Author: Marc Zachary Handler, MD; Chief Editor: Dirk M Elston, MD  more...
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Answer

Antifungal agents

The mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Griseofulvin (Fulvicin)

Griseofulvin is an antibiotic derived from a Penicillium species that is deposited in the keratin precursor cells that are replaced gradually by noninfected tissue. As a result, new keratin becomes highly resistant to fungal invasions. It is active against dermatophytes but not against yeasts or bacteria. Resistant strains of dermatophytes are rare. In its fine particle form, it is absorbed readily from the gut, and absorption is enhanced when fatty food is taken simultaneously. Griseofulvin accumulates in the keratin of the stratum corneum, hair, and nails. It has a long record of safety, but newer regimens may prove more cost effective.

Itraconazole (Sporanox)

Itraconazole is one of two triazole antimycotic medications with the potential for treatment of superficial dermatophyte infections in the pediatric population. Since it is poorly water soluble, it should be taken with a fatty meal to improve absorption. Most of the  absorbed itraconazole is bound to plasma albumin. Because of its lipophilic property, it is found in highest concentrations in fat, omentum, skin, nails, and vaginal and cervical tissues. Antimycotically significant concentrations may remain in skin up to 4 weeks after cessation of medication.

Hydroxyitraconazole is one of 30 metabolites active pharmacologically. The terminal elimination half-life of itraconazole is 20-60 hours, which indicates that steady-state concentrations are reached only after at least 2 weeks of daily administration. Large biliary excretion of itraconazole and its metabolites occurs because of their large molecular sizes and high molecular weights. They are excreted 65% in feces and 35% in urine. No indication exists for dosage adjustment for impaired hepatic and renal functions. Itraconazole has significantly greater selectivity for inhibiting fungal enzymes than does ketoconazole.

The results of several clinical trials indicated that itraconazole is a safe and effective alternative to griseofulvin-failed cases. Itraconazole has a slightly higher cure rate in children with tinea capitis infection caused by T violaceum, compared with treatment with terbinafine. The treatment duration is 2 weeks. In children with T tonsurans infection treated with 1-3 pulses of itraconazole, a 100% cure rate has been reported by Gupta et al in a small series. The pulse schedule was itraconazole 5 mg/kg/d for 1 week, then 2 weeks with no drug, followed by 1 week with medication. When a third pulse was required, 3 weeks elapsed between the second and third drug treatments.

Ketoconazole (Nizoral)

Many safer alternatives are available. Ketoconazole is rarely used to treat tinea capitis. It is a broad-spectrum synthetic antifungal compound of the azole group. When orally administered, it is active against anthropophilic dermatophytes. It is hydrophilic and high concentrations of the drug develop within the skin, making it potentially beneficial for treating superficial dermatophytosis. Delivery of this drug to the skin is accomplished through normal blood circulation and sweat. Some excretion occurs into the sebum and epidermal basal layer. In the presence of normal gastric acidity, it is well absorbed, and peak plasma concentrations are achieved in 3-4 days. Of the drug, 99% is bound to plasma proteins.

Ketoconazole is extensively metabolized through oxidation and degradation of the imidazole ring, O-dealkylation, oxidative degradation of the piperazine ring, and aromatic hydroxylation. Untransformed ketoconazole is the only active antifungal compound. None of the metabolites possesses therapeutic activity.

Despite active metabolism, ketoconazole is excreted in bile and eliminated unchanged. Dosage adjustment is not required in patients with impaired renal function in view of the rapid metabolism and active biliary excretion.

Fluconazole (Diflucan)

Fluconazole is a triazole compound that is relatively water soluble and well absorbed upon ingestion. Peak plasma concentration is achieved within 1-2 hours after oral administration. The drug is distributed widely to body tissues, and fluids free without binding to plasma proteins. The drug has a long half-life of 22-30 hours in adults, and steady-state levels are reached within 6-10 days after initiation of treatment. Most of the drug is excreted unchanged in urine with little hepatic metabolism. It is eliminated slower from skin than from plasma, which contributes therapeutic benefits against superficial dermatophytosis, even after the dosage has been discontinued. Dosage adjustment is required for patients with renal impairment, since drug is eliminated primarily by the kidneys.

More dosing regimen studies are needed. It is available in orange flavor oral suspension as 10-40 mg/mL.

Terbinafine (Lamisil)

Terbinafine is an allylamine with antifungal properties. It is well absorbed upon oral administration. The peak plasma concentration is reached in approximately 2 hours. The drug has strong plasma protein binding. It has a large lymphatic distribution and is associated with chylomicrons. Preferential uptake into fat results in relatively high concentrations in the skin. Concentration within the stratum corneum reaches 75 times that of plasma concentration during first 2 weeks of therapy. Antifungal activity remains in the skin for 2 months after the plasma concentration has depleted, following cessation of medication. Fifteen inactive metabolites following ingestion have been identified. Terbinafine is metabolized through N -demethylation and aromatic ring oxidation. Most metabolites are eliminated by the kidneys; therefore, a dosage adjustment is indicated in patients with renal or hepatic dysfunction.

Compared with itraconazole, terbinafine has a slightly lower cure rate; 4 weeks of treatment with terbinafine is reported as effective as 8 weeks of griseofulvin therapy.

High cure rates of fungal infections in children are reported.


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