Tinea capitis, a fungal infection of the hair follicles of the
head, is the most common dermatophyte infection in children. It can vary in
severity from a seborrheic type to kerion formation. The pathogen responsible
for most t. capitis episodes in the United States is Trichophyton
tonsurans. Other pathogens can also produce tinea capitis, but are less
Topical therapy is not effective, and thus systemic antifungals
are necessary for resolution. Griseofulvin, an antifungal agent that has been
available for more than 40 years, is generally still considered first-line
therapy. However, because of potential resistance to griseofulvin and because
of extended treatment durations with its use, newer agents that have been used
mostly in adults for other fungal infections are attracting the attention of
pediatric clinicians. This months column will review these agents and
their usefulness in the treatment of tinea capitis.
Griseofulvin has been and largely continues to be the standard of
therapy for t. capitis. It works well, it is largely devoid of significant
adverse effects, and clinicians have considerable experience with its use.
Published controlled trials of griseofulvin reveal success rates of 80% to 90%.
Griseofulvin concentrates in skin and contributes to its high efficacy.
Dosing guidelines from the package insert are 7.3 mg/kg/day to 11
mg/kg/day, depending upon the formulation used. Various griseofulvin products
are available (tablets, capsules, suspension) and in two pharmaceutical forms
microsize and ultramicrosize. These dosage forms serve to decrease
particle size and increase surface area of the product to enhance dissolution
in the gastrointestinal (GI) tract, thus promoting absorption.
Griseofulvin should be taken with a fatty meal (eg, peanut butter
or ice cream) to increase absorption, for it is largely insoluble in the
aqueous media of the upper GI tract. The ultramicrosize products (tablets only)
further decrease particle size, increasing absorption, allowing use of a
smaller dose (7.26 mg/kg/day). The clinical benefits of this reduced dose, if
any, are not clear. The liquid form, perhaps most useful to a pediatrician
treating a young child, is composed of the microsize particles. The current
primary literature indicates, however, that many experts are recommending
higher doses 15 mg/kg/day to 25 mg/kg/day (microsize formulation). The
American Academy of Pediatrics 2000 Red Book: Report of the
Committee on Infectious Diseases states that doses of 20 mg/kg/day to 25
mg/kg/day may be necessary.
Treatment durations of 4-6 weeks are usually recommended,
although some experts are recommending that 8-week treatment durations may be
necessary, or that retreatment may be needed in some patients.
Doses and treatment durations have risen because of increases in
treatment failures as noted in several published reports. It is certainly
possible that resistance to griseofulvin is responsible, although this is
speculative, as resistance guidelines have not been well defined or
standardized (eg, as with bacteria and antibiotics) for many fungal organisms.
Generally, griseofulvin continues to be recommended as first-line
therapy for t. capitis, for it is effective and has a good safety record.
Although other drugs have been explored as treatment alternatives, griseofulvin
is the only systemic agent currently approved by the FDA for pediatric t.
capitis treatment. (One must, of course, keep this in perspective, as many
drugs commonly used in children are not officially approved by the FDA for
The most common adverse effects of griseofulvin include headache
(which can diminish with continued use) and GI (eg, nausea/vomiting), and these
are generally infrequent. There is no need to monitor hepatic transaminase
enzymes, as with the newer treatments. Additionally, griseofulvin adversely
interacts with relatively few other drugs. As explained below, some of the
newer agents can interact with numerous other medications. The absorption of
griseofulvin can widely vary (25% to 70% absorption rate), which may also
explain treatment failures. When efficacy is less than desired for a specific
patient, clinicians can consider increasing the dose, as the patient may not be
absorbing the drug well. One should verify that each dose of griseofulvin was
administered with a fatty meal. Because of a long treatment duration, continued
compliance with therapy should be stressed.
Ketoconazole (Nizoral, Janssen), an imidzole antifungal agent, is
approved for use in adults for various fungal infections, including severe,
recalcitrant cutaneous dermatophyte infections unresponsive to griseofulvin.
Package labeling indicates that data with children are limited.
Of the newer antifungals, ketoconazole is the least useful in
children because of its potential to cause hepatotoxicity. Although not common,
hepatotoxicity from ketoconazole use may be fatal. An estimated incidence of
hepatotoxicity occurrence is 1:10,000, although this estimate mostly likely is
higher, as underreporting probably occurs. Several fatal cases have been
reported in children. Because of its potential to inhibit an important enzyme
of the hepatic drug metabolizing cytochrome P450 system (3A4 isoenzyme),
numerous drug interactions exist with ketoconazole use. Because of these
concerns, ketoconazole has essentially no role in the treatment of pediatric t.
PATRICIA TREADWELL, MD
Itraconazole (Sporanox, Janssen), a
trizole antifungal, is not approved for use in t. capitis treatment, nor does
it have any pediatric indications. Pediatric efficacy and pharmacokinetic data
are limited. Itraconzole also inhibits the hepatic drug metabolizing 3A4
isoenzyme and numerous drugs may be affected (eg, midazolam, cyclosporine,
others). The potential for these interactions to occur should always be
verified in patients prescribed itraconzole, by soliciting a drug history of
other concomitant drug therapies the patient may be currently receiving.
Itraconazole use also has been reported to result in hepatotoxicity. Although
generally reversible, some fatalities have occurred. Cases have primarily
occurred in patients with significant concomitant comorbidities.
When itraconazole is prescribed, hepatic transaminases should be
taken at baseline and during therapy (eg, at 2-3 weeks). Patients should be
told about symptoms of potential hepatoxicity (eg, jaundiced appearance, dark
urine, anorexia and malaise). More common adverse effects include nausea and
vomiting, although they are not usually limiting.
Fluconazole (Diflucan, Pfizer), a triazole antifungal, is
indicated for use in children (>6 months) for oropharyngeal
candidiasis (and may be useful for other indications), but is not approved for
t. capitis. Similar to itraconazole, fluconazole inhibits the hepatic
cytochrome P450 drug metabolizing system (3A4), resulting in the potential for
numerous drug-drug interactions (eg, midazolam, cyclosporine, phenytoin,
The patients other concomitant drug therapies should be
reviewed prior to fluconazole use. Patients should be counseled on the
potential for these interactions to occur, if any new therapies are begun while
fluconazole is administered. The hepatotoxicity profile of fluconazole is not
unlike itraconazole, in that this effect is uncommon, and is most likely to
occur in patients with significant comorbidities. Fatalities have also been
reported. Hepatic transaminase and clinical monitoring should proceed as with
itraconazole. GI adverse effects (nausea, vomiting) are more common, but most
are usually mild. Fluconazole is available as a liquid formulation
(orange-flavored, in two concentrations).
PATRICIA TREADWELL, MD
Terbinafine (Lamisil, Novartis), an
allyamine agent, is approved for onychomycosis of the fingers or toes. It has
no pediatric labeling, although some pediatric pharmacokinetic studies have
been published. A potential benefit of terbinafine includes a shorter treatment
duration 2-4 weeks vs. 4-6 weeks for fluconazole and itraconazole.
Terbinafine may rarely result in hepatobiliary dysfunction, or cholestatic
hepatitis. It is generally recommended that monitoring of hepatic transaminases
proceed with treatment courses of 6 weeks or longer, which is greater than the
2-4 week duration recommended for t. capitis treatment. Adverse effects most
common with terbinafine therapy, although usually mild, include mainly
gastrointestinal effects. Terbinafine does not exhibit the degree of potential
drug interactions as do itraconazole and fluconazole. However, because it does
interact with the hepatic cytochrome P450 system, concomitant drug therapies of
the patient and their potential for interaction should be reviewed prior to
use. Unlike itraconazole or fluconazole, terbinafine is not available as an
As stated above, griseofulvin is effective for the treatment of
pediatric t. capitis and is generally considered first-line therapy. Published
controlled trials indicate 80% to 90% efficacy. However, recent reports suggest
efficacy rates that are significantly lower. Whether this is secondary to
fungal resistance or other factors is not yet clear. When griseofulvin is used,
clinicians should consider prescribing higher doses (see table), as is
currently recommended by some experts. The newer agents described above have
not been well studied for t. capitis treatment, although limited data for this
use and data on their use in other fungal infections, together with their
pharmacokinetic advantages of good distribution and sustained concentration at
the site of infection, suggest that their role may be important. The 2000
Red Book states that itraconzole, fluconazole and terbinafine are all
effective therapies for t. capitis.
Griseofulvin should continue to be first-line therapy for
pediatric t. capitis. Because of fungal resistance, it is reasonable to begin
therapy with doses higher than stated in the package labeling. It is also
reasonable to extended treatment durations to 6-8 weeks.
Griseofulvin has a good safety profile, which is advantageous
when compared with the adverse effect profiles of the newer agents. When used,
patients should be counseled about administration of griseofulvin with a fatty
meal and the importance of compliance with the extended treatment duration. The
newer agents should be reserved for patients not adequately responding to
griseofulvin, for even though they may be as or more effective than
griseofulvin, their relative lack of pediatric experience, potential for
significant hepatic toxicity, and drug-drug interactions are reason for
cautious use. Clinicians should also consider obtaining cultures of infecting
pathogens, for sensitivities of the various fungi to the antifungal agents
For more information:
- Elewski BE. Tinea capitis: a current perspective.
Journal of the American Academy of Dermatology. 2000;42:1-20.
- Abdel-Rahman SM. Response to initial griseofulvin therapy in
pediatric patients with tinea capitis. Annals of Pharmacotherapy.
- Caceres-Rios H. Comparison of terbinafine and griseofulvin
in the treatment of tinea capitis. Journal of the American Academy of
- Abdel-Rahman SM. Oral terbinafine: a new antifungal agent.
Annals of Pharmacotherapy. 1997;31:445-456.