Griseofulvin

ROCHESTER, MINN. -- Griseofulvin remains the drug of choice in pediatric tinea capitis, Dr. Stella D. Calobrisi said at a dermatology meeting sponsored by the Mayo Foundation.

There are newer, costlier alternatives. But griseofulvin deserves the nod because it is probably the most cost-effective agent, it is available on most formularies, it is extremely well tolerated, no lab testing is needed, and a child-friendly suspension is available, she said.

Moreover, griseofulvin remains the sole agent approved by the Food and Drug Administration for tinea capitis in children, continued Dr. Calobrisi, director of pediatric dermatology at the Mayo Clinic.

The top two causes of treatment failure with this 4-decade-old drug--and she sees this a lot--are underdosing and too brief a course of therapy.

The underdosing problem is exacerbated by woefully out-of-date dosage recommendations in the Physicians' Desk Reference, she said at the meeting, also sponsored by the Minnesota Dermatologic Society.

Dr. Calobrisi starts children off with 20 mg/kg per day griseofulvin microsize. And some recent studies suggest 22-25 mg/kg per day may be even better.

She favors oral suspensions in children when possible. Having the patient also use a selenium sulfide shampoo two or three times per week eliminates spores and boosts the griseofulvin success rate.

Fungal cultures should be obtained at the beginning of treatment and again after it ends (8-12 weeks later) to document clearance.

Side effects are generally of the minor gastrointestinal variety, and Dr. Calobrisi said she tends not to discontinue griseofulvin because of them. The main drug interaction in the pediatric age group is with phenobarbital.

The dermatologist stressed that she considers itraconazole, terbinafine, and fluconazole to be appropriate backup oral agents for use in children. All have excellent safety profiles, although she advises routinely ordering liver function tests and a CBC before and again after concluding therapy with any of the three drugs.

In patients who fail 8-12 weeks of griseofulvin, she typically turns first to 4 continuous weeks of itraconazole (Sporanox). The drug has excellent efficacy against dermatophytes, yeasts, and saprophytes. Like most pediatric dermatologists, she avoids using itraconazole suspension in children because it has been shown to cause pancreatic adenocarcinoma in lab rats at human doses.

"When we use Sporanox, what we've been doing is breaking the capsules and sprinkling the drug on foods such as applesauce and pudding," she explained.

An alternative to continuous therapy with Sporanox is pulse therapy With capsules, this entails giving 5 mg/kg per day for 1 week, followed by a 3-week separation, then an additional one to three pulses as needed, each separated by 3 weeks.

Itraconazole interacts with many other drugs, since it is metabolized by the cytochrome p450 pathway. Probably the most relevant interactions in children are with oral anticonvulsants.

The downside of itraconazole is its expense, particularly when the cost of lab work is added in, Dr. Calobrisi said. Efforts are underway to demonstrate that shorter-course therapy is effective.

Terbinafine (Lamasil) is a good first backup in griseofulvin failures when it's clear the patient is infected with Trichophyton tonsurans. In fact, a case can be made for terbinafine as first-line therapy for tinea capitis in African American children, since their disease is caused most often by T. tonsurans. The drug does not, however, provide good coverage against Microsporum canis.

Dr. Calobrisi prescribes terbinafine for 4 weeks, although some recent small studies suggest 2 weeks is just as effective. Alternatively pulse therapy can be given on a 1-week-on, 2-weeks-off basis for a maximum of three cycles.

Dosing is a single 250-mg tablet per day in patients heavier than 40kg, half a-tablet in children weighing 20-40 kg, and half-a-tablet every other day in smaller children. Trying to quarter these tablets is an exercise in frustration.

Terbinafine has few drug interactions. The most noteworthy is with cimetidine.

Dr. Calobrisi confessed she doesn't use fluconazole (Diflucan) for tinea capitis. "There are better drugs," in her opinion. She does know of colleagues who typically prescribe 6 mg/kg per day for 2-4 weeks. Once-weekly dosing for 4 weeks is under investigation.

A fluconazole suspension is particularly well tolerated by children. But like itraconazole, fluconazole interacts with the p450 system, so the list of drug interactions is lengthy

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