Intermittent short duration therapy with ¯uconazole is effectivefor tinea capitis

A.K.GUPTA, P.ADAM,* S.L.R.HOFSTADER,² C.W.LYNDE,³ P.TABORDA,§

V.TABORDA,§ N.MORAR,¶ N.DLOVA,¶ N.RABOOBEE,¶ N.KONNIKOV,**J.ABOOBAKER¶ AND R.C.SUMMERBELL²²

Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Sunnybrook Site) and

the University of Toronto, Toronto N6K 1L6, Canada

*Division of Dermatology, Department of Medicine, St Michael's Hospital and the University of Toronto, Toronto, Canada²Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Women's College

Site) and the University of Toronto, Toronto, Canada

³Division of Dermatology, Department of Medicine, Toronto Western Hospital and the University of Toronto, Toronto, Canada

§Division of Dermatology, Instituto Lauro S.Lima, SaÄo Paulo, Brazil¶Department of Dermatology, King Edward VII Hospital and the University of Natal, Durban, South Africa

**Department of Dermatology, New England Medical Center, Boston, MA, U.S.A.

²²Ontario Ministry of Health Mycology Laboratory and the Department of Laboratory Medicine and Pathobiology,University of Toronto, Toronto, Canada

Accepted for publication 19 February 1999

Summary We have demonstrated in an open multicentre investigation that oral ¯uconazole 6 mg/kg daily for

2 weeks, followed, if clinically indicated four weeks from the start of therapy, by an extra week oftreatment at the same dosage, may be effective and safe in the treatment of tinea capitis. Of a total of

48 patients, there were 42 evaluable children <18 years old (19 boys, 23 girls; mean age 6´2 years,

range 1´5±16). The causative organisms were Trichophyton tonsurans (38 subjects) and T. violaceum(four). In the 42 evaluable patients, a 2-week course of ¯uconazole was administered in 21, with the

remainder requiring 1 additional week of therapy. At follow-up 12 weeks from the start of therapy,

mycological and clinical cure was recorded in 37 of the 42 evaluable patients (88´1%, 95%con®dence interval 83´1±93´1%). The treatment was well tolerated, with no clinical adverse effects.

This regimen appears to be effective and safe, and is associated with high compliance. The

preliminary results of the investigation need to be evaluated in a larger sample of patients, and intinea capitis caused by zoophilic species.

Key words: ¯uconazole, intermittent therapy, tinea capitis

Fluconazole is a triazole that is used widely to treat

mycoses1,2 (¯uconazole package insert, P®zer Roerig,

New York, U.S.A., February 1997). There are severalregimens in the literature for the treatment of tinea

capitis using ¯uconazole.3±5 However, none of these has

become established as the recommended protocol.

Subjects and methods

In an open, multicentre evaluation, patients with tinea

capitis were treated with ¯uconazole tablets, 6 mg/kg

daily (dose rounded up to nearest 50 mg), for 2 weeks,with an assessment performed 4 weeks from the start of

therapy. If indicated on clinical grounds, an extra week

of treatment at the same dosage was offered to the

patient at this time-point. The protocol was approvedby the Institutional Review Board. The inclusion criteria

were: children >6 months old, tinea capitis present

clinically with positive mycological identi®cation of thecausative organism, no concomitant therapy with

systemic or topical agents, and no topical or oral

antifungal agents for 2 and 4 weeks, respectively, priorto commencement of therapy. Full blood count and liver

function tests were performed only if warranted by

clinical symptoms and signs.Patients were seen in follow-up at weeks 4, 8 and 12

from the start of therapy. Clinical evaluation consisted of

assessing the scalp for scaling, erythema, pruritus,pustules/vesiculation, oedema and nodules, and

British Journal of Dermatology 1999; 141: 304±306.

304 q 1999 British Association of Dermatologists

Correspondence: Aditya K.Gupta.E-mail: agupta@execulink.com

lymphadenopathy. Each feature was rated on a four-point scale: 0, absent; 1, mild; 2, moderate; and 3,

severe. The overall extent of the tinea capitis was

graded as clear, mild, moderate or severe. Mycologicalexamination of the scalp was performed before therapy,

and at weeks 4 and 12 after the start of therapy. An

evaluation of the effectiveness of therapy carried out12 weeks after commencing treatment was graded as:

(i) complete clinical and mycological cure (negative

light microscopy and culture); (ii) mycological curewith few residual symptoms and signs (sum of ratings

of clinical features # 2); (iii) improvement (positive

mycology with substantial clinical improvement ornegative mycology with no clinical improvement); or

(iv) failure. Patients were regarded as being cured if their

evaluation fell in the ®rst two categories. Therapy wasrecorded as ineffective if there was only improvement or

failure.

Results

Forty-eight patients with tinea capitis were evaluated inthis open, multicentre investigation. Six children were

lost to follow-up and have not been included in the

ef®cacy calculation, but were evaluated for safety. The42 evaluable children <18 years old comprised 19 boys,

23 girls; mean age 6´2 years, range 1´5±16; weightrange 8´5±65 kg; three white, two Asian, 37 black. The

organisms isolated from the scalp were Trichophyton

tonsurans (38 patients) and T. violaceum (four).Before therapy, the extent of the tinea capitis was

rated as: mild (eight subjects), moderate (21) and severe

(13). In 21 of the 42 evaluable subjects, clinical curewas recorded when evaluated 4 weeks from the start of

therapy. These patients did not receive extra therapy

and 19 (90%) of the 21 children were consideredclinically and mycologically cured at week 12 from the

start of therapy. Only one of these children had positive

mycology at week 4 (there was generally a 2±4 week lagtime between clinical examination and the availability

of culture results). In 21 of the 42 evaluable children,

an extra week of treatment was given at week 4, basedon the clinical appearance of the scalp. In 10 of the 21

children, mycology was still positive at week 4. In this

group, cure occurred in 18 (86%) of 21 children at week12. Overall, there was cure (clinical and mycological) in

37 of 42 patients (88´1%, 95% con®dence interval

83´1±93´1%) at week 12 from starting treatment.Two patients with kerion were cured following 2 and

3 weeks of ¯uconazole, respectively. Two HIV-positive

girls, each 9 years old, with severe tinea capitis at

baseline, exhibited complete cure at week 12 followinga total of 3 weeks of ¯uconazole. Three of ®ve patients

who were mycological failures required the extra week

of therapy at week 4. The extent of tinea capitis beforetherapy in these ®ve subjects was mild (one patient) and

moderate (four). None of the 42 evaluable patients

complained of a clinical adverse effect. In no instancewas there an adverse effect that required laboratory

monitoring. In the six patients who were lost to follow-

up, ®ve failed to return for the week 4 visit and one forthe week 8 visit. None of these patients reported an

adverse event.

Discussion

The complete cure rate of 88´1% that we observed in 37of 42 evaluable patients without the use of adjunctive

therapy is similar to that given with a protocol using

¯uconazole 6 mg/kg daily for 20 days (mycological curerate 89%, n�9 patients).3 Our protocol reduces the

duration of active therapy in many patients to 2 weeks,

with one-half of the patients requiring no additionaltreatment. The protocol individualizes therapy to the

response exhibited by the patients, attempts to provide

cost-effective treatment and reduces the potential foradverse effects by minimizing the duration and amount

of active therapy. The amount of drug that needs to beadministered could possibly be reduced further by

evaluating the patient at week 6 rather than at week

4, and then deciding whether additional therapy isindicated. The pharmacokinetic data support the use

of both continuous and intermittent ¯uconazole to treat

tinea capitis.6,7 Other protocols using ¯uconazole totreat tinea capitis are once-weekly dosing of 8 mg/kg

per day for 6±8 weeks (n�20 patients)4 and 5 mg/kg

per day for 4 weeks.5

Fluconazole has been reported to be safe in children

6 months±13 years old at doses of 3±12 mg/kg daily8,9

(¯uconazole package insert, P®zer Roerig, New York,U.S.A., February 1997). There were no adverse effects

in this study. The regimen appeared to be effective and

safe, and compliance was high. The preliminary resultsneed to be evaluated in a larger sample of patients, and

in tinea capitis caused by zoophilic species.

Fluconazole is available as an oral suspension insome countries. It is bene®cial that the tablets can be

crushed with no requirement for a fed state to

maximize bioavailability. Another advantage of¯uconazole is that it is already approved in some

countries for the treatment of certain systemic mycoses

in children.

INTERMITTENT FLUCONAZOLE FOR TINEA CAPITIS 305

q 1999 British Association of Dermatologists, British Journal of Dermatology, 141, 304±306

Acknowledgments

This study was supported in part by P®zer.

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306 A.K.GUPTA et al.

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