A double-blind, randomized, comparative trial of itraconazoleversus terbinafine for 2 weeks in tinea capitis

M.JAHANGIR, I.HUSSAIN, M.UL HASAN AND T.S.HAROONDepartment of Dermatology, King Edward Medical College/Mayo Hospital, Lahore, Pakistan

Accepted for publication 3 May 1998

Summary In this randomized, double-blind study, the efficacy and safety of oral itraconazole (n ¼ 28) andterbinafine (n ¼ 27), each given for 2 weeks, was compared in patients with tinea capitis. Trichophy-ton violaceum was the major pathogen in both groups (82·1% and 88·9%, respectively). The finalevaluation at week 12 showed a cure rate of 85·7% and 77·8%, respectively (P>0·05). Adverseevents noted were mild and did not warrant discontinuation of therapy.

Many studies have confirmed the efficacy and safety ofitraconazole and terbinafine in tinea capitis.1–9 Basedon their peculiar pharmacokinetic properties and pre-vious data, it can be presumed that both these drugs willbe effective when given as continuous therapy for2 weeks. To the best of our knowledge, the efficacyand safety profiles of these drugs have not been com-pared in the treatment of tinea capitis, and this studywas planned for this purpose.

Subjects and methods

Subjects of either sex and any age, weighing >10 kgand suffering from mycologically confirmed (culture-positive) tinea capitis were registered in the study.Exclusion criteria were history of allergy to imidazolesor allylamines, use of oral antifungals within 8 weeks ortopical antifungals within 4 weeks before screening,concurrent therapy with rifampicin, phenytoin,digoxin, oral anticoagulants, cyclosporin, astemizoleand terfenadine, psoriasis of the scalp, history of anysystemic illness or abnormal liver and renal functiontests.

After giving informed consent, enrolled patients wererandomized in a double-blind manner to receive eitheritraconazole or terbinafine. Both drugs were givenorally according to the patients’ body weight for aperiod of 2 weeks. The doses of itraconazole and terbi-nafine were, respectively: 50 mg and 62·5 mg for<20 kg; 100 mg and 125 mg for 20–40 kg; 200 mgand 250 mg for >40 kg body weight. During the

screening visit, a detailed medical history was obtained,and a thorough examination was performed. Variousclinical signs and symptoms were rated according to afour-point scale from 0 to 3 (0 ¼ absent, 1 ¼ mild,2 ¼ moderate and 3 ¼ severe). After commencement oftherapy, patients were followed up at weeks 2 (end oftreatment period), 4, 8 and 12. At each visit, a clinicalassessment was made, and material was taken formycological examination. The therapeutic efficacy wasevaluated at week 12. Mycological samples (skin scrap-ings and hair) were subjected to KOH wet mounts andculture on Sabouraud’s dextrose agar containing cyclo-heximide and chloramphenicol. Nutrient agar was usedwhere indicated. The pathogens were identified accord-ing to the macroscopic and microscopic features of thegrown colonies. Blood was tested for biochemical andhaematological profile at baseline and then repeated atthe end of weeks 2 and 4, or more frequently ifwarranted. The assessment of efficacy was based onthe combined evaluation of mycological results and thesum of clinical scores at week 12 according to thefollowing scheme.

Effective therapy included: (i) complete cure: noresidual clinical signs and symptoms except alopeciawith negative mycology (on both microscopy and cul-ture), or (ii) mycological cure: minimal residual signs andsymptoms (sum score < 2) excluding alopecia with nega-tive mycology. Ineffective therapy comprised: (i) improve-ment: positive mycology (either microscopy or culture)with significant (>50%) clinical improvement or negativemycology with no clinical improvement, or (ii) failure: noclinical or mycological improvement. Adverse events wererecorded as volunteered by patients or discovered onphysical examination or laboratory investigations.

British Journal of Dermatology 1998; 139: 672–674.

672 q 1998 British Association of Dermatologists

Correspondence: Dr M.Jahangir, 635-Nishtar Block, Allama IqbalTown, Lahore, Pakistan. E-mail: dderma@paknet1.ptc.pk

Chi-square and Student’s t-tests were used for statis-tical analysis

Results

Of 60 patients enrolled, 55 were evaluable at the end ofthe study. The remaining five dropped out because ofirregular follow-up unrelated to therapy. Twenty-eightwere treated with itraconazole and 27 with terbinafine.The pretreatment parameters in the respective groupswere: mean (6 SD) age, 7·9 6 4·58 years vs.7·8 6 4·58 years; male to female ratio, 1 : 1 vs. 1 : 1·3;and patients <12 years, 27 vs. 26. Trichophyton viola-ceum was the predominant pathogen in both itracona-zole and terbinafine groups, 23 (82·1%) vs. 24 (88·9%).Other isolates included T. tonsurans, 2 (7·1%) vs. 1(3·7%); T. mentagrophytes, 2 (7·1%) vs. 1 (3·7%); andT. verrucosum, 1 (3·7%) vs. 1 (3·7%). No case caused byMicrosporum species was detected.

At the end of week 12, positive mycology had fallenfrom 100% to 14·3% and 22·2% in the itraconazoleand terbinafine groups, respectively (P>0·05). Simi-larly, the mean sum score of clinical signs and symp-toms was reduced by 83·7% in the itraconazole groupand 84·9% in the terbinafine group (P>0·05). After12 weeks, 85·7% and 77·8% patients were consideredto be cured in the itraconazole and terbinafine groups,respectively, as shown in Table 1 (P>0·05). All thefailures in both groups [itraconazole (n ¼ 4) and terbi-nafine (n ¼ 6)] had tinea capitis caused by T. violaceum.Two (7·1%) patients reported with urticaria in theitraconazole group, while fever, body aches and vertigowere seen in one case each (3·7%) in the terbinafinegroup. However, none of the patients showed any sig-nificant alteration in their haematological or biochem-ical profile.

Discussion

Any new therapy for tinea capitis should bring aboutrapid clinical and mycological cure without relapse andpossess fewer side-effects. The results of our studysuggest that both these drugs fulfil the above criteriaequally well. Subjective and objective clinical improve-ment, negative mycology and efficacy at week 12 do notshow any significant difference. These results demon-strate that both drugs are highly effective when givenfor 2 weeks. As T. violaceum was the major pathogen, itappears that 2 weeks of therapy with either itraconazoleor terbinafine is effective in eradicating this infection inmost of the patients. However, all 10 non-respondershad this dermatophyte, suggesting that the duration oftherapy has to be extended beyond 2 weeks in certaincases of T. violaceum infection. Although the number ofcases resulting from other pathogens was small, they dorespond to this short-term therapy with either drug.These results are in accordance with previous data.1–9

As no case attributable to Microsporum species wastreated, it is not possible to deduce how this infectionwould respond to 2 weeks of therapy with either drug.

Both itraconazole and terbinafine are highly lipophi-lic and keratinophilic.10 They persist in the stratumcorneum and hair in high concentrations for 3–4 weeksafter therapy is discontinued. These levels are well abovethe minimum inhibitory concentrations for most ofdermatophytes, and hence sufficient to inhibit fungalgrowth.10 This enables both these drugs to be effectiveas short-term therapy for tinea capitis. Our results showthat both drugs are safe and well tolerated. The fewadverse events noted (itraconazole, n ¼ 2 and terbina-fine, n ¼ 3), were mild and did not warrant discontinua-tion of the therapy. This is also consistent with previousdata.10 Our results suggest that both itraconazole andterbinafine are equally effective, safe and well toleratedas short-term, 2-week therapy for tinea capitis.

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q 1998 British Association of Dermatologists, British Journal of Dermatology, 139, 672–674

Table 1. Comparison of efficacy (at week 12)

Itraconazole (n ¼ 28) Terbinafine (n ¼ 27)

Effective therapy*Complete cure 18 (64·3%) 16 (59·3%)Mycological cure 6 (21·4%) 5 (18·5%)Total 24 (85·7%) 21 (77·8%)

Ineffective therapyImprovement – 2 (7·4%)Failure 4 (14·3%) 4 (14·8%)Total 4 (14·3%) 6 (22·2%)

*P>0·05.

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