Itraconazole Pulse Research Articles

Tinea capitis: an overview with emphasis on management.

Tinea capitis is perhaps the most common mycotic infection in children. In North America the epidemiology of tinea capitis has changed so that Trichophyton tonsurans now predominates over Micro-sporum audouinii. With this transition the utility of the Wood's light for diagnosis has been reduced since T. tonsurans infection is Wood's light negative. Griseofulvin has been the mainstay of therapy for the last 40 years. The newer antifungal agents-itraconazole, terbinafine, and fluconazole-appear to be effective and safe for the treatment of tinea capitis. When tinea capitis is due to T. tonsurans or other endothrix species the following regimens have been used: itraconazole continuous regimen (5 mg/kg/day for 4 weeks), itraconazole pulse regimen with capsules (5 mg/kg/day for 1 week plus 1-3 pulses 3 weeks apart), and itraconazole pulse regimen with oral solution (3 mg/kg/day for 1 week plus 1-3 pulses 3 weeks apart). With terbinafine tablets the continuous regimen (>40 kg body weight, 250 mg/day; 20-40 kg, 125 mg/day; and <20 kg, 125 mg/day) is given for 2 to 4 weeks. Fluconazole tablets or oral suspension (6 mg/kg/day) were administered for 20 days in one trial. Another possibility may be 6 mg/kg/day for 2 weeks and evaluating the scalp 4 weeks later. An extra week of therapy (6 mg/kg/day) can be administered if clinically indicated at that time. A once-weekly regimen may also be effective. When ectothrix organisms (e.g., Microsporum canis) are present, a longer duration of therapy may be required. The data suggest that the newer agents are effective, safe with few adverse effects, and have a high benefit:risk ratio. It remains to be seen to what extent griseofulvin will be superseded for the treatment of tinea capitis. Adjunctive therapies may help decrease the risk of infection to other individuals. Appropriate measures should be taken to reduce the possibility of reinfection.

Mitogen-induced response and flow cytometric analysys of lymphocyte subsets in patients with onychmycosis treatment using pulses of itraconazole

Mitogen-induced response and flow cytometric analysys of lymphocyte subsets in patients with onychmycosis treatment using pulses of itraconazole

Evaluation of certain neutrophil functions and receptor expression in patients with onychomycosis treatment pulses of itraconazole

Evaluation of certain neutrophil functions and receptor expression in patients with onychomycosis treatment pulses of itraconazole

Update on the safety of itraconazole pulse therapy in onychomycosis

Update on the safety of itraconazole pulse therapy in onychomycosis

Efficacy and safety of itraconazole pulse therapy: Brazilian multicentric study on toenail onychomycosis caused by dermatophytes

AbstractBackgroundItraconazole is a large spectrum triazole with known efficacy in both continuous and pulse therapy for various mycoses.ObjectivesEvaluate the efficacy and tolerability of itraconazole pulse therapy for onychomycosis of the toenails due to dermatophytes, in a prospective, open, non‐comparative and multicentric investigation.Patients and methodsThe trial was completed by 72 patients of an initial total of 89. Treatment consisted of four cycles of itraconazole, 200 mg twice a day, for seven consecutive days each month. Patients were evaluated clinically, mycologically and biochemically before, during and at the end of the investigation, and were divided into two groups according to the measure of normal portion of the most affected nail (target nail), as follows: Group 1: 0–5.9 mm; and Group 2: more than 6 mm.ResultsImprovement was satisfactory and progressive. Results were statistically significant, when comparing the three moments. of the study: pre‐treatment, end of therapy (fourth month) and follow‐up (ninth month) in both groups.ConclusionsItraconazole pulse therapy was efficient and safe for the treatment of onychomycosis caused by dermatophytes, although a much higher daily dosage than the known continuous administration was used. Group 1, with nails initially more extensively affected, had a more evident improvement, by the mean variation in millimeters of normal portion of the target nail. This group showed a very satisfactory response, although not reaching total cure, thus demonstrating the great importance of early treatment of this disease. A residual therapeutic effect is maintained even after suspension of the drug. Group 2 obtained better total cure rates, and four pulses were, in general, sufficient, whereas more cycles would have been beneficial for the Group 1 patients with more extensive involvement.

Efficacy and safety of itraconazole pulse therapy: Brazilian multicentric study on toenail onychomycosis caused by dermatophytes

Background Itraconazole is a large spectrum triazole with known efficacy in both continuous and pulse therapy for various mycoses.Objectives Evaluate the efficacy and tolerability of itraconazole pulse therapy for onychomycosis of the toenails due to dermatophytes, in a prospective, open, non-comparative and multicentric investigation.Patients and methods The trial was completed by 72 patients of an initial total of 89. Treatment consisted of four cycles of itraconazole, 200 mg twice a day, for seven consecutive days each month. Patients were evaluated clinically, mycologically and biochemically before, during and at the end of the investigation, and were divided into two groups according to the measure of normal portion of the most affected nail (target nail), as follows: Group 1: 0–5.9 mm; and Group 2: more than 6 mm.Results Improvement was satisfactory and progressive. Results were statistically significant, when comparing the three moments of the study: pre-treatment, end of therapy (fourth month) and follow-up (ninth month) in both groups.Conclusions Itraconazole pulse therapy was efficient and safe for the treatment of onychomycosis caused by dermatophytes, although a much higher daily dosage than the known continuous administration was used. Group 1, with nails initially more extensively affected, had a more evident improvement, by the mean variation in millimeters of normal portion of the target nail. This group showed a very satisfactory response, although not reaching total cure, thus demonstrating the great importance of early treatment of this disease. A residual therapeutic effect is maintained even after suspension of the drug. Group 2 obtained better total cure rates, and four pulses were, in general, sufficient, whereas more cycles would have been beneficial for the Group 1 patients with more extensive involvement.

An analysis of the efficacy, safety, and tolerability of terbinafine versus pulsed itraconazole in the treatment of toenail onychomycosis

An analysis of the efficacy, safety, and tolerability of terbinafine versus pulsed itraconazole in the treatment of toenail onychomycosis

Treatment of tinea capitis with itraconazole capsule pulse therapy

Background: The number of newly diagnosed cases of tinea capitis in children appears to be on the rise, particularly in urban centers. Objective: The purpose of this study was to assess the effectiveness, safety, and compliance of itraconazole pulse therapy for tinea capitis. Methods: Fifty subjects (48 children [less than 18 years of age] and 2 adults) with tinea capitis were treated with pulse itraconazole in a multicenter evaluation. Each pulse lasted 1 week, with 2 weeks between the first two pulses and 3 weeks between the second and third pulses. The decision to administer a second or third pulse was determined by the response of the subject at the time that the next pulse was due. During the 1-week pulse of active therapy, itraconazole (5 mg/kg/day) was dosed as follows: more than 40 kg, 200 mg per day (two capsules per day); 20 to 40 kg, 100 mg per day (one capsule per day); and 10 to 19 kg, 50 mg per day (one half of a capsule per day). The duration of the study was 12 weeks with mycologic evaluation at this time. Subjects who were classified as treatment failures at 12 weeks after the start of therapy were given the option of receiving an additional 1-week pulse of active therapy, with 3 weeks between successive pulses. Results: The causative organisms were Trichophyton tonsurans (41 subjects), T. violaceum (7), T. soudanense (1), and T. rubrum (1). Thirteen subjects were lost to follow-up, with 37 subjects (35 children and 2 adults) available for evaluation 12 weeks after the start of therapy. At this time, cure (clinical and mycologic) was observed in 30 (81%) of 37 subjects. When the tinea capitis was mild, cure was obtained after one pulse in two subjects and after two pulses in five subjects. With tinea capitis of moderate extent, complete cure was obtained after one pulse in one subject, two pulses in eight subjects, and after three pulses in seven subjects. When tinea capitis was severe, two and three pulses produced complete cure in one and six subjects, respectively. Of the seven subjects whose conditions failed to respond (three subjects with moderate disease and four subjects with severe disease), five subjects chose to receive extra itraconazole. Clinical and mycologic cure was observed after four pulses in four subjects and after five pulses in one subject. There were no associated clinical adverse effects with itraconazole therapy. Conclusion: With tinea capitis, itraconazole pulse therapy is effective and safe and is associated with high compliance. The pulse regimen enables the duration of treatment to be individualized, according to the extent of disease and its rate of resolution. (J Am Acad Dermatol 1998;39:216-9.)

Itraconazole Pulse Therapy for Tinea Capitis: A Novel Treatment Schedule

Abstract: Itraconazole 5 mg/kg/day given as pulse therapy, each of 1 week duration, for 1 to 3 pulses appears to be an effective and safe method of treating tinea capitis. The number of pulses of therapy may depend upon several factors, including the severity of disease and area of involvement. Controlled studies are needed to determine the number of pulses of itraconazole required to treat tinea capitis.

Itraconazole for the treatment of onychomycosis.

The broad spectrum of activity of itraconazole in vitro manifests itself clinically with the drug being effective for the treatment of onychomycosis caused by dermatophytes, Candida and some non-dermatophyte molds. The pharmacokinetics of itraconazole in the nail results in drug remaining at therapeutic levels for 6-9 months after completion of therapy. An overview of studies where continuous or pulse itraconazole therapy has been used in the treatment of fingernail and toenail onychomycosis. Following continuous therapy at 200 mg/day for 3 months for toenail onychomycosis (n = 1741), the rates of clinical cure, clinical response and mycologic cure were: (meta-average +/- 95% standard error (SE)), 52 +/- 9%, 86 +/- 2%, and 74 +/- 3%, respectively, at follow-up 12 months following start of therapy. In fingernail onychomycosis (n = 211), the duration of therapy was 6 weeks and the corresponding efficacy rates at follow-up, 9 months after start of therapy, were meta-average (+/- S.E.) 82 +/- 5%, 90 +/- 2%, and 86 +/- 3%, respectively. In toenail onychomycosis treated with 3 pulses of therapy (n = 1389), the clinical response, clinical cure and mycologic cure were observed in meta-average (+/- S.E.) 58 +/- 10%, 82 +/- 3%, and 77 +/- 5% patients, respectively, at follow-up 12 months after the start of therapy. In fingernail onychomycosis treated with 2 pulses of therapy (n = 210), at follow-up 9 months after the start of therapy, the corresponding efficacy rates were meta-average (+/- S.E.) 78 +/- 10%, 89 +/- 6%, and 87 +/- 8%, respectively. Both the continuous and pulse therapy regimens are safe with few adverse effects. Compared to continuous therapy, the pulse regimen has an improved adverse-effects profile, is more cost-effective, and is preferred by many patients.

Current issues in onychomycosis.

To review the epidemiology, mycology, clinical features and diagnosis, current pharmacotherapy, and pharmacoeconomics of onychomycosis. We conducted a MEDLINE search from 1966 to May 1997. References from these articles, manufacturers of the discussed antimycotics, and relevant abstracts from recent dermatology conferences were used to collect pertinent data. Data were obtained from published controlled studies and case reports. In the pharmacotherapy section, the most weight was placed on fully reported, randomized, controlled comparative trials, but abstracts and case series were included when well-controlled studies were unavailable. Onychomycosis is a common nail disorder that has a substantial impact on patients' quality of life. It is most commonly caused by dermatophytes, but yeasts and molds can also be involved. Diagnosis is made through clinical presentation, potassium hydroxide preparations, and culture of tissue/nail samples. Griseofulvin was the drug of choice for many years, but its low cure rates and the development of newer, more effective drugs made it fall out of favor. Current therapeutic alternatives include fluconazole, itraconazole, and terbinafine. Data on the use of fluconazole are limited to case series and reports. Continuous dosing of itraconazole and terbinafine are well-proven therapies. New data are becoming available on the use of pulse itraconazole dosing, which has recently been approved by the Food and Drug Administration for fingernail infections. These drugs are well tolerated, but attention to drug interactions is necessary with the azoles. Currently, continuous terbinafine appears to be the most cost-effective drug for dermatophyte onychomycosis.

Relapses of Onychomycosis after Successful Treatment with Systemic Antifungals: A Three-Year Follow-Up

Background: Data about relapses of onychomycosis after treatment with the new systemic antifungals vary among the different studies, with figures ranging from 3 to 20% for terbinafine and from 21 to 27% for itraconazole, depending on the follow-up duration. Objective: To determine the prevalence of relapses of onychomycosis cured by terbinafine compared with that of onychomycosis cured by itraconazole. Methods: We followed up 47 patients whose toenail onychomycosis had been mycologically cured in an open randomized study comparing intermittent itraconazole treatment with continuous terbinafine treatment and intermittent terbinafine therapy. Patients were examined every 3 months for up to 3 years after the end of therapy. At each visit clinical and mycologic (direct microscopy and cultures) evaluations were performed. Results: Eight of the 36 patients (22.2%) who completed the study had a relapse of onychomycosis during the follow-up period, including 2 patients of the terbinafine 250 mg group, 2 patients of the terbinafine 500 mg group and 4 patients in the itraconazole 400 mg group. As the original infection, the relapse was caused in all cases by Trichophyton rubrum. Conclusions: This study shows that 22.2% of patients with onychomycosis successfully treated with systemic antifungals experienced a relapse. The relapse rate increased from 8.3% at month 12 to 19.4% at month 24 and to 22.2% at month 36. Relapses were more common in patients treated with pulse itraconazole (4/11) than in patients treated with continuous (2/12) or intermittent (2/13) terbinafine. Statistical analysis did not reveal any significant difference between relapse rates in the three groups.

Itraconazole in the Treatment of Onychomycosis: A Double-Blind Comparison with Miconazole

Background: In recent years, itraconazole pulse therapy for onychomycosis has been developed [three 1-week pulses with itraconazole 400 (2 × 200) mg daily every month]. This has proved an effective and safe regimen which requires only 50% of the medication used for continuous dosing schedules. Parallel to the development of the new dosage schedule, additional studies were conducted to further document the safety and efficacy of itraconazole 200 mg once daily for 3 months to treat onychomycosis. Objective: To compare the safety of itraconazole 200 mg once daily for 3 months, with or without itraconazole 200 mg once weekly for a further 3 months, with that of miconazole cream twice daily for 6 months, in the treatment of onychomycosis. Treatment efficacy was compared as a secondary objective. Methods: In this multicenter, double-blind study, patients were randomized to receive itraconazole 200 mg once daily for 3 months followed by either itraconazole 200 mg once weekly for 3 months (ITR-ITR group, n = 599) or oral placebo once weekly for 3 months (ITR-PLAC group, n = 613), or to receive miconazole cream twice daily for 6 months (MIC-MIC group, n = 396). The primary variable was elevation of alanine aminotransferase (ALT) concentration above 50 U/l. Results: Overall incidence of elevation of ALT concentration above 50 U/l, adverse events and rate of withdrawal because of adverse events were low and similar in the three treatment groups. Efficacy was significantly greater in the ITR groups than the MIC-MIC group. Conclusion: Itraconazole and miconazole were well tolerated and had no significant effect on liver function, but itraconazole was significantly more effective.

Itraconazole pulse therapy for onychomycosis and dermatomycoses: An overview

Background: Itraconazole is a broad-spectrum antifungal agent that has been used to treat dermatomycosis and onychomycosis using continuous therapy. More recently the drug has been used as pulse dosing. Objective: Our purpose was to review the studies in which itraconazole pulse therapy (PT) has been administered in the management of dermatomycoses. Results: For tinea pedis and manuum, the recommended dosage is itraconazole 200 mg twice daily for 1 week ( n = 220). A clinical response and mycologic cure rate of 90% ± 4% and 76% ± 6%, respectively, has been obtained. For tinea corporis/cruris, itraconazole 200 mg/day for 1 week ( n = 354) resulted in a clinical response and mycologic cure rate of 90% ± 4% and 77% ± 6%, respectively. When three pulses of itraconazole are used to treat toenail onychomycosis ( n = 1389), the clinical cure rate, clinical response, and mycologic cure rate at follow-up 12 months after the start of therapy were 58% ± 10%, 82% ± 3%, and 77% ± 5%, respectively. With two pulses for onychomycosis of the fingernails, the clinical cure rate, clinical response, and mycologic cure rate at follow-up, 9 months after the start of therapy, were 78% ± 10%, 89% ± 6%, and 87% ± 8%, respectively. Conclusion: Itraconazole PT is effective and safe in the treatment of tinea pedis/manuum, tinea corporis/cruris, and onychomycosis. (J Am Acad Dermatol 1997;37:969-74.)

P361 Two cases of the yellow nail syndrome successfully treated with pulses of itraconazole

P361 Two cases of the yellow nail syndrome successfully treated with pulses of itraconazole

A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe–nail onychomycosis

A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe–nail onychomycosis

A multicenter, placebo-controlled, double-blind study of intermittent therapy with itraconazole for the treatment of onychomycosis of the fingernail

Background: Onychomycosis is the most frequent cause of nail disease and represents 30% of all mycotic infections of the skin. Objective: Our purpose was to compare the effectiveness and tolerability of intermittent dosing of itraconazole ("pulse therapy") with placebo in fingernail onychomycosis. Methods: Seventy-three patients with clinically and mycologically diagnosed fingernailonychomycosis were randomly selected to receive itraconazole, 200 mg twice daily, or placebo for the first week of each month for 2 consecutive months; patients were observed for 19 weeks. Seventy-one patients received the study medication and were included in the safety analysis. Efficacy of treatment was evaluated in 46 patients. Results: A significantly greater proportion of itraconazole-treated patients than placebo-treated patients achieved clinical success (77% vs 0%), mycologic success (73% vs 13%), and overall success (68% vs 0%). No itraconazole-treated patient had a clinical or mycologic relapse during the follow-up period. Ten itraconazole-treated patients (28%) and nine placebo-treated patients (26%) had adverse events. Three patients discontinued treatment for safety reasons. Conclusion: Pulse therapy with itraconazole for 2 consecutive months produces significantly greater clinical, mycologic, and overall success than placebo. Short-term itraconazole pulse therapy for fingernail onychomycosis is effective and well tolerated. (J Am Acad Dermatol 1997;36:231-5.)

A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe-nail onychomycosis

In this multicentre, double-blind, parallel group study, we evaluated the efficacy and safety of continuous treatment with itraconazole, 200 mg daily for 3 months, in comparison with itraconazole pulse therapy, 400 mg daily 1 week per month for 3 months, in the treatment of toe-nail onychomycosis. The study included 129 patients with distal subungual onychomycosis of the toe-nails, confirmed by microscopy and positive for dermatophyte culture; 65 received continuous treatment and 64 received pulse therapy. Patients were followed up for 9 months after treatment. After 12 months, there were 62 evaluable patients in the continuous group and 59 evaluable patients in the pulse group. The clinical response (i.e. the size of the affected area and the progress of the infection) and mycological cure (i.e. negative results on microscopy and culture) were the main outcome measures. A clinical response was defined as a cure or a marked improvement. Clinical response rates were 69%, in the continuous group, and 81% in the pulse group at month 12; the corresponding mycological cure rates were 66 and 69%. A better improvement in signs and symptoms was noted in the pulse group. Six patients were withdrawn from treatment because of adverse events, not all of which were thought to be drug-related. There were no clinically relevant laboratory abnormalities. We conclude that both regimens are effective, safe and well tolerated. The superiority of one treatment over the other was not established, but the results tended to favour pulse therapy. Equivalence testing confirmed that pulse therapy was at least equivalent to continuous treatment.

Onychomycosis due to Scopulariopsis brevicaulis: clinical features and response to systemic antifungals.

Six cases of Scopulariopsis onychomycosis, including four patients with onychomycosis exclusively caused by Scopulariopsis brevicaulis and two patients with a mixed nail infection (S. brevicaulis + Tricophyton rubrum and S. brevicaulis + T. interdigitale), are reported. Four patients presented with a typical distal subungual onychomycosis characterized by subungual hyperkeratosis and onycholysis of the distal nail plate. In two patients, Scopulariopsis infection produced a total dystrophic onychomycosis associated with painful periungual inflammation. Three patients were treated with four pulses of itraconazole, 400 mg daily for 1 week a month, and three patients with terbinafine, 250 mg daily for 4 months. The mycological examination 8 months after discontinuation of treatment showed that one patient was mycologically cured whereas the remaining five patients still carried S. brevicaulis in their nails. The clinical examination at the end of the follow-up period showed a complete cure of the nail abnormalities in only one patient.

Yellow Nail Syndrome and Onychomycosis

We describe the case of a female patient suffering from yellow nail syndrome (YNS) accompanied by bronchial hyperactivity and sinusitis. A dermatophyte onychomycosis was evident on some of her nails. Following treatment of the respiratory pathology and oral administration of vitamin E, there was an improvement in the nails. The improvement of the yellow nails was however more discernible subsequent to the introduction of itraconazole pulse therapy for secondary onychomycosis suggesting an effect of this treatment on ungual growth.