Itraconazole For Onychomycosis Research Articles

Retrospective Analysis of Liver Enzyme Abnormalities in Patients Prescribed Terbinafine and Itraconazole for Onychomycosis.

Introduction Onychomycosis (OM) is defined as a nail fungal infection. Its prevalence increases with advancing age. Human-to-human transmission makes it a serious public health risk. Although OM is not a life-threatening disease, it has a detrimental effect on patients' quality of life. Due to the long therapy duration and potential side effects of systemic antifungal medicines, physicians may be reluctant to treat OM orally. In this study, we aimed to evaluate the effect of terbinafine and itraconazole on liver transaminases, the side effects of these treatments, and patients' adherence to systemic treatment of OM. Methods This is a retrospective study conducted in our dermatology department (Ordu University, Ordu) between June 2020 and October 2021. Hospital records were analyzed, and patients with the diagnosis of tinea unguium (ICD code B35.1) were investigated. Patients who were prescribed terbinafine or itraconazole were included in the study. Following a clinical diagnosis of OM, the researchers first tried to confirm it through direct microscopic examination with potassium hydroxide (KOH). If the direct microscopic examination was negative but the suspicion about OM continued, confirmation was done through a fungal culture. Results This study included 735 patients, of whom 409 (55.6%) were female and 326 (44.4%) were male. The research covered all of the patients who were given one of these two medications. To find patients who could apply to other hospitals, the Turkish National Healthcare System was checked in addition to hospital information. To identify patients who could apply to other healthcare institutions, all hospitals share their data with this national healthcare system. Terbinafine was used by 433 patients (76.4%), 75 patients (13.2%), and 37 patients (6.5%), respectively, for one, two, and three months. A total of 119 patients (70.8%) took itraconazole for a month, 32 patients (19%) took it for two months, and four patients (2.33%) took it for three months. At the end of the first month, the proportion of the patients with elevated aspartate transaminase (AST) levels was 5.2% for terbinafine and 0% for itraconazole. Eighteen (8.4%) patients with terbinafine had elevated alanine aminotransferase (ALT) levels, and four patients (7.5%) who were on itraconazole treatment had high ALT levels. None of the patients reported cutaneous adverse drug reactions, gastrointestinal disturbances, or headaches due to OM treatment. Also, no patients discontinued treatment because of hepatotoxicity. Conclusion In this study, none of the patients discontinued the treatment because of hepatotoxicity. According to the results of this study, oral terbinafine and itraconazole can be used with close follow-up. Baseline and regular laboratory monitoring for AST and ALT should be done to monitor liver toxicity with terbinafine and itraconazole. Besides, we did not observe other side effects like cutaneous or cardiac side effects or drug-drug interactions.

Arrhythmic Side Effect of Itraconazole Monotherapy: A Case Report

A 39-year-old woman treated with itraconazole for onychomycosis developed palpitation and dizziness during her treatment. Premature ventricular contractions (PVC) were detected during monitoring in the emergency room. Twenty-four hour holter electrocardiogram revealed aberrant premature atrial contractions (PACs) and PVCs. Corrected QT interval was in normal limits. After discontinuing the therapy, her complaints disappeared couple of days later. Her 24-h holter ECG displayed no PACs or PVCs. In this case the etiology of extra systoles is not wellknown. She did not have any other infection or used any other medication which may interfere with the metabolism of itraconazole. Enhanced cardiac automaticity may be a probable mechanism instead of more commonly encountered QT prolongation. Cardiac side-effects of itraconazole is rare but may be life threatening. Arrhythmic side effects should be monitored carefully even in otherwise healthy patients.

Fatal Hepatitis After Long-Term Pulse Itraconazole Treatment for Onychomycosis

To report the occurrence of acute cytolytic hepatitis in a patient exposed to pulse itraconazole therapy for 24 weeks and provide a concise review of the literature on cases of itraconazole-induced hepatitis. A 61-year-old woman with no apparent risk factors for liver injury developed acute hepatitis one week after the final dose of a long-term course of pulse itraconazole therapy (200 mg orally twice daily, 1 wk on, 3 wk off, for 24 wk) for onychomycosis. Monitoring of liver enzymes was not performed during the treatment period. Serologic evaluations on presentation ruled out infectious diseases or other etiological factors. Liver function tests showed alanine aminotransferase 3330 U/L, aspartate aminotransferase 3250 U/L, and bilirubin 21 mg/dL. Liver function continued to deteriorate, and the patient underwent liver transplantation 17 days after admission. Her liver displayed reduced volume and there was a mild accumulation of ascitic fluid in the retroperitoneal cavity. Histologic evaluation showed massive panlobular necrosis. Complications occurred after transplantation and a rejection crisis worsened the clinical picture until the patient died about 4 months later. Use of the Naranjo probability scale showed the relationship of itraconazole therapy and the occurrence of acute hepatitis as probable. Itraconazole pulse therapy for onychomycosis appears to be at least as effective as and safer than a continuous treatment regimen, particularly from the perspective of potential liver damage. Only one case of severe symptomatic hepatitis occurring after pulse therapy with itraconazole for onychomycosis and requiring transplantation has been reported previously. In that case, as well as the one reported here, hepatitis symptoms occurred after completion of long-term treatment in patients who were asymptomatic both before and during therapy. Prolonged exposure to itraconazole, administered either continuously or intermittently, may precipitate severe and irreversible hepatotoxic events. Accordingly, careful monitoring of liver function parameters should be performed both during and after treatment when onychomycosis requires prolonged itraconazole administration, even in asymptomatic patients lacking apparent risk factors of hepatic injury.

Pharmacoeconomic Assessment of Ciclopirox Topical Solution, 8%, Oral Terbinafine, and Oral Itraconazole for Onychomycosis

Most pharmacoeconomic data available for antifungal agents are based on US or European cost parameters. Similar data have not been reported in a Canadian health care system. A pharmacoeconomic analysis was performed considering the costs of drug acquisition and medical management, which were representative of the Canadian health care system, for each of the therapies approved for use in toenail onychomycosis in Canada: continuous oral terbinafine, oral pulse itraconazole, and topical ciclopirox 8% nail lacquer. A survey of provincial fee schedules was conducted to determine the representative costs of parameters relating to onychomycosis treatment, such as consultation visit cost, return visit cost, mycology testing, liver function testing, and complete blood count analysis. Manufacturers' costs were used to calculate representative drug acquisition costs. Meta-analysis was used to determine the average mycologic cure rates of each therapy, and the medical literature was consulted to determine the relapse rates for each therapy. Ciclopirox nail lacquer had the lowest drug acquisition costs compared with continuous terbinafine and pulse itraconazole ($197.89 vs $311.39 and $323.40, respectively). Using the pharmacoeconomic model with three 1-year treatment phases, in which failures or relapses were re-treated with the primary drug, the expected cost per patient was $601.52 with ciclopirox nail lacquer, $746.72 with oral terbinafine, and $938.42 with itraconazole. The main analysis assumed that two bottles of ciclopirox nail lacquer were required per treatment. The cost for the ciclopirox lacquer exceeded continuous terbinafine but remained lower than pulse itraconazole when three bottles of ciclopirox nail lacquer were considered in the calculation of cost per mycological cure. A variety of relapse rates were tested, and ciclopirox using two or fewer bottles remained cost-effective compared with continuous terbinafine or pulse itraconazole, regardless of the relapse rate. Where three bottles are required, the cost-effectiveness of ciclopirox nail lacquer is less than that of continuous terbinafine but more cost-effective than that of pulse itraconazole.

Pulse itraconazole vs. continuous terbinafine for the treatment of dermatophyte toenail onychomycosis in patients with diabetes mellitus

Oral terbinafine and oral itraconazole are two of the most common agents used for the treatment of toenail dermatophyte onychomycosis. Despite the fact that diabetic patients are more likely to have onychomycosis than normal individuals are, there is little research into the efficacy of standard oral regimens of terbinafine and itraconazole for onychomycosis in the diabetic population. We present a prospective, randomized, single-blind, parallel group, comparator-controlled, multi-centre study designed to assess the efficacy of the pulse itraconazole (200 mg twice daily, 1 week on, 3 weeks off, for 12 weeks) vs. continuous terbinafine (250 mg once daily for 12 weeks) oral therapies in the treatment of dermatophyte toenail distal and lateral subungual onychomycosis (DLSO) in the diabetic population. EFFICACY PARAMETERS: Primary efficacy measures included mycological cure rate (negative KOH and culture) and effective cure (mycological cure plus nail plate involvement of 10% or less) at Week 48. At Week 48, mycological cure was attained by 88.2% (30 of 34) and 79.3% (23 of 29) of patients in the itraconazole and terbinafine groups, respectively (P not significant). Effective cure (mycological cure with <or=10% of nail plate involvement) was attained by 52.9% (18 of 34) of the itraconazole group and 51.7% (15 of 29) of the terbinafine group (P not significant). Three itraconazole patients experienced side effects in the form of gastrointestinal problems. There were no serious adverse events and no interactions with concomitant medications recorded. Both continuous terbinafine and itraconazole pulse therapy are effective and safe in the management of dermatophyte toenail onychomycosis in people with diabetes.

Liver failure and transplantation after itraconazole treatment for toenail onychomycosis

Three weeks after completing a 4-pulse course of itraconazole for toenail onychomycosis, a 25-year-old woman patient developed severe liver crisis and required an emergency liver transplant. We report the case and discuss the use of itraconazole in onychomycosis and dermatomycoses.

Intermittent pulse therapy with itraconazole for onychomycosis. Experience in Hong Kong Chinese.

Forty-four Hong Kong Chinese adults comprising 10 cases of fingernail and 42 cases of toenail onychomycosis were recruited for a 3-weekly itraconazole pulse therapy. Each pulse consisted of seven consecutive daily 400 mg doses with a 3-week interval between treatments. All patients in the fingernail group and 37 in the toenail group completed the study. The clinical cure, clinical response and mycological cure rates at week 36 were 70, 90 and 90% for fingernail and 35, 81 and 68% for toenail groups, respectively. Side-effects including biochemical abnormalities were minimal, and returned to normal upon cessation of treatment. We conclude that itraconazole pulse therapy is very effective, safe and well-tolerated for fingernail and toenail onychomycosis.

Therapeutic Efficacy and Safety of One-Week Intermittent Therapy with Itraconazole for Onychomycosis in a Chinese Patient Population

Objective: To evaluate the efficacy and safety of a 1-week intermittent itraconazole dosing schedule for onychomycosis. Methods: In this multicenter, open-label study, 646 patients received itraconazole 200 mg twice daily for 1 week/month, followed by 3 weeks without therapy. Patients with fingernail infections received 2 treatment cycles, patients with toenail or combined toenail and fingernail infections received 3 cycles. Efficacy was evaluated at week 9 (2-month regimen), week 13 (3-month regimen) and 3, 6 or 9 (toenails only) months after completion of therapy. Results: Clinical and mycologic cure rates for fingernails were greater than 90% 6 months after completion of 2 treatment cycles. Clinical and mycologic cure rates for toenails were 84 and 98%, respectively, 9 months after completion of 3 cycles. Treatment was well tolerated; adverse events (mostly mild) occurred in 4.6% of patients. Conclusion: A 1-week intermittent itraconazole dosing regimen is a safe and effective treatment for onychomycosis.

Itraconazole in onychomycosis. Open and double-blind studies.

Fifteen patients with onychomycosis caused by Trichophyton rubrum or T. mentagrophytes were treated with 50 mg itraconazole daily for 3 to 6 months. Fingernail infections were cured in two patients and two responded with marked improvement, e.g. small residual lesion remained and positive microscopy. The infected toenails were markedly improved in nine of 13 patients. Twenty-seven patients with T. rubrum infected nails were given 100 mg itraconazole daily for 6 to 8 months. Fingernails were cured in nine of eleven patients, while toenail infections were cured in one and markedly improved in 14 of 25 cases. Responses to 100 mg itraconazole versus 500 mg griseofulvin daily for 6 months were compared and evaluated in 20 patients with onychomycosis caused by T. rubrum or T. mentagrophytes. Fingernail infections responded equally well to both drugs with half of the cases cured or markedly improved, whereas toenails responded better to itraconazole, e.g. 4 of 9 were markedly improved versus one of 10 on griseofulvin. In patients given 50 mg itraconazole daily a significantly better response was observed in persons below 30 years of age compared to older individuals. Also, side-effects which were mainly mild and located to the gastro-intestinal tract or the central nervous system were seen less often in this group of patients on the low dose. Follow-up studies showed that cured nails remained cured, that markedly improved toenails continued to improve until cure in three of 21 patients but that aggravation took place through the one year of follow-up in more than half of the patients evaluated as markedly improved at the end of treatment.