An exploration of the optimum dosage and number of cycles of itraconazole pulse therapy for severe onychomycosis

Abstract

Although standard itraconazole pulse therapy is a well-established regimen for toenail onychomycosis, the cure rate for onychomycosis remains low. To evaluate the efficacy and safety of different cycles of itraconazole pulse therapy, determine the optimal dosage and number of cycles for onychomycosis. A total of 90 outpatients of our hospital with onychomycosis were randomised into three treatment groups: (1) standard itraconazole pulse therapy (200 mg twice per day, 1 week each month for three pulses); (2) long-term pulse therapy (200 mg twice per day, 1 week each month for six pulses); (3) low-dose and long-term pulse therapy (200 mg/d, 1 week per month for six pulses) and were followed up for 15 months. Of the initial patients, the trial was completed by 81 patients. The complete cure rates were 32.43% for three cycles and 75% for six cycles (P< .001). For six cycles, despite the administration of half-dose for patients weighing no more than 55 kg, there was no statistical difference in the complete cure rate (P = .862). Long-term therapy is effective and safe for the treatment of toenail onychomycosis. For patients weighing no more than 55 kg, long-term half-dose itraconazole pulse therapy is recommended .

Acitretin: Could it be a new therapeutic player in the field of onychomycosis?

“…On the contrary, our clearance rate was higher than that reported by Zhang et al 20 who showed mycological cure in 41% of a group of patients who received itraconazole-pulse therapy in the same dose and duration. Our higher response may be attributed to the prevalence of fingernail onychomycosis (90%) in our study which has a better therapeutic outcome, compared to toenail disease in the other study.…”

“…On the contrary, our clearance rate was much lower than the same study performed by Zhang et al 20 who treated another group of patients with 6 pulses of itraconazole, with 91% mycological cure.…”

Race reporting and representation in onychomycosis clinical trials: A systematic review

“…Of the 302 PubMed initial search results, 182 clinical trials (28,352 participants) met inclusion criteria and were included in the final analysis 6–186 . The PRISMA study selection process is detailed in Figure 1.…”

Combination Therapy Should Be Reserved as Second-Line Treatment of Onychomycosis: A Systematic Review of Onychomycosis Clinical Trials

“…Importantly, trial lengths were relatively short, with average follow-up of 46.1 weeks (SD: 21.5; range: 24–78.2 weeks). In contrast, pivotal RCTs on oral terbinafine [ 8 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ], oral itraconazole [ 8 , 50 , 52 , 53 , 54 , 56 , 58 , 59 , 60 , 63 , 64 , 65 , 66 , 67 ], and topical efinaconazole [ 68 , 69 , 70 , 71 ] had average follow-ups of 69.0 (SD: 49.1; range: 36–252), 66.4 (SD: 55.8; range: 19–252), and 62.1 (SD: 28.7; range: 40–104.3) weeks, respectively. Taken together, medicine-only combination therapy trials were much less rigorously designed than pivotal monotherapy trials, and therefore should be interpreted with caution.…”

“…In the terbinafine package insert, liver enzyme abnormalities and taste disturbances were only reported in 3.3% and 2.8% of patients, respectively, with a discontinuation rate of 0.2% for both ( , accessed on 18 January 2022). Oral itraconazole monotherapy is well tolerated, with the most common reported adverse events being gastrointestinal discomfort and headache, both mild and transient [ 66 ], and with safety profiles similar between placebo and itraconazole treatment groups in a phase-III RCT [ 64 ]. In two phase-III multicenter RCTs assessing topical efinaconazole monotherapy [ 68 ], rates of adverse events were similar between treatment and vehicle groups in both studies, with most mild or moderate in severity, low rates of treatment-related discontinuation, and no clinically meaningful laboratory or vital sign changes from baseline.…”