“I have finger nail infection. I am told it is a fungal infection called Tinea. I have used Griseofulvin in the past. Recently I was put on Itraconazole capsulesby my healthcare provider. My healthcare provider asked me take 200mg twice daily for 1 week, repeat the same for another 1 week the second month and do another 1 week for the third month. The dosing is unusual for me. Will it work?”. Yes it will work. It is called Pulse therapy. The alternative is to take 200mg daily for 3 months.
In response to this enquiry I will be using a combination of materials from the American Family Physician 2001 Feb 15;63(4):663-673 and the Indian Journal of Dermatology, Venereology and Leprology Year : 2007 | Volume : 73 | Issue : 6 | Page : 373-376.
Onychomycosis (tinea unguium) is a fungal infection of the nail bed, matrix or plate. Toenails are affected more often than finger-nails. Onychomycosis accounts for one third of integumentary fungal infections and one half of all nail disease. Tinea unguium occurs primarily in adults, most commonly after 60 years of age. The incidence of this infection is probably much higher than the reported 2 to 14 percent. Occlusive footwear, locker room exposure and the dissemination of different strains of fungus worldwide have contributed to the increased incidence of onychomycosis.
Tinea unguium is more than a cosmetic problem, although persons with this infection are often embarrassed about their nail disfigurement. Because it can sometimes limit mobility, onychomycosis may indirectly decrease peripheral circulation, thereby worsening conditions such as venous stasis and diabetic foot ulcers. Fungal infections of the nails can also be spread to other areas of the body and, perhaps, to other persons.Onychomycosis is most commonly caused by dermatophytes, although Candida species and nondermatophyte molds may also cause disease. Therapeutic options for the treatment of onychomycosis range from no therapy, palliative care, mechanical or chemical debridement, topical and systemic antifungal agents to a combination of two or more of these modalities. Factors that influence the choice of therapy include the presentation and severity of the disease, current medications the patient is taking, previous therapies for onychomycosis and their response, physician and patient preference and the cost of therapy. The primary aim of treatment is to eradicate the organism as demonstrated by microscopy and culture. However, eradication of the fungus does not always render the nails normal as they may have been dystrophic prior to infection. Such dystrophy may be due to trauma or nonfungal nail disease; this is particularly likely in cases where yeasts or nondermatophyte molds (secondary pathogens and saprophytes respectively) are isolated. Historically, the treatment of onychomycosis has been challenging. Orally administered Griseofulvin has been available for many years, but its use is limited by a narrow spectrum, the necessity for long courses of treatment, cure rates (around 30%) and high relapse rates. I am not surprised the enquirer had similar experiences with Griseofulvin.Onychomycosis has long been treated with topical antifungal preparations. However, these agents are inconvenient to use, and results are often disappointing.Triazole (e.g. Itraconazole) and allylamine (Terbinafine) antifungal drugs have largely replaced griseofulvin as first-line medications in the treatment of onychomycosis. These agents offer shorter treatment courses, higher cure rates and fewer relapses.
Terbinafine is an allylamine antifungal agent that is active against dermatophytes, which are responsible for the majority of onychomycosis cases. This agent is notably less effective against nondermatophytes, including Candida species and molds.Terbinafine is superior to itraconazole for dermatophyte onychomycosis and should be considered first-line treatment. with itraconazole as the next best alternative. Cure rates of 80-90% for fingernail infection and 70-80% for toenail infection can be expected. These medications share characteristics that enhance their effectiveness: prompt penetration of the nail and nail bed, persistence in the nail for months after discontinuation of therapy and generally good safety profiles.Terbinafine is the drug of choice in tinea unguium. In addition to transient tolerance problems, terbinafine has several important drug interactions because of its hepatic metabolism. Terbinafine is not recommended for patients with chronic or active liver disease.Terbinafine 250 mg per day is given continuously for 12 weeks to treat toenail infections and for 6 weeks to treat fingernail infections. Studies have shown that the regimen for toenails results in a mycologic cure rate of 71-82% and a clinical cure rate of 60-70%.Studies comparing terbinafine pulse therapy of 250 mg twice a day for 1 week of each month for 3 months with continuous therapy over 3 months showed no difference in efficacy.
Itraconazole has a broad antifungal spectrum that includes dermatophytes, many nondermatophytic molds and Candida species. Hepatic toxicity is rare. Because itraconazole is metabolized by the hepatic cytochrome P450 system, significant drug interactions can occur notably with statins (e.g. Atorvastatin), quinidine, pimozide, and benzodiazepines (e.g. Diazepam), amongst others. Increased gastric pH decreases the absorption of itraconazole. Therefore, the effectiveness of this antifungal agent can be decreased by histamine H 2 blockers (e.g. Cimetidine) and proton pump inhibitors (e.g. Omeprazole).For this reason, itraconazole should be taken with food.The dosage of itraconazole is 200 mg once daily taken continuously for 12 weeks to treat toenail infections and for 6 weeks to treat fingernail infections. Pulse treatment consists of 200 mg taken twice daily for 1 week per month, with the treatment repeated for 2-3 months (i.e., two to three ‘pulses’) for fingernail infections. This dosage, given in three to four pulses, has also been shown to be effective in the treatment of toenail infections. Published studies have demonstrated similar success rates for continuous and pulse therapies, with mycologic cure (negative KOH preparation or negative cultures) rates ranging from 45 to 70% and clinical cure (normal nail morphology) rates ranging from 35 to 80%.
Like itraconazole, fluconazole is active against common dermatophytes, Candida species and some nondermatophytic molds. Studies using Fluconazole for onychomycosis ranged from 100 mg to 450 mg weekly and 150 mg daily, and durations ranged from 12 weeks to 12 months. Most of the studies evaluated the efficacy of fluconazole in patients with toenail onychomycosis due to dermatophyte infection. Fluconazole was superior to placebo, with mycologic eradication rates ranging from 36% to 100%. In one of the comparative studies, the mycologic cure rate was lower with fluconazole (31.2%) compared with terbinafine (75%) and itraconazole (61.1%). Fluconazole is less effective than terbinafine and itraconazole in the treatment of onychomycosis. However, fluconazole may be preferred in patients unable to tolerate other oral antifungal agents due to the dosing regimen, adverse effect profile, and drug interactions.
Tinea unguium is more than a cosmetic problem, although persons with this infection are often embarrassed about their nail disfigurement. It can be a source of emotional problems and even affect daily activities.
DR. EDWARD O. AMPORFUL
CHIEF PHARMACIST
COCOA CLINIC
