Efficacy and safety of terbinafine in the treatment of dermatophytosis at Nghean provincipal leprosy, dermatology centre (2015-2016)

JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016<br /> <br /> EFFICACY AND SAFETY OF TERBINAFINE IN THE TREATMENT<br /> OF DERMATOPHYTOSIS AT NGHEAN PROVINCIPAL LEPROSY,<br /> DERMATOLOGY CENTRE (2015 - 2016)<br /> Nguyen Thai Dung*; Le Tran Anh**; Nguyen Khac Luc**<br /> SUMMARY<br /> Terbinafine - an allylamine drug has been shown to be fungicidal against dermatophytes and<br /> has been approved by Vietnam’s Ministry of Health for treating dermatophytosis, but no study<br /> on evaluating its effect and safety has been done in Vietnam. Objective: To evaluate the efficacy<br /> and safety of the drug in the treatment of tinea. Subjects and methods: 29 patients with mild,<br /> moderate lesions of ringworm take topical terbinafine 1% for 2 - 4 weeks (group 1); 27 patients<br /> with extensive tinea or respond poorly to topical treatment take a combination of topical and oral<br /> terbinafine for 1 - 14 days (group 2). Clinical and mycological assessments were made at 2 and<br /> 4 weeks after starting treatment. Results: The clinical cure after 2 weeks was 73.21% and<br /> mycological cure was 85.71%; complete cure was 68.76%. The rate of complete cure in group 1<br /> (82.76%) was higher than group 2 (50%; p < 0.05). 4 weeks after treatment, all patients were<br /> cured completely. Patients taking only topical medication did not have undesirable effects.<br /> Some patients in group 2 experienced side effects such as nausea (25.93%); flatulence (3.70%)<br /> and dizziness (40.74%). Conclusion: Terbinafine is effective and safe in the treatment of ringworm.<br /> * Key words: Ringworm; Terbinafine; Efficacy; Safety.<br /> <br /> INTRODUCTION<br /> Tinea is common disease in the<br /> community and can be treated by topical<br /> or systemic antifungal agents. There are<br /> many drugs to treat the disease with<br /> different advantages and disadvantages.<br /> Terbinafine is an allylamine antifungal<br /> with good profile of efficacy and safety.<br /> Around the world, there have been many<br /> studies assessing the effects of the drug<br /> in the treatment of different types of tinea.<br /> In Vietnam, the drug is also included in<br /> the list of medications to treat ringworm<br /> but no study has yet been done to<br /> evaluate its effect and safety. This study<br /> has been conducted to evaluate the efficacy<br /> <br /> and safety of this drug in patients with<br /> dermatophytosis at the Nghean Provincial<br /> Leprosy, Dermatology Centre.<br /> SUBJECTS AND METHOD<br /> 1. Patients.<br /> Patients with ringworm and agree to<br /> be involved in the study.<br /> 2. Materials.<br /> Drugs: Terbinafine (brand name TERBISIL)<br /> 250 mg (SANTA FARMA ILAC SANAYII<br /> A.S Turkey). TRIGENOL cream 1%; (NEW<br /> GENE PHARM Inc., Korea).<br /> KOH solution 10 - 20%; Sabouraud<br /> medium.<br /> <br /> * Nghean Provincial Leprosy - Dermatology Centre<br /> ** Military Medical University<br /> Corresponding author: Le Tran Anh (anh_lt@vmmu.edu.vn)<br /> <br /> 53<br /> <br /> JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016<br /> <br /> 3. Study design.<br /> Uncontrolled clinical trial.<br /> Patients with ringworm (have lesions<br /> and positive mycology test by direct<br /> examination or culture) were graded as<br /> mild, moderate and severe according to<br /> criteria by Vietnam Dermatology Association<br /> (mild: 1 lesion and lesion area < 1 hand;<br /> moderate: 2 - 5 lesions and/or area of<br /> lesion from 2 - 5 hands; severe: more<br /> than 5 lesions and/or lesions covering an<br /> area of more than 5 hands). 29 patients<br /> with mild or moderate lesions of ringworm<br /> take topical terbinafine 1% daily for 2 - 4<br /> weeks (group 1); 27 patients with extensive<br /> tinea or responding poorly to topical<br /> treatment take a combination of topical<br /> and oral terbinafine (250 mg twice a day<br /> for 1 - 14 days (group 2). Mycological and<br /> clinical assessments were made after<br /> 2 and 4 weeks of treatment. Clinical<br /> response was qualified as following:<br /> <br /> clinical cure: clearing of 70 - 100% of<br /> lesions; decrease: clearing 50 - 69% of<br /> lesions; not curing: clearing < 50% of<br /> lesions. Complete cure was defined as<br /> mycological cure (negative microscopy)<br /> and clinical cure.<br /> * Site and time:<br /> Nghean Provincial Leprosy, Dermatology<br /> Centre and fungal laboratory, Department<br /> of Parasitology, Vietnam Military Medical<br /> University.<br /> Time: October 2015 to August 2016.<br /> * Statistical analysis: by SPSS 11.5<br /> software.<br /> * Ethnic: this study was approved by<br /> the ethics committee of Vietnam National<br /> Institute of Malariology Parasitology and<br /> Entomology. All patients were well-informed<br /> and voluntarily provided information. The<br /> information is kept confidentially and used<br /> for research only.<br /> <br /> RESULTS AND DISCUSSION<br /> Table 1: Demographic characteristics of patients (n = 56).<br /> Criteria<br /> Age<br /> <br /> Number<br /> <br /> Percentage (%)<br /> <br /> 2-9<br /> <br /> 2<br /> <br /> 3.57<br /> <br /> 10 - 19<br /> <br /> 14<br /> <br /> 25.00<br /> <br /> 20 - 29<br /> <br /> 19<br /> <br /> 33.93<br /> <br /> 30 - 39<br /> <br /> 11<br /> <br /> 19.64<br /> <br /> 40 - 49<br /> <br /> 1<br /> <br /> 1.79<br /> <br /> 50 - 59<br /> <br /> 6<br /> <br /> 10.71<br /> <br /> 60 - 69<br /> <br /> 3<br /> <br /> 5.36<br /> <br /> Group<br /> <br /> 30.02 ± 15.067<br /> <br /> Mean ( X ±SD)<br /> Gender<br /> <br /> Male<br /> <br /> 34<br /> <br /> 60.71<br /> <br /> Female<br /> <br /> 22<br /> <br /> 39.29<br /> <br /> The average age of patients was 30.02 years old; mostly men (60.71%).<br /> The patients involved in the study were characterized by ringworm, a disease mostly<br /> affects male and young people [1, 3].<br /> 54<br /> <br /> JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016<br /> <br /> Table 2: Treatment regimens according to characteristics of lesions (n = 56).<br /> Group<br /> <br /> Criteria<br /> <br /> Total<br /> <br /> 1<br /> <br /> 2<br /> <br /> Number<br /> <br /> Percentage<br /> <br /> Mild<br /> <br /> 26<br /> <br /> 2<br /> <br /> 28<br /> <br /> 50.00<br /> <br /> Moderate<br /> <br /> 3<br /> <br /> 18<br /> <br /> 21<br /> <br /> 37.50<br /> <br /> Severe<br /> <br /> 0<br /> <br /> 7<br /> <br /> 7<br /> <br /> 12.50<br /> <br /> 1<br /> <br /> 26<br /> <br /> 4<br /> <br /> 30<br /> <br /> 53.57<br /> <br /> 2-5<br /> <br /> 3<br /> <br /> 16<br /> <br /> 19<br /> <br /> 33.93<br /> <br /> >5<br /> <br /> 0<br /> <br /> 7<br /> <br /> 7<br /> <br /> 12.50<br /> <br /> Small<br /> <br /> 25<br /> <br /> 2<br /> <br /> 27<br /> <br /> 48.21<br /> <br /> Medium<br /> <br /> 4<br /> <br /> 18<br /> <br /> 22<br /> <br /> 39.29<br /> <br /> Large<br /> <br /> 0<br /> <br /> 7<br /> <br /> 7<br /> <br /> 12.50<br /> <br /> Corporis<br /> <br /> 19<br /> <br /> 22<br /> <br /> 41<br /> <br /> 73.21<br /> <br /> Crusis<br /> <br /> 7<br /> <br /> 12<br /> <br /> 19<br /> <br /> 33.93<br /> <br /> Hand<br /> <br /> 0<br /> <br /> 3<br /> <br /> 3<br /> <br /> 5.36<br /> <br /> Feed<br /> <br /> 2<br /> <br /> 3<br /> <br /> 5<br /> <br /> 8.93<br /> <br /> Face<br /> <br /> 2<br /> <br /> 4<br /> <br /> 6<br /> <br /> 10.71<br /> <br /> Head<br /> <br /> 1<br /> <br /> 0<br /> <br /> 1<br /> <br /> 1.79<br /> <br /> 29<br /> <br /> 27<br /> <br /> 56<br /> <br /> 100<br /> <br /> Grade<br /> <br /> Number of<br /> lesions<br /> <br /> Size of<br /> lesions<br /> <br /> Locations of<br /> lesions*<br /> <br /> Total<br /> <br /> (* Some patients have multiple lesions)<br /> Topical terbinafine was first-line treatment for patients with mild or moderate lesions<br /> while oral terbinafine for extensive tinea that responded poorly to topical treatment<br /> alone. The regimen based on characteristics of lesions focusing on disease severity,<br /> lesion size, lesion location was consistent with the guidance of the Ministry of Health [4]<br /> and recommendation by some authors [10].<br /> Table 3: Results after 2 weeks of treatment (n = 56).<br /> Mycology<br /> <br /> Criteria<br /> Clinical<br /> <br /> Total<br /> <br /> Total<br /> <br /> Negative<br /> <br /> Positive<br /> <br /> Number<br /> <br /> Percentage<br /> <br /> Cure<br /> <br /> 38<br /> <br /> 3<br /> <br /> 41<br /> <br /> 73.21<br /> <br /> Decrease<br /> <br /> 10<br /> <br /> 5<br /> <br /> 15<br /> <br /> 26.79<br /> <br /> Not cure<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> Number<br /> <br /> 48<br /> <br /> 8<br /> <br /> 56<br /> <br /> 100<br /> <br /> Percentage (%)<br /> <br /> 85.71<br /> <br /> 14.29<br /> <br /> After 2 weeks of treatment, the rates of clinical, mycological and complete cure were<br /> 73.21%; 85.71% and 68.76%, respectively.<br /> 55<br /> <br /> JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016<br /> <br /> Table 4: Impact of lesion on treatment effect.<br /> Group<br /> <br /> Criteria<br /> Grade<br /> <br /> Total<br /> <br /> 1<br /> <br /> 2<br /> <br /> Mild<br /> <br /> 3<br /> <br /> 1<br /> <br /> 4<br /> <br /> Moderate<br /> <br /> 2<br /> <br /> 8<br /> <br /> 10<br /> <br /> Severe<br /> <br /> 0<br /> <br /> 4<br /> <br /> 4<br /> <br /> Number of<br /> lesions<br /> <br /> 1<br /> <br /> 3<br /> <br /> 3<br /> <br /> 6<br /> <br /> 2-5<br /> <br /> 2<br /> <br /> 6<br /> <br /> 8<br /> <br /> >5<br /> <br /> 0<br /> <br /> 4<br /> <br /> 4<br /> <br /> Size of lesions<br /> <br /> Small<br /> <br /> 2<br /> <br /> 1<br /> <br /> 3<br /> <br /> Medium<br /> <br /> 3<br /> <br /> 8<br /> <br /> 11<br /> <br /> Large<br /> <br /> 0<br /> <br /> 4<br /> <br /> 4<br /> <br /> 5<br /> <br /> 13<br /> <br /> 18<br /> <br /> Total<br /> <br /> There were 18 patients with different grades, number and extent of lesions. The<br /> complete cure rate in group 1 (82.76%) was higher than that in group 2 (50%; p < 0.05).<br /> Table 4: Results after 4 weeks of treatment.<br /> Criteria<br /> Clinical<br /> <br /> Mycology<br /> <br /> Number<br /> <br /> Percentage<br /> <br /> Cure<br /> <br /> 49<br /> <br /> 87.5<br /> <br /> Not cure<br /> <br /> 0<br /> <br /> 0<br /> <br /> Not return<br /> <br /> 7<br /> <br /> 12.5<br /> 100.0<br /> <br /> Total<br /> <br /> 56<br /> <br /> Negative<br /> <br /> 6<br /> <br /> Positive<br /> <br /> 0<br /> <br /> Not return<br /> <br /> 2<br /> <br /> Total<br /> <br /> 8<br /> <br /> After 4 weeks, 100% of the examined<br /> cases were completely cured. Two cases<br /> had a positive mycological test at the first<br /> assessment but did not come back to<br /> retest.<br /> The results showed that the drug has a<br /> good efficacy on the treatment of tinea.<br /> These results are similar to many other<br /> studies evaluating the efficacy of terbinafine<br /> with rates of complete cure of about 70 100%. Vidhya Lakshmi CP et al (2003)<br /> studied the efficacy of terbinafine topical<br /> 56<br /> <br /> treatment of tinea corporis and tinea<br /> cruris and found that after 2 weeks of<br /> treatment 100% of patients had clinical<br /> cure and negative test [8]. Bonifaz A,<br /> Saul A (2000) using terbinafine cream<br /> (1 week topical treatment of tinea corporis<br /> and tinea cruris) found that the mycological<br /> cure rate was 94% and complete cure<br /> rate was 72% [6]. Ledezma E (1999)<br /> found the cure rate of terbinafine 1%<br /> cream evaluated after 16 days was<br /> 71%; and after 30 days was 75% [9].<br /> <br /> JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016<br /> <br /> In general, topical use of antifungal<br /> drugs can be effective in infections of<br /> limited area but oral formulations may be<br /> required for infections of more severe or<br /> more widespread presentation [5]. Patients<br /> with spreading lesions or at special locations<br /> such as nails, hair or thick skin areas<br /> require oral antifungal therapy. In the study,<br /> those patients with spread or recurrent<br /> lesion were prescribed oral terbinafine<br /> combined with topical medication. This<br /> regiment had good efficacy in 100% of reexamined patients completely cured. Oral<br /> terbinafine was demonstrated efficacy in<br /> the treatment of ringworm even in a short<br /> duration, in special types of the disease or<br /> on patients with disorder of immunity or<br /> <br /> endocrine. The clinical and mycology cure<br /> rate two weeks after taking oral<br /> terbinafine alone were 47.1% and 47.1%<br /> in patients taking the drug for two days<br /> and 66.7% and 66.7% for three days [13].<br /> Rich P (2001) assessed the efficacy of<br /> short-duration oral terbinafine six weeks<br /> after the treatment, the rate of cure was<br /> 100% for HIV-infected patients and 83%<br /> for patients with diabetes [11]. With tinea<br /> imbricata, a special type of tinea caused<br /> by Trichophyton concentricum with lesion<br /> spread peripherally over many years,<br /> 4 weeks of oral medication had a complete<br /> cure rate of 100% and recurrent rate 16%<br /> compared to that of itraconazole (89%<br /> and 75%, respectively) [7].<br /> <br /> Table 6: Side effects.<br /> Effects<br /> <br /> Group 1 (n = 26)<br /> <br /> Group 2 (n = 27)<br /> <br /> Number<br /> <br /> Percentage<br /> <br /> Number<br /> <br /> Percentage<br /> <br /> Nausea<br /> <br /> 0<br /> <br /> 0<br /> <br /> 7<br /> <br /> 25.93<br /> <br /> Constipation<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> Flatulence<br /> <br /> 0<br /> <br /> 0<br /> <br /> 1<br /> <br /> 3.70<br /> <br /> Diarrhea<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> Dizziness<br /> <br /> 0<br /> <br /> 0<br /> <br /> 11<br /> <br /> 40.74<br /> <br /> Excitement<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> Skin lesion<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> 0<br /> <br /> (* the information of side effects could not be completed in 3 patients)<br /> Some patients in group 2 suffered from<br /> side effects such as nausea, flatulence<br /> or dizziness. The results showed that<br /> terbinafine was relatively safe to use.<br /> Research by Rich P (2001) also found<br /> that even patients with HIV infection or<br /> diabetes did not show any adverse effects<br /> when taking terbinafine [11]. Although<br /> there is some concern about the potential<br /> effects of elevations of liver enzyme [5],<br /> but this risk is very low. Skorepova M<br /> (2004) found that the rate of liver damage<br /> <br /> after treatment with terbinafine for<br /> onychomycosis was 1/45.000 - 50.000<br /> patients, equivalent to paracetamol, a<br /> very common drug (5.5/100,000) [11].<br /> Due to some difficulties, liver function<br /> tests had not been done, but with a short<br /> duration of terbinafine, the risk is very low.<br /> CONCLUSION<br /> Through a research on the efficacy<br /> and safety of terbinafine on 56 patients,<br /> we found the following results:<br /> 57<br /> <br />