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

Objective: To evaluate the efficacy and safety of the drug in the treatment of tinea. Subjects and methods: 29 patients with mild, moderate lesions of ringworm take topical terbinafine 1% for 2 - 4 weeks (group 1); 27 patients with extensive tinea or respond poorly to topical treatment take a combination of topical and oral terbinafine for 1 - 14 days (group 2).

JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016 EFFICACY AND SAFETY OF TERBINAFINE IN THE TREATMENT OF DERMATOPHYTOSIS AT NGHEAN PROVINCIPAL LEPROSY, DERMATOLOGY CENTRE (2015 - 2016) Nguyen Thai Dung*; Le Tran Anh**; Nguyen Khac Luc** SUMMARY Terbinafine - an allylamine drug has been shown to be fungicidal against dermatophytes and has been approved by Vietnam’s Ministry of Health for treating dermatophytosis, but no study on evaluating its effect and safety has been done in Vietnam Objective: To evaluate the efficacy and safety of the drug in the treatment of tinea Subjects and methods: 29 patients with mild, moderate lesions of ringworm take topical terbinafine 1% for - weeks (group 1); 27 patients with extensive tinea or respond poorly to topical treatment take a combination of topical and oral terbinafine for - 14 days (group 2) Clinical and mycological assessments were made at and weeks after starting treatment Results: The clinical cure after weeks was 73.21% and mycological cure was 85.71%; complete cure was 68.76% The rate of complete cure in group (82.76%) was higher than group (50%; p < 0.05) weeks after treatment, all patients were cured completely Patients taking only topical medication did not have undesirable effects Some patients in group experienced side effects such as nausea (25.93%); flatulence (3.70%) and dizziness (40.74%) Conclusion: Terbinafine is effective and safe in the treatment of ringworm * Key words: Ringworm; Terbinafine; Efficacy; Safety INTRODUCTION Tinea is common disease in the community and can be treated by topical or systemic antifungal agents There are many drugs to treat the disease with different advantages and disadvantages Terbinafine is an allylamine antifungal with good profile of efficacy and safety Around the world, there have been many studies assessing the effects of the drug in the treatment of different types of tinea In Vietnam, the drug is also included in the list of medications to treat ringworm but no study has yet been done to evaluate its effect and safety This study has been conducted to evaluate the efficacy and safety of this drug in patients with dermatophytosis at the Nghean Provincial Leprosy, Dermatology Centre SUBJECTS AND METHOD Patients Patients with ringworm and agree to be involved in the study Materials Drugs: Terbinafine (brand name TERBISIL) 250 mg (SANTA FARMA ILAC SANAYII A.S Turkey) TRIGENOL cream 1%; (NEW GENE PHARM Inc., Korea) KOH solution 10 - 20%; Sabouraud medium * Nghean Provincial Leprosy - Dermatology Centre ** Military Medical University Corresponding author: Le Tran Anh (anh_lt@vmmu.edu.vn) 53 JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016 Study design Uncontrolled clinical trial Patients with ringworm (have lesions and positive mycology test by direct examination or culture) were graded as mild, moderate and severe according to criteria by Vietnam Dermatology Association (mild: lesion and lesion area < hand; moderate: - lesions and/or area of lesion from - hands; severe: more than lesions and/or lesions covering an area of more than hands) 29 patients with mild or moderate lesions of ringworm take topical terbinafine 1% daily for - weeks (group 1); 27 patients with extensive tinea or responding poorly to topical treatment take a combination of topical and oral terbinafine (250 mg twice a day for - 14 days (group 2) Mycological and clinical assessments were made after and weeks of treatment Clinical response was qualified as following: clinical cure: clearing of 70 - 100% of lesions; decrease: clearing 50 - 69% of lesions; not curing: clearing < 50% of lesions Complete cure was defined as mycological cure (negative microscopy) and clinical cure * Site and time: Nghean Provincial Leprosy, Dermatology Centre and fungal laboratory, Department of Parasitology, Vietnam Military Medical University Time: October 2015 to August 2016 * Statistical analysis: by SPSS 11.5 software * Ethnic: this study was approved by the ethics committee of Vietnam National Institute of Malariology Parasitology and Entomology All patients were well-informed and voluntarily provided information The information is kept confidentially and used for research only RESULTS AND DISCUSSION Table 1: Demographic characteristics of patients (n = 56) Criteria Age Number Percentage (%) 2-9 3.57 10 - 19 14 25.00 20 - 29 19 33.93 30 - 39 11 19.64 40 - 49 1.79 50 - 59 10.71 60 - 69 5.36 Group 30.02 ± 15.067 Mean ( X ±SD) Gender Male 34 60.71 Female 22 39.29 The average age of patients was 30.02 years old; mostly men (60.71%) The patients involved in the study were characterized by ringworm, a disease mostly affects male and young people [1, 3] 54 JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016 Table 2: Treatment regimens according to characteristics of lesions (n = 56) Group Criteria Total Number Percentage Mild 26 28 50.00 Moderate 18 21 37.50 Severe 7 12.50 26 30 53.57 2-5 16 19 33.93 >5 7 12.50 Small 25 27 48.21 Medium 18 22 39.29 Large 7 12.50 Corporis 19 22 41 73.21 Crusis 12 19 33.93 Hand 3 5.36 Feed 8.93 Face 10.71 Head 1 1.79 29 27 56 100 Grade Number of lesions Size of lesions Locations of lesions* Total (* Some patients have multiple lesions) Topical terbinafine was first-line treatment for patients with mild or moderate lesions while oral terbinafine for extensive tinea that responded poorly to topical treatment alone The regimen based on characteristics of lesions focusing on disease severity, lesion size, lesion location was consistent with the guidance of the Ministry of Health [4] and recommendation by some authors [10] Table 3: Results after weeks of treatment (n = 56) Mycology Criteria Clinical Total Total Negative Positive Number Percentage Cure 38 41 73.21 Decrease 10 15 26.79 Not cure 0 0 Number 48 56 100 Percentage (%) 85.71 14.29 After weeks of treatment, the rates of clinical, mycological and complete cure were 73.21%; 85.71% and 68.76%, respectively 55 JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016 Table 4: Impact of lesion on treatment effect Group Criteria Grade Total Mild Moderate 10 Severe 4 Number of lesions 3 2-5 >5 4 Size of lesions Small Medium 11 Large 4 13 18 Total There were 18 patients with different grades, number and extent of lesions The complete cure rate in group (82.76%) was higher than that in group (50%; p < 0.05) Table 4: Results after weeks of treatment Criteria Clinical Mycology Number Percentage Cure 49 87.5 Not cure 0 Not return 12.5 100.0 Total 56 Negative Positive Not return Total After weeks, 100% of the examined cases were completely cured Two cases had a positive mycological test at the first assessment but did not come back to retest The results showed that the drug has a good efficacy on the treatment of tinea These results are similar to many other studies evaluating the efficacy of terbinafine with rates of complete cure of about 70 100% Vidhya Lakshmi CP et al (2003) studied the efficacy of terbinafine topical 56 treatment of tinea corporis and tinea cruris and found that after weeks of treatment 100% of patients had clinical cure and negative test [8] Bonifaz A, Saul A (2000) using terbinafine cream (1 week topical treatment of tinea corporis and tinea cruris) found that the mycological cure rate was 94% and complete cure rate was 72% [6] Ledezma E (1999) found the cure rate of terbinafine 1% cream evaluated after 16 days was 71%; and after 30 days was 75% [9] JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016 In general, topical use of antifungal drugs can be effective in infections of limited area but oral formulations may be required for infections of more severe or more widespread presentation [5] Patients with spreading lesions or at special locations such as nails, hair or thick skin areas require oral antifungal therapy In the study, those patients with spread or recurrent lesion were prescribed oral terbinafine combined with topical medication This regiment had good efficacy in 100% of reexamined patients completely cured Oral terbinafine was demonstrated efficacy in the treatment of ringworm even in a short duration, in special types of the disease or on patients with disorder of immunity or endocrine The clinical and mycology cure rate two weeks after taking oral terbinafine alone were 47.1% and 47.1% in patients taking the drug for two days and 66.7% and 66.7% for three days [13] Rich P (2001) assessed the efficacy of short-duration oral terbinafine six weeks after the treatment, the rate of cure was 100% for HIV-infected patients and 83% for patients with diabetes [11] With tinea imbricata, a special type of tinea caused by Trichophyton concentricum with lesion spread peripherally over many years, weeks of oral medication had a complete cure rate of 100% and recurrent rate 16% compared to that of itraconazole (89% and 75%, respectively) [7] Table 6: Side effects Effects Group (n = 26) Group (n = 27) Number Percentage Number Percentage Nausea 0 25.93 Constipation 0 0 Flatulence 0 3.70 Diarrhea 0 0 Dizziness 0 11 40.74 Excitement 0 0 Skin lesion 0 0 (* the information of side effects could not be completed in patients) Some patients in group suffered from side effects such as nausea, flatulence or dizziness The results showed that terbinafine was relatively safe to use Research by Rich P (2001) also found that even patients with HIV infection or diabetes did not show any adverse effects when taking terbinafine [11] Although there is some concern about the potential effects of elevations of liver enzyme [5], but this risk is very low Skorepova M (2004) found that the rate of liver damage after treatment with terbinafine for onychomycosis was 1/45.000 - 50.000 patients, equivalent to paracetamol, a very common drug (5.5/100,000) [11] Due to some difficulties, liver function tests had not been done, but with a short duration of terbinafine, the risk is very low CONCLUSION Through a research on the efficacy and safety of terbinafine on 56 patients, we found the following results: 57 JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016 - weeks after treatment, the rate of clinical, mycological and complete cure were 73.21%; 85.71% and 68.76%, respectively The rate of complete cure of topical therapy was 82.76%; higher than that of combination between topical and oral therapy (50%; p < 0.05) - weeks after treatment, all patients were completely cured - Some patients experienced side effects when taking oral terbinafine: nausea (26.2%); flatulence (3.85%) and dizziness (42.31%) REFERENCES Tôn Nữ Phương Anh, Ngô Thị Minh Châu, Nguyễn Thị Hóa, Nguyễn Phước Vinh, Hà Thị Ngọc Thúy Nghiên cứu tình hình bệnh nấm da bệnh nhân đến xét nghiệm Khoa Ký sinh trùng, Bệnh viện Trường Đại học Y Dược Huế Phòng chống sốt rét bệnh ký sinh trùng 2012, số 4, tr.59-71 Lê Trần Anh, Vũ Văn Tiến Một số yếu tố ảnh hưởng bệnh nấm da bệnh nhân đến khám điều trị Bệnh viện Quaan y 103 (2013 - 2014) Phòng chống sốt rét bệnh ký sinh trùng 2014, tập 82, số 5, tr.62-68 Trương Quang Ánh, Tôn Nữ Phương Anh Bước đầu khảo sát tình hình nhiễm nấm da nấm ngoại biên bệnh nhân xét nghiệm nấm Khoa Ký sinh trùng, Bệnh viện Trường Đại học Y khoa Huế năm 2003 Phòng chống sốt rét bệnh ký sinh trùng 2004, số 6, tr.80-85 Bộ Y tế Hướng dẫn chẩn đoán điều trị bệnh da liễu ban hành kèm theo định số 75 /QĐ-BYT ngày 13/01/2015 2015 Anaissie EJ, McGinnis MR, Pfaller MA, Anstead GM, Arora A Clinical Mycology (second edi) Elsevier Inc 2009 58 Bonifaz A, Saul A Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and tinea Corporis Eur J Dermatol 2000, 10 (2), pp.107-109 Budimulja U, Kuswadji K, Bramono S, Basuki J, Judanarso LS, Untung S et al A double-blind, randomized, stratified controlled study of the treatment of tinea imbricata with oral terbinafine or itraconazole Br J Dermatol 1994, 130, Suppl 43, pp.29-31 CP Vidhya Lakshmi, Girish M Bengalorkar, V Shiva Kumar Clinical efficacy of topical terbinafine versus topical luliconazole in treatment of tinea corporis/tinea cruris patients British Journal of Pharmaceutical Research 2013, (4), pp.1001-1014 Ledezma E, JC Lopez, Marin P, Romero H, G Ferrara, De Sousa L et al Ajoene shortterm in the topical treatment of tinea cruris and tinea corporis in humans Randomized comparative study with terbinafine Arzneimittelforschung 1999, 49 (6), pp.544-547 10 M Pereiro Ferreirós Jr, FJ GarcíaMartínez, J Alonso-González Update on the treatment of superficial mycoses Actas Dermosifiliogr 2012, 103 (9), pp.778-783 11 Rich P, Houpt KR, Lamarca A, Lovén KH, Marbury TC, Matheson R, Miller B, Smith S, Wolf J Tinea corporis/tinea cruris research group, safety and efficacy of short-duration oral terbinafine for the treatment of tinea or tinea cruris corporis in subjects with HIV infection or diabetes Cutis 2001, Jul, 68 (1 Suppl), pp.15-22 12 Skorepova M Risk of liver damage caused by modern systemic antimycotics Ces-lov Derm 2004, 79 (2), pp.59-61 13 Shiraki Y, Hiruma M, Inoue A, Matsushita A, Ogawa H A short-term treatment of tinea cruris corporis with oral terbinafine and tinea [Article in Japanese] Nihon Ishinkin zasshi Gakkai 2003, 44 (2), pp.121-125  ... retest The results showed that the drug has a good efficacy on the treatment of tinea These results are similar to many other studies evaluating the efficacy of terbinafine with rates of complete... cure of about 70 100% Vidhya Lakshmi CP et al (2003) studied the efficacy of terbinafine topical 56 treatment of tinea corporis and tinea cruris and found that after weeks of treatment 100% of patients... terbinafine combined with topical medication This regiment had good efficacy in 100% of reexamined patients completely cured Oral terbinafine was demonstrated efficacy in the treatment of ringworm