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

Nội dung text: Efficacy and safety of terbinafine in the treatment of dermatophytosis at nghean provincipal leprosy, dermatology centre (2015 - 2016)

1. JOURNAL OF MILITARY PHARMACO-MEDICINE N 07-2016 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 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). Clinical and mycological assessments were made at 2 and 4 weeks after starting treatment. Results: The clinical cure after 2 weeks was 73.21% and mycological cure was 85.71%; complete cure was 68.76%. The rate of complete cure in group 1 (82.76%) was higher than group 2 (50%; p < 0.05). 4 weeks after treatment, all patients were cured completely. Patients taking only topical medication did not have undesirable effects. Some patients in group 2 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 and safety of this drug in patients with dermatophytosis at the Nghean Provincial Tinea is common disease in the Leprosy, Dermatology Centre. community and can be treated by topical or systemic antifungal agents. There are SUBJECTS AND METHOD many drugs to treat the disease with different advantages and disadvantages. 1. Patients. Terbinafine is an allylamine antifungal Patients with ringworm and agree to with good profile of efficacy and safety. be involved in the study. Around the world, there have been many 2. Materials. studies assessing the effects of the drug in the treatment of different types of tinea. Drugs: Terbinafine (brand name TERBISIL) In Vietnam, the drug is also included in 250 mg (SANTA FARMA ILAC SANAYII the list of medications to treat ringworm A.S Turkey). TRIGENOL cream 1%; (NEW but no study has yet been done to GENE PHARM Inc., Korea). evaluate its effect and safety. This study KOH solution 10 - 20%; Sabouraud has been conducted to evaluate the efficacy medium. * Nghean Provincial Leprosy - Dermatology Centre ** Military Medical University Corresponding author: Le Tran Anh (anh_lt@vmmu.edu.vn) 53
2. JOURNAL OF MILITARY PHARMACO-MEDICINE N 07-2016 3. Study design. clinical cure: clearing of 70 - 100% of Uncontrolled clinical trial. lesions; decrease: clearing 50 - 69% of lesions; not curing: clearing < 50% of Patients with ringworm (have lesions lesions. Complete cure was defined as and positive mycology test by direct mycological cure (negative microscopy) examination or culture) were graded as and clinical cure. mild, moderate and severe according to criteria by Vietnam Dermatology Association * Site and time: (mild: 1 lesion and lesion area < 1 hand; Nghean Provincial Leprosy, Dermatology moderate: 2 - 5 lesions and/or area of Centre and fungal laboratory, Department lesion from 2 - 5 hands; severe: more of Parasitology, Vietnam Military Medical than 5 lesions and/or lesions covering an University. area of more than 5 hands). 29 patients Time: October 2015 to August 2016. with mild or moderate lesions of ringworm * Statistical analysis: by SPSS 11.5 take topical terbinafine 1% daily for 2 - 4 software. weeks (group 1); 27 patients with extensive tinea or responding poorly to topical * Ethnic: this study was approved by treatment take a combination of topical the ethics committee of Vietnam National and oral terbinafine (250 mg twice a day Institute of Malariology Parasitology and for 1 - 14 days (group 2). Mycological and Entomology. All patients were well-informed clinical assessments were made after and voluntarily provided information. The 2 and 4 weeks of treatment. Clinical information is kept confidentially and used response was qualified as following: for research only. RESULTS AND DISCUSSION Table 1: Demographic characteristics of patients (n = 56). Criteria Number Percentage (%) Age Group 2 - 9 2 3.57 10 - 19 14 25.00 20 - 29 19 33.93 30 - 39 11 19.64 40 - 49 1 1.79 50 - 59 6 10.71 60 - 69 3 5.36 Mean ( X ±SD) 30.02 ± 15.067 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
3. JOURNAL OF MILITARY PHARMACO-MEDICINE N 07-2016 Table 2: Treatment regimens according to characteristics of lesions (n = 56). Criteria Group Total 1 2 Number Percentage Grade Mild 26 2 28 50.00 Moderate 3 18 21 37.50 Severe 0 7 7 12.50 Number of 1 26 4 30 53.57 lesions 2 - 5 3 16 19 33.93 > 5 0 7 7 12.50 Size of Small 25 2 27 48.21 lesions Medium 4 18 22 39.29 Large 0 7 7 12.50 Locations of Corporis 19 22 41 73.21 lesions* Crusis 7 12 19 33.93 Hand 0 3 3 5.36 Feed 2 3 5 8.93 Face 2 4 6 10.71 Head 1 0 1 1.79 Total 29 27 56 100 (* 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 2 weeks of treatment (n = 56). Mycology Total Criteria Negative Positive Number Percentage Clinical Cure 38 3 41 73.21 Decrease 10 5 15 26.79 Not cure 0 0 0 0 Total Number 48 8 56 100 Percentage (%) 85.71 14.29 After 2 weeks of treatment, the rates of clinical, mycological and complete cure were 73.21%; 85.71% and 68.76%, respectively. 55
4. JOURNAL OF MILITARY PHARMACO-MEDICINE N 07-2016 Table 4: Impact of lesion on treatment effect. Group Criteria Total 1 2 Grade Mild 3 1 4 Moderate 2 8 10 Severe 0 4 4 Number of 1 3 3 6 lesions 2 - 5 2 6 8 > 5 0 4 4 Size of lesions Small 2 1 3 Medium 3 8 11 Large 0 4 4 Total 5 13 18 There were 18 patients with different grades, number and extent of lesions. The complete cure rate in group 1 (82.76%) was higher than that in group 2 (50%; p < 0.05). Table 4: Results after 4 weeks of treatment. Criteria Number Percentage Clinical Cure 49 87.5 Not cure 0 0 Not return 7 12.5 Total 56 100.0 Mycology Negative 6 Positive 0 Not return 2 Total 8 After 4 weeks, 100% of the examined treatment of tinea corporis and tinea cases were completely cured. Two cases cruris and found that after 2 weeks of had a positive mycological test at the first treatment 100% of patients had clinical assessment but did not come back to cure and negative test [8]. Bonifaz A, retest. Saul A (2000) using terbinafine cream The results showed that the drug has a (1 week topical treatment of tinea corporis good efficacy on the treatment of tinea. and tinea cruris) found that the mycological These results are similar to many other cure rate was 94% and complete cure studies evaluating the efficacy of terbinafine rate was 72% [6]. Ledezma E (1999) with rates of complete cure of about 70 - found the cure rate of terbinafine 1% 100%. Vidhya Lakshmi CP et al (2003) cream evaluated after 16 days was studied the efficacy of terbinafine topical 71%; and after 30 days was 75% [9]. 56
5. JOURNAL OF MILITARY PHARMACO-MEDICINE N 07-2016 In general, topical use of antifungal endocrine. The clinical and mycology cure drugs can be effective in infections of rate two weeks after taking oral limited area but oral formulations may be terbinafine alone were 47.1% and 47.1% required for infections of more severe or in patients taking the drug for two days more widespread presentation [5]. Patients and 66.7% and 66.7% for three days [13]. with spreading lesions or at special locations Rich P (2001) assessed the efficacy of such as nails, hair or thick skin areas short-duration oral terbinafine six weeks require oral antifungal therapy. In the study, after the treatment, the rate of cure was those patients with spread or recurrent 100% for HIV-infected patients and 83% lesion were prescribed oral terbinafine for patients with diabetes [11]. With tinea combined with topical medication. This imbricata, a special type of tinea caused regiment had good efficacy in 100% of re- by Trichophyton concentricum with lesion examined patients completely cured. Oral spread peripherally over many years, terbinafine was demonstrated efficacy in 4 weeks of oral medication had a complete the treatment of ringworm even in a short cure rate of 100% and recurrent rate 16% duration, in special types of the disease or compared to that of itraconazole (89% on patients with disorder of immunity or and 75%, respectively) [7]. Table 6: Side effects. Effects Group 1 (n = 26) Group 2 (n = 27) Number Percentage Number Percentage Nausea 0 0 7 25.93 Constipation 0 0 0 0 Flatulence 0 0 1 3.70 Diarrhea 0 0 0 0 Dizziness 0 0 11 40.74 Excitement 0 0 0 0 Skin lesion 0 0 0 0 (* the information of side effects could not be completed in 3 patients) Some patients in group 2 suffered from after treatment with terbinafine for side effects such as nausea, flatulence onychomycosis was 1/45.000 - 50.000 or dizziness. The results showed that patients, equivalent to paracetamol, a terbinafine was relatively safe to use. very common drug (5.5/100,000) [11]. Research by Rich P (2001) also found Due to some difficulties, liver function that even patients with HIV infection or tests had not been done, but with a short diabetes did not show any adverse effects duration of terbinafine, the risk is very low. when taking terbinafine [11]. Although there is some concern about the potential CONCLUSION effects of elevations of liver enzyme [5], Through a research on the efficacy but this risk is very low. Skorepova M and safety of terbinafine on 56 patients, (2004) found that the rate of liver damage we found the following results: 57
6. JOURNAL OF MILITARY PHARMACO-MEDICINE N 07-2016 - 2 weeks after treatment, the rate of 6. Bonifaz A, Saul A. Comparative study clinical, mycological and complete cure between terbinafine 1% emulsion-gel versus were 73.21%; 85.71% and 68.76%, ketoconazole 2% cream in tinea cruris and tinea Corporis. Eur J Dermatol. 2000, 10 (2), respectively. The rate of complete cure of pp.107-109. topical therapy was 82.76%; higher than 7. Budimulja U, Kuswadji K, Bramono S, that of combination between topical and Basuki J, Judanarso LS, Untung S et al. A oral therapy (50%; p < 0.05). double-blind, randomized, stratified controlled - 4 weeks after treatment, all patients study of the treatment of tinea imbricata with were completely cured. oral terbinafine or itraconazole. Br J Dermatol. 1994, 130, Suppl 43, pp.29-31. - Some patients experienced side 8. CP. Vidhya Lakshmi, Girish M. effects when taking oral terbinafine: Bengalorkar, V. Shiva Kumar. Clinical efficacy nausea (26.2%); flatulence (3.85%) and of topical terbinafine versus topical luliconazole dizziness (42.31%). in treatment of tinea corporis/tinea cruris patients. British Journal of Pharmaceutical REFERENCES Research. 2013, 3 (4), pp.1001-1014. 1. Tôn N ữ Ph ươ ng Anh, Ngô Th ị Minh 9. Ledezma E, JC Lopez, Marin P, Romero Châu, Nguy ễn Th ị Hóa, Nguy ễn Ph ước Vinh, H, G Ferrara, De Sousa L et al. Ajoene short- Hà Th ị Ng ọc Thúy. Nghiên c ứu tình hình b ệnh term in the topical treatment of tinea cruris nấm ở da c ủa các b ệnh nhân đế n xét nghi ệm and tinea corporis in humans. Randomized tại Khoa Ký sinh trùng, B ệnh vi ện Tr ường Đạ i comparative study with terbinafine. học Y D ược Hu ế. Phòng ch ống s ốt rét và các Arzneimittelforschung. 1999, 49 (6), pp.544-547. bệnh ký sinh trùng. 2012, s ố 4, tr.59-71. 10. M. Pereiro Ferreirós Jr, FJ García- 2. Lê Tr ần Anh, V ũ V ăn Ti ến. M ột s ố y ếu Martínez, J. Alonso-González. Update on the tố ảnh h ưởng b ệnh n ấm da trên b ệnh nhân treatment of superficial mycoses. Actas đến khám và điều tr ị t ại B ệnh vi ện Quaan y Dermosifiliogr. 2012, 103 (9), pp.778-783. 103 (2013 - 2014). Phòng ch ống s ốt rét và 11. Rich P, Houpt KR, Lamarca A, Lovén các b ệnh ký sinh trùng. 2014, t ập 82, s ố 5, KH, Marbury TC, Matheson R, Miller B, Smith tr.62-68. S, Wolf J. Tinea corporis/tinea cruris research group, safety and efficacy of short-duration 3. Tr ươ ng Quang Ánh, Tôn N ữ Ph ươ ng oral terbinafine for the treatment of tinea or Anh. Bước đầ u kh ảo sát tình hình nhi ễm n ấm tinea cruris corporis in subjects with HIV da và n ấm ngo ại biên ở b ệnh nhân được xét infection or diabetes. Cutis. 2001, Jul, 68 nghi ệm n ấm t ại Khoa Ký sinh trùng, B ệnh (1 Suppl), pp.15-22. vi ện Tr ường Đạ i h ọc Y khoa Hu ế trong n ăm 12. Skorepova M. Risk of liver damage 2003. Phòng ch ống s ốt rét và các b ệnh ký caused by modern systemic antimycotics. sinh trùng. 2004, s ố 6, tr.80-85. Ces-lov Derm. 2004, 79 (2), pp.59-61. 4. Bộ Y t ế. H ướng d ẫn ch ẩn đoán và điều 13. Shiraki Y, Hiruma M, Inoue A, tr ị các b ệnh da li ễu ban hành kèm theo quy ết Matsushita A, Ogawa H. A short-term định s ố 75 /Q Đ-BYT ngày 13/01/2015. 2015. treatment of tinea cruris corporis with oral 5. Anaissie EJ, McGinnis MR, Pfaller MA, terbinafine and tinea. [Article in Japanese] Anstead GM, Arora A. Clinical Mycology Nihon Ishinkin zasshi Gakkai. 2003, 44 (2), (second edi). Elsevier Inc. 2009. pp.121-125. 58