968 Rajathilagam T. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(8): 968-973.

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A STUDY OF PRESCRIBING PATTERN OF ANTIFUNGAL DRUGS IN DERMATOLOGY OUTPATIENT (OPD) OF A TERTIARY CARE HOSPITAL

T. Rajathilagam*1, Tasneem Sandozi2, V. Rajagopalan3, R. Jamuna Rani1

1Department of Pharmacology, SRM Medical College Hospital & Research Center, SRM University, Tamilnadu, India. 2Department of Pharmacology, Dr.V.R.K. Women's Medical College, Hyderabad, Andhra Pradesh, India. 3Department of Dermatology, SRM Medical College Hospital & Research Center, SRM University, Tamilnadu, India.

ABSTRACT A prospective cross-sectional study was done for 5 months (June - October 2011) in the dermatology outpatient department of SRM Medical College Hospital & Research Center, SRM university, Tamil Nadu to evaluate the drug utilization pattern of antifungal drugs. The prescription data of 100 patients with fungal infections of the skin was analyzed in this study. 72% of the patients presented with a single fungal lesion and 28% with fungal infections in multiple regions. The patients were predominantly (85%) treated with a combination of an oral along with a topical antifungal drug at an average of 2.32 drugs per patient. Imidazoles were the most commonly prescribed group of antifungal drugs (78%) followed by triazoles (63%), allylamines (40%) and antibiotics (4%). Fluconazole was noted to be the predominantly prescribed oral antifungal agent in the treatment of superficial fungal infections. In the topical agents eberconazole (45%) and clotrimazole (31%) were the primarily prescribed drugs. There were no reports of any severe adverse drug reactions or drug interactions during the study.

Key Words: Fungal infection, Antifungal drugs, Imidazoles, Fluconazole, Eberconazole.

INTRODUCTION antifungal therapies is limited because of toxicity, low The last two decades has seen an increase in efficacy rates and drug resistance new formulations are incidence of invasive fungal infections. The major factors being prepared to improve absorption and efficacy of some which predispose patients to invasive fungal disease of these standard therapies. Various new antifungal drugs – include chemotherapy induced prolonged neutropenia, azoles with three new additional drugs and echinocandins immunodeficiency and immunosuppression associated have also demonstrated therapeutic potential (John E. with organ transplantation, HIV infection and prolonged Bennett, 2011). corticosteroid therapy. This study was planned to evaluate the utilization of Amphotericin B was the only effective antifungal these various new antifungal drugs that may provide drug available for systemic use for a number of years. additional options for the treatment of superficial fungal Despite being highly effective in many serious infections it infections and help to overcome the limitations of current is also a very toxic drug (Don Sheppard & Harry W. treatments. The aim of the study was to evaluate the Lampiris, 2009). Currently, as the use of standard prescribing pattern of antifungal drugs in the Dermatology outpatient department of a tertiary care hospital, Chennai, Corresponding Author India.

T. Rajathilagam MATERIALS & METHODS Email: [email protected] 969 Rajathilagam T. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(8): 968-973.

Study design RESULTS Prospective, observational, cross sectional study. The prescription data of 100 patients was The study was done in the Dermatology outpatient analyzed. 61% of the patients were men and 39% were department of SRM Medical College Hospital and women (Table 1 & Figure 1). Research Centre. A prospective cross-sectional study was The men to women ratio was 1.56.The average done for 5 months (June –October 2011) after getting age of all patients was 31.96 years.Average ages of men approval from the Institutional ethical committee. The and women were 29.03 and 36.54 years respectively.72% drugs prescribed for patients with fungal infections of the of the patients presented with a single fungal lesion and skin who attended this outpatient department were noted 28% with fungal infections in multiple regions. The single down after taking verbal consent from them. lesion fungal infections were mainly (dermatophytosis) like tinea corporis, tinea versicolor, tinea cruris, tinea faciei Inclusion criteria and tinea pedis. (Table 2 & Figure 2). Fungal infections at All adult patients with fungal infections of the multiple sites included tinea cruris and glutealis, tinea skin attending the Dermatology outpatient department were cruris and corporis, tinea corporis and glutealis and tinea included in this study. cruris, corporis and glutealis. (Table 2 & Figure 3). It has been observed in this study that an average Exclusion criteria of 2.32 drugs was prescribed per patient. Majority of the Inpatients, patients with deep seated and systemic patients (85) were prescribed a combination of a topical fungal infections and children were excluded from this with an oral antifungal drug followed by solely topical or study. oral antifungal drugs in 13 and 2 patients respectively. The collected data was analyzed to estimate the prescribing (Table 3 & Figure 4). indicators and patient indicators. Imidazoles were the most commonly prescribed Prescribing indicators include: group of antifungal drugs (78%) followed by triazoles a) Average number of drugs prescribed per patient (63%), allylamines (40%) and antibiotics (4%). (Table 4 & b) % of utilization of the different classes of antifungal Figure 5). drugs Among the topical antifungals, eberconazole c) % of encounters (prescription) with an antihistaminic (45%) and clotrimazole (31%) were most frequently prescribed prescribed in this study. The other topical antifungals d) % of encounters (prescription) with a topical prescribed were terbinafine (18%), ketoconazole (3%), antifungal prescribed fluconazole (2%) and miconazole (1%). (Table 5 & Figure e) % of encounters (prescription) with a topical antibiotic 6). prescribed In the topical + oral antifungal combination therapy, Eberconazole + Fluconazole was prescribed to Patient indicators include: 31% and Clotrimazole + Fluconazole to 24% of the a) Average age of men patients. The other antifungal drugs which were prescribed b) Average age of women in combination were terbinafine, griseofulvin and c) Average age in years of all patients miconazole (Table 6 & Figure 7). d) Men to women ratio Along with antifungal drugs, antihistamines, Type of fungal infection (diagnosis) antifungal shampoos and soaps, dusting powder and antibiotics were also prescribed. (Table 7 & Figure 8).

Table 1. Sex Distribution N=100 Men 61 Women 39

Table 2. Types of fungal infection Types of fungal infection (n= 100) Fungal infection (Single lesion ) Fungal infection (multiple regions) (n= 72) (n= 28) Tinea corporis 35% (25 patients) Tinea cruris & glutealis 32% (9 patients) Tinea versicolor 29% (21 patients) Tinea cruris & corporis 29% (8 patients) Tinea cruris 26% (19 patients) Tinea corporis & glutealis 25% (7 patients) Tinea faciei 6% (4 patients) Tinea cruris, corporis & glutealis 14% (4 patients) Tinea pedis 4% (3 patients) 970 Rajathilagam T. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(8): 968-973.

Table 3. Antifungal Therapy n=100 Drug therapy Number of patients Topical + oral antifungal 85 Topical antifungal only 13 Oral antifungal only 2 Other co administered drugs 50

Table 4. Commonly prescribed antifungal drugs Drug group Percentage (%) Imidazoles 78 % (78 patients) a) Eberconazole 44% (44 patients) b) Clotrimazole 30% (30 patients) c) Ketoconazole 3% (3 patients) d) Miconazole 1% (1 patient) Triazoles -Fluconazole 63% (63 patients) Allylamines -Terbinafine 40% (40 patients) Antibiotics -Griseofulvin 4% (4 patients)

Table 5. Topical antifungal therapy n=98 Drug Percentage (% ) Eberconazole 45% (45 patients) Clotrimazole 31% (30 patients) Terbinafine 18% (17 patients) Ketoconazole 3% (3 patients) Fluconazole 2% (2 patients) Miconazole 1% (1 patient)

Table 6. Topical + Oral antifungal therapy (n=85) Drugs Percentage (% ) Eberconazole + Fluconazole 31% (26 patients) Clotrimazole + Fluconazole 24% (20 patients) Terbinafine + Fluconazole 16% (14 patients) Eberconazole + Terbinafine 15% (13 patients) Terbinafine + Terbinafine 7% (5 patients) Clotrimazole + Griseofulvin 2% (2 patients) Clotrimazole + Terbinafine 2% (2 patients) Fluconazole + Terbinafine 2% (2 patients)

Miconazole + Fluconazole 1% (1 patient)

Table 7. Other co administered drugs n= 50 Drug group Percentage (%) Antihistamines 40 patients (80%) Antifungal shampoo 3 patients (6%) Dusting powder 3 patients (6%) Antifungal soap 3 patients (6%) Antibiotics 1 patient (2%)

971 Rajathilagam T. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(8): 968-973.

Figure 1. Sex Distribution Figure 2. Fungal infection (Single Lesion)

Figure 3. Fungal infection (Multiple Regions) Figure 4. Antifungal Therapy

Figure 5. Commonly prescribed antifungal drugs Figure 6. Topical antifungal therapy

Figure 7. Topical + Oral antifungal therapy Figure 8. Other co administered drugs

972 Rajathilagam T. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(8): 968-973.

DISCUSSION triazoles by being less selective and having greater This study has shown that fungal infections were propensity to inhibit mammalian cytochrome P450 more common in men (61%) compared to women (39%). enzymes. As it has fallen out of clinical use currently being The patients mainly (72%) presented with single lesion available only for topical use as cream, foam, gel or fungal infections (tinea corporis, tinea versicolor or tinea shampoo it was prescribed topically to a very small cruris). Mixed multiple sites fungal infections (tinea cruris number of patients. and glutealis) were seen only in about 28% of the patients. Terbinafine was the second commonly prescribed The patients were predominantly (85%) treated with a antifungal drug. It is well tolerated orally. It does not seem combination of an oral along with a topical antifungal drug to affect microsomal enzyme system and has not exhibited at an average of 2.32 drugs per patient. Solely topical or any significant drug interactions till date (Don Sheppard & oral antifungal drugs were prescribed in 13 and 2% of the Harry W. Lampiris, 2009). This drug accumulates in the patients respectively. skin, nails and fat. It is effective in tinea capitis but more Antifungal agents can be discussed under two effective for onychomycoses (Sharon CA Chen and Tania main headings – systemic and topical. The antifungal C Sorrell, 2007). Topically it is more effective in tinea agents like azoles and allylamines can either be used corporis, cruris and pedis. It is less effective against topically or systemically. Many superficial mycoses may candida species but the cream can also be used in be treated systemically or topically. The azoles are cutaneous candidiasis and tinea versicolor. synthetic compounds which can be further subdivided into Topical antifungal treatment is useful in many imidazoles and triazoles depending on the number of superficial fungal infections, those confined to the stratum nitrogen atoms in their five ringed structure (Daniel J. corneum, squamous mucosa or cornea. Such diseases Sheehan et al., 1999). The imidazoles include clotrimazole, include dermatophytoses (ringworm), candidiasis and tinea ketoconazole, miconazole and eberconazole and the versicolor. Topical administration of antifungal agents is triazoles include fluconazole, itraconazole, voriconazole usually not successful for mycoses of the nails and posaconazole. Terbinafine is the antifungal drug (onychomycoses) and hair (tinea capitis). The efficacy of belonging to the allylamines. the topical agents in the treatment of superficial mycoses This study demonstrated azoles (imidazoles-78% depends on the type of lesion and also the formulation of and triazoles- 63%) as the predominantly prescribed the drug (John E. Bennett, 2011). topical as well as systemic antifungal agent. Topical imidazoles including clotrimazole, Indications for topical antifungal use are ketoconazaole, eberconazole and miconazole have a wide superficial fungal infections – dermatophytoses range of activity against dermatophytes and yeasts (ringworm), tinea versicolor and mucocutaneous (candidiasis). When applied once or twice daily to the candidiasis. Resistance to imidazoles and triazoles is very affected area it generally results in clearing of the rare among fungi that cause ringworm. Selection of one of dermatological infection in 2-3 weeks although medication these agents for topical use is based on cost and availability has to be continued until complete eradication of the of the drug as in vitro testing of fungal susceptibility to organism is confirmed (Don Sheppard & Harry W. these drugs does not predict clinical responses (John E. Lampiris, 2009). Bennett, 2011). The two most commonly used topical antifungal Systemic triazoles compared to imidazoles are agents are clotrimazole and miconazole. In this study metabolized more slowly and have less effect on human eberconazole (45%) and clotrimazole (31%) followed by sterol synthesis. On account of these advantages new terbinafine (18%) were noted to be the frequently congeners under development are mostly triazoles (John E. prescribed topical antifungal drugs. Miconazole was Bennett, 2011). Fluconazole belonging to the triazoles is prescribed only to one patient. Eberconazole has been the agent most commonly used for the treatment of shown to have broad antimicrobial spectrum of activity in mucocutaneous candidiasis. This study has also established vitro. It was found to be effective in dermatophytosis, fluconazole (63%) as the primarily prescribed oral candidiasis, infection by other yeasts such as Malassezzia antifungal drug. Its other advantages include fewer drug furfur and causative agents of pityriasis versicolor in in interactions and better gastrointestinal tolerance. Hence, it vitro and animal studies. Its effectiveness against most has the widest therapeutic index of the azoles permitting triazole resistant yeasts (Candida krusei and Candida more aggressive dosing in a variety of fungal infections glabrata) and also fluconazole resistant Candida [Don Sheppard & Harry W. Lampiris 2009]. Despite being albicans has also been demonstrated in vitro. In addition it an inhibitor of CYP 3A4 and CYP2C9, drug interactions has also been shown to be effective against Gram-positive are seen only in azotemic patients with high fluconazole bacteria. Eberconazole is also distinct from other levels or patients who receive more than 400 mg daily imidazoles in having anti-inflammatory activity which also (John E. Bennett, 2011). favors its use in the management of inflamed Ketoconazole belonging to the imidazoles was the dermatophytic infections (Latha Subramanya Moodahadu- first azole to be discovered. It is distinguished from Bangera et al., 2012). 973 Rajathilagam T. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(8): 968-973.

Irritable itching, blisters and oozing raised patches fungal infection. are few of the predominant symptoms of superficial fungal infections especially dermatophytoses. Hence in addition CONCLUSION to the relevant antifungal therapy 50% of the patients were Fluconazole was noted to be the predominantly prescribed adjuvant drugs. Antihistaminics constituted the prescribed oral antifungal agent in the treatment of bulk (80%) of these concurrently prescribed drugs along superficial fungal infections. In the topical agents with a small number of patients being prescribed antifungal eberconazole and clotrimazole were the primarily shampoo, dusting powder and antifungal soap (6% each). prescribed drugs. Terbinafine was the next choice of Antibiotics were prescribed as adjuvant drugs only in 2% antifungal agent prescribed in this study. of the patients. There were no reports of any severe adverse drug ACKNOWLEDGEMENT reactions or drug interactions during the study although all We thank Dr. James Pandian, Dean, SRM azoles are prone to drug interaction as they affect Medical College Hospital and Research Center for cytochrome P450 system of enzymes to some extent. As permitting us to conduct this study. We are also grateful to none of the patients sought advice subsequently it was the staff and faculty of Dermatology for extending all their assumed that all the patients were cured of their topical help to us during this study.

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