Prescribing Pattern of Tablet form Antihistamines: An Overview of Cost and Expenditure in A Dermatology Clinic in Malaysia

Vol. 12, No. 4, 2022,


Introduction
Antihistaminic drugs are one of the most commonly and widely used systemic medications in the management of dermatological disorders (Kolasani et al., 2016).They are good in treating itching caused by histamine release (Ahmed & Menshawy, 2021) and mostly used for the symptomatic relief of allergic reactions like urticaria, angioedema, rhinitis, conjunctivitis, and pruritus that are associated with skin problems (Kolasani et al., 2016).There are two general types of antihistamines; first-generation antihistamines (sedating antihistamines e.g.chlorphenamine, hydroxyzine and promethazine) and second-generation antihistamines (non-sedating antihistamines e.g.loratadine, desloratadine, cetirizine and levocetirizine).In the initial choice of therapy, the prescribers prefer the second-generation antihistamines more, over the older first-generation antihistamines because they cause less sedation and cholinergic side effects (Ahmed & Menshawy, 2021).
All dermatological disorders are persistent and need lifelong treatment.As a result, antihistamine drugs are commonly prescribed in dermatology clinics.Due to the prolonged nature of the use, prescribers should undertake appropriate diagnosis and provide rational prescription of drugs by understanding both benefit and risk of drugs for patients as these are predominant in drug therapy (Suhaina, 2018).It is important to understand whether the prescriber's decision in prescribing antihistamine is influenced by factors, such as gender, age, or indication.The wide range of antihistamine availables, choices of other treatment modalities, and the complexity of interpreting specialist treatment algorithms may also influence prescribing patterns of appropriate antihistamine for each patient (Baharudin et al., 2019).Evaluation of the prescribing patterns of antihistamine can advise the prescribers on the rational drug use and improve therapeutic efficacy.Thus, this study aims are to determine; • the prescribing pattern of solid dosage form i.e., tablet (tab) for antihistamines among patients attending a dermatology clinic in Malaysia and; • the cost for each type of antihistamines prescribed.

Material and Methods
A retrospective cross-sectional study was carried out using patients' medical records who attended a dermatology clinic in Malaysia.Data was collected from electronic Information System (eIS) during the study period in 3 months from 1 January to 31 March 2021 in the dermatology clinic.The study participants included all patients who visited the dermatology Clinic during the period.Data collected consists of patients' ID (kept anonymous), prescription number, age, gender, dosage form, prescribed antihistamines, strength, dose, frequency, duration, total tablet dispensed, indications and prices of the drugs.
Collected data is entered in Microsoft Excel and analyzed for the demographic, tablet types and count, as well as cost of all the total of antihistamine that is used in dermatology Clinic.Then, the collected data also will be exported into Statistical Package for Social Science, SPSS version 26 for Windows.Pearson's Chi-square test was used to prove and show the relationship between two categorical variables (if any).The categorical variables that showed a relationship between them and were statistically significant will be the confounding factors in contributing to the prescribing pattern.A p-value of < .05 is considered significant.The collected indications were observed of antihistamine and the quantity of each antihistamine use in that particular disorder were recorded.Demographic variables, total utilization of antihistamines and use rate of first and second-generations of antihistamine among patients in Dermatology Clinic will be analyzed and summarized as frequency as well as percentages.

Result and Discussion
A total of 648 prescriptions were analyzed during the study period from 1 st January to 31 st March 2021.There were 301 male patients (46.45%) and 347 female patients (53.55%) who received antihistamine in the dermatology Clinic.
The ratio of male to female patients who have been prescribed antihistamines is close to 1:1, which reflects the overall general population in Malaysia (Mahidin, 2021).The number of male patients is slightly lesser than female patients, however the difference is not significant.Either gender has been reported to have a slightly larger sum (Kolasani et. al., 2016, Kumar & Beenta, 2009).Age demographic data (Figure 1) revealed that the highest demographic age group prescribed with antihistamines were in the age group of adults (25-59 years) followed by the elderly (60 years and above).Studies from Sarkar et al. (2003) and Kolasani et. al., (2016) show similarities with our finding where their subjects were mostly in the age group of adults, however the 60 years and above patients were recorded as the least in receiving antihistamines.
Tallies of the total number of prescriptions that include antihistamines and tablet count for each (Table 1) revealed that loratadine is the highest antihistamine prescribed in the dermatology clinic in Malaysia.However, previous reports suggest that the most prescribed antihistamines vary between studies.Kumar & Beenta (2009) found that chlorpheniramine was the most prescribed among antihistamine prescriptions.Manjusha et al. ( 2014) reported levocetirizine as the highest antihistamines type, in contrast to our data by which levocetirizine represented the least prescribed antihistamine.

Figure2: Distribution of antihistamine prescriptions based on generation
The second-generation antihistamines are prescribed more compared to the firstgeneration antihistamines with a percentage of 60.96% and 39.04% respectively (Figure 2).Four main second generation antihistamines prescribed in the dermatological clinic are loratadine, desloratadine, levocetirizine and cetirizine (Table 2).The most second-generation antihistamine that is prescribed by doctors is loratadine with 70.1%.(Table 2).Meanwhile, hydroxyzine and chlorpheniramine are the major prescribed first generation of antihistamine.Chlorpheniramine with 74.14% is the most prescribed antihistamine between the two.Second-generation antihistamines are preferred over first-generation antihistamines (Figure 2) mainly due to their favourable efficacy/safety ratio, pharmacokinetics, and lack of anticholinergic and sedative side effects, second-generation antihistamines are preferred over first-generation antihistamines (Kolasani et al., 2016).Prescriber often choose the second-generation due to having the property of being more lipophobic or hydrophilic.Furthermore, second-generation antihistamines have fewer central nervous system and anticholinergic side effects, such as sedation and dry mouth, than first-generation antihistamines (Kolasani et al., 2016).Their longer half-life allows for a more patient-friendly dosing regimen, which improves patient compliance (Kolasani et al., 2016).Therefore, the second-generation of antihistamines is more effective as they also act through different mechanisms as well.
Table 3 showed the price per tablet for each type of antihistamine prescribed in the dermatological clinic.Desloratadine (RM 0.34) is the most expensive while chlorpheniramine (RM 0.03) is the cheapest antihistamine priced per tablet.The total cost for each type is calculated based on the total tablet dispensed.The total cost of prescribed antihistamine and in use in dermatology clinic from 1 st January until 31 st March 2021 showed that loratadine has spent the highest cost (RM 3142.54)among other antihistamines with 22772 tablets prescribed, which is 50% of the total expenditure.However, the total cost of each antihistamine does not depend on its total utilisation or number of tablets prescribed.Data also suggest that the price of antihistamine per tablet dictates the total cost (Table 3), as chlorpheniramine showed that even though the total tablet prescribed is the second highest with 13990 tablets, its total cost is only the fourth highest (RM 433.69) due to price per tablet is the cheapest (RM 0.031/tab).In addition, the total cost of hydroxyzine becomes the second highest (RM 1729.92)although its total tablets prescribed (5406 tablets) is not as high as the total utilization of chlorpheniramine and cetirizine, again due to its costlier price per tablet (RM 0.32/tab).
The account on dermatology disorder and antihistamine prescription (Figure 3) is in agreement with previous studies.Manjusha et al ( 2014) suggests that the most common dermatological diseases were acne problems (31.25%)followed by eczema and psoriasis.Meanwhile, Kolasani et al. (2016) reported that psoriasis, eczema, and allergic contact dermatitis were the most common skin disorders for which antihistamines were prescribed in their study.These reports are again, in line with our finding, bar acne as most Malaysians do not seek clinic advice for the management of acne, but rather self-treat using over the counter cosmetics.The specific nature of this study limits direct comparison to other studies as there are not many recent studies that perform cost analysis (Table 3) which just focus on antihistamine in a dermatology clinic.The prescribed antihistamine that spends the highest cost in this study was loratadine, which is in contrast with the report by Kumar & Beenta (2009), which stated that diphenhydramine hydrochloride is the highest average cost in their study, followed by promethazine, chlorpheniramine maleate and cetirizine.This might be because their study was implemented to find out the cost of antihistamine use in different problems at the University Health Centre and not focused on skin diseases only.The cost cannot be the confounding factor that contributes to the prescribing pattern because there is no obvious relationship between the price and prescribing pattern.For example, loratadine is the most prescribed antihistamine although its price is not the cheapest among others.In short, the proper treatment guidelines for antihistamines prescribing may be needed to provide the cost-effective treatment by antihistamines (Kumar & Beenta, 2009).
When the types of prescribed antihistamines are analysed or broken down based on the indications (Table 4), loratadine recorded 124 prescriptions (41.47%) to treat eczema.In fact, loratadine is the most prescribed antihistamine for all indications bar for urticaria which cetirizine recorded the highest antihistamine with 9 prescriptions compared to loratadine (with 6 prescriptions).

= % calculated over total antihistamine tab
There is no policy for antihistamine prescriptions in dermatology clinics in Malaysia.However, Table 4 revealed that the trend for each antihistamine prescribed follow the dermatological disorder, recording the highest number eczema, followed by psoriasis (bar cetirizine-higher for dermatitis, and levocetirizine-higher in urticaria) and the other indications.This possible trend is confirmed by running a Chi-Square test between the indications and type of antihistamines.
The Pearson Chi-Square test showed that the p-value is less than < .05(p = .00).The analysis affirms that indications are associated with the type of antihistamine; thus, an indication (dermatological disorder) is the confounding factor that contributes to the prescribing pattern of antihistamine in the dermatology clinic.
As a comparison, other confounding factors are analysed.Pearson's Chi-Squared test was carried out to assess whether gender and age indication also bare influence on the type of antihistamine prescribed.The Pearson Chi-Square test shows that both factors have pvalue > .05(p= .053,for gender, p=.051 for age).Hence, we accept the null hypothesis as it was proved that gender and age is not related to the type of antihistamine being prescribed.

Conclusion
In conclusion, the association between indications (dermatology disorder) and type of antihistamines which was confirmed statistically saw similar outcomes reported by which the physicians prescribed the suitable antihistamine not only based on its indication but also based on patient's diagnosis as well as condition.According to Korfitis et al (2017), urticaria treatment is recommended to give preference for the second-generation H1 antihistamines as first-line therapy compared to first-generation antihistamines.This is in line with our report (Table 4) that shows second-generation antihistamines (21 prescriptions) are more prescribed in urticaria than first-generation antihistamines (hydroxyzine and chlorpheniramine with 9 prescriptions).Our study findings have shown that an indication/ type of skin disorder is the factor that contributed to the prescribing pattern while gender and age are not the factors which are similar to the study carried out by Wang et al. (2013) stating that there was no relationship between gender, age, patients' financial situation and job satisfaction with the prescription quality.In addition, the significance of the result is to appraise the rationality of antihistamine prescribing patterns.This is important to ensure rational drug use and avoid inappropriate medication to the patients.

Figure 1 :
Figure 1: Patients distribution based on age groups

Table 1 :
The total number of prescriptions that include antihistamines and tablet count for each

Table 2 :
Proportion of first and second generations antihistamine

Table 3 :
Tablet price total cost of prescribed antihistamine Type of Antihistamine Total Tablet Dispensed Price per Tablet (RM) Total Cost (RM)

Table 4 :
Prescribed antihistamine based on the different indications Indications