Adverse drug reactions(ADRs) are a worldwide problem that affects all drugs and their users also an important cause of morbidity and mortality 1. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use 2. ADRs are monitored in many countries and by the World Health Organization (WHO) since the 1960s using spontaneous reporting systems, also called ‘early warning’ systems 1. As of March 2007, the system held 3,800,000 individual case safety reports (ICSRs) contributed by national centers. By October 2014, the number of ICSRs had increased to over 10 million reports to over 150,000 medicines and vaccines. Recognizing the increasingly important role of the general public in pharmacovigilance and medicine safety a platform for the general public to access VigiBase called VigiAccess which was launched on April 17, 20153. VigiAccess database which is search database allows you to browse and view data on suspected side effects or adverse drug reactions also called ICSRs from various medicinal products more than 100 000 different medicinal products collected by national drug authorities in over 110 countries sourced from VigiBase®, the World Health Organization’s (the “WHO”) global database for ADRs, maintained by the Uppsala Monitoring Centre (the “UMC”). VigiAccess allows an opportunity to better understand how our bodies interact with medicines and help us learn more about possible side effects.
Isotretinoin (13-cis-retinoic acid) in Saudi Arabiais marketed under (XERACTAN®, ROACCUTANE® and CURACNE®). Isotretinoinis a synthetic vitamin A analog that was approved by FDA in 1982 for recalcitrant severe nodulocystic acne that has not responded toconventional therapy including:antibiotics and topical treatment.Isotretinoin has become a widely prescribed medication despite its well-known teratogenic effects due to highly potent inducing fetal abortions and malformations which is the most sever safety issue.The continued availability of Isotretinoin has been challenged due to its teratogenicity warranting further emphasis on continued patient education and the introduction of a structured, traceable, and mandated risk management program (). Other challenges have included reports of potential associations with depression, suicidal ideation, and inflammatory bowel disease. However, continued pharmacovigilance has demonstrated that these alleged risks have not been definitively associated with Isotretinoin as the causative factor and are not common enough to take away the accessibility of Isotretinoin to the millions of patients with severe acne who have experienced major improvements in their quality of life after Isotretinoin treatment. Continued vigilance and assessments of outcomes related to how Isotretinoin is utilized allows for frequent re-evaluation of how efficacy and safety can be optimized 4.
According to the FDA label the most frequent side effects (incidence ?5%) are: back pain, dry eye, arthralgia, epistaxis, lip dry, dry skin, headache, blood creatine kinase increased, cheilitis, musculoskeletal discomfort, nasopharyngitis, chapped lips, dermatitis, upper respiratory tract infection and visual acuity reduced. Isotretinoin is associated with a number of adverse effects that can be severe and limit its use for example Inflammatory bowel disease has been listed in the package insert as an adverse gastrointestinal effect of Isotretinoin.Inflammatory bowel disease (IBD) is an idiopathic and chronic intestinal inflammation. Ulcerative colitis and Crohn’s disease are the two major types of IBD. The exact mechanism by which Isotretinoin may induce IBD is unknown.
Due to limited data on the gastrointestinal ADRs and Isotretinoin use despite many published case reports also lack of study using VigiAccess database as source of information , so the aim of this study was to review all ADR reportedassociated with Isotretinoin using VigiAccess database and to particularly review ADR cases reported in gastrointestinal ADRs.
A retrospective search of the VigiAccess database from Jaunary 10, 2017 to December 22, 2017.
2.1. Data extraction:
VigiAccess database ADR search criteria include either the trade names or generic name of medications reported to cause ADRs both strategy will give same results we used the generic name (Isotretinoin) for the search. Data was collected and extracted by AA and HS on Excel file for data cleaning and management and plotted on graphs for further clarification. Focusing on the most common ADRs which are Gastrointestinal disorders, Psychiatric disorders and Skin and subcutaneous tissue disorders also the ADRs reported on pregnancy due to safety issue and well known teratogenicity finally congenital ADRs. Data was classified based on ADRs type each type extracted in individual Excel sheet. Furthermore, data about geographical distribution, age, patient sex and ADR reported by year are extracted in different Excel sheet for further management.
2.2. Data analysis
Descriptive statistics were used to analyze the data (frequency and percentages; mean ± standard deviation). Statistical analysis was performed using the Statistical Package for Social Science (SPSS) (version).
VigiAccess database shows that 3840 reports of ulcerative colitis as a suspected adverse drug reaction from Isotretinoin use and 2764 reports of Crohn’s diseas during Isotretinoin treatment this results on December, 2017.
Narrow it down by category (most common to less common)
The most commonly reported adverse reactions are Gastrointestinal disorders (13998), General disorders and administration site conditions (10309), Psychiatric disorders (12513) and Skin and subcutaneous tissue disorders (10821). In our study we focused on Gastrointestinal disorders, Psychiatric disorders, Skin and subcutaneous tissue disorders also pregnancy and congenital ADRs due to.
ICSRs reports influenced by many different factors, including but not limited to the extent of use of the product, publicity and the nature of the reactions. No information is provided on the number of patients exposed to a particular product, and it is therefore, based on the ICSRs, not possible to calculate frequency of any ADR. Moreover, collection of data is, due to e.g. differing national legislation and policies, heterogeneous between different countries. For these reasons, any interpretation of ADR data, and particularly those based on comparisons between various medicinal products, may be misleading.