Pharmacovigilance and Ranitidine Withdrawal Awareness among Libyan Private Pharmacies (Gharyan): A Cross-Sectional Study

INTRODUCTION

Drug safety is linked to the term pharmacovigilance (PV), which identifies adverse drug reactions (ADRs) after their use and marketing. PV infrastructure in low- and middle-income countries remains underdeveloped [1]. Ranitidine, a histamine-2 blocker, was withdrawn in 2020, after N-nitrosodimethylamine (NDMA) — a potent carcinogen — was detected in formulations [2][3]. Libya’s PV framework is only being initiated, with limited infrastructure for drug safety monitoring. Ranitidine remains available in some pharmacies, causing public health risks [4].

The aim of the study — to detect pharmacovigilance challenges among Gharyan pharmacies and explore the new growth areas based on awareness of ranitidine withdrawal and safety issues among pharmacy employees.

MATERIALS AND METHODS

Study design and participants. A descriptive cross-sectional study was conducted from January to March 2023, involving 130 employees from 58 private pharmacies in Gharyan City, Aljabal Algharbi area — Libya. Participants included pharmacists, trainees, physicians, and non-medical staff.

Sample size. Calculated using Lemeshow and Lwanga’s formula (1991)¹ according to the equation of Steven K. Thompson as follows:

(N-1) (d×d/z×z)] +p(1–p), (1)

where: n, sample size; N, population size; P, probability (50%); d, error proportion (0.05); z: T-value confidence level 95%.

Questionnaire development. A structured questionnaire was designed in collaboration with faculty experts specialising in medical and applied statistics. This tool was based on validated surveys from prior studies and peer-reviewed literature to ensure robustness. The first section captured essential demographic characteristics of the participants. These included age (categorised as 19–24, 25–30, 31–36, 37–42, 43–48), sex (male/female), professional specialisation (trainee student, intermediate institute pharmacy diploma, advanced institute pharmacy diploma, pharmacy bachelor’s degree, dentist, general physician, non-medical profession), distinguishing between private and public sector practice where applicable for trainee student, intermediate institute pharmacy diploma, advanced institute pharmacy diploma, and pharmacy bachelor’s degree, and years of professional experience (grouped as 1–5, 6–10, 11–15, 16 and above). The second section focuses on the concept of PV and contains six questions about the PV fundamentals that can be answered with “Yes” or “No”. Meanwhile, the third section relates to knowledge about ranitidine and the reasons for its withdrawal from the pharmaceutical market. It also includes six questions that can be answered with “Yes” or “No”.

Data collection. Surveys were conducted in person at participating pharmacies during both morning and evening shifts to provide diverse staff availability. Participation was fully voluntary, and informed consent was secured before the questionnaires were distributed. Researchers were on hand to clarify any questions immediately, ensuring everything was understood. Ethical practices were prioritised by anonymising responses and underscoring the importance of respondent choice. This approach effectively combined comprehensive questionnaire design with a systematic and ethically responsible method of data collection, aimed at identifying gaps in knowledge regarding PV and drug safety practices.

Statistical analysis. Frequencies and percentages were computed using IBM SPSS Statistics Version No. 23.

RESULTS

To study the demographic factors, the researchers worked with a total of 130 employees. The largest age group was 25–30 years, with a total number of participants 45 (34.6%), and the smallest age groups were 37–42 and 43–48 years, 8 employees each (6.2%). The workforce was relatively young, with the majority (67.7%) being 30 years old or younger. The Figure 1 shows the age distribution of the employees in private pharmacies in Gharyan city.

Regarding gender distribution, there were 46 (35.4%) male employees, while the female employees made 84 (64.6%). Otherwise, Table 1 provides a clear overview of the educational background of the participants.

The most common qualification was “higher diploma in pharmacy (private)”, with 38 (29.2%) employees. “General medicine”, a slightly lower qualification, was reported in 37 employees (28.5%). While the least common qualifications were “intermediate diploma in pharmacy (private)” and “non-medical profession”, each held by 2 employees, or 1.5% of the total. As for the number of pharmacists who held bachelor’s degrees, they represented only 10 (7.7%) of the total number. Meanwhile, according to the years of experience of the study sample, it was found that most employees had 1–5 years of experience, with 84 (64.6%) sampled. As the experience increased, the percentage of participants decreased, so we found that only 7 (5.4%) employees had an experience of 16 years or more, which constitutes the lowest percentage (Fig. 2).

For the PV concepts, nearly a third of participants (36.2%) did not know the term “pharmacovigilance”, and more than two-thirds of participants (63.8%) did not know that there was a PV center in Libya. This contradicts the participants’ answers about the center’s distribution of reports on drug side effects, as approximately (82%) answered “Yes”, and a small percentage of participants (16.2%) had previously prepared reports on drug side effects. Regarding the participants’ awareness about previous drug withdrawals due to their risks, less than two-thirds of the participants (55.4%) were aware of drug withdrawals by the Food and Drug Administration (FDA), while 44.6% were not aware of withdrawals (see Table 2).

Concerning ranitidine withdrawal variables, the majority of responses (79.2%) are “Yes” for prescription of ranitidine recently in pharmacy, which indicates a lack of vigilance regarding withdrawing ranitidine by FDA². 69.2% of respondents did not know that ranitidine is a H2 blocker and misclassified it as an antihistamine, 61.5% of respondents answer “Yes” for that ranitidine causes carcinogenic impurity due to manufacturing, suggesting that most respondents are not aware of cancer risk due to improper storage or expired manufacturing dates exactly (Table 3).

DISCUSSION

This study reveals significant gaps in PV awareness and knowledge regarding ranitidine withdrawal among private pharmacy employees in Gharyan City, Libya. Although 63.8% of surveyed individuals reported familiarity with PV concepts, only previously filled out ADR reporting protocols (see Table 2). This notable disparity between theoretical awareness of the participants and practical knowledge points to systemic challenges observed in other low-resource settings, such as Morocco and Egypt, with fragmented PV systems and insufficient training regarding effective drug safety practices [1][5].

A concerning revelation is that 79.2% of respondents continued dispensing ranitidine despite its global withdrawal in 2020. This regulatory noncompliance underscores gaps in both policy enforcement and availability of updated drug safety information. For instance, ranitidine is not a typical antihistamine. While it is classified as an H2 receptor antagonist, 30.8% responded that ranitidine is an antihistamine, which indicates a lack of understanding of the drug’s classification by employees. Similar misclassifications have been documented in Saudi Arabia, where even licensed pharmacists struggled with drug categorisation, indicating broader regional educational deficiencies [6].

Notably, a survey revealed that while 61.5% of respondents linked NDMA impurities with manufacturing, only 36.1% understood its association with improper storage. This observation supports existing research indicating that high temperatures can lead to increased NDMA levels in ranitidine — a detail that is often overlooked in discussions of drug safety [2][7]. The emphasis on manufacturing over storage risks may reflect a broader oversight in PV training programs, which rarely address real-world drug-handling scenarios. Such gaps highlight the urgent need for context-specific educational interventions that bridge theoretical knowledge and practical application.

The study’s cross-sectional design limits causal inferences, and self-reported data may introduce recall bias. Geographic restriction to Gharyan City also affects generalisability, though the predominantly young, female workforce mirror demographic trends in Libyan urban pharmacies [4]. Despite these limitations, the findings underscore actionable priorities: integrating PV modules into pharmacy education, enforcing drug withdrawal protocols, and launching community initiatives stimulating public activity to emphasise NDMA risks. Collaborative efforts between policymakers and educators, as seen in Tunisia’s successful PV reforms, could serve as a model for Libya [8].

CONCLUSION

This study reveals critical gaps in PV awareness and ranitidine-related knowledge among Gharyan City’s private pharmacy employees. In particular, low PV awareness goes with ranitidine being dispensed from the pharmacies and pharmacy employees misclassifying the drug / underestimating its risks. Persistent dispensing of withdrawn medications, coupled with pharmacological misclassifications, points out the need for urgent systemic reforms. To mitigate public health risks, Libya’s Ministry of Health must prioritise standardised PV training, stringent regulatory oversight, and multidisciplinary collaborations to enhance drug safety guidelines. Future research should evaluate the long-term impact of educational interventions and assess NDMA contamination levels in retained ranitidine stocks. By addressing these gaps, Libya has the opportunity to enhance its PV practices in line with global standards, ensuring the health and safety of patients within the changing pharmaceutical vision.

Authors’ contributions. All the authors confirm that they meet the ICMJE criteria for authorship. The most significant contributions were as follows. Ali A. Abeed drafted the manuscript and revised it based on the peer-review results. Alaa M. Abousaken worked with databases, drafted the manuscript, and prepared illustrations. Fathya M. Abd alwafy and Khadija M. Akef developed the general study concept, managed the project, and approved the final version. Murooj A. Artail and Raneem M. Aboabdulla designed the study and edited the manuscript.

Вклад авторов. Все авторы подтверждают соответствие своего авторства критериям ICMJE. Наибольший вклад распределен следующим образом: Али А. Абид — написание текста рукописи, доработка после рецензирования; Алаа М. Абусакен — работа с базами данных, подготовка графических материалов; Фатхья М. Абд Альвафи и Хадижа М. Аскеф — концепция работы, критический пересмотр текста рукописи, утверждение окончательной версии рукописи для публикации; Мурудж А. Артаиль и Раним М. Абуабдулла — дизайн исследования, редактирование текста рукописи.