List of medicines under additional safety monitoring

The list includes SFDA authorized medicines in the following categories:

• New active substance
• New biological/biosimilar product
• Advanced therapy
• Genomic variation
• Potential Class effect
• Safety in special population

List of Medicines Under Close Monitoring (XLSX)

Drug Safety Monitoring Initiatives

Proactive Drug Safety Monitoring Program

In 2019, The Saudi Food and Drug Authority (SFDA) initiated The Proactive Drug Safety Monitoring Program for post-marketing monitoring of all registered medications’ safety, including that of biosimilar and orphan medications, to monitor the safety of medicinal products more proactively and efficiently.

The objectives of this program are:

• To develop an efficient and sustainable framework for monitoring the safety of marketed medicinal products in Saudi Arabia.
• To identify a proactive approach for detecting safety signals.
• To perform a formal assessment of identified safety concerns to share with other stakeholders and the scientific community.
• To improve medication safety in the kingdom.

The SFDA action plan includes the following actions:

The drug safety assessment utilized several evidence sources, including causality assessment of global cases retrieved from the World Health Organization (WHO)’s global database of individual case safety reports (VigiBase) and local cases retrieved from the adverse drug reactions database of the national pharmacovigilance center at SFDA, literature, stringent regulatory authorities’ reviews and Periodic Benefit Risk Evaluation Reports. The WHO-Uppsala Monitoring Centre (UMC) causality assessment system and Bradford Hill criteria were used to evaluate the association between targeted drugs and potential safety signals. Based on the findings of the safety assessment review, regulatory action will be recommended.

The risk assessment may lead to requesting update to the product safety information, significant changing in marketing status (e.g., restrictions on indications or treated populations, suspension of the product license or withdrawal of the product from the market), implementing additional risk minimization measures, requesting additional data from pharmaceutical companies, or keeping the signal under routine monitoring. In some cases, no regulatory action may be needed.

Pharmacogenomics-Pharmacovigilance Project

Pharmacogenomics plays an important role in improving medication safety. The incorporation of pharmacogenomic data into pharmacovigilance activities has the potential to reduce the occurrence of adverse drug events (ADEs), thereby promoting patient safety. In 2023, The Saudi Food and Drug Authority (SFDA) initiated the Pharmacogenomics-Pharmacovigilance Project which aimed to emphasizes the significance of pharmacovigilance in the identification of potential safety signals of pharmacogenomics related ADEs. The successful implementation of this project would improve identification and evaluation of potential safety signals/information related to biomarkers associated with medication use.

The SFDA action plan includes the following actions:

• Create a comprehensive list of medicinal products that are registered by SFDA containing pharmacogenomic biomarkers.
• Perform a drug labeling assessment regarding the effect of these biomarkers on potential risk of drug-induced ADEs exclude labeled ADEs.
• Conduct a comprehensive drug safety review of the potential safety signals (unlabeled ADEs) linked to the biomarkers of interest by using various sources of evidence including unpublished clinical trials, literature, and local and global case reports and other relevant regulatory documents such as Periodic Benefit-Risk Evaluation Reports of medicinal products.

Post-Marketing Surveillance of Advanced Therapies Medicinal Products (ATMPs):

This project aims to assess ATMPs post-marketing safety by detecting and evaluating potential safety signals related to ATMPs registered in Saudi Arabia. The anticipated outcomes of this project include ensuring up to date important safety information in the labeling and to detect early any safety concerns and potential signals related to ATMPs use. These outcomes will improve the SFDA’s role in ATMPs pharmacovigilance, which will enhance the overall drug safety in Saudi Arabia and worldwide.

The SFDA action plan includes the following actions:

• Create a list ATMPs registered in Saudi Arabia for safety assessment.
• Conduct a causality assessment of global cases retrieved from VigiBase and local cases retrieved from the adverse drug reactions database of the National Pharmacovigilance Center.
• Appropriate actions will be taken based on the assessment outcomes. These may include label updates or preparing comprehensive safety reviews for potential signals using several evidence sources including unpublished clinical trials, literature, local and global case reports and Periodic Benefit-Risk Evaluation Reports of medicinal products.

Safety of Biosimilars project

This project aims to monitor the safety of biosimilar drugs marketed in Saudi Arabia. Biosimilars are substitutable drugs for innovator biologics with expectation of similar efficacy and safety. The experience of biosimilars’ post marketing monitoring is limited in the Saudi Arabia. However, biosimilar drugs is becoming broadly used worldwide.

The SFDA action plan includes the following actions:

• Retrieve local cases from the adverse drug reactions database of the national pharmacovigilance center at SFDA related to the marketed biosimilars and their reference products.
• Estimate the local reporting rates of lack of efficacy and hypersensitivity reactions to determine any significant variations between reference and biosimilar products.
• Evaluate the global adverse drug events (ADEs)’ reporting trends of reference and biosimilar products.
• Appropriate actions will be taken based on the assessment results. These may include label updates or preparing comprehensive safety reviews for potential signals using several evidence sources including unpublished clinical trials, literature, local and global spontaneous reports and Periodic Benefit-Risk Evaluation Reports.

Safety of Orphan medications Project

This project aims to monitor the safety of medications with orphan indication registered in Saudi Arabia. Orphan medications are developed to treat rare diseases. However, the indications of a medication may also be considered as ' orphan ' since may be used in the treatment of a frequent disease but may not have been developed for another additional rare indication.

The SFDA action plan includes the following actions:

• Retrieve the ADEs case reports of the selected medications from AdisInsight database.
• Conduct labelness assessment on the retrieved ADEs lists to exclude labeled ADEs.
• Prepare a comprehensive drug safety review for the safety signals (unlabeled ADEs) using several evidence sources including unpublished clinical trials, literature, local and global spontaneous reports and Periodic Benefit-Risk Evaluation Reports.

Handling and Disposal of Hazardous Medications

The SFDA initiated a project to ensure safe handling and disposal of hazardous oral medication, for the protection of public health and the environment.

According to National Institute for Occupational Safety and Health (NIOSH) in the United States (US), medications are classified as hazardous when they exhibit one or more of the following toxicity criteria in humans, animal models, or in vitro systems:

• Carcinogenicity
• Developmental toxicity (including teratogenicity)
• Reproductive toxicity
• Genotoxicity
• Organ toxicity at low doses
• Chemical structure and toxicity profile that mimic existing drugs determined to be hazardous

The SFDA action plan includes the following actions:

• Create a list of all registered hazardous oral medications.
• Assess the information in Section 6.6, “Special Precautions for Disposal,” included in the current product information of all registered hazardous oral medications.
• Request updating to the product information of hazardous oral medications to add instructions about safe handling and disposal of these medications based on the available evidence.

Safety of medication during pregnancy and lactation

During the development of new medicines, pregnant and breastfeeding women are usually excluded from clinical trials. Therefore, the post-marketing data are critically important to obtain knowledge on potential risks of medications during pregnancy and lactation. The SFDA initiated The Safety of Medication during Pregnancy and Lactation Project to detect potentially teratogenic medications, and to ensure safe use of medication during pregnancy and lactation.

The SFDA action plan includes the following actions:

• Assess the information in Section 4.6, “Fertility, Pregnancy and Lactation,” of current product information for potentially teratogenic medications registered by the SFDA.
• Classify the information in Section 4.6 as complete or incomplete based on the available evidence.
• Conduct a comprehensive drug safety review for medications with potential risk of teratogenicity using several evidence sources, including unpublished clinical trials, literature, local and global spontaneous reports, and Periodic Benefit-Risk Evaluation Reports.
• Request an update to the local product information based on available evidence.

Drug Safety in Pediatrics

The SFDA initiated The Drug Safety in Pediatrics Project to improve medication safety in children by identifying medications associated with a high risk for adverse drug events and ensure their accurate labeling and safe handling among the public and healthcare providers. The anticipated outcomes of this project include improving and ensuring accurate labeling and safe handling of high-risk medications used in the pediatric population. These outcomes will enhance the SFDA’s role in medication safety for children, which will enhance overall medication safety for children in Saudi Arabia.

The SFDA action plan includes the following actions:

• High-risk medications for children were identified based on the latest local and international studies, including the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list, which was published in 2020 as a reference tool for high-risk medications in the pediatric population. In addition, the top reported pediatric drug-ADR pairs from local and global databases of ADRs and literature
• Medications selected for the project met the following criteria: high-risk medications with strong to moderate evidence, registered in Saudi Arabia and currently used in clinical practice.
• Appropriate actions will be taken based on the assessment results. These may include label updates or preparing comprehensive safety reviews for potential signals using several evidence sources including unpublished clinical trials, literature, local and global spontaneous reports and Periodic Benefit-Risk Evaluation Reports.

Post-Marketing Surveillance of Vaccines

This project aims to ensure post-marketing safety and tolerability of vaccines recently registered in Saudi Arabia. The anticipated outcomes include improving and ensuring accurate labeling and safe handling of vaccines recently registered in Saudi Arabia and improving the formal assessment of identified safety concerns and potential signals for vaccines. These outcomes will enhance the SFDA’s role in vaccine pharmacovigilance, which will enhance overall medication safety among the Saudi population.

The SFDA action plan includes the following actions:

• Create a list of vaccines registered in the last three years for safety assessment.
• Investigation for all relevant safety data of these vaccines, including local and international labeling as well as WHO safety communications.
• Appropriate actions will be taken based on the assessment results. These may include label updates or preparing comprehensive safety reviews for potential signals using several evidence sources including unpublished clinical trials, literature, local and global spontaneous reports and Periodic Benefit-Risk Evaluation Reports.

Drug-Herbal and Drug-Drug Interaction Project

This project aims to detect potential safety signals related to drug-herbal interactions and drug-drug interactions and assess these signals based on scientific evidence to ensure safe use of medications and herbal products. Ultimately, the project outcomes will raise awareness of drug herbal and drug-drug interactions among healthcare providers and the public.

The SFDA action plan includes the following actions:

• Create a list of registered herbal products used in Saudi Arabia and a list of highly interactive medications with clinically important interactions.
• Conduct a causality assessment of global cases retrieved from VigiBase and local cases retrieved from the adverse drug reactions database of the national pharmacovigilance center at SFDA to detect potential drug-herbal interactions and drug-drug interactions.
• Conduct a review of the labelness of the current product information for the targeted herbal products and medications for assessment of potential drug-herbal interactions and drug-drug interactions.
• Conduct a systematic literature search for available evidence regarding unlabeled drug-herbal interactions and drug-drug interactions.