– Swalife Foundation; Biopress Division 1.1 Definition of Pharmacovigilance Pharmacovigilance is the science and activities related to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems. It certifies the reliability of medicinal products and protects public health by tracking potential threats and benefits of pharmaceutical products over the course of their life. 1.2 Concept of Pharmacovigilance: Pharmacovigilance is an essential element of the healthcare framework and involves the following fundamental features: i. Adverse Drug Reaction (ADR) Monitoring : Detecting and notifying adverse effects caused by drugs upon being marketed e.g. monitoring severe side effects of a recently introduced vaccine. ii .

Risk Assessment and Management: Evaluating the risks associated with a drug and implementing strategies to minimize them e.g. adding warning labels to a drug if it is found to cause liver damage. iii. Signal Detection: Identifying potential safety concerns based on data from clinical trials, post-marketing surveillance, and other sources e.g. detecting a signal that a drug may increase the risk of heart attacks. iv. Regulatory Compliance: Guaranteeing adherence of pharmaceutical companies to regulatory standards for drug safety monitoring e.g. providing regular safety update submissions to regulatory authorities. v.

Public Health Protection: Safeguarding patients by ensuring that the advantages of a drug surpass its drawbacks e.g. recalling a medication if it is found to cause severe side effects. vi. Global Collaboration: Sharing drug safety information across countries to improve global health outcomes e.g. WHO’s International Drug Monitoring Program. 1.2.1 Importance of Pharmacovigilance: Assures the safe use of medicines, identifies unexplored adverse effects, enhances patient care and public health and enhances faith in pharmaceutical products and healthcare systems. 1.2.2 Practical Example to understand Pharmacovigilance: Scenario: A new antibiotic, Xyzin, is approved for treating bacterial infections.

After its release, patients and healthcare providers start reporting unexpected side effects. Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Table 1: Shows steps taken after receiving unexpected side effects a new antibiotic S.NO. DETECTION REASONS/ACTIONS Step 1 Detection of Adverse Drug Reaction (ADR) A patient taking Xyzin for a urinary tract infection develops severe liver damage, which was not observed during clinical trials.

The healthcare provider reports this adverse event to the national pharmacovigilance center or the drug manufacturer. Step 2 Data Collection and Analysis Spontaneous reports from healthcare providers. Patient complaints.

Literature reviews Clinical studies They analyze the data to identify patterns or signals suggesting a link between Xyzin and liver damage. Step 3 Risk Assessment The team evaluates the severity, frequency, and causality of the adverse event. They determine if the liver damage is a rare but serious side effect of Xyzin.

Step 4 Regulatory Action If the risk is confirmed, regulatory authorities (e.g., FDA, EMA) may take action, such as: Updating the drug label with a warning about liver damage. Restricting the use of Xyzin in patients with pre-existing liver conditions. In extreme cases, withdrawing the drug from the market.

Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Step 5 Communication and Prevention Healthcare providers and patients are informed about the risks through: Drug safety alerts. Updated prescribing guidelines This helps prevent further cases of liver damage and ensures safer use of the drug. Key takeaways from Xyzin case: - Pharmacovigilance is a continuous process that begins after a drug is marketed. - It relies on collaboration between healthcare providers, patients, regulators, and pharmaceutical companies. - The ultimate goal is to protect public health by minimizing risks associated with medication use 1 . 1.3 History and development of pharmacovigilance The history and development of pharmacovigilance is a fascinating journey that reflects the evolution of drug safety monitoring over the decades.

Table 2: Journey of Pharmacovigilance from beginning to present S.No. Year since beginning Happenings 1 Early Beginnings (Pre-20th Century) The concept of monitoring drug safety dates back to ancient times when natural remedies were used, and their effects were observed. However, systematic pharmacovigilance did not exist until the 20th century. 2 The Thalidomide Tragedy (1960s) The thalidomide disaster in the early 1960s established a transformative phase in the history of pharmacovigilance.

Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Thalidomide, a drug prescribed for morning sickness in pregnant women, led to severe birth abnormalities (Phocomelia) in thousands of babies globally. This tragedy focused on the requirement for systematic monitoring of drug safety and resulted in the formation of formal pharmacovigilance systems. 3 Establishment of Regulatory Frameworks (1960s-1970s) In rection to the thalidomide tragedy, numerous nations founded regulatory agencies to monitor drug safety. The World Health Organization (WHO) started the International Drug Monitoring Program in 1968 to gather and evaluate adverse drug reaction (ADR) data globally.

The U.S. Food and Drug Administration (FDA) enforced tighter guidelines for drug approval and post-marketing surveillance. 4 Growth of Pharmacovigilance Systems (1980s-1990s) During this period, pharmacovigilance systems became more structured and sophisticated. The European Medicines Agency (EMA) was established in 1995, reinforcing drug safety monitoring in Europe.

The concept of risk management and signal detection gained prominence. 5 Modern Pharmacovigilance (21st Century) Pharmacovigilance has evolved into a global science with advanced tools and technologies. Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division The use of big data, artificial intelligence (AI), and real-world evidence (RWE) has revolutionized drug safety monitoring. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) established protocols like ICH E2E to standardize pharmacovigilance practices worldwide.

The focus has shifted from reactive pharmacovigilance (responding to ADRs) to proactive risk management and prevention. 1.3.1 Key Milestones in Pharmacovigilance: Table 3: Milestones in Pharmacovigilance from 1961 to present S.NO. YEAR HAPPENING 1 1961 Thalidomide tragedy highlights the need for drug safety monitoring. 2 1968 WHO launches the International Drug Monitoring Program. 3 1995 Establishment of the European Medicines Agency (EMA). 4 2004 ICH E2E guidelines on pharmacovigilance planning. 5 2010 Introduction of risk management plans (RMPs) and pharmacovigilance legislation in the EU. 6 2020 Use of AI and big data for real-time pharmacovigilance. 1.4 Importance of safety monitoring of medicines Ensuring the safety of medicines is paramount in healthcare, as it directly impacts patient well-being and public health. Safety monitoring, or pharmacovigilance, involves the Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems.

This approach is significant for a number of reasons: i. Detection of Adverse Drug Reactions (ADRs): despite conducting thorough clinical trials, partial potential adverse effects of a medication may be identified. Persistent observation facilitates the discovery of infrequent or prolonged ADRs that may not have been noticeable throughout pre-market testing. ii.

Ensuring Patient Safety: By detecting and evaluating ADRs, healthcare providers can reach knowledgeable conclusions about prescribing practices, consequently lessening patient harm. iii. Regulatory Compliance: Pharmacovigilance is a legal requirement in many countries. Regulatory agencies mandate the reporting and monitoring of drug safety to ensure that the benefits of a medication outweigh its risks. iv.

Enhancing Public Health: Monitoring the safety of medicines contributes to the overall health of the population by preventing widespread adverse effects and ensuring the availability of safe therapeutic options 2 . 1.4.1 Practical example: Real-world scenario to highlight the necessity of medication safety tracking Safety monitoring of medicines, also known as pharmacovigilance, is essential for guaranteeing that drugs are safe and effective for public use. Even after rigorous clinical trials, some adverse effects may only become apparent when a drug is used by a larger, more diverse population over a longer period. Safety monitoring helps identify, evaluate, and mitigate these risks, protecting patients and improving public health.

The Case of Rofecoxib (Vioxx) Rofecoxib, marketed as Vioxx, was a widely prescribed nonsteroidal anti-inflammatory drug (NSAID) approved for pain relief, particularly for arthritis. During clinical trials, it showed promise for reducing gastrointestinal side effects compared to older NSAIDs. However, after its approval and widespread use, concerns about its cardiovascular safety emerged.

Table 4: Steps taken after receiving unexpected side effects of Vioxx (NSAID) Steps Step name Reasons/actions Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Step 1 Post-Marketing Surveillance After Vioxx was released, reports of heart attacks and strokes in patients taking the drug began to surface. These adverse events were not fully identified during pre-marketing clinical trials, which involved a smaller, controlled population. Step 2 Data Collection and Signal Detection Pharmacovigilance systems collected data from: Spontaneous reports from healthcare providers.

Observational studies and clinical trials. Patient registries and databases. Patient registries and databases.

A signal was detected suggesting a potential link between Vioxx and increased cardiovascular risks. Step 3 Risk Assessment Researchers analyzed the data and found that long-term use of Vioxx significantly increased the risk of heart attacks and strokes. The risk was particularly high in patients with pre-existing cardiovascular conditions.

Step 4 Regulatory Action In 2004, the manufacturer voluntarily withdrew Vioxx from the market after discussions with regulatory authorities like the FDA (U.S. Food and Drug Administration). This decision was based on the evidence of increased cardiovascular risks associated with the drug.

Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Step 5 Communication and Prevention Regulatory agencies issued public health advisories to inform healthcare providers and patients about the risks of Vioxx. Prescribing practices were updated, and alternative treatments were recommended for patients requiring pain relief. Importance of Safety Monitoring in This Case: i.

Identifying Unknown Risks: Clinical trials cannot detect all adverse effects, especially rare or long-term ones. Safety monitoring helps identify these risks post-approval. ii. Protecting Public Health: The withdrawal of Vioxx prevented further harm to patients and highlighted the importance of ongoing surveillance. iii.

Improving Drug Safety: The matter caused the implementation of tougher guidelines and superior pharmacovigilance practices for monitoring drug safety. iv. Building Trust: Effective safety monitoring ensures that patients and healthcare providers can trust the medicines they use. Safety monitoring is essential because clinical trials have limitations in detecting all potential risks.

Pharmacovigilance systems play a critical role in protecting patients and ensuring the safe use of medicines. The Vioxx case is a landmark example of how safety monitoring can prevent widespread harm and improve drug regulation 3 . 1.5 WHO International drug monitoring programme The WHO Programme for International Drug Monitoring (PIDM) is a global pharmacovigilance initiative aimed at detecting, assessing, preventing, and understanding adverse drug reactions (ADRs) and other drug-related problems. It was initiated in 1968 as a reaction to the thalidomide disaster, which emphasized the necessity for a global drug safety monitoring system. 1.5.1 Objectives of WHO PIDM The main objectives of the WHO International Drug Monitoring Programme are: Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division i.

Early Detection of ADRs – Identifying unknown or serious side effects of medicines. ii. Improving Drug Safety – Guaranteeing the worldwide use of medications are safe and effective. iii. Preventing Harm to Patients – Reducing the risk of medication-related injuries. iv.

Regulatory Decision Support – Providing data to help governments and regulatory agencies to make evidence-based decisions v. Promoting Global Pharmacovigilance Standards – Encouraging countries to adopt best practices in drug safety monitoring. 1.5.2 Uppsala Monitoring Centre (UMC) Since 1978, the Uppsala Monitoring Centre (UMC) in Sweden has been responsible for managing the WHO PIDM. It maintains VigiBase, the global database of reported ADRs.

UMC provides tools, training, and technical support to national pharmacovigilance centers. 1.5.3 How the WHO PIDM Works i. National Pharmacovigilance Centers (NPCs): Each member country has a national agency that collects reports on ADRs. ii. Data Submission to UMC: NPCs submit ADR reports to VigiBase. iii.

Signal Detection and Analysis: WHO and UMC analyze global ADR trends to detect new drug risks. iv. Regulatory Action: If a serious issue is identified, WHO may issue safety alerts, recommend label changes, or even suggest a drug recall. Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division 1.5.4 WHO steps to extend global reach As of 2022, the WHO PIDM includes 151 full member countries and 21 associate members.

This network covers over 99% of the world’s population. In 2015, WHO launched VigiAccess, an online portal for the public to access ADR data. 1.5.5 Practical example: A real-world example or case study can help in understanding the WHO International Drug Monitoring Programme more effectively. The Thalidomide Tragedy Thalidomide is a medication that was introduced and commercialized during the late 1950s and early 1960s as a sedative and treatment for morning sickness in pregnant women.

It was widely used in several countries, but its safety profile was not thoroughly understood. Destructively, thalidomide led to serious congenital abnormalities, such as phocomelia (malformed limbs), affecting thousands of infants globally. The thalidomide tragedy was a pivotal moment in the history of pharmacovigilance and led to the establishment of the WHO Programme for International Drug Monitoring (PIDM) in 1968.

Here's how the case relates to the programme: Table 5: Steps taken by WHO International Drug Monitoring Programme for The Thalidomide Tragedy S.NO. NAME OF STEP REASONS/ACTIONS Step 1 Detection of Adverse Drug Reactions (ADRs) In the early 1960s, doctors began noticing a sharp increase in babies born with severe limb deformities. Independent researchers, such as Dr.

Widukind Lenz in Germany and Dr. William McBride in Australia, linked these birth defects to thalidomide use during pregnancy. Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Step 2 Global Response and Withdrawal Once the connection was established, thalidomide was withdrawn from the market in most countries by 1961-1962.

However, the tragedy highlighted the lack of a global system for monitoring drug safety and sharing information about adverse effects. Step 3 Establishment of the WHO PIDM Following the thalidomide tragedy, the World Health Organization (WHO) established the International Drug Monitoring Programme in 1968. The initiative was designed to: Collect and analyze reports of adverse drug reactions from member countries.

Facilitate international collaboration in pharmacovigilance. Provide early warnings about drug safety issues. Step 4 Implementation of Pharmacovigilance Systems The WHO PIDM encouraged countries to establish national pharmacovigilance centers.

These centers gather information on adverse drug reactions and contribute it to VigiBase, the WHO’s global database, which acts as a centralized hub for drug safety data. Step 5 Lessons Learned and Impact The thalidomide tragedy underscored the importance of: Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Rigorous pre-marketing testing of drugs, especially for use in vulnerable populations like pregnant women. Continuous post-marketing surveillance to detect rare or long-term adverse effects.

International collaboration in pharmacovigilance to prevent similar tragedies. Key takeaways from the Thalidomide tragedy i. Global Collaboration: The WHO PIDM enables countries to share drug safety data and respond quickly to emerging risks. ii.

Early Warning System: Programmes like VigiBase help identify safety signals that may not be apparent in individual countries. iii. Preventing Future Tragedies: The thalidomide case led to stricter drug regulations and the establishment of robust pharmacovigilance systems worldwide. iv.Ongoing Vigilance: The WHO Programme for International Drug Monitoring (PIDM) remains essential in safeguarding the safety of medications worldwide. v.The thalidomide tragedy is a stark reminder of the importance of pharmacovigilance and International cooperation in drug safety monitoring. The WHO International Drug Monitoring Programme was a direct response to this tragedy and has since become a cornerstone of global efforts to protect public health 3 . 1.6 Pharmacovigilance program in India The Central Drugs Standard Control Organisation (CDSCO), New Delhi, under the aegis of Ministry of Health & Family Welfare, Government of India has initiated a nation-wide pharmacovigilance programme in July, 2010, with the All India Institute of Medical Sciences (AIIMS), New Delhi as the The National Coordinating Centre (NCC) was established to monitor Adverse Drug Reactions (ADRs) in India and protect public health.

In 2010, 22 ADR Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Monitoring Centres (AMCs), including one at AIIMS, New Delhi, were set up under this program. To make the program more effective, the NCC was moved from AIIMS, New Delhi, to the Indian Pharmacopoeia Commission (IPC) in Ghaziabad, Uttar Pradesh, in April 2011. The mission of the Pharmacovigilance Programme of India (PvPI) is to protect the health of Indians by ensuring that the benefits of medicines outweigh their risks.

Adverse drug reactions can have serious social and economic impacts, so it’s important to involve healthcare professionals and the public in a structured program to monitor ADRs across the country. The goal of PvPI is to collect and analyze data on ADRs, use the findings to recommend regulatory actions, and communicate risks to healthcare providers and the public. Beyond ADRs, the program also focuses on issues like substandard medicines, medication errors, counterfeit drugs, antimicrobial resistance, and the need for real-time monitoring during mass vaccination campaigns.

The vision of PvPI is to enhance patient safety and well-being in India by monitoring drug safety and reducing the risks associated with medicine use. The ultimate safety decisions on medicines may need considerations of comparative benefit/risk evaluations between products for similar indications, so the complexity is great. 1.6.1 Scope and Objectives Table 6: Shows the scope and objectives of Pharmacovigilance program in India S.No. Scope and Objectives of PvPI 1 To establish a nationwide system for reporting and ensuring patient safety. 2 To detect and evaluate new safety signals from reported cases. 3 To assess the balance between benefits and risks of medications available in the market. 4 To produce evidence-based insights on the safety of medicines. 5 To assist regulatory authorities in making informed decisions about medication use.

Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division 6 To become a leading center of excellence for pharmacovigilance activities in the country. 7 To share safety-related information with stakeholders to reduce risks associated with medicine use. 8 To work collaboratively with other national centers for information sharing and effective data management. 9 To offer training and consultancy services to pharmacovigilance centers worldwide. 10 To encourage the rational and appropriate use of medicines. Short Term Goals To create and implement a pharmacovigilance system across India, to initially include all medical colleges approved by the Medical Council of India, ensuring coverage in the northern, southern, eastern, and western regions of the country, to motivate healthcare professionals to report adverse reactions related to drugs, vaccines, medical devices, and biological products and to gather case reports and data for analysis and monitoring. Long Term Goals To extend the pharmacovigilance program to include all hospitals (both government and private) and public health centers across India, to design and implement an electronic reporting system (e-reporting) for efficient data collection, to foster a culture of reporting among healthcare professionals and to mandate adverse drug reaction (ADR) reporting for all healthcare professionals 6 . 1.6.2 Reporting ADRs 1.6.2.1 Who can report Table 7: Persons who can report adverse drug reactions S.NO.

WHO CAN REPORT Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division 1 Consumers/patients Fig 1: Patient can report ADR (Courtesy: www. healthcarebusinessclub.com ) 2 Physicians Fig 2: Physicians can report ADR (Courtesy: www. writergirl.com ) 3 Pharmacists Fig 3: Pharmacists can report ADR Courtesy: www. goodrx.com 4 Nurses Fig 4: Nurses can report ADR (Courtesy: www. alamy.com ) 5 Healthcare professionals Fig 5: Healthcare professionals can report ADR (Courtesy: www. myhealthcareinsider.com ) Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division 6 Pharmaceutical companies Fig 6: Pharmaceutical comapnies can report ADR (Courtesy: www. indoreinstitute.com ) 7 ADR Monitoring centres (Hospitals) Fig 7: AMCs can report ADR (Courtesy: www. manipal.edu ) 1.6.2.2 Whom to report? Table 8: Shows the concerned person/organization to whom adverse drug reactions will be reported and how S.NO. WHOM TO REPORT HOW TO REPORT PICTORIAL EXPLANATION 1 National Coordination Centre (NCC) Online form submission available on website http://www.ipc.gov.in or htttp://www.cdsco.nic.in Fig 8: National Coordination Centre (NCC) (Courtesy: http://www.ipc.gov.in) 2 ADR monitoring centres (AMCs) Hospitals Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Fig 9: ADR monitoring centres (AMCs) (Courtesy: www. manipal.edu ) 3 Pharmacovigilance programme in India (PvPI) Helpline 1800-180-3024 Fig 10: Pharmacovigilance programme in India (PvPI) Helpline (Courtesy: http://www.ipc.gov.in) 4 Pharmacovigilance programme in India (PvPI) Mobile app ADR PvPI Fig 11: Pharmacovigilance programme in India (PvPI) Mobile app (Courtesy: http://www.ipc.gov.in) 5 Email icsr.nccpvpi@gmail.com and pvpi.compat@gmail.com Fig 12: Email (Courtesy: www. play.google.com ) 6 National Formulary of India (NFI) The ADR reporting form, included at the end of the National Formulary of India (NFI) 2016, is used to document suspected adverse drug reactions.

Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Fig 13: National Formulary of India (NFI) (Courtesy: http://www.ipc.gov.in) 1.6.2.3 Why to report? Table 9: Shows purpose of reporting adverse drug reactions S.NO. REASONS 1 To ensure health safety. 2 To use research and evidence to minimize risks associated with drugs. 3 To use data to promote the safe use of medicines. 4 To support quick regulatory decisions through a comprehensive database. 5 To increase awareness and encourage reporting of adverse drug reactions (ADRs). 1.6.2.4 What to report?

Table 10: What to report regarding adverse drug reactions S.NO. WHAT TO REPORT? FOR WHAT? 1 ADRs/Suspected ADRs Known or unknown, Serious or non-serious, Frequent or rare, Medicines, Medical Devices, Biologicals including Vaccines, Herbal Drugs/Nutraceuticals, etc 2 Off-label Use Using medications for conditions or purposes not officially approved.

Administering medicines to age groups, at dosages, or through routes not authorized or recommended. Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division 3 Misuse Using a medication for a purpose or in a way that differs from its approved instructions or intended use. Consuming medication in higher doses, more frequently, or over an extended duration than prescribed. 4 Overdose Taking or applying a medication in amounts significantly higher than the recommended dose.

An overdose can occur either deliberately or unintentionally. 5 Abuse Using a substance for psychological effects, to create dependency, or as part of a suicide attempt or gesture, outside of medical purposes. Any use of substances for enjoyment or leisure purposes, regardless of the reason. 6 Special focus on drug use in Pregnancy Lactation Paediatric population Geriatric population 1.6.3 Drug safety alerts published by the Pharmacovigilance Programme of India (PvPI) between April 2018 and March 2019. Table 11: Drugs safety alerts issued by Pharmacovigilance program in India from April 2018 to March 2019 S.

No. Suspect Drug Indication/s Adverse Drug Reaction Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division 1 Cefixime Used to treat otitis media, respiratory tract infections, and uncomplicated urinary tract infections (UTIs), and effective against infections caused by Enterobacteriaceae and Haemophilus influenzae species. Skin Hyperpigmentation (excess production of melanin, the pigment responsible for skin color) 2 Dexamethasone Used as an additional treatment in emergency cases of anaphylaxis, for short-term control of inflammation in allergic conditions, for managing adrenocortical insufficiency, and for ocular-related issues.

Peripheral Neuropathy (dysfunction of the nerves outside the brain and spinal cord) 3 Fluoxetine Bipolar disorder, Depressive episode Hypoacusis (Hearing impairment) 4 Telmisartan Hypertension Lichenoid Keratosis (small and scaly patch on the skin) 5 Miltefosine Directly Observed Therapy (DOT) for treating visceral leishmaniasis caused by Leishmania donovani . Acute Pancreatitis (sudden inflammation of the pancreas) 6 Levetiracetam Anti-epileptic uses: 1. As a standalone treatment for partial onset seizures, with or without secondary generalization, in patients over 16 years who are newly diagnosed. 2.

As an additional treatment for myoclonic seizures in adults and Anencephaly (severe congenital birth defect, baby born without parts of the brain and skull) Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division adolescents aged 12 years and older. 3. For treating primary generalized tonic-clonic seizures in adults and adolescents aged 12 years and older with idiopathic generalized epilepsy. 7 Cetirizine Used to treat seasonal or year-round allergic rhinitis and chronic idiopathic urticaria in infants and children. Tachycardia (faster-than-normal heart rate) 8 Dabigatran Used to prevent stroke and systemic embolism, as well as to reduce vascular mortality, in adult patients with atrial fibrillation.

Alopecia (Hair loss or baldness) 9 Sertraline Major depressive disorders, obsessive-compulsive disorders (OCD), and panic disorders. Maculopathy (Disease affecting the central part of the retina in the eye) 1.6.4 Monitoring of Antitubercular Drugs Tuberculosis (TB) is a major public health issue in India, and antitubercular drugs like Isoniazid, Rifampicin, and Pyrazinamide are widely used. While these drugs are effective, they are also associated with significant adverse effects, such as hepatotoxicity (liver damage), peripheral neuropathy, and gastrointestinal issues.

The PvPI plays a critical role in monitoring these adverse effects and ensuring the safe use of antitubercular drugs. Table 12: Monitoring of antitubercular drugs under pharmacovigilance program in India S.NO. NAME OF STEP REASONS/ACTIONS Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Step 1 ADR Reporting A patient undergoing TB treatment develops severe jaundice and liver dysfunction after starting antitubercular therapy.

The healthcare provider suspects drug-induced hepatotoxicity and reports the case to the nearest Adverse Drug Reaction Monitoring Center (AMC), which is part of the PvPI network. Step 2 Data Collection and Analysis The AMC collects detailed information about the patient, including: Demographics (age, gender, weight). Medical history Details of the suspected drugs (dose, duration, combination therapy) Description of the adverse reaction The data is entered into the PvPI database and shared with the National Coordination Centre (NCC) at the Indian Pharmacopoeia Commission.

Step 3 Signal Detection and Risk Assessment The NCC analyzes the data to identify patterns or signals of hepatotoxicity associated with antitubercular drugs. If a significant number of similar ADR reports are received, the NCC conducts a detailed risk assessment to determine the causality and severity of the adverse effect. Step 4 Regulatory Action and Communication Based on the findings, the NCC may recommend: Updating the drug label to include a warning about hepatotoxicity.

Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division Revising treatment guidelines to include regular liver function tests for patients on antitubercular therapy. Educating healthcare providers and patients about the risks and symptoms of liver damage. The findings are also shared with the World Health Organization (WHO) through the Uppsala Monitoring Centre (UMC) to contribute to global pharmacovigilance efforts.

Step 5 Prevention and Follow-Up The PvPI ensures that healthcare providers are aware of the risks and monitoring requirements for antitubercular drugs. Patients are advised to report any symptoms of liver damage, such as jaundice, dark urine, or abdominal pain, immediately. The program also conducts follow-up studies to assess the effectiveness of the interventions and monitor long-term safety.

Key takeaways from monitoring of Antitubercular drugs i. Patient Safety: The PvPI ensures that adverse effects of medicines are promptly identified and addressed to protect patients. ii. Healthcare Provider Awareness: The program educates healthcare providers about the risks associated with commonly used drugs like antitubercular medications. iii.

Data-Driven Decisions: The PvPI relies on data collection and analysis to make evidence-based recommendations for drug safety. iv. Global Contribution: India's pharmacovigilance efforts contribute to global drug safety monitoring through collaboration with the WHO. Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division The Pharmacovigilance Programme of India (PvPI) is crucial for promoting the safe and effective use of medications across the country.

The monitoring of antitubercular drugs is a practical example of how the program identifies, assesses, and mitigates risks associated with widely used medications, ultimately safeguarding public health 3 . 1.7 Conclusion: This chapter focuses on Pharmacovigilance, which ensures the safety of medicines and protects public health by monitoring the risks and benefits of drugs throughout their lifecycle. It covers the history and development of Pharmacovigilance, explaining how it started and evolved over time. The chapter also highlights the importance of safety monitoring of medicines, which involves detecting, assessing, understanding, and preventing side effects or other drug-related issues.

Additionally, it discusses the WHO Programme for International Drug Monitoring, a global initiative that emphasizes the need for worldwide drug safety monitoring. The chapter also explores the Pharmacovigilance Programme of India, which identifies and analyzes new safety signals from reported cases of adverse drug reactions. To make the topics easier to understand, the chapter includes practical examples.

These examples help students, researchers, and professionals grasp the concepts clearly and apply them effectively in their studies, work, or research. Disclaimer: Assistance from ChatGPT AI, Deepseek AI, Quillbot paraphrasing tool, and Galaxy synonym generator was utilized in drafting this chapter. 1.8 References: 1. Waller, P., & Harrison-Woolrych, M.

(2017). Pharmacovigilance: Principles and practice (1st ed.). Wiley-Blackwell. 2.

Gupta, S. K., & Srivastava, S. (2018).

Textbook of pharmacovigilance: Ensuring the safe use of medicines (2nd ed.). Jaypee Brothers Medical Publishers. 3. Mann, R.

D., & Andrews, E. B. (2007).

Pharmacovigilance: Principles, regulation, and risk management. Wiley. 4. WHO-Uppsala Monitoring Centre (WHO-UMC), https://who-umc.org , Uppsala, Sweden 5.

WHO Pharmacovigilance Guidelines, https://www.who.int/publications-detail-redirect Textbook of Pharmacovigilance | Publisher – Swalife Foundation; Biopress Division 6. Indian Pharmacopoeia Commission. Pharmacovigilance Programme of India (PvPI).

National Coordination Centre - Pharmacovigilance Programme of India (NCC-PvPI). Retrieved [20/02/2025], from https://www.ipc.gov.in/PvPI/pv 7. Indian Pharmacopoeia Commission.

(2019). Pharmacovigilance Programme of India (PvPI), Performance Report 2018-19. Ministry of Health & Family Welfare, Government of India.

Retrieved [21/02/2025], from [www.ipc.gov.in]