Drug safety and pharmacovigilance remains a dynamic clinical and scientific discipline. Pharmacovigilance is defined by the World Health Organization (WHO) as ‘the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem’ 1. Pharmacovigilance plays an important role in the rational use of medicines by providing information and evidence about adverse drug reactions (ADRs) in the general population 2. The shortcomings of clinical trials consist in the fact that they are performed under controlled conditions, usually enlist a limited number of patients and may not include some sectors of the population 3. Therefore, post marketing surveillance of drugs is necessary to ensure an understanding of the safety profile in the general population. Every country needs to have its own pharmacovigilance program due to differences in disease patterns and incidence of adverse reactions 4. The expansion of a better system of reporting ADRs has been proposed as a top priority action to prevent ADRs and adverse drug events (ADEs) in hospitals 5.
In several countries, pharmacists involved in pharmacovigilance have played an important role in suspecting ADR, providing information and instructions on the safe and appropriate use of drugs, and reducing the prevalence of adverse reactions and underreporting 6, which is probable because pharmacists who counsel patients directly, especially in the context of pharmaceutical care, are more likely to detect ADR.
Pharmacovigilance studies are essential in oncology. Antineoplastic agents are well studied and are extremely useful in the treatment of cancer, but they are used with caution due to their high toxicity and narrow therapeutic window 7. ADRs are so common and predictable in oncology that they came around to being accepted as an inevitable component of the treatment 8. Thus, onco-pharmacovigilance was developed, which is a subsystem of monitoring drugs derived from pharmacovigilance to monitor ADRs to cytotoxic antineoplastic drugs 9,10 Pharmacists specialized in oncology are in charge for a wide variety of functions, including monitoring, notification, prevention, and relief of reactions associated with chemotherapy 11.
In a one Japanese study, pharmacists were responsible for the prevention and treatment of emesis, peripheral neuropathy, hand-foot syndrome, mucositis, localized pain, constipation, vascular pain, allergy, hyperglycemia, diarrhea and other conditions 12. One study calculated the preventability of adverse drugs reactions in cancer patients and found that 53% of ADRs, such as alopecia, cannot be prevented, while 45% and 2% of reactions are probably and definitely preventable, respectively 8.
However, the lack of doctors’ ability to suspect or detect drug-related adverse events could lead to inadequate management of adverse events, exposing patients to additional risks of drugs. To minimize the suffering of patients from adverse reactions, although it is difficult, it is essential to establish a causal relationship between the drug and the event, which is the assessment of causality. By definition, causality assessment is the assessment of the probability that a particular treatment is the cause of an observed adverse event. 13 To evaluate the relationship between a pharmacological treatment and the appearance of an adverse event. It is an important component of pharmacovigilance, which contributes to a better assessment of drug risk-benefit profiles 14 and is an essential part of the evaluation of ADRs reports in early warning systems and for regulatory purposes. 15
Pharmacovigilance in Nepal
To the health of Nepalese population, Adverse drug reactions (ADRs) can be a threat. Since, there is no mandate to report ADRs by any regulatory authorities in Nepal 16. Pharmacovigilance in Nepal is still in childhood. To date, only health professionals participate and the problem of lack of notification is displayed. The National Pharmacovigilance Center is located at the national regulatory authority of Nepal, namely the Department of Drug Administration (DDA). The lack of adequate human resources to manage the pharmacovigilance program in Nepal has been a limitation for the growth of pharmacovigilance activities. Currently, there is no participation of community pharmacists in the notification process of ADR (Adverse Drug Reaction) or consumer participation in it 17.
In Nepal, hospitals report various ADRs to the regional pharmacovigilance centers and from there reports are sent to the national pharmacovigilance center at Department of Drug Administration (DDA), Ministry of Health. From here reports are sent to the Uppsala Monitoring Center (UMC), Sweden. At present, there are eight regional pharmacovigilance centers in Nepal located in teaching hospitals. These regional centers report ADRs to the national center via a web based system called ‘Vigiflow’.
In Nepal, there is no mandatory law requiring drug manufacturers to submit safety data for the Nepalese population prior to drug approval. Therefore, it is very necessary to monitor the side effects of the medicines available on the market because the information collected during the pre-marketing phase is inevitably incomplete compared to the possible ADR 18. Nepal is a developing country and has several problems with the use of medicines. Most of the drugs used are manufactured in foreign countries and the safety profile of the excipients, diluents, binders, stabilizers and other additives used to prepare the drugs are not known. The genetic composition of the Nepalese population is varied and could be a predisposing factor for adverse drug reactions 19, 20. The annual consumption of narcotics in Nepal is estimated at over 3719.3 million Nepalese rupees (53.12 million US dollars), with an estimated 28.5% increase in consumption each year. 21.
Drug and Therapeutic Committee (DTC) and Pharmacovigilance in NCHRC
Drug and Therapeutic committee (DTC) was established in Nepal Cancer Hospital and Research Centre at mid-July, 2016 for promoting rational use of drugs in our hospital and also to develop strategy to improve medicine use and safety of medications. Drug and Therapeutics committees (DTCs) are a key recommendation for promoting the rational use of medicines 22. DTCs can carry out each academic and managerial interventions to improve remedy use. In our oncology Hospital, the hospital pharmacy and Clinical Pharmacy runs under the guidance of the DTC. Nepal Cancer Hospital and Research Centre has been recognized as a regional pharmacovigilance center since 1 January, 2018. The pharmacovigilance activity is an assurance of DTC.
Need of Pharmacovigilance in Nepal Copied but written in own language
There are still many things unidentified regarding the safety of the new drug, when a medicine is introduced into the market. These drugs are used by diverse patients for diverse diseases that could use different other drugs and must be different traditions and diets that can negatively impact the impact of medicine on them. Furthermore, the same drug may be different in the form of production and ingredients. In addition, adverse drug reactions (ADRs) may also occur when drugs are taken together with traditional herbal medicines that need to be controlled by pharmacovigilance. In some cases, adverse drug reactions (ADRs) of some drugs can only occur in one country or region. Pharmacovigilance proves to be an important system for monitoring the safety of medicines in a country with support from doctors, pharmacists, nurses and other health professionals in the country which prevent any undue physical, mental and financial suffering of patients. The significance of pharmacovigilance is Safety monitoring of medicinal products, clinical trials, Pharmacoepidemiological studies, case reports, developing case series, analysis of case series, use of data mining to identify product -event combination and Spontaneous reporting 23. Clinical trials cannot always detect rare adverse reactions. In addition, In Nepal practice with the prevailing practice in heterogeneous: allopathy, ayurveda, homeopathy, and medical complexities between these different systems to exchange views on further highlights need for efficient monitoring system.
Establishing a Pharmacovigilance Centre in NCHRC
Oncology is one of the areas of medicine with the most active research carried out on new drugs. The new pharmacological entities often enter the clinical field and, therefore, the safety profile of carcinogens deserves constant monitoring. However, only suspected (very rare) and unusual (ADR) adverse reactions are reported, as cancer patients develop ADR very frequently and some practical selectivity should be used 24. Pharmacovigilance and its studies is an increasingly important science in an ambience of hospital, especially in the field of oncology. Pharmacovigilance is an essential in oncology due to the high toxicity and narrow therapeutic window of antineoplastic agents. However, educating and training health professionals about the prerequisite to report these reactions is more imperative than studying adverse reactions 25.
Several meetings were arranged with the clinicians and other related health care professionals regarding pharmacovigilance activities. Meetings were arranged formally and informally with all the concerned personnel periodically. A training programme regarding the process of spontaneous reporting of observed ADRs was conducted. The ADR reporting forms were designed and placed in all the wards and outpatient departments. If requested, information on the management of the ADR will be provided.
The hospital management of NCHRC is supportive of this Pharmacovigilance program. There are numerous boundaries however. The hospital is oncology-specialized. The orientation and training program on Pharmacovigilance, that’s a continuous process, is repeated within brief intervals for new staff including every department in Oncology Hospital, Medical Oncologists, medical officers, Nurses, pharmacist and who is potential to report ADRs.
Structure and organization of Pharmacovigilance in NCHRC
Availability of ADR reporting form to Medical Oncologists, Medical Officers, Nurses and Pharmacist
Collection, Classification and Storage of Data
The effectiveness of national pharmacovigilance activities in Nepal depends directly on the active participation of health professionals. More information on Chemotherapy Induced ADRs will certainly be useful for creating a national database. Efforts are being made to encourage medical oncologists, doctors, nurses, pharmacists and other health professionals to report all adverse reactions, including suspected ones, in order to improve the use of drugs.