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ORIGINAL ARTICLE
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Package inserts: Are they present to guide our patients?


1 Department of Pharmacology, Indian Armed Forces Medical Services, Lucknow, Uttar Pradesh, India
2 Medical Officer, Armed Forces Medical Stores Depot, Lucknow, Uttar Pradesh, India
3 Medical Officer, Command Hospital, Lucknow, Uttar Pradesh, India

Date of Submission18-May-2021
Date of Decision25-Apr-2022
Date of Acceptance27-Apr-2022

Correspondence Address:
Tejus Anantharamu,
Armed Forces Medical Stores Depot, Lucknow - 226 002, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_366_21

  Abstract 


Background: The information regarding the prescribed medication has to be given to the patients who consume the same. Most medicines now need a valid prescription for dispensing by a registered pharmacist. This chain of medicine distribution takes away the decision-making rights of the consumers, thereby greatly increasing the responsibility of the prescribers and dispensers. The availability of Package Inserts (PIs) has been made mandatory by most agencies globally. Materials and Methods: Each saleable unit of all the available medicines in the medical stores were analyzed for the availability of the PIs. The medicines for which PIs were available were classified into those manufactured within India and outside. All the PIs were assessed for their completeness. Results: Only a minor fraction (20.9%) of the saleable units of the available medicines carried PIs. All PIs carried information on therapeutic indications including posology and method of administration. The main difference between the imported and indigenous medication PIs was with regard to information on antidotes for overdosings, list of excipients, incompatibilities, shelf life, and specific instructions for use/handling.Conclusion: The availability and quality of PIs must be checked regularly by the concerned regulators and suitable punishment clauses must be introduced through legislations to ensure all manufacturers to adhere the same. The ultimate goal of good PIs must not only be to provide information to health care professionals but also to enhance the knowledge of the healthcare consumers to make informed decision-making and thereby enhancing the quality of healthcare.

Keywords: Healthcare consumers, knowledge, package inserts



How to cite this URL:
Anantharamu T, Narain NS, Mathur AG, Roy P, Gupta A. Package inserts: Are they present to guide our patients?. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Dec 1]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=346450




  Introduction Top


The information regarding the prescribed medication has to be given to the patient who consumes the same. This requirement was first given due cognizance by the drug regulatory authority in the USA by introducing federal laws. The United States Food and Drug Administration (US-FDA) in 1930 restricted the availability of medicines over the counter and most of them now need a valid prescription from a registered medical practitioner and can be dispensed only by a registered pharmacist. Although this chain of medicine distribution was mandated to provide safeguards against unscrupulous drug manufacturers, it indirectly took away the decision-making rights of the consumers and placed it in the hands of prescribers and dispensers. This has greatly increased the responsibility of the prescribers and dispensers who invariably occupy the position of primary source of information to the consumers.[1],[2],[3],[4]

This practice continued for over 30 years, when this inherent flaw in this system was realized, and hence in 1960s, the US-FDA started asking pharmaceutical companies to design methods which could provide all the essential and useful scientific information to the consumers in a non-technical language. It all started with isoproterenol inhalation in 1968, wherein FDA asked the promoters to include two specific warnings on the medicine container, followed by that for oral contraceptives in 1970. Later on, it was realized that a practical method of achieving the objective is that the information be provided with the medicine as a leaflet, and in 1978, the US-FDA further revised labeling regulations to include more details.[1],[2],[3]

The patient information leaflets (PILs) or package inserts (PIs) are considered to be an important tool for improving patient's knowledge as it can reinforce the information provided by physicians and pharmacists. Studies clearly suggest that PILs are the most commonly used sources of drug information used by doctors and pharmacists especially regarding adverse drug reactions (ADRs). Other sources such as television, print media, family/friends, books and internet although used but were considered less trustworthy by the patients.[4],[5] But the availability of multiple sources could also contribute to overload of information providing contradictory information and can often impact the adherence negatively.[5] Hence a well designed PI can help the patient to make an informed decision.[5]

The availability of PIs have been made mandatory with the product by most agencies globally including the European Union, Brazil, and in fact, the US-FDA now requires three written materials (medication guide, patient PIs, and consumer medication information) accompanying each medicine packet.[6] In India, the Drugs and Cosmetics Act of 1940 and the Drugs and Cosmetics Rules 1945 and its amendments specifies guidelines regarding PIs under section 6 of Schedule D (II).[7] In India, PIs were never made compulsory legally until the ministry of Health and Family welfare notification GSR 813 (E) dated August 27, 2018, amending the Drugs and Cosmetics Act 1940 making PI mandatory with each saleable unit of the new drug.

Section 6.1 under section 6 of Schedule D (II) mandates the PI to be in English language and must include therapeutic indications including posology, method of administration, contraindications, special warnings and precautions, drug interactions, contraindications in pregnancy and lactation, contraindications to drive or use machines, side effects, and any antidote for overdosing. Section 6.2 under section 6 of Schedule D (II) mandates that PIs should include following information of pharmaceuticals including list of excipients, any incompatibilities, shelf life, and any special precaution for storage, container nature, and specification and instructions for use or handling.[7]

A number of studies have been conducted across the globe to assess the PIs for their completeness with regard to the guidelines, but the presence of PIs in all the medication packages is assessed rarely by studies.[7],[8],[9],[10],[11],[12] This assumes significance with August 27, 2018, notification amending the Drugs and Cosmetics Rules, 1945, making it compulsorily for a PI to accompany each saleable unit of new drug and the same was notified to be implemented from first day of January 2019.[12] Hence, this study has been planned to assess the presence of PIs and their completeness with regard to the Drugs and Cosmetics Act, 1945.


  Methodology Top


The study was conducted as a cross-sectional observational study in a medical store depot and medical stores of a tertiary care service hospital in Uttar Pradesh. The study was conducted over a period of 2 months after obtaining approval from the Institutional Ethics Committee. Each saleable unit of all the available medicines in the medical stores were analyzed for the availability of the PIs. The cold storage items were excluded from the study to avoid any break in cold chain or making it unusable due to the opening of the packet.

The medicines for which PIs were available were classified into those manufactured within India and those manufactured outside the country and are imported to be marketed. All the PIs were assessed for their completeness with regard to the section 6.1 and section 6.2 under section 6 of Schedule D (II) of the Drugs and Cosmetics Act 1940. The available PIs were classified according to the drug groups to analyze which drug group carry the most PIs.


  Results Top


A total of 335 medicines which were available during study period were assessed for the availability of PIs, out of which only 20.9% were carrying PIs. All the PIs were published in English language as per the Drugs and Cosmetics Act. Out of the medicines carrying PIs, 59 were manufactured indigenously and the rest (n = 11) were manufactured outside country and were imported to be marketed in India [Figure 1]. There was no uniformity in length, size, and the quality of paper of PIs or the font size of words typed in PIs. All the PIs of imported medications carried a bar code which was not found in any of the indigenously manufactured medicines.
Figure 1: Percentage of package inserts availability

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Among those medicines carrying PIs, anticancer drugs predominated which contributes to almost 30% of all the medicines (n = 20) carrying PIs. Following anticancer drugs are antimicrobial agents including antibacterial, antiviral, and antifungal drugs (n = 12), czardiovascular drugs including those acting on blood (n = 12), respiratory (n = 3) and anesthetic agents (n = 2), drugs used in eye and ENT (n = 3), non-steroidal anti-inflammatory drugs including those acting against Gout (n = 2), and others including those acting on gastrointestinal system (n = 8) [Figure 2].
Figure 2: Classification of drugs carrying package inserts

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During the assessment of PIs as per the sections 6.1 and 6.2 under section 6 of Schedule D (II) of the Drugs and Cosmetics Act 1940 it was noted that 100% PIs possess information on therapeutic indications including posology and method of administration. A relatively less percentage of PIs manufactured indigenously carried information on contraindications (96.61%), special warnings and precautions (98.3%), drug interactions (84.74%), contraindications in pregnancy, lactation (91.53%), and side effects (91.53%), whereas 100% of the PIs of the medicines manufactured outside India and imported carried these information.

A significantly less number of PIs of medicines manufactured in India carried information on contraindications for driving/using machines (0.07%) and antidotes for overdosings (0.19%). In comparison, 36.37% and 90.9% of the imported medicines' PIs carried the same information. There was a notable difference between indigenous and imported medicines with regard to percentage of PIs carrying information on the list of excipients (11.86% Vs 72.73%), any incompatibilities (20.39% Vs 811.82%), shelf life (45.76% Vs 81.82%), and specification/instructions for use or handling (25.42% Vs 72.73%). The information on special precaution for storage/container nature was carried almost equally among indigenous (96.61%) and imported (90.9%) medicine PIs.


  Discussion Top


Our study has clearly brought out that only a minor fraction (20.9%) of the saleable units of the available medicines in a tertiary medical store depot and a medical store of tertiary care hospital carried a PI. Although the quality of PIs has been an area of debate with many studies suggesting a need for further improving the quality and information available on PIs. Similar to our study, Khamas SS et al.[8] in their study to evaluate the PIs in Iran reported that only 37 of the top 100 selling medications in Iran carried a PI. To best of our knowledge, ours is the first study in India to record this data on the availability of PIs.[7],[8],[9],[10],[11]Although an effort has been made to make the same compulsory by the notification, the said amendment has been drafted in a way which leans heavily toward the Pharma companies rather than to enhance the knowledge and help the readers of PIs.

(What exactly is the rule regarding new drugs? Are they exempted from PIs? If so, it needs to be clearly stated) The addition of the term “New drugs” in the notification takes out the real sheen of the notification as the “New drug” by definition according to the rule 122E of the Drugs and Cosmetics rules includes those drugs that are not used significantly in the country for any prescribed condition duly recommended/suggested in its label or those drugs that are recognized as not effective and safe or those drugs marketed which are proposed to be marketed with newer/modified claims or fixed dose combinations. A new drug continues to enjoy its status for a 4-year period from its approval date/the day it is included in the Indian Pharmacopoeia, whichever falls earlier.[13] This definition excludes all those drugs marketed and are used widely, hence providing a vent for the escape from the application of the new notification by the government.

In our study, 100% of the PIs carried information on therapeutic indications including posology and method of administration. In line with our study, Prasad NS et al.,[14] in their study to assess the completeness of the PIs of the drugs available in India, reported that 100% of the PIs (n = 50) carried information on therapeutic indications and posology. In our study, almost all the PIs carried information on contraindications, special warnings, precautions, drug interactions, contraindications in pregnancy, and lactation. Similar results were seen in most other studies globally assessing the same parameters.[7],[8],[9],[10],[11] [Table 1] and [Table 2].
Table 1: Evaluation of package inserts as per section 6.1 under section 6 of schedule D (II) of the Drugs and Cosmetics Act

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Table 2: Evaluation of package inserts as per section 6.2 under section 6 of schedule D (II) of the Drugs and Cosmetics Act

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In our study, the main difference between the imported and indigenous medication PIs was with regard to information on antidotes for overdosing (90.9% vs. 0.19%), list of excipients (72.73% vs. 11.86%), incompatibilities (81.82% vs. 20.39%), shelf life (81.82% vs. 45.76%), and specific instructions for use/handling (72.73% vs. 25.42%). In line with our results, Qatmosh SA et al.,[3] in their comparative analysis of local and imported PIs of antihypertensive medications in Palestine, reported that only 6.6% of the local PIs carried information on inactive ingredients in comparison to 100% of those imported.

Ramdas D et al.,[7] in their study to assess the PIs in Southern India in 2013, reported that none of the 134 PIs they studied carried information on shelf life, and in comparison, our study reports PIs carried information on shelf life which is visible improvement in the quality of information carried by PIs. All the above-mentioned areas wherein our indigenously manufactured medicines PIs lack in their information in comparison to imported medications PIs, it is high time the drug regulatory authorities take adequate measures at the time of drug approval in India to ensure the same to be carried by PIs and also the already approved, marketed medicines must be made to update the same in their PIs.

Another visible difference between indigenous and imported medicine PIs include the presence of bar codes. Bar codes are encoded as small strings of data represented as adjacent bars placed in parallel which helps in universal identification of goods. This technology greatly helps to counter the counterfeit medicines, which are often considered as a menace in India.[15],[16],[17]


  Conclusions Top


PI must not be treated as a mere formality by the drug manufacturers and a sincere effort must be made by them to not only enhance the availability of PIs but also to improve the quality of the same. The availability and quality of PIs must be checked regularly by the concerned regulators and suitable punishment clauses must be introduced through legislations to ensure all manufacturers to adhere the same. In a country like ours, where questions are often raised on the quality of medicines, a good quality PIs can help to quell most of these questions and help our country to progress and excel in the field of pharmaceuticals. The ultimate goal of good PIs must not only to provide information to health care professionals and patients, at the core of it must be a basic idea to enhance the knowledge of the consumers of healthcare to make informed decision-making and which indirectly can help to enhance the quality of healthcare.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Qatmosh SA, Koni AA, Qeeno BG, Arandy DA, Abu-Hashia M, Al-hroub BM, et al. Comparative analysis of package inserts of local and imported antihypertensive medications in Palestine. BMC Public Health 2017;17:741.  Back to cited text no. 3
    
4.
O'Donovan B, Rodgers RM, Cox AR, Krska J. Use of information sources regarding medicine side effects among the general population: A cross-sectional survey. Prim Health Care Res Dev 2019;20:e153. doi: 10.1017/S1463423619000574.  Back to cited text no. 4
    
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Pizzol TDSD, Moraes CG, Arrais PSD, Bertoldi AD, Ramos LR, Farias MR, et al. Medicine package inserts from the users' perspective: Are they read and understood? Rev Bras Epidemiol 2019;22:E190009. doi: 10.1590/1980-549720190009.  Back to cited text no. 6
    
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Ramdas D, Chakraborty A, Hs S, Faizan S, Kumar V P, Bn S. A study of package inserts in southern India. J Clin Diagn Res 2013;7:2475-7.  Back to cited text no. 7
    
8.
Khamas SS, Jafari A, Zarif-Yeganeh M, Taghvaye-Masoumi H. Evaluation of medication package inserts in Iran. J Res Pharm Pract 2019;8:45-51.  Back to cited text no. 8
[PUBMED]  [Full text]  
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Eteraf-Oskouei T, Abdollahpour S, Najafi M, Zarea Gavgani V. Do drug package inserts meet the rules and regulations of Iran's food and drug administration in terms of informing patients? Health Promot Perspect 2019;9:214-22.  Back to cited text no. 9
    
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Sillo HB, Masota NE, Kisoma S, Rago L, Mgoyela V, Kaale EA. Conformity of package inserts information to regulatory requirements among selected branded and generic medicinal products circulating on the East African market. PLoS One 2018;13:e0197490.  Back to cited text no. 10
    
11.
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G.S.R. 813(E), Ministry of Helath and Family Welfare, Department of health and Family welfare. Published on 27th August, 2018. Available from Central drug standard control organisation website.  Back to cited text no. 12
    
13.
Bhaduri S, Kipgen T. 'New drugs' approvals in India: An institutional perspective. Sci Technol Soc 2018;23:444-62.  Back to cited text no. 13
    
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Prasad S N, Revankar SP, Vedavathi H, Manjunath H, Hegde S. Analysis of completeness of drug package inserts available in India. Natl J Physiol Pharm Pharmacol 2017;7:1139-43.  Back to cited text no. 14
    
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Shruti DA, Sarala N, Bhuvana K. Analysis of package inserts of drugs utilized in a tertiary care hospital. J Young Pharm 2016;8:275-8.  Back to cited text no. 15
    
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Khan AN, Khar RK. Current scenario of spurious and substandard medicines in India: A systematic review. Indian J Pharm Sci 2015;77:2-7.  Back to cited text no. 16
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