INTRODUCTION:

Drugs constitute a major part of the therapeutic modality for most of the patients. Drugs not only contain the active ingredient but excipients and binders as well.¹Binding agents and excipients have a well-defined role in drug formulations.^2,3,4,5Medication errors are a problem that affect people all over the world and can result in adverse drug reactions, drug resistance, etc.⁶

Medication errors can be attributed toinsufficient information provided by a physician to his patient. Since doctor cannot give detailed information about the drug and even the patient cannot remember it, therefore it becomes preferable to have such information in writingwhich can easily be understood.⁷Drug package insert (PI) approved by the administrative licensing authority is the primary source of such information. In a developing country like India where doctors are overburdened, Package inserts (PIs) can serve very important role in minimizing the medication errors. PIis a printed leaflet enclosed within the package of the drug which contains a summary of all the preclinical and clinical data accumulated during drug development. The concept of PI is directed by Drug and Cosmetic Act (1940) and Rules (1945) in India. Section 6 of Schedule D of the rules provides the headings according to which information should be present in the PI. Section 6.2 states that the inserts should be in English and must provide information on various aspects like posology, contraindications, precations, etc. Section 6.3 reveals the information regarding the list of excipients; incompatibilities; shelf life as packaged etc.Information provided in the PI must be in accordance to the guidelines of the region where the product is to be marketed. Previous studies have shown that PIs can improve patient compliance.^8,9,10 PIs act as a buffer against irrational prescribing and administration errors.^6,11 PIs need to be updated regularly, but despite regulations studies have shown that Indian PIs provide inadequate information.^12,13

Since, no such study has been conducted in Kashmir, this prompted us to frame the present study to look for the completeness of PIs with regards to the information provided.

METHODS:

Thisobservational study was carried out for a period of 3 months from June 2022 to September 2022. 139 PIs were collected from drug store of tertiary care hospital of government medical college, Srinagar and local pharmacies in its surrounding vicinity. PIs of different drug classes as well as different dosage forms were collected. Out of 139 PIs, 17 were duplicates and henceexcluded. The remaining PIs were evaluated according to section 6.2, 6.3 of schedule D (II), Drugs and Cosmetics Act (1940) and Rules (1945). Data was entered in Microsoft Excel Sheet and then analyzed.

RESULTS:

Figure No: 1 Classification of package inserts according to class of drug.

Figure No: 2 Classification of package insert according to the formulation.

Table No:1 Information in the package insert as per section 6.2 of Schedule D (II), Drugs and Cosmetic Act (1940) and Rules (1945).

Section 6.2	Number of Package Inserts	Percentage
Posology and method of administration	122	100%
Contraindication	115	94%
Special precautions and warnings	118	97%
Interaction	115	94%
Pregnancy and lactation if contraindicated	113	93%
Effect on ability to drive or operate machines	50	41%
Undesirable effects / side effects	117	96%
Anti-dote for overdosing	108	89%

Table No: 2 Information in the package insert as per section 6.3 of Schedule D (II), Drugs and Cosmetic Act (1940) and Rules (1945).

Section 6.3	Number of Package Inserts	Percentage
List of excipients	95	78%
Incompatibilities	60	49%
Shelf life in the product package for sale	34	28%
Shelf life after dilution / reconstitution	36	30%
Shelf life after opening the container	29	24%
Special precautions for storage	107	88%
Nature and specifications of container	107	88%
Instructions for use / handling	115	94%

The package inserts even contained additional information likegeneric name, content of active ingredient per dosage form, special font or color which was present in all the inserts (100%). Therapeutic indicators were present in 94% inserts, drug description in 71%, pharmacokinetics/pharmacodynamics in 85%

DISCUSSION:

The total number ofpackage inserts analysed were 122. These PIs belonged to various classes of drugs like antibiotics, GIT drugs, analgesics etc. (Figure 1). Maximum package inserts were of antibiotics (15%) and anti-diabetics (15%) followed by CNS drugs (14%). Our findings were similar to the studies conducted by Yuwnate AH et al¹⁴ and Ramdas D et al.¹⁵Among these 122 package inserts, 60% were of oral preparations followed by intravenous injections 17% etc (Figure 2). Similar findings were reported by Barkondaj B et al¹⁶and Sudha MJ et al¹⁷. In their studies 63% and 53% belonged to oral preparations, 29% and 19% were of injectables respectively.

Table no 1 deals with various components of Section 6.2 of Schedule D (II), Drug and Cosmetic Act. Posology and method of administration was present in 100% inserts. This is similar to the results reported by Agharia MAM et al.¹⁸ In the present study special precautions and warnings were mentionedin 97% of inserts and side effects in 96% of inserts. In the study conducted by Chhayya et al¹⁹side effects were mentioned in 97% of inserts while in the study conducted by Ramdas D¹⁵ it was mentioned in only 37.69% inserts.Disparity in the result can be attributed to the improvement in quality of PIs since Ramdas D conducted his study.The inserts we analyzed had contraindication in 94% which was more than the results obtained by Shruti et al²⁰ and Sowmya et al²¹. In the current study, interaction were mentioned in 94% of inserts which was more than the results reported by Sudhamadhuri et al²² where it was mentioned in 83.6% of inserts.In our study, contraindication in pregnancy and lactation was present in 93% inserts which was less than the results reported by Yuwnate AH et al¹⁴where it was 98%. In the current study antidote for overdosing was present in 89% insertswhile only 40% and 4% inserts mentioned it in the study conducted by Yuwnate et al¹⁴ and Kalam et al²³respectively. Effect on ability to drive or operate machines was present in 41% inserts analyzed in our study. It was mostly present in those drugs who showed central nervous system effects. It was mentioned in 30% and 17% inserts evaluated by Yuwnate AH et al¹⁴ and Shruti et al²⁰respectively.

Table no 2 deals with various criteria of Section 6.3 of Drugs and Cosmetic Act. In our study excipients were mentioned in 78% inserts. Excipients and modified excipients are pharmacologically inactive non drug components.^24,25In the study conducted by Yuwnate et al¹⁴ and Chhaya et al.¹⁹excipients were mentioned in 60% and 12% inserts respectively. Excipientsand co excipients can occasionally cause allergies, hence lack of such information may causes many ADRs.^26,27Incompatibility (such as mixing of two or more drugs in the same syringe or bottle) was mentionedonly in 49% inserts.Stability of a drug is dependent on its shelf life²⁸. In our study,information about shelf life was comparable to that of mentioned by Yuwnate AH et al¹⁴.Special precautions for storage were present in 88% of analyzed inserts. Our results were higher than that reported by Sudhamadhuri etal²²(62%) and Kalam et al²³(58%). Instructions for use and handling were present in 94% analyzed inserts which was much higher than the results reported by Soumya B et al²¹ and Ramdas et al.¹⁵Such information helps the patient to use the drug properly thereby providing maximum benefit.

As for the additional information, therapeutic indicators were present in 94% inserts, drug description in 71%, pharmacokinetics /pharmacodynamics in 85% inserts similar to the study conducted by Agharia MAM¹⁸. In the analyzed inserts pediatric/ geriatric use was present in 72% comparableto the study conducted by Barkondaj B et al¹⁶where pediatric /geriatric use was present in 81.4% inserts.

LIMITATIONS:

Our study had certain limitations. The number of PIs evaluated were less.We included the inserts from medical store of a single tertiary care hospital and local pharmacies around it. For a better evaluation different pharmaciesand hospitals of Kashmir should have been included. Also we did not do analysis of different brands of the same drug in our study. It would have given us an idea which brand provides complete and patient friendly information in its insert.

CONCLUSION:

Our study concluded that only a few inserts contained all the headings of Section 6.2 and 6.3 of Drug and Cosmetic Act (1945). Completeness of information has improved a lot as compared to past, still a lot needs to be done so that patients can derive maximum benefit from them. This demands strict scrutiny of inserts by regulatory authorities. An attempt should be made to make the insert more patient friendly. It would be better if the inserts contained pictographic representations of method of administration (like in inhalers used for asthma) and side effects. This approach is of benefit in a country like India where different regions have different languages.

ACKNOWLEDGEMENT:

The authors would like to acknowledge the In-charge of drug store of Government Medical College, Srinagar and all the local pharmacies who provided inserts for the study.

CONFLICT OF INTEREST:

Nil.

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Received on 25.10.2022 Modified on 30.01.2023

Research J. Pharm. and Tech 2023; 16(12):5744-5747.

DOI: 10.52711/0974-360X.2023.00929