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Year : 2019  |  Volume : 8  |  Issue : 1  |  Page : 15-18

Drug utilization pattern in neonatal intensive care unit of a tertiary care hospital with particular emphasis on off-label drug use

Department of Pediatrics, Shri Ram Murti Smarak Institute of Medical Sciences, Bhojipura, Bareilly, Uttar Pradesh, India

Date of Web Publication29-Jan-2019

Correspondence Address:
Dr. Anita Kumari
Department of Pediatrics, Shri Ram Murti Smarak Institute of Medical Sciences, Bhojipura, Bareilly - 243 202, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcn.JCN_52_18

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Context: Drugs should be used rationally in the newborn admitted to a neonatal intensive care unit (NICU), especially in view of their higher susceptibility to the adverse effects owing to relative immaturity of body functions. However, not infrequently, drugs are used not keeping with the guidelines, such use being called “off-label drug use.” Aims: The aim of this study was to evaluate the drug utilization pattern in an NICU of a tertiary care hospital and to know the frequency of off-label drug use of various types. Settings and Design: A prospective, observational study was carried out in an NICU for a period of 3 months. Materials and Methods: Demographic details, diagnosis, and treatment given were recorded. The World Health Organization drug utilization core indicators and proportion of off-label usage of drugs were evaluated. Results: Among 560 prescription items used in 81 neonates over a 3-month period, the most commonly used drugs were antimicrobials, followed by vitamins and minerals and then sedatives and anticonvulsants. Hypoxic–ischemic encephalopathy and neonatal sepsis were the most common diagnoses. Overall, off-label usage of drug use was 43%. Antimicrobials were the most common group of drugs (136/240) used off label, followed by sedatives and anticonvulsants (42/240). While antimicrobials were commonly used off label in dose followed by frequency and age, anticonvulsants and sedatives were mostly used off label in the age category. Conclusions: The present study highlights a trend toward multiple drug usage with high off-label drug use in sick neonates and the need for further studies for safety and efficacy of drugs used in NICUs.

Keywords: Drug utilization, neonatal intensive care unit, off-label drug use, prescription

How to cite this article:
Kumari A, Prasad PL, Satyender. Drug utilization pattern in neonatal intensive care unit of a tertiary care hospital with particular emphasis on off-label drug use. J Clin Neonatol 2019;8:15-8

How to cite this URL:
Kumari A, Prasad PL, Satyender. Drug utilization pattern in neonatal intensive care unit of a tertiary care hospital with particular emphasis on off-label drug use. J Clin Neonatol [serial online] 2019 [cited 2021 Jul 26];8:15-8. Available from: https://www.jcnonweb.com/text.asp?2019/8/1/15/250980

  Introduction Top

A neonatal intensive care unit (NICU) is a highly specialized unit that provides care to ill newborns, including preterm and low-birth-weight babies. Neonates are a vulnerable group of patients and are particularly susceptible for adverse drug reactions owing to their unique pharmacodynamic and pharmacokinetic responses because of the relative immaturity of various organ functions. Needless to say, a special caution is required while using any medication in newborns. The World Health Organization (WHO) defines drug utilization as “the marketing, distribution, prescription and use of drugs in a society with special emphasis on resulting medical, social and economic consequences.”[1] However, in spite of many advances in neonatal care, there are, yet, no guidelines that are universally standardized for rational use of drugs in an NICU. Most of the drugs available today have not included neonates for safety and efficacy during their clinical trials. Several drugs, when used in neonates, may be prescribed outside the terms of the product license, the use being called “off-label use.” There could be other situations as well. An off-label drug use refers to the use of a drug that is either not licensed for use in neonates, using a drug in lower or higher than recommended dose, using a drug for an indication for which the drug is not licensed, or giving a drug by alternative routes of administration.[2] The aim of the present study is to determine the drug utilization patterns particularly focusing on their off-label use in the NICU of a tertiary care hospital.

  Materials and Methods Top

This was a prospective, observational study conducted at the NICU of Shri Ram Murti Smarak (SRMS) Institute of Medical Sciences, Bareilly, Uttar Pradesh, India. All neonates admitted to the NICU from October 1, 2017, to December 31, 2017, were included in the study. Demographic details, the diagnosis of each newborn, and the drugs given to them (except intravenous fluids, vaccines, Vitamin K, oxygen, and blood products) along with the doses and routes of administration were recorded. The treating physicians, including the resident doctors, were not aware of this record being kept. The “WHO drug utilization core indicators” were applied, and off-label status of the drug use was determined by referring to the “British National Formulary for Children (2011–2012)” for any deviation with respect to the indication, dose, frequency, route of administration, and age.[3] The generic names of drugs and the drug formulations were obtained from the Indian Drug Review, January–February 2015.[4] For the purpose of analysis, an individual drug prescribed to each neonate was considered as a “prescription item” irrespective of the total duration of its use.

  Results Top

A total number of 81 neonates admitted to the NICU during the 3-month period (October 1, 2017, to December 31, 2017) constituted the data. It was analyzed, apart from the drug use, for other parameters, for example, age, sex, and birth weight. The data show that males (66.6%) significantly outnumbered female neonates (30.86%). The mean birth weight of the newborns was 2611 g, and the percentage of term and preterm infants was 71.6 and 27.16, respectively; there was no postterm newborn. Most of the newborns were admitted on day 1 of birth. The mean duration of their hospital stay was 6 days.

As for the drugs used, while the drug(s) prescribed to each newborn ranged from 1 to 14 in number, a total of 560 different drugs were prescribed in all. The average number of drugs per prescription was 6.9 [Table 1]. As shown in [Table 2], the most frequently prescribed therapeutic class of drugs was antimicrobial agents (45.5%), followed by vitamins and minerals (25.3%) and sedatives and anticonvulsants (16%). Out of all antimicrobials, the most frequently prescribed agent belonged to the aminoglycosides group (amikacin – 29.4%), closely followed by cephalosporins (cefotaxime – 28.2%); all these drugs were given by parenteral route. While prescribing, generic names were used in most cases, and only 36.5% of drugs were prescribed by brand names. As shown in [Table 3], various types of off-label drug use were given, i.e., for age, dose, frequency, indication, and route of administration. [Table 4] depicts various therapeutic classes of drugs used under various categories of off-label use. The frequency of off-label drug use was 43% (240/560). While the most common off-label use for the type of therapeutic agent pertained to antibiotics, the type of off-label use was the most common in dose, followed by age and frequency [Table 3] and [Table 4].
Table 1: Analysis of prescription pattern of drugs as per the World Health Organization/ International Network of Rational Use of Drugs (INURD) indicators

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Table 2: Distribution of various therapeutic classes of drugs

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Table 3: Categories of off-label drug prescription in neonatal intensive care unit

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Table 4: Categories of various classes of drugs used off label

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  Discussion Top

The average number of drugs prescribed per patient was 6.9 in the study. This is quite comparable to another similar study, which reported mean drug usage of 7 per newborn.[5] However, some other studies give a significantly higher and lower figure of 11.1 and 4.8 per encounter, respectively.[6],[7] In the present study, drugs were prescribed by their generic names in 63.5% cases, but in another study, 79.7% drugs were prescribed by generic names.[7] There is a consensus that an increase in generic prescribing would rationalize the use and reduce the cost of drugs. In the present study, total encounters with injections were 70.5%, while in another study, this usage was 61.9%.[8] Although parenteral route is widely seen in NICUs, it was less in comparison to other studies.[9] In our study, 89.4% of the drugs were prescribed from the WHO model list of Essential Medicines 2017.[1] However, in some other studies, this was much lower (69.4% and 53.96%, respectively).[9],[10] This could be due to factors such as availability of drugs and clinicians' preference.

Neonates are a vulnerable group, and adverse events such as asphyxia, infection, and complications of prematurity during early neonatal days require special attention. In the present study, the most commonly prescribed drugs were antibiotics, followed by vitamins and minerals and anticonvulsants and sedatives. High incidence of antibiotic use in NICU could be due to the common practice of empirical usage of antibiotics without waiting for the outcome of blood culture. The most commonly prescribed antibiotics in our study were amikacin (29.4%) and cefotaxime (28.2%).

In the present study, 43% of the prescriptions in NICU are, in fact, off-label use. Other studies from developed countries have reported the prevalence of off-label drug use in neonates in a wide range from 36% to 93%.[2],[11],[12] In the present study, the most common off-label used medications were antibiotics and anticonvulsants, which are quite comparable to the findings of another study from India, done in the pediatric age group.[13] There may be differences in off-label drug use in different studies, which can be explained by types of morbidities found in different settings. In our setup, majority of the newborns had birth asphyxia with hypoxic–ischemic encephalopathy and neonatal sepsis; they were followed by respiratory distress in preterm, meconium aspiration syndrome (MAS), and neonatal jaundice. Unlike this pattern, in a study done by Rakhia et al., the major causes of admission were sepsis (29.2%) and low birth weight (23.4%), followed by birth asphyxia, neonatal jaundice, and MAS, while in another study done by Uppal et al., the largest number of neonates was in the premature category (78.5%), birth asphyxia (36.2%), jaundice (28.8%), and respiratory distress (24.8%).[6],[14] It has been seen that birth asphyxia, sepsis, and prematurity are the most common causes of overall neonatal morbidity and mortality in India.[15]

In the present study, category wise, the most common off-label use of antibiotics was in dose and frequency categories, followed by their use in age category. Conversely, all anticonvulsants used off label were in age category while bronchodilators and steroids were frequently used off label in route and indication categories. Looking at other similar studies, in a study by Jain et al., antibiotics and anticonvulsants were off label in age and dose categories.[16] Carvalho et al. reported ampicillin as the most commonly prescribed off-label drug in dose and frequency categories, while paracetamol was the most commonly used off label for age.[17] Differences in off-label drug use reported in different studies can be attributed to differences in neonatal conditions, duration of hospitalization, availability of drugs, and different resource materials (formularies/labels) used to determine off-label status.

  Conclusions Top

The present study gives an overall pattern of drug use profile in a tertiary care NICU and reflects the problems for which neonates were admitted to the NICU. It also shows that the off-label drug use in neonates is significantly high, which calls for further studies for evaluation of safety and efficacy of drugs used in sick newborns.


We are deeply indebted to Prof. S.C. Agrawal for his critical analysis of the subjects. We also acknowledge the management of SRMS Institute of Medical Sciences, Bareilly, for all the help and support, particularly in getting the data of patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

World Health Organization. What is drug utilization research and why is it needed. Introduction to Drug Utilization Research. Ch. 1. Oslo: World Health Organization; 2003. p. 8-12.  Back to cited text no. 1
Turner S, Longworth A, Nunn AJ, Choonara I. Unlicensed and off label drug use in paediatric wards: Prospective study. BMJ 1998;316:343-5.  Back to cited text no. 2
BMJ Publishing Group, London. The British National Formulary for Children; 2011-2012. Available from: http://www.sbp.com.br/pdfs/British_National_Formulary_for_Children_2011-2012.pdf. [Last assesed on 2018 May 05].  Back to cited text no. 3
Desai S, editor. Indian Drug Review-triple I. Bangalore, India: CMP Medica India Pvt. Limited; 2015. p. 1.  Back to cited text no. 4
Neubert A, Lukas K, Leis T, Dormann H, Brune K, Rascher W, et al. Drug utilisation on a preterm and neonatal intensive care unit in Germany: A prospective, cohort-based analysis. Eur J Clin Pharmacol 2010;66:87-95.  Back to cited text no. 5
Uppal R, Chhabra A, Narang A. Pattern of drug use in neonatal intensive care unit. Indian Pediatr 1998;35:647-9.  Back to cited text no. 6
Chatterjee S, Mandal A, Lyle N, Mukherjee S, Singh AK. Drug utilization study in a neonatology unit of a tertiary care hospital in Eastern India. Pharmacoepidemiol Drug Saf 2007;16:1141-5.  Back to cited text no. 7
Chauthankar SA, Marathe PA, Potey AV, Nanavati RN. Drug utilization in neonatal intensive care unit of a tertiary-care hospital in Mumbai, India. Indian Pediatr 2017;54:931-4.  Back to cited text no. 8
Vaghela JP, Sukhlecha A. Drug utilization study in neonatal intensive care unit of a tertiary care teaching hospital. Int J Basic Clin Pharmacol 2017;6:2510-5.  Back to cited text no. 9
Choure KM, Jadhav RR, Padwal SL. Drug utilization study in neonatal intensive care unit at rural tertiary care hospital. Asian J Pharm Clin Res 2017;10:102-4.  Back to cited text no. 10
Kumar P, Walker J, Hurt KM, Bennet KM, Grosshans N, Fotis M. Medication use in the neonatal intensive care unit: Current patterns and off-label use of parenteral medications. J Pediatr 2008;152:412-5.  Back to cited text no. 11
O'Donnell CP, Stone RJ, Morley CJ. Unlicensed and off-label use in an Australian neonatal intensive care unit. Pediatrics 2002;110:e52.  Back to cited text no. 12
Jain SS, Bavedkar SB, Gogaty NJ, Sadwareta PA. Off label drug use in children. Indian J Pediatr 2008;75:1133-6.  Back to cited text no. 13
Rakhia A, Khan M, Memon AA, Dahar SA. Pattern and outcome of neonatal ailments in a tertiary care hospital. Pak J Med Res 2014;14:14-6.  Back to cited text no. 14
Million Death Study Collaborators, Bassani DG, Kumar R, Awasthi S, Morris SK, Paul VK, et al. Causes of neonatal and child mortality in India: A nationally representative mortality survey. Lancet 2010;376:1853-60.  Back to cited text no. 15
Jain S, Saini SS, Chawla D, Kumar P, Dhir S. Off-label use of drugs in neonatal intensive care units. Indian Pediatr 2014;51:644-6.  Back to cited text no. 16
Carvalho CG, Ribeiro MR, Bonilha MM, Fernandes M Jr., Procianoy RS, Silveira RC. Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores. J Pediatr (Rio J) 2012;88:465-70.  Back to cited text no. 17


  [Table 1], [Table 2], [Table 3], [Table 4]

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