Off-Label Medicine Use In Neonatal Intensive Care Unit Of A Secondary Hospital Of Ad Dakhiliyah Governorate Of Oman
Keywords:
Off-label prescribing, Neonates, NICU, Medication safety, Oman, High-alert drugsAbstract
Off-label drug use, defined as the prescription of medications for indications, dosages, or routes not sanctioned by regulatory authorities, is prevalent in neonatal intensive care units (NICUs). This prevalence is primarily attributed to the limited availability of evidence-based, regulatory-approved options for neonates. However, such practices raise concerns regarding safety and standardization. In Oman, there is a paucity of data on off-label prescribing within neonatal populations. This study aimed to evaluate the prevalence, patterns, and clinical associations of off-label medication use among neonates admitted to the NICU at Nizwa Hospital. A retrospective cross-sectional analysis was conducted over an 18-month period (January 2023–June 2024), involving neonates aged ≤28 days who received at least one off-label medication. Data were sourced from the hospital’s Al Shifa Plus system and the Vigiflow pharmacovigilance platform. Of the 638 NICU admissions, 182 neonates (28.5%) received off-label prescriptions. The primary reasons for off-label use were unapproved routes of administration (47.2%) and age-specific contraindications (22.4%). Frequently used off-label medications included sodium chloride 3% and omeprazole, with 25.9% classified as high-alert drugs. Significant associations were identified between the number of off-label drugs and discharge outcomes (p = 0.019), as well as between gender and discharge disposition (p = 0.012). No adverse drug reactions were reported. These findings underscore the necessity for neonatal-specific prescribing guidelines, pharmacist-led medication reviews, and enhanced pharmacovigilance and training initiatives to promote safer and more consistent medication use in NICUs.
Downloads
Metrics
References
Aagaard, L., & Hansen, E. H. (2011). Prescribing of medicines in the Danish paediatric population outwith the licensed age group: Characteristics of adverse drug reactions. British Journal of Clinical Pharmacology, 71(5), 751–757. https://doi.org/10.1111/j.1365-2125.2011.03915.x
Abeer, K., & Jumaa, J. (2021). Off-label drugs used in pediatrics: Review article. Global Akıcı, N., Kırmızı, N. İ., Aydın, V., Bayar, B., Aksoy, M., & Akıcı, A. (2020). Off-label drug use in pediatric patients: A comparative analysis with nationwide routine prescription data. The Turkish Journal of Pediatrics, 62(6), 949–961.
AlAzmi, A., Alasmari, Z., Yousef, C., Alenazi, A., AlOtaibi, M., AlSaedi, H., & Alahmari, M. (2021). Off-label drug use in pediatric out-patient care: A multi-center observational study. Hospital Pharmacy, 56(6), 690–696. https://doi.org/10.1177/00185787211013219
Allen, H. C., Garbe, M. C., Lees, J., Aziz, N., Chaaban, H., Miller, J. L., & DeLeon, S. (2018). Off-label medication use in children, more common than we think: A systematic review of the literature. The Journal of the Oklahoma State Medical Association, 111(8), 776–783.
Alonso, A. S., Avila-Alvarez, A., Eiriz, M. C., Roca, C. M., Gómez, P. Y., López, A. C., & Díaz, S. P. (2019). Use of off-label drugs in neonatal intensive care. Anales de Pediatría (English Edition), 91(4), 237–243. https://doi.org/10.1016/j.anpede.2018.10.013
Alyami, D., Alyami, A. A., Alhossan, A., Salah, M., & Alyami, A. (2022). Awareness and views of pharmacists and physicians toward prescribing of drugs for off-label use in the Middle East. International Journal of Clinical Pharmacy, 44(1), 1–10.
Balan, S., Hassali, M. A. A., & Mak, V. S. (2018). Two decades of off-label prescribing in children: A literature review. World Journal of Pediatrics, 14(6), 528–540. https://doi.org/10.1007/s12519-018-0197-3
BMJ Group & Royal Pharmaceutical Society. (2023). British National Formulary for Children: 2023–2024. Pharmaceutical Press.
Farajallah, A. A., Zainal, H., & Palaian, S. (2024). Medication reconciliation practices in Gulf Cooperation Council countries: A review. Journal of Applied Pharmaceutical Science, 14(2), 61–72. https://doi.org/10.7324/JAPS.2024.140206
Fung, A., Yue, X., Wigle, P. R., & Guo, J. J. (2021). Off-label medication use in rare pediatric diseases in the United States. Intractable & Rare Diseases Research, 10(4), 238–245. https://doi.org/10.5582/irdr.2021.01116
García-López, I., Vendrell, M. C. M., Romero, I. M., de Noriega, I., González, J. B., & Martino-Alba, R. (2020). Off-label and unlicensed drugs in pediatric palliative care: A prospective observational study. Journal of Pain and Symptom Management, 60(5), 923–932. https://doi.org/10.1016/j.jpainsymman.2020.05.008
Giurin, M. S., Trojniak, M. P., Arbo, A., Carrozzi, M., Abbracciavento, G., Monasta, L., & Zanus, C. (2022). Safety of off-label pharmacological treatment in pediatric neuropsychiatric disorders: A global perspective from an observational study at an Italian third level children’s hospital. Frontiers in Pharmacology, 13, 837692. https://doi.org/10.3389/fphar.2022.837692
Hoon, D., Taylor, M. T., Kapadia, P., Gerhard, T., Strom, B. L., & Horton, D. B. (2019). Trends in off-label drug use in ambulatory settings: 2006–2015. Pediatrics, 144(4), e20190896. https://doi.org/10.1542/peds.2019-0896
IBM Watson Health. (2023). Micromedex Solutions (27th ed.). Truven Health Analytics.
Koszma, E. I. A., Bispo, A. J. B., Santana, I. A. D. O., & Santos, C. N. O. D. B. D. (2021). Use of off-label medications in a neonatal intensive care unit. Revista Paulista de Pediatria, 39, e2020063. https://doi.org/10.1590/1984-0462/2021/39/2020063
Lexicomp. (2022). Pediatric and Neonatal Lexi-Drugs Online (25th ed.). Wolters Kluwer.
Mazhar, F., Akram, S., Haider, N., Hadi, M. A., & Sultana, J. (2018). Off-label and unlicensed drug use in hospitalized newborns in a Saudi tertiary care hospital: A cohort study. International Journal of Clinical Pharmacy, 40(3), 700–703. https://doi.org/10.1007/s11096-018-0615-9
Meng, M., Zhou, Q., Lei, W., Tian, M., Wang, P., Liu, Y., & Li, Q. (2022). Recommendations on off-label drug use in pediatric guidelines. Frontiers in Pharmacology, 13, 892574. https://doi.org/10.3389/fphar.2022.892574
Schrier, L., Hadjipanayis, A., Stiris, T., Ross-Russell, R. I., Valiulis, A., Turner, M. A., & van Den Anker, J. (2020). Off-label use of medicines in neonates, infants, children, and adolescents: A joint policy statement by the European Academy of Paediatrics and the European Society for Developmental Perinatal and Pediatric Pharmacology. European Journal of Pediatrics, 179(6), 839–847. https://doi.org/10.1007/s00431-020-03556-9
Tschudy, M. M., & Arcara, K. M. (Eds.). (2021). The Harriet Lane Handbook (22nd ed.). Elsevier.
van der Zanden, T. M., Mooij, M. G., Vet, N. J., Neubert, A., Rascher, W., Lagler, F. B., & de Wildt, S. N. (2021). Benefit–risk assessment of off-label drug use in children: The Bravo framework. Clinical Pharmacology & Therapeutics, 110(4), 952–965. https://doi.org/10.1002/cpt.2267
van der Zanden, T. M., Smeets, N. J., de Hoop‐Sommen, M., Schwerzel, M. F., Huang, H. J., Barten, L. J., & de Wildt, S. N. (2022). Off-label, but on-evidence: A review of the level of evidence for pediatric pharmacotherapy. Clinical Pharmacology & Therapeutics, 112(6), 1243–1253. https://doi.org/10.1002/cpt.2647
Yackey, K., Stukus, K., Cohen, D., Kline, D., Zhao, S., & Stanley, R. (2019). Off-label medication prescribing patterns in pediatrics: An update. Hospital Pediatrics, 9(3), 186–193. https://doi.org/10.1542/hpeds.2018-0222
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
