Countries the world over require that drugs used in the country are licensed by an appropriate authority. Yet, it is not uncommon to observe that in neonatal practice a large number of unlicensed and off-label drugs are used. In NICUs in most developed nations, the proportion of unlicensed drugs used is about 10% and offlabel drugs usage ranges from 47–62%<xref ref-type="bibr" rid="bib001">1</xref>-<xref ref-type="bibr" rid="bib003">3</xref>. Most drugs have adequate pharmacokinetic data in adults but the same are not licensed for use in neonates. Commonly used unlicensed drugs used in most NICUs include morphine, dopamine and phenobarbitone. There are many licensed drugs used outside their approved terms of use (off-label) in the neonate. Common example includes theophylline for apnea of prematurity or phosphorous for osteopenia of prematurity. There is thus a need to closely monitor adverse effects of these drugs to ensure that neonates are protected from the adverse effects of these medications.Though there are no guidelines for pharmacovigilance in neonates, there are recent guidelines published for the pediatric population which can be extended to the neonatal age group. There are a number of stakeholders in the pharmacovigilance process and include, besides the patients, their parents, pharmaceutical firms, regulatory bodies, health care professionals and the media.</sec><sec id="sec002"><title>Special problems of Pediatric and neonatal pharmacovigilance

Journal of Neonatology

0971-2179

National Neonatology Forum

jn-21-1-013

Commentary

Pharmacovigilance in neonates

Ramji

Deptt. of Pediatrics, Maulana Azad Medical College, New Delhi-110001. E-mail: sumsid@vsnl.com

1–32007

2116464

Countries the world over require that drugs used in the country are licensed by an appropriate authority. Yet, it is not uncommon to observe that in neonatal practice a large number of unlicensed and off-label drugs are used. In NICUs in most developed nations, the proportion of unlicensed drugs used is about 10% and offlabel drugs usage ranges from 47–62%<xref ref-type="bibr" rid="bib001">1</xref>-<xref ref-type="bibr" rid="bib003">3</xref>. Most drugs have adequate pharmacokinetic data in adults but the same are not licensed for use in neonates. Commonly used unlicensed drugs used in most NICUs include morphine, dopamine and phenobarbitone. There are many licensed drugs used outside their approved terms of use (off-label) in the neonate. Common example includes theophylline for apnea of prematurity or phosphorous for osteopenia of prematurity. There is thus a need to closely monitor adverse effects of these drugs to ensure that neonates are protected from the adverse effects of these medications.Though there are no guidelines for pharmacovigilance in neonates, there are recent guidelines published for the pediatric population which can be extended to the neonatal age group. There are a number of stakeholders in the pharmacovigilance process and include, besides the patients, their parents, pharmaceutical firms, regulatory bodies, health care professionals and the media.</sec><sec id="sec002"><title>Special problems of Pediatric and neonatal pharmacovigilance

This age group poses special problems since there are not sufficient clinical trials with safety data. There is risk of both over and under dosing since pharmacokinetic data are insufficient and adult data are often extrapolated to this age group and also use of adult formulations for neonates can result in dosing problems when diluted for neonatal use.

Safety data also cannot be extrapolated from adult populations since the maturation of neonates and children is vastly different. The problem is more acute in the neonatal period since one deals with a wide gestation age group with varying maturity. Besides drugs used by the mother, can have potentially serious adverse effects on both the fetus and the newborn. Most importantly, neonates and children cannot communicate the adverse effects and therefore one has to be far more vigilant when using medications in this age group.

Pharmacovigilance methods

Methods must be put into place for data collection of adverse drug reactions in neonates, especially since these subjects cannot communicate their symptoms⁴. Spontaneous reporting is the most important source of pediatric adverse drug reactions (ADR). Parents and hospitals form an important source of this information. Medication errors are probably the most common reasons for ADRs. However, health professionals often are reluctant to report ADRs especially when it relates to unlicensed and off-label drugs due the fear of liabilities. This reluctance can be overcome if we can improve the awareness and motivation of health professionals. These can be facilitated by communication and training, working with professional pediatric societies and research networks, better collaboration with pediatric and neonatal hospital units, and greater involvement of pharmacologists interested in pediatric medications and pharmacology.

Periodic safety update reports must be made available by the pharmaceutical firms and drug regulatory authorities. Nodal surveillance centers must be set up for collating and documenting reported ADRs. This surveillance must also have the responsibility of scanning published literature on ADRs in neonates and communicating them to the appropriate authorities, health professionals and the public at large.

References1Avenel

Bomkratz

Dassieu

Janaud

Danan

. The incidence of prescriptions without marketing product license in a neonatal intensive care unit. Arch Pediatr. 2000; 7: 143–147.2Conroy

McIntyre

Choonara

. Unlicensed and off-label drug use in neonates. Arch Dis Child Fetal Neonatal Ed. 1999; 80: F142–F1443O'Donnell

CPF

Stone

Morley

. Unlicensed and Off-Label Drug Use in an Australian Neonatal Intensive Care Unit. Pediatrics, 2002; 110:e524Committee for Medicinal products for Human Use. Guidelineson conduct of Pharmacovigilance for medicines used by the pediatric population. European Medicine agency EMEA/CHMP/PhVWP/235910/2005 (www.emea.europa.eu)