Page 30 - ITPS-7-4

INNOSC Theranostics and
Pharmacological Sciences Pediatric drug regulations in India

increased cases of kernicterus. This disorder is caused by
bilirubin entering the brain, leading to seizures, yellowing
of brain tissue, and eventually death. This susceptibility
is due to reduced glucuronosyl transferase activity in
infants, which reduces their ability to process bilirubin.
In addition, the immature blood–brain barrier allows
more free bilirubin to reach the brain and cause injury.
Since bilirubin is expelled from plasma proteins, a higher
proportion remains free in plasma, making it easier for
bilirubin to enter the brain. 30
Figure 3. Categorization of juvenile age groups 21
Abbreviations: ICH: International Council for Harmonization; 4.2. Chloramphenicol (Gray baby syndrome)
US FDA: United States Food and Drug Administration.
Gray baby syndrome is an uncommon yet severe adverse
from research, legislation, and the availability of suitable reaction observed in infants, particularly premature
formulations compared to adults. ones, after receiving chloramphenicol – a bacteriostatic
antibiotic – through intravenous administration. This
The lack of a mandate for studying the efficacy and safety syndrome was initially documented in neonates in 1959. It
of medicines in pediatrics, considering their particular is believed that the underdeveloped glucuronyl transferase
and distinct qualities, has led to numerous unfortunate activity and the lack of renal excretion of chloramphenicol
incidents over time, some of which have even resulted in and its by-products contribute to the development of the
fatal consequences. gray baby syndrome. 30

One of the earliest instances of concern occurred in
1938 when children were administered the antibiotic elixir 4.3. Benzyl alcohol
sulfanilamide. Although adults had previously utilized In 1982, benzyl alcohol, a commonly used additive,
this antibiotic in the form of pills and capsules, a liquid was linked to neonatal gasping syndrome and preterm
form was created for pediatric use due to their difficulty infant fatalities. It is utilized as a preservation agent in
swallowing solid dosage forms. To make the antibiotic intravenous line flushes but has been found to cause severe
more palatable, diethylene glycol – a sweet solvent whose symptoms such as acidosis, respiratory distress, circulatory
safety had not been investigated before – was added to failure, bleeding in the brain, seizures, and eventually
elixir sulfanilamide. Tragically, it later became evident fatalities. This situation serves as a reminder that additives
28
that this substance caused over 100 pediatric deaths. This can have significant effects on the body. The issue with the
incident highlights the toxicology implications of excipient differential metabolism of benzyl alcohol in infants further
safety, which is an essential consideration in pediatric drug complicates matters; it is believed that neonates process
development. benzyl alcohol into benzoic acid, which then stores and
In addition, during the 1950s, the thalidomide tragedy leads to toxic effects. 19
– widely recognized for causing irreversible birth defects in Other adverse drug reactions seen in children include
over 1000 babies whose mothers used it for its anti-nausea liver damage from sodium valproate use, increased risk
31
properties during pregnancy – demonstrated the critical of Reye’s syndrome when using salicylates during viral
importance of pediatric research and the need to ensure infections, growth suppression or adrenal function effects
32
drug safety concerning teratogenic effects. 29 from long-term corticosteroid use, gastrointestinal
33
This discussion highlights the serious outcomes bleeding caused by non-steroidal anti-inflammatory
35
34
of insufficient research on medications for children, drugs, and arthropathy risk associated with ciprofloxacin
particularly among the youngest age groups. Several notable use in children resulting in serious consequences.
adverse reactions have been linked to commonly prescribed Adverse reactions such as bronchospasm from
drugs for pediatric use, emphasizing the importance of antiasthmatic drugs, due to benzalkonium chloride,
19
targeted research in this vulnerable population. headaches, and seizures, induced by aspartame, cross-
36
sensitivity reactions in pediatrics with allergies to
4.1. Sulfisoxazole (Kernictures) sulphonamides caused by saccharin-induced compounds,
The most significant incident of drug-related harm in and hyperosmolality and lactic acidosis induced by
children occurred in 1956 when it was discovered that propylene glycol are among the effects resulting from
newborns administered sulfisoxazole were experiencing improper use of excipients in pediatric formulations. 37

Volume 7 Issue 4 (2024) 5 doi: 10.36922/itps.3831