formation of toxic substances, an acceptable limit is the time
taken for 10 % decomposition of the drug. When toxic
substances are produced stricter limits may be imposed.
Because of the risk of microbial contamination a maximum
time limit of 24 hours may be appropriate for additions made
elsewhere than in hospital pharmacies offering central
additive service.
Certain injections must be protected from light during
continuous infusion to minimise oxidation, e.g. sodium
nitroprusside.
Drugs given by continuous intravenous
infusion to neonates
The information provided inBNF for Childrencovers dilution
withGlucose intravenous infusion 5 % and 10 % andSodium
chloride intravenous infusion 0. 9 %. Compatibility with glucose
5 % and with sodium chloride 0. 9 % indicates compatibility
withSodium chloride and glucose intravenous infusion.
Infusion of a large volume of hypotonic solution should be
avoided, therefore care should be taken if water for
injections is used.Prescribing in hepatic impairment
Overview
Children have a large reserve of hepatic metabolic capacity
and modification of the choice and dosage of drugs is usually
unnecessary even in apparently severe liver disease.
However, special consideration is required in the following
situations:
.liver failure characterised by severe derangement of liver
enzymes and profound jaundice; the use of sedative
drugs, opioids, and drugs such as diuretics and
amphotericin p. 373 which produce hypokalaemia may
precipitate hepatic encephalopathy;
.impaired coagulation, which can affect response to oral
anticoagulants;
.in cholestatic jaundice elimination may be impaired of
drugs such as fusidic acid p. 357 and rifampicin p. 364
which are excreted in the bile;.in hypoproteinaemia, the effect of highly protein-bound
drugs such as phenytoin p. 205 , prednisolone p. 442 ,
warfarin sodium p. 97 , and benzodiazepines may be
increased;
.use of hepatotoxic drugs is more likely to cause toxicity
in children with liver disease; such drugs should be
avoided if possible;
.in neonates, particularly preterm neonates, and also in
infants metabolic pathways may differ from older
children and adults because liver enzyme pathways may
be immature.
Where care is needed when prescribing in hepatic
impairment, this is indicated under the relevant drug inBNF
for Children.Prescribing in renal impairment
Issues encountered in renal impairment
The use of drugs in children with reduced renal function can
give rise to problems for several reasons:
.reduced renal excretion of a drug or its metabolites may
produce toxicity;
.sensitivity to some drugs is increased even if elimination
is unimpaired;
.many side-effects are tolerated poorly by children with
renal impairment;
.some drugs are not effective when renal function is
reduced;
.neonates, particularly preterm, may have immature
renal function.Many of these problems can be avoided by reducing the dose
or by using alternative drugs.
Principles of dose adjustment in renal
impairment
The level of renal function below which the dose of a drug
must be reduced depends on the proportion of the drug
eliminated by renal excretion and its toxicity.
For many drugs with only minor or no dose-related side-
effects, very precise modification of the dose regimen is
unnecessary and a simple scheme for dose reduction is
sufficient.
For more toxic drugs with a small safety margin dose
regimens based on glomerularfiltration rate should be used.
When both efficacy and toxicity are closely related to
plasma-drug concentration, recommended regimens should
be regarded only as a guide to initial treatment; subsequent
doses must be adjusted according to clinical response and
plasma-drug concentration.
The total daily maintenance dose of a drug can be reduced
either by reducing the size of the individual doses or by
increasing the interval between doses. For some drugs,
although the size of the maintenance dose is reduced it is
important to give a loading dose if an immediate effect is
required. This is because it takes aboutfive times the half-
life of the drug to achieve steady-state plasma
concentration. Because the plasma half-life of drugs
excreted by the kidney is prolonged in renal impairment, it
can take many doses at the reduced dosage to achieve a
therapeutic plasma concentration. The loading dose should
usually be the same as the initial dose for a child with normal
renal function.
Nephrotoxic drugsshould, if possible, be avoided in
children with renal disease because the consequences of
nephrotoxicity are likely to be more serious when the renal
reserve is already reduced.
Glomerularfiltration rate is low at birth and increases rapidly
during thefirst 6 months. Thereafter, glomerularfiltration
rate increases gradually to reach adult levels by 1 – 2 years of
age, when standardised to a typical adult body surface area
( 1. 73 m^2 ). In thefirst weeks after birth, serum creatinine
falls; a single measure of serum creatinine provides only aBNFC 2018 – 2019 Prescribing in renal impairment 17
Prescribing in hepatic impairment