Monograph: |
Netilmicin Sulphate
A semisynthetic derivative of sissomicin. 1.5 g of monograph
lubstance is approximately equivalent to I g of netilmicin.
A white to pale yellowish-white very hygroscopic powder.
Very or freely soluble in water, practically insoluble in alco-
hol, in dehydrated alcohol, in acetone, and in ether. A 4% so-
lution in water has a pH between 3.5 and 5.5. Store in airtight
containers. Protect from light.
Incompatibilities. For discussion of the incompatibility of
aminoglycosides, including netilmicin, with beta lactams, see
under Gentamycin Sulphate. Netilmicin is also report-
ed to be incompatible with frusemide, heparin, and vitamin B
complex.
Adverse Effects, Treatment, and Precautions
As for Gentamicin Sulphate. Some studies
suggest that netilmicin is less nephrotoxic and oto-
toxic than gentamicin or tobramycin, although oth-
ers have not found any significant differences in
their toxic effects.
Peak plasma concentrations of netilmicin greater
than 16 mcg per mL. and trough concentrations great-
er than 4 ng per mL should be avoided and some
sources suggest that peaks below 12 mcg per mL and
troughs below 2 mcg per mL are preferable.
Effects on the cardiovascular system. Severe hypoten-
sion was associated with administration of netilmicin in a pa-
tient undergoing artificial ventilation. Hypotensive episodes
were of short duration and coincided with netilmicin injec-
tion. They almost disappeared when sedation was stopped.
Interactions
As for Gentamicin Sulphate.
Antirnicrobial Action
As for Gentamicin Sulphate. It is active
against a similar range of organisms although it is
also reported to have some activity against Nocar-
dia. It may be somewhat less effective against Pseu-
domonas aeruginosa. MICs of netilmicin for the
most sensitive organisms range from about 0.25 to
2 ng per mL, but organisms with MICs less than
about 8 ng per mL are considered sensitive. It is not
degraded by all of the enzymes responsible for
aminoglycoside resistance, and may be active
against some strains resistant to gentamicin or to-
bramycin. but this is less marked than with ami-
kacin: for example, gentamicin-resistant Proteus,
Providencia, Pseudomonas, and Serratia ale usually
also netilmicin-resistant. Between about 5 and 20%
of Gram-negative isolates are reported to be resist-
ant to netilmicin.
Pharmacokinetics
As for Gentamicin Sulphate.
Following intramuscular injection of netilmicin,
peak plasma concentrations are achieved within half
to I hour. and concentrations of about 7 ng per mL
have been reported following doses of 2 mg per kg
body-weight; similar concentrations are obtained
after intravenous infusion of the same dose over I
hour. Peak concentrations following rapid intrave-
nous injection may transiently be 2 or 3 times higher
than those following infusion. Administration of
standard, once-daily doses may produce transient
peak concentrations of 20 to 30 mcg per mL. In mul-
tiple dosing studies, administration of netilmicin in
usual doses every 12 hours produced steady-state
concentrations on the second day which were less
than 20% higher than those seen after the first dose.
The half-life of netilmicin is usually 2.0 to 2.5
hours. About 80% of a dose is excreted in the urine
within 24 hours.
Uses and Administration
Netilmicin is a semisynthetic aminoglycoside anti-
biotic with actions and uses similar to those of gen-
tamicin . It may be used as an alternative to
amikacin in the treatment of infections
caused by susceptible bacteria that are resistant to
gentamicin and tobramycin. As with gentamicin,
netilmicin may be used with penicillins and with ce-
phalosporins; the injections should be given sepa-
rately.
Netilmicin is given as the sulphate but doses are ex-
pressed in terms of the equivalent amount of base. It
is usually given intramuscularly in doses equivalent
to netilmicin 4 to 6 mg per kg body-weight daily as
a single dose; alternatively, it may be given in equal-
ly divided doses every 8 or 12 hours: for the control
of life-threatening infections, up to 7.5 mg per kg
may be given daily in divided doses every 8 hours
for short periods. In the management of urinary-
tract infections regimens consisting of either a sin-
gle daily dose of 150 mg or of 3 to 4 mg per kg daily
in divided doses every 12 hours have been suggest-
ed. A single dose of 300 mg has been suggested for
gonorrhoea although it is not recommended
in current treatment guidelines.
The same doses may be given by slow intravenous
injection over 3 to 5 minutes or infused intravenous-
ly over half to 2 hours in 50 to 200 mL of infusion
fluid: proportionately less fluid should be given to
children.
Treatment with netilmicin is usually given for 7 to
14 days. Prolonged peak plasma concentrations
greater than 16 mcg per mL and trough plasma con-
centrations greater than 4 mcg per mL should be
avoided. Some sources suggest peaks below 12 ng
per mL and troughs below 2 mcg per mL for divided
daily dose regimens.
Dosage recommendations in infants and children
vary somewhat. One suggested regimen is the equiv-
alent of 7.5 to 9.0 mg of netilmicin per kg daily in
infants and neonates older than I week, and 6.0 to
7.5 mg per kg daily in older children, both given in
divided doses every 8 hours. Premature infants, and
neonates less than I week old. would be given 6 mg
per kg daily in divided doses of 3 mg per kg every
12 hours. An alternative regimen is 4 to 6.5 mg per
kg daily in neonates less than 6 weeks of age, in di-
vided doses every 12 hours, and 5.5 to 8.0 mg per kg
daily in divided doses every 8 or 12 hours in older
infants and children.
It is recommended that dosage should be adjusted in
all patients according to plasma-netilmicin concen-
trations. and this is particularly important where fac-
tors such as age, renal impairment or dose may
predispose to toxicity, or where there is a risk of sub-
therapeutic concentrations.
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