Datasheet

GENTAMICIN INJECTION
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GENTAMICIN
Gentamicin 80mg/2mL injection as gentamicin sulphate

Presentation
Gentamicin Injection BP is a sterile, preservative-free solution containing Gentamicin (as Gentamicin
Sulfate BP) 80mg/2mL and Disodium Edetate BP in Water for Injections BP.

Uses
Actions
Class: Aminoglycoside antibiotic.
Microbiology: Gentamicin is bactericidal and acts by inhibiting protein synthesis in susceptible
bacteria. Cell death results. It is active against a wide range of pathogenic Gram-negative organisms
including Escherichia coli, Pseudomonas aeruginosa, Proteus sp (both indole positive and indole
negative), Klebsiellia, Enterobacter and Serratia species. It is also active against some Gram-positive
organisms, e.g. Staphylococcus (including methicillin and penicillin resistant strains). In vitro,
gentamicin is also active against Salmonella and Shigella. Some species have demonstrated resistance
to aminoglycosides including Streptococcus pneumoniae and anaerobic organisms such as Bacteroides
or Clostridium species.
Pharmacokinetics
Gentamicin is rapidly absorbed after IM injection and peak serum levels are usually achieved within
30 to 90 minutes and are measurable for 6-8 hours. Following parenteral administration, gentamicin
can be detected in tissues and body fluids. Following absorption, gentamicin is widely distributed into
body fluid including ascitic, pericardial, pleural, synovial and abscess fluids. Concentration in bile is
low.
Gentamicin does not appear to be metabolised and is excreted virtually unchanged in the Gentamicin
is excreted almost entirely by renal glomerular filtration, hence the half-life of the medicine is
prolonged in the presence of renal failure. Adjustments in the frequency of administration of
gentamicin are necessary to allow for the degree of renal failure (see Dosage and Administration).
The serum half-life of gentamicin is approximately 2-3 hours in adults with normal renal function. It is
prolonged in patients with impaired renal function and in premature or newborn infants.
Indications
For the treatment of infections due to one or more susceptible strains of bacteria, including
Pseudomonas aeruginosa, Proteus species (indole positive and indole negative), Escherichia coli,
Klebsiella, Enterobacter, Serratia species and Staphylococcus (including strains resistant to other
antibiotics).
Gentamicin may also be used for the treatment of the following conditions when caused by
susceptible organisms: bacteraemia, respiratory tract infections, urinary tract infections, skin and
skin structure infections, bone infections, peritonitis, septic abortion and burns complicated by
sepsis. Aminoglycosides, including gentamicin are generally not indicated in uncomplicated
initial episodes of urinary tract infection unless the causative organisms are not susceptible to less
toxic antibiotics.
In suspected or documented Gram-negative sepsis, gentamicin should be considered for initial
microbial therapy. Therapy may be instituted before obtaining results of susceptibility tests. The
decision to continue therapy is based on results of the susceptibility tests, the severity of the
infection and risk of toxicity. If anaerobic organisms are suspected, antimicrobial therapy in
addition to the gentamicin regimen should be considered.

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Dosage and Administration

Each ampoule is for use in a single patient on one occasion only.
Gentamicin is normally given by IM injection. Intravenous administration may be used for particular
indications when the IM route is not appropriate The dosage is the same for either route of
administration. It is desirable to measure both peak and trough serum levels during treatment.
Prior to administration, the patient's bodyweight should be measured for the correct calculation of
dosage. In obese patients, the appropriate dose can be calculated by assuming the bodyweight is the
patient's estimated lean bodyweight plus 40% of the excess.
Blood specimens for the determination of peak gentamicin concentrations should be obtained
approximately one hour following IM administration and 30 minutes after completion of a 30 minute
infusion. Blood specimens for the trough gentamicin concentration should be obtained immediately
prior to the next IM or IV dose.
Intravenous administration
For IV administration, the prescribed dose of gentamicin may be diluted in 100-200mL of sterile
normal saline or 5% glucose in water. The concentration of gentamicin in the solution should not
exceed 1mg/mL. Infusion periods of 30 minutes to 2 hours have been advocated.
Administration of the dose by bolus injection produces serum levels which are initially in excess of
what is regarded as being safe from toxic side effects. The high serum level does however rapidly fall
and the potential danger or safety of this method is yet to be established.
Gentamicin Injection must not be mixed with other drugs, but should be administered by separate
infusion.
Adults (Dosage in patients with normal renal function)
For serious infections (Systemic and urinary tract infections): 3mg/kg/day in three doses given every
8 hours.
Life threatening infections: Up to 5mg/kg/day in 3 or 4 equal doses with reduction to 3mg/kg/day as
soon as clinically indicated. Doses should never exceed 5mg/kg/day unless serum levels are
monitored. The following table should be used as a guide:
Table One: Dosage Guidelines For Adults With Normal Renal Function
Type of Infection
Systemic and
infections*

urinary

Dosage

Time interval Duration of therapy

between doses

tract 3mg/kg/day (where bodyweight** 8 hours

>60kg, usual dose is 80mg, where
bodyweight=60kg, usual dose is 60mg)

Life threatening and respiratory 5mg/kg/day initially then 3mg/kg/day 6-8 hours
tract infections and infections as soon as improvement is indicated
with
relatively
resistant
organisms i.e. Pseudomonas

7-10 days

7-10 days. Longer therapy may

be required. If so, auditory,
renal & vestibular functions
should be monitored

Note:
* Gentamicin activity is increased at pH 7.5. It may therefore be advantageous to alkalinise the
patient's urine before therapy.
** Use lean bodyweight.
Paediatrics
The following table should be used as a guide:
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Table Two: Dosage In Paediatrics With Normal Renal Function

Type of Infection

Age

Dosage #

Dosage Interval

Systemic infections

0-7 days

5mg/kg/day initially

12 hours

1 week - 1 year

6mg/kg/day initially

12 hours

1 year - 12 years

4.5mg/kg/day initially

8 hours

3mg/kg/day

8-12 hours

0-7 days

5mg/kg/day initially

12 hours

1 week - 1 year

7.5mg/kg/day initially

8 hours

1 year - 12 years

6mg/kg/day initially

8 hours

Uncomplicated
infections

urinary

tract

Life threatening infections

Note:
# In neonates, infants and children, where possible, serum levels should be measured and the dose
adjusted to provide the desired serum level.
Dosage in patients with impaired renal function
Dosage should be adjusted to minimise the risk of toxicity. The first dose should be as normal, e.g.
80mg (bodyweight > 60kg) and subsequent doses should be given less frequently, depending on the
degree of renal impairment. The following table should be used as a guide:
Table Three: Approximate Dosage Guidelines For Adult Patients Based On Renal Function
Body Weight of Adult
Dose
Patient
(mg)
(kg)

Creatinine
Rate
(mL/min)

Over 60

Over 70

Less than 12

Less than 6.5

8 hours

35-70

0.12-0.17

6.5-10

12 hours

24-34

0.18-0.25

11-14

18 hours

16-23

0.26-0.33

15-18

24 hours

10-15

0.34-0.47

19-26

36 hours

5-9

0.48-0.64

27-36

48 hours

60 or less

80

60

Clearance

Serum Creatinine Serum

urea Interval
(mmol/L)
(mmol/L)
Between Doses

(Same as above)

When only a serum urea concentration is available, this value may be utilised initially, however, it
should be supplemented with a serum creatinine level or creatinine clearance rate whenever possible.
N.B. The standard dose of 80mg three times daily may be inappropriate and a more appropriate dose
can be calculated using a nomogram which takes into account the patients serum creatinine levels,
body weight and age. This dose can be adjusted, if necessary, following determination of serum
creatinine levels. Desirable serum levels of gentamicin are 5-8mcg/mL as a peak and a 1-2mcg/mL as
a trough.
Note: In children with impaired renal function serum levels should be monitored and frequency of
dosage reduced if indicated.
In adults with renal failure undergoing haemodialysis, the amount of gentamicin removed from the
blood may vary depending upon several factors including the dialysis method used. An eight hour
haemodialysis may reduce serum concentrations of gentamicin by approximately 50%. The
recommended dosage at the end of each dialysis period is 1 to 1.7 mg/kg depending upon the severity
of infection.
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Contraindications
Known hypersensitivity to gentamicin or disodium edetate or
Patients who have experienced previous toxic reactions (ototoxicity, nephrotoxicity) resulting
from aminoglycoside therapy.

Warnings and Precautions

Nephrotoxicity and ototoxicity: As for other aminoglycosides, patients being treated with
gentamicin should be under close clinical observation during treatment because of the potential
toxicity associated with their use. Gentamicin, as with other aminoglycosides, is potentially
nephrotoxic and ototoxic.
Ototoxicity may be manifested by both vestibular and auditory ototoxicity. These auditory
changes are generally irreversible, usually bilateral and may be partial or total. Other
manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and
convulsions. The risk of this toxicity is higher in patients receiving high doses, prolonged
treatment, or with impaired renal function. Gentamicin should therefore be used with caution in
patients with impaired renal function. In such patients the frequency of administration should be
reduced and renal function should be monitored. Prolonged concentrations above 10
microgram/mL should be avoided and trough concentrations should not exceed 2 microgram/mL.
In neonates, infants and children, dosage reductions may also be necessary to avoid toxicity.
Peak and trough blood levels should be constantly monitored as should renal and eighth cranial
nerve function, especially in patients with known or suspected reduced renal function at onset of
therapy and also in those whose renal function is initially normal but who develop signs of renal
dysfunction during therapy. Where possible, it is recommended that serial audiograms be
obtained in patients old enough to be tested, particularly high risk patients. Evidence of
ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears or hearing loss) or nephrotoxicity
requires dosage adjustment or discontinuance of the drug. As with the other aminoglycosides, on
rare occasions changes in renal and eighth cranial nerve function may not become manifest until
soon after completion of therapy. Treatment period should not normally exceed 10-14 days.
Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or
nephrotoxic drugs, (see Interactions) should be avoided. This includes concurrent use with potent
diuretics, cephalosporins or other aminoglycosides. Other factors which may increase the risk of
toxicity are dehydration and advancing age. Patients should be well hydrated during therapy.
Recent evidence suggests that neurotoxic and nephrotoxic antibiotics may be absorbed in
significant quantities from body surfaces after local irrigation or application. The potential toxic
effect of antibiotics administered in this fashion should be considered and inadvertent contact
with the skin should be removed with water.
Allergic reactions: May occur after administration of gentamicin. Cross allergenicity among
aminoglycosides has also been known to occur.
Use during anaesthesia: The possibility of prolonged or secondary apnoea should be considered
if the drug is administered to anaesthetised patients who are concurrently receiving
neuromuscular blocking agents such as suxamethonium (succinylcholine), tubocurarine or
decamethonium. This also applies to patients who are receiving massive transfusions of citrated
blood. If neuromuscular blockade occurs, it may be reversed by the administration of calcium
salts.
Aminoglycosides should be used cautiously in patients with neuromuscular disorders such as
myasthenia gravis or parkinsonism. In such cases, gentamicin may aggravate muscle weakness
because of its curare-like effect on neuro-muscular function.
Treatment with gentamicin may lead to an over-growth of non-susceptible organisms. If
overgrowth of non-susceptible organisms occurs, appropriate therapy should be initiated.

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Paediatric Use:
Gentamicin should be used with caution in premature and neonatal infants because their renal
immaturity may result in the prolongation of the serum half-life of the drug and subsequent gentamicin
induced toxicity.
Use in the elderly:
Because of its toxicity, gentamicin should be used with caution in elderly patients only after less toxic
alternatives have been considered and/or found ineffective. Elderly patients are more likely to have an
age related decrease in renal function which may not be evident in the results of routine screening test
such as serum urea or serum creatinine. A creatinine clearance determination may be more useful.
Recommended doses should not be exceeded, and the patient's renal function should be carefully
monitored during therapy. Elderly patients may require smaller daily doses of gentamicin in
accordance with their increased age, decreased renal function, and possibly, decreased weight. In
addition, loss of hearing may result even in patients with normal renal function.
Use in pregnancy:
Category D. There is evidence of selective uptake of aminoglycosides by the fetal kidney resulting in
damage (probably reversible) to immature nephrons. Eighth cranial nerve damage has also been
reported following in utero exposure to some of the aminoglycosides. Because of their chemical
similarity, all aminoglycosides must be considered potentially nephrotoxic and ototoxic to the fetus. It
should also be noted that therapeutic blood concentrations in the mother do not equate with safety for
the fetus.
Use in lactation:
Small amounts of gentamicin have been detected in breast milk. Because of the potential risk to the
newborn, it is recommended that breastfeeding be discontinued during therapy unless the expected
benefits outweigh any potential risk.

Adverse Effects
Serious or life-threatening reactions
Otic: (See Precautions.) Serious adverse effects on both vestibular and auditory branches of the eighth
cranial nerves have been reported, primarily in patients with renal impairment (especially if dialysis is
required), and in patients on high doses and/or prolonged therapy. Symptoms reported include
dizziness, vertigo, tinnitus, roaring in the ears and hearing loss may be irreversible. Hearing loss is
usually manifested initially by diminution of high tone acuity. Other factors that may increase the risk
of toxicity include excessive dosage, dehydration and previous exposure to other ototoxic drugs.
Renal: (See Precautions.) Adverse renal effects have been reported, and are demonstrated by the
presence of casts, cells or protein in the urine or by rising serum urea, NPN, serum creatinine or
oliguria. They occur more frequently in patients with a history of renal impairment and in patients who
have been treated for longer periods or with larger dosage than recommended.
More common reactions
Neurological: Peripheral neuropathy or encephalopathy, including numbness, skin tingling, muscle
twitching, convulsions and a myasthenia gravis-like syndrome, have also been reported.
Dermatological and hypersensitivity: Rash, itching, urticaria, purpura, generalised burning,
anaphylactoid reactions may occur.
Pulmonary: Respiratory depression, laryngeal oedema, pumonary fibrosis may occur.
Gastrointestinal: Nausea, vomiting, increased salivation and stomatitis may also occur.

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Other adverse reactions: Lethargy, confusion, depression, visual disturbances, decreased appetite,
weight loss, hypotension and hypertension; fever and headache, pseudotumor cerebri, acute organic
brain syndrome, alopecia, joint pain, transient hepatomegaly, and splenomegaly.
While local tolerance of gentamicin injection is generally excellent, there has been an occasional
report of pain at the injection site. Subcutaneous atrophy or fat necrosis suggesting local irritation has
been reported rarely.
Laboratory tests: Laboratory abnormalities possibly related to gentamicin include: increased levels of
serum transaminase (ALT, AST), serum LDH and bilirubin; decreased serum calcium, magnesium,
sodium and potassium; anaemia, leucopenia, granulocytopenia, transient agranulocytosis, eosinophilia,
increased and decreased reticulocyte counts, and thrombocytopenia. While clinical laboratory test
abnormalities may be isolated findings, they may also be associated with clinically related signs and
symptoms. For example, tetany and muscle weakness may be associated with hypomagnesaemia,
hypocalcaemia and hypokalaemia.

Interactions
Penicillins: Gentamicin is inactivated by solutions containing beta-lactam antibiotics (penicillins
and cephalosporins) so the two drugs should not be administered simultaneously nor should they
be combined in the intravenous fluid. The inactivation of gentamicin by penicillins may occur in
vivo, especially in patients with renal failure who maintain a higher level of the penicillin for a
longer period of time. Therefore, when gentamicin and penicillins are used together in patients
with renal failure, the time of administration of each drug should be staggered so that several
hours separate each infusion.
Diuretics: Potent diuretics such as ethacrynic acid or frusemide may potentiate the ototoxic
effects of gentamicin.
Other neurotoxic and/or nephrotoxic agents: Since the ototoxic or nephrotoxic effects of
gentamicin may be additive, avoid concurrent or sequential use of other neurotoxic and/or
nephrotoxic antibiotics, including other aminoglycosides, polymyxin B, colistin, cisplatin,
vancomycin, amphotericin, clindamycin and cephalosporins.
Neuromuscular Blocking Agents: Respiratory paralysis and prolongation of neuromuscular
blockade may occur if a neuromuscular blocking agent such as suxamethonium (succinylcholine),
tubocurarine, decamethonium, halogenated hydrocarbon inhalation anaesthetics, opioid
analgesics or massive transfusions with citrated anticoagulated blood are administered to a patient
receiving gentamicin.
Vitamin K: Gentamicin may inhibit the action of intravenous vitamin K upon the synthesis of
clotting factors.
Potential Interactions: In vitro synergism and antagonism have been found between various
antineoplastic agents and aminoglycosides.

Overdosage
As the drug is almost entirely eliminated by the kidneys, fluid loading may hasten its elimination
following overdosage. Peritoneal dialysis or hemodialysis will also aid in the drug's removal.

Pharmaceutical Precautions
Store below 25C. Protect from light. Single use only. Discard unused portion.
Incompatibilities
When gentamicin is used in combination with any other drug, mixing the drugs before administration
should be avoided at all costs.

Medicine Classification
Prescription Medicine.
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Package Quantities
80mg/2mL: 10's and 50's (non-marketed in NZ).

Further Information
Gentamicin sulfate is a complex mixture of the sulfates of antimicrobial substances produced by
Micromonospora purpurea. The potency is not less than 590 IU per milligram, calculated with
reference to the anhydrous substance. It is a white or almost white powder, freely soluble in water,
practically insoluble in alcohol and in ether.

Name and Address

Pfizer New Zealand Ltd
Level 3, Pfizer House
14 Normanby Road
Mt Eden
Auckland
New Zealand
Ph.: (09) 638 0000

Date of Preparation
04 July 2005
(Ref: Aust PI 27/2/02)

July 2005