Consumer medicine information

B. Braun Gentamicin Injection, Intravenous Infusion

Gentamicin

BRAND INFORMATION

Brand name

B. Braun Gentamicin

Active ingredient

Gentamicin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using B. Braun Gentamicin Injection, Intravenous Infusion.

What is in this leaflet?

This leaflet answers some common questions about B. BRAUN GENTAMICIN injection, intravenous infusion (gentamicin).

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given B. BRAUN GENTAMICIN injection, intravenous infusion against the benefits they expect it will have for you.

This medicine is likely to be used while you are at the clinic or in hospital. If possible, please read this leaflet carefully before this medicine is given to you. In some cases this leaflet may be given to you after the medicine has been used.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet in a safe place. You may need to read it again.

What B. BRAUN GENTAMICIN injection, intravenous infusion is used for

Gentamicin is an antibiotic that belongs to a group of medicines called aminoglycosides (pronounced a-my-noe-GLY-koe-sides). It is used to treat serious bacterial infections.

This medicine works by killing bacteria or preventing their growth. It is used for the treatment of serious infections, including:

  • septicaemia (infection of the blood)
  • respiratory tract infections
  • infected wounds
  • bone or tissue infections
  • infected burns
  • urinary tract infections.

Your doctor may have prescribed gentamicin for another reason. Ask your doctor if you have any questions about why gentamicin has been prescribed for you.

This medicine is available only with a doctor’s prescription.

Before you are given B. BRAUN GENTAMICIN injection, intravenous infusion

When you must not be given it

You must not be given B. BRAUN GENTAMICIN injection, intravenous infusion if you have an allergy to gentamicin or other aminoglycoside antibiotics such as:

  • amikacin
  • tobramycin
  • neomycin
  • streptomycin
  • netilmicin

or any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to gentamicin may include:

  • hearing loss or kidney problems
  • shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

You must also not be given B. BRAUN GENTAMICIN injection, intravenous infusion if you have myasthenia gravis.

B. BRAUN GENTAMICIN injection, intravenous infusion should not be given to you if the packaging is torn or shows signs of tampering.

If you are not sure whether you should be given B. BRAUN GENTAMICIN injection, intravenous infusion, talk to your doctor or pharmacist.

Before you are given it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant. Like most aminoglycoside antibiotics, gentamicin is not recommended for use during pregnancy as it may affect your developing baby if you take it during pregnancy. If there is a need for you to be given gentamicin, your doctor or pharmacist will discuss with you the benefits and risks of using it during your pregnancy.

Tell your doctor or pharmacist if you are breast-feeding or plan to breast-feed. If there is a need for you to be given gentamicin, your doctor or pharmacist will discuss the possible risks and benefits of using it during breastfeeding.

Tell your doctor or pharmacist if you have or have had any medical conditions, especially the following:

  • kidney disease or any kidney problems
  • muscular disorders (e.g. Parkinson’s disease)
  • hearing problems.

If you have not told your doctor or pharmacist about any of the above, tell them before you are given gentamicin.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and gentamicin may interfere with each other. These include:

  • fluid tablets (e.g. frusemide, ethacrynic acid, bumetanide)
  • cisplatin, a medicine used to treat cancer
  • antibiotics to treat infection such as colistin, vancomycin, clindamycin, cephalosporins and penicillins
  • amphotericin B, an antifungal medicine
  • anaesthetics (e.g. halothane)
  • muscle relaxants (e.g. succinylcholine).
  • vitamin K
  • any drug that may cause kidney or hearing problems

These medicines may be affected by gentamicin, or may affect how well it works. You may need different amounts of your medicine, or you may need to take/use different medicines. Your doctor or pharmacist will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while receiving gentamicin.

How B. BRAUN GENTAMICIN injection, intravenous infusion is given

How much is given

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight and kidney function.

How it is given

Gentamicin is given intravenously over a period of 30 to 60 minutes. This medicine should only be given by a doctor, nurse or other trained person.

If you take too much (overdose)

As B. BRAUN GENTAMICIN injection, intravenous infusion is usually given to you in hospital under the supervision of your doctor, it is very unlikely that you will receive an overdose. However, if you are given too much gentamicin, you may experience some of the effects listed under "Side Effects" below.

If you experience severe side effects, tell your doctor immediately, or go to the nearest hospital emergency department.

Your doctor or pharmacist has information on how to recognise and treat an overdose. Ask your doctor if you have any concerns.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given gentamicin or after the injection.

Gentamicin helps most people with certain infections, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • tiredness or weakness
  • confusion
  • depression
  • decreased appetite
  • weight loss
  • fever
  • headache
  • nausea or vomiting
  • increased salivation
  • problems with eyes
  • sore mouth, gums and mouth ulcers
  • unusual bleeding or bruising under the skin
  • hair loss
  • joint pain
  • pain at the injection site.

These side effects are usually mild.

Tell your doctor or nurse immediately if you notice any of the following:

  • swelling of the limbs, face, lips, mouth or throat
  • shortness of breath or breathing difficulties
  • rash, itching, hives or severe skin reaction.

These symptoms are signs of an allergic reaction to gentamicin.

If any of the following happen, tell your doctor or nurse immediately:

  • severe headache
  • hearing loss
  • dizziness
  • problems with your balance
  • ringing in the ears
  • numbness
  • skin tingling
  • muscle twitching
  • fits (convulsions)
  • increase or decrease in urination.

These are very serious side effects. You may need urgent medical attention. Serious side effects are rare.

Other side effects not listed above may occur in some patients. Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

After using B. BRAUN GENTAMICIN injection, intravenous infusion

Storage

B. BRAUN GENTAMICIN injection, intravenous infusion will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place where the temperature stays below 25°C.

Product description

What it looks like

B. BRAUN GENTAMICIN injection, intravenous infusion is a clear, colourless liquid and comes in plastic bottles.

Ingredients

Active ingredients:

  • gentamicin sulphate

Other ingredients:

  • disodium edetate (3 mg/mL solution only)
  • sodium chloride
  • water

Genatmicin intravenous infusion is available in the following strengths:

AUST R: 280508: B. BRAUN GENTAMICIN Gentamicin (as Sulfate) 80 mg/80 mL injection, intravenous infusion, bottle.

One 80 mL bottle of B. BRAUN GENTAMICIN Gentamicin (as Sulfate) 1 mg/mL injection, intravenous infusion contains 80 mg gentamicin.

AUST R: 280507: B. BRAUN GENTAMICIN Gentamicin (as Sulfate) 240 mg /80 mL injection, intravenous infusion, bottle.

One 80 mL bottle of B. BRAUN GENTAMICIN Gentamicin (as Sulfate) 3 mg/mL injection, intravenous infusion contains 240 mg gentamicin.

AUST R: 280495: B. BRAUN GENTAMICIN Gentamicin (as Sulfate) 360 mg /120 mL injection, intravenous infusion, bottle.

One 120 mL bottle of B. BRAUN GENTAMICIN Gentamicin (as Sulfate) 3 mg/mL injection, intravenous infusion contains 360 mg gentamicin.

Supplier / Sponsor

B. Braun Australia Pty Ltd
Level 5, 7-9 Irvine Place
Bella Vista NSW 2153
Australia

This leaflet was prepared in November 2020

Published by MIMS March 2021

BRAND INFORMATION

Brand name

B. Braun Gentamicin

Active ingredient

Gentamicin

Schedule

S4

 

1 Name of Medicine

Gentamicin sulfate.

2 Qualitative and Quantitative Composition

B. Braun Gentamicin 1 mg/mL injection, intravenous infusion.

Gentamicin (as sulfate) 1 mg/mL, sodium chloride 9 mg/mL, water for injections q.s. to 1 mL.

B. Braun Gentamicin 3 mg/mL injection, intravenous infusion.

Gentamicin (as sulfate) 3 mg/mL, disodium edetate 10 microgram/mL, sodium chloride 9 mg/mL, water for injections q.s. to 1 mL.

3 Pharmaceutical Form

Injection, intravenous infusion.

4 Clinical Particulars

4.1 Therapeutic 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 and 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 antimicrobial 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.

4.2 Dose and Method of Administration

For single use only.
B. Braun Gentamicin gentamicin (as sulfate) 1 mg/mL injection, intravenous infusion and B. Braun Gentamicin gentamicin (as sulfate) 3 mg/mL injection, intravenous infusion is administered by intravenous infusion over a period of 30-60 minutes. B. Braun Gentamicin gentamicin (as sulfate) 1 mg/mL injection, intravenous infusion and B. Braun Gentamicin gentamicin (as sulfate) 3 mg/mL injection, intravenous infusion is not suitable for intramuscular or slow intravenous injection.
See Section 4.4 Special Warnings and Precautions for Use, Nephrotoxicity and ototoxicity; Section 4.2 Dose and Method of Administration, Monitoring advice.
Gentamicin must not be mixed with other drugs, but should be administered by separate infusion (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Treatment of bacterial infections.

Dosage in patients with normal renal function.

Adults and adolescents.

The daily dose recommended in adolescents and adults with normal renal function is 3 - 5 mg/kg body weight per day as 1 (preferred) up to 2 single doses.
A maximum daily dose of 5 mg/kg may be needed for the treatment of serious infections and when the susceptibility of the pathogen is relatively poor.
5 mg/kg/day may be given initially and reduced to 3 mg/kg/day as soon as improvement is indicated.
Doses should never exceed 5 mg/kg/day unless serum levels are monitored. See Table 1.
Gentamicin has a long-lasting post-antibiotic effect. Recent in vitro and in vivo studies show that the uptake of aminoglycosides into the renal cortex is limited and hence, with higher peak serum gentamicin levels (after single daily dosing) less aminoglycoside is stored in the kidneys than with conventional multiple dosing.
In the case of combination treatment (e.g. with a beta-lactam antibiotic in the normal dosage) it is also possible to administer the total daily dose as a single dose once a day.
Due to the requirement for dose adjustments once daily dosing of gentamicin is not recommended for patients with weakened immunity (e.g. neutropenia), severe renal failure, ascites, bacterial endocarditis, patients with extensive burns (more than 20% of the skin), and in pregnancy.

Paediatric population.

See Table 2.
One 80 mL bottle of B. Braun Gentamicin gentamicin (as sulfate) 1 mg/mL injection, intravenous infusion contains 80 mg gentamicin. One 80 mL bottle of B. Braun Gentamicin gentamicin (as sulfate) 3 mg/mL injection, intravenous infusion contains 240 mg gentamicin. One 120 mL bottle of B. Braun Gentamicin gentamicin (as sulfate) 3 mg/mL injection, intravenous infusion contains 360 mg gentamicin.
Special patient populations.

Dosage in patients with renal impairment.

In impaired renal function, the recommended daily dose has to be decreased and adjusted to the renal function.
Patients with renal function impairment should be monitored in order to adjust the therapeutic concentrations in plasma, either by decreasing the dose or by increasing the dosage interval (see Section 4.4 Special Warnings and Precautions for Use).
Dose reduction and interval prolongation are equivalently suitable solutions. Nonetheless, it should be remembered that doses determined in the way described below are only approximate and that the same dose may lead to different concentrations in the organisms of different patients. Therefore gentamicin serum levels should be determined in the given patient, so that the dosage can then be adapted accordingly.
1) Extension of dosage interval at the normal dose:
Since the gentamicin clearance is directly proportional to the creatinine clearance, the following approximate equation may be used:
Normal dose interval x (normal creatinine clearance/creatinine clearance of the patient) = subsequent dose interval.
Based on a normal creatinine clearance of 100 mL/min and a creatinine clearance of 30 mL/min in the patient, the application interval with a constant dose would in this case be 26 hours (8 x 100/30 [h]). See Table 3.
2) Reduction of dose at the normal dose interval:
After the usual initial dose, dividing the normal recommended dose by the serum creatinine level may be taken as a rough guide for the determination of the reduced dose that should be administered every 8 hours. See Table 4.
30 mg may therefore be administered every 8 hours to a patient weighing 60 kg with a serum creatinine level of 2.0 mg/100 mL after an initial dose of 60 mg (1 mg/kg; 60:2).
Alternatively, after the usual initial dose, subsequent doses every 8 hours may be calculated according to the formula:
Normal dose x creatinine clearance of the patient/normal creatinine clearance (100 mL/min) = subsequent dose.
The creatinine clearance should be preferred as a parameter especially in the elderly and in patients with fluctuating serum-creatinine concentrations, as is observed in severe infections (e.g. sepsis).
It should be emphasized that renal function may change during therapy with gentamicin.

Dosage in patients undergoing haemodialysis.

Gentamicin is dialysable. In the case of a 4 - 5-hour haemodialysis, a 50 - 60% reduction in concentration should be expected and in the case of an 8 - 12-hour haemodialysis, a 70 - 80% reduction in concentration. The dosage must be individually adjusted after each dialysis, based on the gentamicin serum concentration at that time.
The normal recommended dose after dialysis is 1 - 1.7 mg/kg body weight.

Elderly patients.

Elderly patients may require lower maintenance doses than younger adults because of impaired renal function.

Obese patients.

In obese patients the initial dose should be based on ideal body weight plus 40% of weight excess.

Patients with impaired hepatic function.

No dose adjustment is necessary.

Monitoring advice.

Serum concentration monitoring of gentamicin is recommended, especially in elderly, in newborns and in patients with impaired renal function. Blood samples are taken before the start of the next dosage interval (trough level). Trough levels should not exceed 2 microgram/mL when administering gentamicin twice daily and 1 microgram/mL for once daily dosing. See Section 4.4 Special Warnings and Precautions for Use.

Method of administration.

Intravenous use only.
B. Braun Gentamicin gentamicin (as sulfate) 1 mg/mL or 3 mg/mL injection, intravenous infusion is administered by intravenous infusion over a period of 30 - 60 minutes. B. Braun Gentamicin gentamicin (as sulfate) 1 mg/mL or 3 mg/mL injection, intravenous infusion is not suitable for intramuscular or slow intravenous injection.

4.3 Contraindications

Known hypersensitivity to gentamicin or disodium edetate, or patients who have experienced previous toxic reactions (ototoxicity, nephrotoxicity) resulting from aminoglycoside therapy. The use of gentamicin is contraindicated in patients with myasthenia gravis.

4.4 Special Warnings and Precautions for Use

Nephrotoxicity and ototoxicity.

As for other aminoglycosides, patients being treated with gentamicin should be under close clinical observation during and following 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.
There have been observed cases of an increased risk of ototoxicity with aminoglycosides administered to patients with mitochondrial mutations, particularly the m.1555A>G mutation, including cases where the patient's aminoglycoside serum levels were within the recommended range. Some cases were associated with a maternal history of deafness and/or mitochondrial mutation. Mitochondrial mutations are rare, and the penetrance of this observed effect is unknown.
Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs (see Section 4.5 Interactions with Other Medicines and Other Forms of 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 that prolonged or secondary apnoea may occur should be considered if the drug is administered to anaesthetised patients who are also receiving neuromuscular blocking agents such as succinylcholine, tubocurarine or decamethonium or in patients receiving massive transfusions of citrated blood. If neuromuscular blockade occurs it may be reversed by the administration of calcium salts.

Antibiotic-associated diarrhoea, pseudomembranous colitis.

Antibiotic-associated diarrhoea and pseudomembranous colitis have been reported with the use of gentamicin. These diagnoses should be considered in any patient who develops diarrhoea during or shortly after treatment. Gentamicin should be discontinued if severe and/or bloody diarrhoea occurs during treatment and appropriate therapy instituted. Drugs that inhibit peristalsis must not be given (see Section 4.8 Adverse Effects (Undesirable Effects)).

Neuromuscular disorders.

Aminoglycosides should be used cautiously in patients with neuromuscular disorders such as 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 over-growth of non-susceptible organisms occurs, appropriate therapy should be initiated.

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.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of 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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data exists.
(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.
 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.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Serious or life-threatening reactions.

Neurotoxicity (see Section 4.4 Special Warnings and Precautions for Use).

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.

Nephrotoxicity (see Section 4.4 Special Warnings and Precautions for Use).

Adverse renal effects, as demonstrated by the presence of casts, cells or protein in the urine or by rising BUN, NPN, serum creatinine or oliguria, have been reported. They occur more frequently in patients with a history of renal impairment and in patients treated for longer periods or with larger dosage than recommended.
The adverse reactions considered at least possibly related to treatment are listed (see Table 5) by body system organ class and absolute frequency.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Gentamicin has a narrow therapeutic window. In the event of accumulation (e.g. as a result of impaired renal function), renal damage and damage to the vestibulocochlear nerve may occur.

Treatment in the event of overdose.

Discontinue medication. There is no specific antidote. Gentamicin can be removed from the blood by haemodialysis (peritoneal dialysis or haemodialysis will also aid in the drug's removal).

Treatment of neuromuscular blockade.

In the event of neuromuscular blockade, usually caused by interactions, the administration of calcium chloride is advisable and artificial respiration if required.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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), Klebsiella, Enterobacter and Serratia species. It is also active against some Gram-positive organisms, e.g. Staphylococcus sp (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. It is not active against anaerobic organisms.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Gentamicin is rapidly absorbed after intramuscular 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 is excreted almost entirely by renal glomerular filtration, hence the half-life of the drug 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 Section 4.2 Dose and Method of 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.

5.3 Preclinical Safety Data

Genotoxicity.

Non-clinical data reveal no special hazard for humans based on data of safety pharmacology, genotoxicity and carcinogenic potential.

Carcinogenicity.

Gentamicin was not mutagenic in in vitro and in vivo tests. There are no long-term studies on animals on the carcinogenic potential of gentamicin.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

When gentamicin is used in combination with any other drug, mixing the drugs before administration should be avoided at all costs.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. For use in a single patient on one occasion only. Discard any remaining unused contents.

6.5 Nature and Contents of Container

Transparent LDPE infusion bottle fitted with polyethylene twin cap-port containing:
AUST R: 280508 B. Braun Gentamicin gentamicin (as sulfate) 80 mg/80 mL injection, intravenous infusion, bottle; carton of 10 or 20.
AUST R: 280507 B. Braun Gentamicin gentamicin (as sulfate) 240 mg/80 mL injection, intravenous infusion, bottle; carton of 10 or 20.
AUST R: 280495 B. Braun Gentamicin gentamicin (as sulfate) 360 mg/120 mL injection, intravenous infusion, bottle; carton of 10 or 20.
One 80 mL bottle of B. Braun Gentamicin gentamicin (as sulfate) 1 mg/mL injection, intravenous infusion contains 80 mg gentamicin.
One 80 mL bottle of B. Braun Gentamicin gentamicin (as sulfate) 3 mg/mL injection, intravenous infusion contains 240 mg gentamicin.
One 120 mL bottle of B. Braun Gentamicin gentamicin (as sulfate) 3 mg/mL injection, intravenous infusion contains 360 mg gentamicin.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Gentamicin sulfate is a mixture of the sulfates of antimicrobial substances produced by Micromonospora purpurea, the main components being gentamicins C1, C1a, C2, C2a and C2b. It is white or almost white, hygroscopic powder, freely soluble in water, practically insoluble in alcohol.

Chemical structure.

The structural formula is represented below.
See Table 6.

CAS number.

CAS: 1403-66-3 (gentamicin); 1405-41-0 (gentamicin sulfate).

7 Medicine Schedule (Poisons Standard)

Schedule 4 Prescription only medicine.

Summary Table of Changes