Consumer medicine information

Amikacin Wockhardt Solution for Injection or Infusion

Amikacin

BRAND INFORMATION

Brand name

Amikacin Wockhardt

Active ingredient

Amikacin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Amikacin Wockhardt Solution for Injection or Infusion.

What is in this leaflet

This leaflet answers some common questions about Amikacin Injection.

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 Amikacin Injection against the benefits they expect it will have for you.

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 Amikacin Injection is used for

Amikacin 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.

Amikacin works by killing bacteria or preventing their growth.

Your doctor may have prescribed amikacin for another reason.

Ask your doctor if you have any questions about why amikacin has been prescribed for you.

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

Before you are given Amikacin Injection

When you must not be given it

You must not be given Amikacin Injection if you have an allergyto amikacin or any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include:

  • 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 not be given Amikacin Injection if you have experienced serious reactions (such as hearing loss or kidney problems) to amikacin, gentamicin, tobramycin, or neomycin in the past.

You must not be given Amikacin Injection if you have myasthenia gravis, a condition in which the muscles become weak and tire easily.

You must not be given amikacin if you are pregnant or planning to become pregnant. Amikacin may affect your developing baby if you are given it during pregnancy.

You must not be given amikacin if you are breast-feeding. It is not known whether amikacin passes into breast milk.

If you are not sure whether you should be given amikacin, talk to your doctor or pharmacist.

Before you are given it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines, in particular any other antibiotics
  • sulfites /sulfates
  • any other substances, such as foods, preservatives or dyes.

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

  • kidney disease
  • hearing disorders
  • muscular disorders (eg myasthenia gravis, Parkinson’s disease).

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

Taking other medicines

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

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

  • fluid tablets (eg frusemide, ethacrynic acid)
  • cisplatin, a medicine used to treat cancer
  • some other antibiotics (eg vancomycin, clindamycin, colistin, cephalosporins, penicillins,
  • amphotericin, a medicine used to treat some fungal infections
  • suxamethonium, a medicine used during surgery to relax muscles
  • some general anaesthetic agents
  • opioid analgesics (eg codeine, morphine, pethidine,fentanyl).

These medicines may be affected by amikacin, 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 amikacin.

How Amikacin Injection 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

Amikacin Injection is usually given as an injection into a muscle. Amikacin Injection can also be given as a slow injection into a vein (intravenously).

Amikacin Injection must only be given by a doctor or nurse.

How long it is given for

Your doctor will decide what dose and how long you will receive Amikacin Injection. This depends on your infection and other factors, such as your weight. For most infections, Amikacin Injection is usually given in divided doses throughout the day.

Overdose

As Amikacin Injection is most likely to be given to you in hospital under the supervision of your doctor, it is very unlikely that you will receive an overdose. However, if you experience severe side effects, tell your doctor immediately or go to Accident and Emergency at the nearest hospital.

In case of overdose, immediately contact the Poisons Information Centre for advice (telephone 13 11 26 in Australia, or call 0800 764 766 in New Zealand)

Symptoms of an amikacin overdose may include ringing in the ears, hearing difficulties, dizziness, fever, headache, pins and needles in the hands and feet and problems with passing urine.

While you are being given Amikacin Injection

Things you must do

Tell any other doctors, dentists, and pharmacists who are treating you that you are being given Amikacin Injection.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are being given Amikacin Injection..

If you plan to have surgery that needs a general anaesthetic,tell your doctor or dentist that you are being given amikacin.

If you become pregnant while being treated with Amikacin Injection., tell your doctor immediately.

Things to be careful of

Be careful driving or operating machinery until you know how Amikacin Injection affects you. As with other aminoglycoside medicines, amikacin may drowsiness, tiredness or dizziness in some people. Make sure you know how you react to amikacin before you drive a car, operate machinery, or do anything else that could be dangerous if you are drowsy, tired or dizzy. If this occurs do not drive.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given Amikacin Injection..

Amikacin helps most people with 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. If you are over 65 years of age you may have an increased chance of getting side effects.

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

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

  • pain at the injection site
  • dizziness
  • feeling sick
  • decreased appetite
  • headache.
  • nausea and vomiting
  • fever

These side effects are usually mild.

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

  • hearing problems or ringing in the ears.
  • passing less urine than is normal
  • numbness, skin tingling, muscle twitching and convulsions.
  • signs of an allergic reaction, such as rash, itching or hives on the skin; swelling of the face, lips, tongue or other parts of the body; shortness of breath, wheezing or difficulty breathing.

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.

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

After being given Amikacin Injection

Storage

Amikacin Injection will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

Product description

What it looks like

Amikacin Injection comes in a glass vial containing a clear, colourless solution.

Ingredients

Active ingredients:

  • Each mL of Amikacin Injection contains amikacin sulfate equivalent to 250 mg (250,000 international units) of amikacin activity

Other ingredients

  • sodium citrate
  • sodium metabisulfite
  • water for injection.

Amikacin Injection does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Wockhardt Bio Pty Ltd,
Suite 103,
39 East Esplanade
Manly NSW 2095
Australia

Amikacin Injection is available
500 mg/2 mL x 1 vial
AUST R 288798

This leaflet was prepared in Nov 2017

Published by MIMS August 2018

BRAND INFORMATION

Brand name

Amikacin Wockhardt

Active ingredient

Amikacin

Schedule

S4

 

1 Name of Medicine

Amikacin sulfate.

2 Qualitative and Quantitative Composition

Amikacin Wockhardt is a sterile clear, colourless solution of amikacin sulfate, sodium citrate and sodium metabisulfite in water for injections. Sulfuric acid is added to adjust pH to 4.5. Each mL contains amikacin sulfate equivalent to amikacin activity 250 mg (250,000 IU). Amikacin Wockhardt is available in 500 mg/2 mL strength.

Excipient with known effect.

Sodium metabisulfite.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection or infusion.
Amikacin Wockhardt is a sterile clear, colourless solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Amikacin Wockhardt injection is indicated in the short-term treatment of serious infections caused by susceptible strains of Gram-negative bacteria, (see Section 5.1 Pharmacodynamic Properties, Microbiology).
Staphylococcus aureus, including methicillin-resistant strains is the principal Gram-positive organism sensitive to amikacin.
The use of amikacin in the treatment of staphylococcal infections should be restricted to second-line therapy, and should be confined to patients suffering from severe infections caused by susceptible strains of staphylococcus who have failed to respond or are allergic to other available antibiotics.
Amikacin Wockhardt injection is indicated in the treatment of neonatal sepsis when sensitivity testing indicates that other aminoglycosides cannot be used.
In certain severe infections such as neonatal sepsis, concomitant therapy with a penicillin type drug may be indicated because of the possibility of infections due to Gram-positive organisms such as streptococci or pneumococci. If concomitant treatment with a penicillin type drug is indicated, then the drugs should be administered separately because in-vitro mixing of the two drugs causes inactivation of amikacin.
Clinical studies have shown amikacin to be effective in treating bacteraemia, septicaemia including neonatal sepsis and serious infections of the respiratory tract, bones and joints, central nervous system, skin and skin structures (including those resulting from burns), intra-abdominal organs, post-operative infections and complicated and recurrent urinary tract infections, when caused by susceptible organisms.

4.2 Dose and Method of Administration

Dosage.

Dosage of amikacin sulfate is expressed in terms of amikacin and calculated on a body weight basis. Dosage is identical for both routes of administration.

Adults and children.

The usual recommended dose of amikacin is 15 mg/kg daily given in two or three equally divided doses.

Neonates and premature infants.

Dosage given for patients with normal renal function. Initiate treatment with a loading dose of 10 mg/kg followed by 7.5 mg/kg every 12 hours. The maximum total daily dose should not exceed 15 mg/kg. Solution infusions via the IV route should be given over a 1 to 2 hour period.
Insufficient clinical use has not enabled firm dosage guidelines to be established for the use of amikacin in premature infants.

Elderly.

Amikacin is excreted by the renal route. Since renal function could be failing in the elderly, it should be assessed whenever possible and the dosage adjusted accordingly, if necessary. See Section 4.2 Dose and Method of Administration, Dosage adjustment, Renal impairment.

Urinary tract infections (other than pseudomonal infections).

500 mg/day in two equally divided doses is recommended.

Method of administration.

Amikacin Wockhardt injection is for single use in one patient only. Discard any residue.
Uncomplicated infections due to sensitive organisms should respond to treatment within 24 to 48 hours at the recommended dosage. If no improvement occurs within three to five days, the use of amikacin sulfate should be re-evaluated and consideration be given to alternative therapy. Failure of the infection to respond may be due to resistance of the organism or to the presence of septic foci requiring surgical drainage.
Whenever possible, and especially in patients with impaired renal function, peak and trough amikacin serum concentrations should be determined and dosage adjusted where necessary to maintain desired serum concentrations. In general, desired peak concentrations are between 15 to 30 microgram/mL, and trough concentrations should not exceed 5 to 10 microgram/mL. An increased risk of toxicity may be associated with prolonged peak amikacin serum concentrations greater than 30 to 35 microgram/mL.

Intramuscular or intravenous administration.

The intramuscular route is preferred for most infections, but in life-threatening infections or when an intramuscular injection is not feasible, an intravenous infusion (0.25% over 30 to 60 minutes) may be used.
The compatible diluents for intravenous use if required are as follows: 5% Glucose Intravenous Infusion BP in Water for Injections BP and Sodium Chloride Intravenous Infusion BP (0.9%). To reduce microbiological hazard, use as soon as practicable after dilution. See Section 6.4 Special Precautions for Storage for storage instructions.
No antimicrobial preservative is added to the formulation. This product is for single use in one patient only. Discard any residue.

Dosage adjustment.

Renal impairment.

In patients with impaired renal function, either the dose or the dosage interval needs to be adjusted to avoid accumulation. The dosage interval may be calculated using the following formula (see Equation 1):
This formula should not be used to calculate the dosage interval for elderly patients. Instead, it is advisable to base dosage on creatinine clearance. See Table 1.
As renal function may alter appreciably during therapy, the serum creatinine should be checked frequently and the dosage regimen modified accordingly.
If it is desired to administer amikacin at a fixed time interval, the dosage must be reduced. It is recommended that the drug be given every 12 hours. Serum concentrations of the drug should be measured in these patients to ensure accurate administration and to avoid toxic serum levels.
If serum assay determinations are not available and the patient's condition is stable, serum creatinine and creatinine clearance values are the most readily available indicators of the degree of renal impairment to use in determining the dosage.
First, begin therapy by administering 7.5 mg/kg, which is half the normal daily dose.
To determine the size of maintenance doses administered every 12 hours, the initial dose should be reduced in proportion to the reduction in the patient's creatinine clearance rate (cc) (see Equation 2):
An alternate rough guide for determining reduced dosage at 12 hour intervals (for patients whose steady state serum creatinine values are known) is to divide the normally recommended dose by the patient's serum creatinine.
The above dosage schedules are provided as guides to dosage when the measurement of amikacin serum levels is not feasible and are not intended to be rigid recommendations.

4.3 Contraindications

Myasthenia gravis.
Amikacin Wockhardt injection is contraindicated in patients with a known history of hypersensitivity to amikacin, any constituents of the injection (see Section 2 Qualitative and Quantitative Composition) or in patients who may have subclinical renal or eighth nerve damage induced by prior administration of nephrotoxic and/or ototoxic agents, as the toxicity may possibly be additive.
Pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy); Lactation (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).

4.4 Special Warnings and Precautions for Use

Identified precautions.

Treatment with amikacin for more than 14 days has not been established as being safe. Patients undergoing treatment with parenteral aminoglycosides should be under close clinical observation and evaluation because of the potential ototoxicity and nephrotoxicity associated with their use.

Cross allergenicity.

Cross allergenicity among aminoglycosides has been demonstrated. Therefore, caution should be exercised in patients who have shown hypersensitivity to this class of drugs.

Ototoxicity.

In patients treated at higher doses or for periods longer than those recommended, ototoxicity, both auditory and vestibular can occur. Patients with renal damage have the highest risk of developing amikacin induced ototoxicity. The risk of hearing loss due to aminoglycosides increases with the degree of exposure to either high peak or high trough serum concentrations. As with other aminoglycosides, on rare occasions changes in renal and eighth cranial nerve function may not become manifest until soon after completion of therapy. Aminoglycoside induced ototoxicity is usually irreversible.
A pre-treatment audiogram should be obtained and repeated during therapy in patients with renal impairment undergoing treatment for seven days or more as well as in other patients being treated for 10 days. If tinnitus or subjective hearing loss develops; or if follow-up audiograms show significant loss of high frequency response, the use of amikacin sulfate therapy should be discontinued immediately. Lost function may not be fully restored.

Neurotoxicity.

Muscular paralysis and neuromuscular blockade have been demonstrated in the cat with high doses of amikacin (188 mg/kg). The possibility of respiratory paralysis and neuromuscular blockade should be considered when amikacin is administered concomitantly with neuromuscular blocking drugs or anaesthetics. If blockade occurs, calcium salts may reverse this phenomenon. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.

Monitoring of serum levels.

Whenever possible, and especially in patients with renal impairment, peak and trough serum concentrations of amikacin should be determined periodically, and dosage should be adjusted, to maintain desired serum concentrations. In general, desirable peak concentrations of amikacin are 15 to 30 microgram/mL, and trough concentrations of the drug should not exceed 5 to 10 microgram/mL. An increased risk of toxicity may be associated with prolonged peak amikacin serum concentrations greater than 30 to 35 microgram/mL.

Concurrent use with other antibiotics or potent diuretics.

Since the risk of ototoxicity, irreversible deafness and nephrotoxicity is increased when amikacin is used in conjunction with the 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), such therapy should be avoided. This includes concurrent use with potent diuretics and other aminoglycosides. Other factors which may increase the risk of toxicity are dehydration and advancing age.

Patients with muscular disorders.

Amikacin must not be used in patients with myasthenia gravis. Aminoglycosides, including amikacin, should be used with caution in patients with muscular disorders such as parkinsonism, since these drugs may aggravate muscle weakness because of their potential curare-like effect on neuromuscular junction.

Superinfection.

If overgrowth of nonsusceptible organisms occurs, appropriate therapy should be initiated.

Sulfite-sensitivity.

Amikacin Wockhardt injection contains sodium metabisulfite, which may cause allergic-type reactions, including anaphylactic symptoms and life threatening or less severe asthmatic episodes in susceptible people.

Topical use.

Aminoglycosides are quickly and almost totally absorbed when they are applied topically, except to the urinary bladder, in association with surgical procedures. Irreversible deafness, renal failure and death due to neuromuscular blockade have been reported following irrigation of both small and large surgical fields with an aminoglycoside preparation.

Use in renal impairment.

As with other aminoglycosides, amikacin sulfate is potentially nephrotoxic and neurotoxic; therefore, precautions on dosage and adequate hydration should be observed. Renal function should be closely monitored in patients with known or suspected renal impairment (e.g. diminished glomerular filtration), and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy.
Amikacin is present in high concentrations in the renal excretory system; therefore, patients should be well hydrated to minimize chemical irritation/damage of the renal tubules. Prior to initiating therapy, kidney function should be assessed by the usual methods and monitored periodically during the course of treatment.
Hydration should be increased upon signs of renal irritation (casts, white or red cells, or albumin). A reduction in dosage (see Section 4.2 Dose and Method of Administration, Renal impairment) may be desirable if other evidence of renal dysfunction occurs such as decreased creatinine clearance, decreased urine specific gravity, increased serum urea, increased serum creatinine or oliguria. If azotaemia or a progressive decrease in urinary output occurs, treatment should be stopped.

Use in the elderly.

Because of its toxicity, amikacin 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. This may not be evident in the results of routine screening tests 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. Geriatric patients may require smaller daily doses of amikacin 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.

Paediatric use.

The nephrotoxic and ototoxic potential of amikacin in newborn infants is not known. Until more safety reports are available, amikacin should be used in infants only in those specific circumstances where susceptibility testing indicated that other aminoglycosides cannot be used or are otherwise contraindicated, and when the infant can be observed for evidence of toxicity.

Effects on laboratory tests.

Laboratory abnormalities possibly related to aminoglycosides include: increased levels of serum transaminase (ALT, AST) serum LDH and bilirubin; decreased serum calcium, magnesium, sodium and potassium; anemia, leukopenia, 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 hypomagnesemia, hypocalcemia and hypokalemia.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Potent diuretics.

If possible, do not give amikacin in conjunction with ethacrynic acid, frusemide or other potent diuretics which may themselves cause ototoxicity or enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Other neurotoxic and/or nephrotoxic agents.

If possible, avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic antibiotics, including other aminoglycosides, polymyxin B, colistin, cisplatin, vancomycin, amphotericin B, clindamycin and cephalosporins.

Anaesthetics/neuromuscular blocking agents or medications with neuromuscular blocking activity.

Concurrent use of amikacin with agents with neuromuscular blocking activity e.g. succinylcholine, tubocurarine, decamethonium, halogenated hydrocarbon inhalation anaesthetics, opioid analgesics and massive transfusions with citrated anticoagulated blood, should be carefully monitored; neuromuscular blockade may be enhanced, resulting in skeletal muscle weakness and respiratory depression or paralysis (apnea); caution is recommended when these medications and amikacin are used concurrently during surgery or in the postoperative period, especially if there is a possibility of incomplete reversal of neuromuscular blockade postoperatively; treatment with anticholinesterase agents or calcium salts may help to reverse the blockade.

Penicillins.

Aminoglycosides are inactivated by solutions containing penicillins. This inactivation is brought about by the opening of the beta-lactam ring and combination of the penicillin with an amino group of the aminoglycoside to form a biologically inactive amide. For this reason, amikacin and penicillins should not be combined in intravenous injections/infusions. The inactivation of some aminoglycosides by penicillins has been reported in vivo, especially in patients with renal failure who maintain a higher level of the penicillin for a longer period of time compared to patients with normal renal function. Therefore, when amikacin 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.

Compatibilities.

Amikacin sulfate is stable for 24 hours at room temperature in the presence of light at 5 mg/mL and 0.25 mg/mL in 0.9% Sodium Chloride Intravenous Infusion BP and 5% Glucose Intravenous Infusion BP solutions.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In reproduction toxicity studies in mice and rats, no effects on fertility or fetal toxicity were reported.
(Category D*)
Gentamicin and other aminoglycosides cross the placenta. There is evidence of selective uptake of gentamicin by the foetal 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 the chemical similarity, all aminoglycosides must be considered potentially nephrotoxic and ototoxic to the foetus. It should also be noted that therapeutic blood levels in the mother do not equate with safety for the foetus.
* Category D: Drugs which have caused, are suspected to have caused or may be caused or maybe expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs may also have pharmacological effects.
 It is not known whether amikacin is excreted in breast milk. Since the possible harmful effect on the infant is not known, it is recommended that if nursing mothers must be given amikacin, the infants should not be breast fed during therapy.

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)

Amikacin induced hepatotoxicity is not a common side effect, however it may occur. Increased serum transaminases (ALT, AST) increased serum bilirubin, hepatomegaly, and hepatic necrosis have been reported.
The percentages below refer to incidence in clinical trials.

More common reactions.

Auditory and vestibular.

Hearing loss (4%) (permanent in some cases). Hearing loss is usually manifested initially by diminution of high-tone acuity.

Biochemical abnormalities.

Increased serum urea, decreased creatinine clearance, elevated serum creatinine, azotaemia.

Genitourinary.

Reduced renal function, oliguria.

Injection site reactions.

Pain at site of intramuscular injection (6%).

Less common reactions.

Auditory and vestibular.

Tinnitus, vertigo, dizziness, nystagmus, changes in caloric testing or electronystagmograms.

Biochemical abnormalities.

Casts, cells or protein in the urine, eosinophilia, increase in AST.

Dermatological.

Pruritus, rash.

Gastrointestinal.

Nausea, vomiting.

General.

Drug fever.

Genitourinary.

Renal failure.

Haematological.

Anaemia.

Musculoskeletal.

Arthralgia.

Nervous system.

Paraesthesia, tremor.

Serious or life-threatening reactions.

Serious adverse effects on both vestibular and auditory branches of the eighth cranial nerve have been reported, primarily in patients with renal impairment (especially if dialysis is required), and in patients on high doses and/or prolonged therapy. Other factors which may increase the risk of toxicity include excessive dosage, dehydration and previous exposure to ototoxic drugs.

Other reactions.

Other adverse effects reported with the use of aminoglycosides include: respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight loss, anorexia, hypotension and hypertension, urticaria, generalised burning, laryngeal edema, anaphylactoid reactions, headache, increased salivation, stomatitis, purpura, pseudotumor cerebri, acute organic brain syndrome, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly, splenomegaly, convulsions and a myasthenia gravis-like syndrome.

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

Management.

In the event of overdosage or toxic reactions peritoneal dialysis or haemodialysis should be considered. These procedures are of particular importance in patients with impaired renal function. In the newborn infant, exchange transfusion may also be considered.

Clinical features.

Likely signs and symptoms include tinnitus, vertigo, reversible or irreversible deafness, skin rash, drug fever, headache, paraesthesia, reduced renal function or renal failure.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Amikacin is a semisynthetic aminoglycoside antibiotic derived from kanamycin.

Microbiology.

Amikacin is active, in vitro, against the following organisms (see Table 2):
Amikacin's structure has been altered to reduce the possible route of enzymatic deactivation, thus reducing bacterial resistance. Many strains of Gram-negative organisms resistant to gentamicin and tobramycin have shown to be sensitive to amikacin in vitro.

Susceptibility testing.

The Kirby-Bauer test can determine the sensitivity of an organism to amikacin. This test operates on the principle that antibiotics will diffuse from a paper disc into an agar medium containing test organisms. Inhibition is observed as a failure of the organism to grow in the region of the antibiotic.
When the Kirby-Bauer method of disc susceptibility is used, a 30 microgram amikacin disc should give a zone of 17 mm or greater when tested against an amikacin susceptible bacterial strain. Such a result indicates that the infecting organism is likely to respond to therapy. A zone size of 14 mm or less indicates resistance, or that the infecting organism is unlikely to respond to therapy. Zone sizes of 15 to 16 mm indicate intermediate susceptibility, in other words the organism will probably be susceptible if the infection is confined to tissues and fluids (e.g. urine) in which high antibiotic levels are obtained.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following IM administration of a single dose of amikacin of 7.5 mg/kg in adults with normal renal function, peak plasma amikacin concentrations of 17 to 25 microgram/mL are attained within 45 minutes to 2 hours.
Following IV infusion of the same dose given over 1 hour peak plasma concentrations of the drug average 38 microgram/mL immediately following the infusion, 5.5 microgram/mL at 4 hours, and 1.3 microgram/mL at 8 hours.

Distribution.

Following administration of usual dosages of amikacin, amikacin has been found in bone, heart, gallbladder, and lung tissue. Amikacin is also distributed into bile, sputum, bronchial secretions, and interstitial, pleural, and synovial fluids.

Excretion.

The plasma elimination half-life of amikacin is usually 2 to 3 hours in adults with normal renal function and is reported to range from 30 to 86 hours in adults with severe renal impairment.
In adults with normal renal function, 94 to 98% of a single IM or IV dose of amikacin is excreted unchanged by glomerular filtration within 24 hours. The drug may be completely recovered within approximately 10 to 20 days in patients with normal renal function. Terminal elimination half-lives of greater than 100 hours have been reported in adults with normal renal function following repeated IM or IV administration of the drug.
In patients with impaired renal function, the clearance of amikacin is decreased; the more severe the impairment, the slower the clearance. Therefore, the interval between doses should be adjusted according to the degree of renal impairment. Endogenous creatinine clearance rate and serum creatinine which have high correlation with serum half-life of amikacin, may be used as a guide for this purpose (see Section 4.2 Dose and Method of Administration, Dosage adjustment, Renal impairment).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium citrate, sodium metabisulfite and water for injections.

6.2 Incompatibilities

Amikacin Wockhardt injection may be prescribed as concurrent therapy with other antibacterial agents in mixed or superinfections. In such situations, Amikacin Wockhardt injection should never be physically mixed with other antibacterial agents in infusion bags, syringes or any other container equipment. Each agent should be administered separately following the manufacturer's recommended route.

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

Unopened vial.

Store below 25°C.

Opened/ diluted vial.

To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 25°C for not more than 6 hours.

6.5 Nature and Contents of Container

Strength.

500 mg (500,000 IU)/2 mL.

Pack size.

1 x 2 mL vials.
Vials are clear, type I, glass vials with rubber stopper and aluminium cap with grey polypropylene lid in carton with product information leaflet.

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

It is described chemically as 6-O-(3-Amino-3-deoxy-α-D- glucopyranosyl)-4-O-(6-amino-6-deoxy-α-D- glucopyranosyl)-1-N-[(2S)-4-amino- 2-hydroxybutanoyl]-2-deoxy-D-streptamine sulfate.
Molecular formula: C22H43N5O13.2H2SO4.
Molecular weight: 781.8.
Amikacin sulfate is a white crystalline powder. It is freely soluble in water and practically insoluble in alcohol and acetone. 1.3 g of amikacin sulfate is approximately equivalent to 1 g of amikacin.

Chemical structure.


CAS number.

39831-55-5.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes