DBL™ Amikacin

Main information

  • Trade name:
  • DBL™ Amikacin 500 mg/2mL Solution for injection
  • Dosage:
  • 500 mg/2mL
  • Pharmaceutical form:
  • Solution for injection
  • Units in package:
  • Vial, 5 x 2mL, 10 mL
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Qilu Tianhe Pharmaceutical Co Ltd

Documents

Localization

  • Available in:
  • DBL™ Amikacin 500 mg/2mL Solution for injection
    New Zealand
  • Language:
  • English

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 6712
  • Authorization date:
  • 11-02-1992
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

Data Sheet – New Zealand

Version 5.0

DBL

AMIKACIN INJECTION

Description

Amikacin is a semisynthetic aminoglycoside antibiotic derived from kanamycin. Amikacin occurs as a

white, crystalline powder and is sparingly soluble in water. The injection consists of the sulfate salt. The

molecular formula is C

and the chemical structure is shown below.

Amikacin Sulfate

Amikacin Injection is a sterile clear, colourless solution, free from specks, lint, or other visible

evidence of contamination. Each 2 mL vial contains amikacin sulfate equivalent to amikacin activity 500

mg (500,000 I.U.). The vial also contains 50 mg Sodium Citrate B.P. and 4.8 mg Sodium Metabisulfite

B.P. No antimicrobial preservative is added to the formulation.

Pharmacology

Microbiology

Amikacin is active, in vitro, against the following organisms:

Gram-negative

MIC microgram/mL

Pseudomonas species

1.6 - 12.5

Proteus species (indole-positive and indole negative)

1.6 - 3.1

Klebsiella pneumoniae

1.6 - 3.1

Enterobacter cloacae

1.6 - 3.1

Serratia species

0.8 - 3.1

Acinetobacter

No information available

Providencia stuartii

Citrobacter freundii

1 - 8

Escherichia coli

1.6 - 3.1

Gram-positive

Staphylococcus species

(penicillinase and nonpenicillinase producing,

including methicillin resistant strains)

0.4 - 5.0

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.

Data Sheet – New Zealand

Version 5.0

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.

Pharmacokinetics

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 17-25 micrograms/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 micrograms/mL immediately following the infusion, 5.5 micrograms/mL at 4 hours, and 1.3

micrograms/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.

Elimination

The plasma elimination half-life of amikacin is usually 2-3 hours in adults with normal renal function and is

reported to range from 30-86 hours in adults with severe renal impairment.

In adults with normal renal function, 94-98% 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-

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

Dosage and Administration - Impaired Renal Function).

Indications

Amikacin Injection is indicated in the short-term treatment of serious infections caused by

susceptible strains of Gram-negative bacteria, (see 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 stapylococcus who have failed to respond or are allergic to other available antibiotics.

Amikacin Injection is indicated in the treatment of neonatal sepsis when sensitivity testing indicates

that other aminoglycosides cannot be used.

Data Sheet – New Zealand

Version 5.0

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 and at different sites 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.

Contraindications

Myasthenia Gravis

Amikacin Injection is contraindicated in patients with a known history of hypersensitivity to

amikacin, any constituents of the injection (see Description) 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 Use in Pregnancy); Lactation (see, Use in Lactation).

Warnings and Precautions

Treatment with amikacin for more than 10 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.

Nephrotoxicity:

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 Dosage in Impaired Renal Function) 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.

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

Data Sheet – New Zealand

Version 5.0

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 (188mg/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

15-30 micrograms/mL, and trough concentrations of the drug should not exceed 5-10

micrograms/mL. An increased risk of toxicity may be associated with prolonged peak amikacin serum

concentrations greater than 30-35 micrograms/mL.

Concurrent use with other antibiotics or potent diuretics:

Since the risk of ototoxicity, irreversible deafness and nephrotoxocity is increased when amikacin is

used in conjunction with the systemic or topical use of other potentially neurotoxic and/or nephrotoxic

drugs, (see Interactions with other Drugs), 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.

Geriatric:

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:

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.

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 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

Data Sheet – New Zealand

Version 5.0

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 Pregnancy

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.

In reproduction toxicity studies in mice and rats, no effects on fertility or foetal toxicity were reported

Use in Lactation

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.

Interactions with Other Drugs

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 B.P. and 5% Glucose Intravenous Infusion B.P.

solutions.

Data Sheet – New Zealand

Version 5.0

Incompatibilities

Amikacin Injection may be prescribed as concurrent therapy with other antibacterial agents in

mixed or superinfections. In such situations, DBL

Amikacin 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 and at different sites following the manufacturer's recommended route.

Adverse Reactions

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 reactions 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.

Data Sheet – New Zealand

Version 5.0

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.

Dosage and Administration

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 micrograms/mL, and

trough concentrations should not exceed 5 to 10 micrograms/mL. An increased risk of toxicity may be

associated with prolonged peak amikacin serum concentrations greater than 30 to 35 micrograms/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

B.P. in Water for Injections B.P. and Sodium Chloride Intravenous Infusion B.P. (0.9%). Use solutions for

I.V. administration within 12 hours after preparation.

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 15mg/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 I.V. 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. Refer to "Impaired renal

function" of dosage description.

Urinary Tract Infections (other than pseudomonal infections):

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

Impaired Renal Function:

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:

Data Sheet – New Zealand

Version 5.0

Serum creatinine concentration (mg / 100 mL) x 9 = dosage interval (hours)

This formula should not be used to calculate the dosage interval for elderly patients. Instead, it is

advisable to base dosage on creatinine clearance.

Serum Creatinine

Concentration

(mg / 100 mL)

Interval between doses

of 7.5 mg/kg (hours)

x 9 =

13.5

22.5

31.5

40.5

45.9

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):

Maintenance dose every 12

hours

Observed cc in mL/min

Calculated initial dose in mg

normal cc in mL/min

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.

Overdosage

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.

Data Sheet – New Zealand

Version 5.0

Medicine Classification

Prescription Only Medicine

Storage

Store below 25°C.

Presentation

Code

Strength

Pack Size

1220B

500 mg (500,000 I.U.)/2mL

5 x 2 mL vials

Name and Address

Toll Free Number: 0800 736 363

Date of Preparation

03 August 2017

Pfizer New Zealand Limited,

PO Box 3998

Auckland, New Zealand, 1140

3-8-2018

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