Amikacin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Serious nosocomial Gram-negative bacillary infections
• Uncomplicated urinary tract infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity or serious toxic reactions to other aminoglycosides
• Asthmatics (due to sulphite hypersensitivity)

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Elderly
• Myasthenia gravis
• Pre-existing muscular disorders
• Parkinsonism
• Pre-existing hearing damage
• Pre-existing vestibular damage
• Prolonged use
• High doses
• Subclinical renal or eighth nerve damage induced by prior administration of nephrotoxic and/or ototoxic agents
• Dehydration
• Irrigation of both small and large surgical fields with aminoglycoside preparations
• Intravitreous administration
• Premature and neonatal infants
• Obese patients receiving high doses
• Cystic fibrosis patients receiving high doses
• Sodium restricted diets (certain formulations)
• Coadministration of systemic, oral or topical neurotoxic or nephrotoxic agents (particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin or other aminoglycosides)
• May impair ability to drive or operate machinery

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• General dosing range
• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enterica (enteritis salmonella), Serratia liquefaciens, Serratia marcescens, Shigella spp., Nocardia sp.

General dosing range
- Multiple daily dose

• IV/IM: 7.5mg/kg, 12hrly; Target peak: 15-30μg/ml, Trough: 5-10μg/ml

- Once daily dose

• IV/IM: 15mg/kg, dly; Target peak: 56-64μg/ml, Trough: <1μg/ml

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See additional prescribing points for dilution and administration directions

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Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Treatment of tuberculosis in patients with drug-induced liver injury
- For short-term use, as an alternative to linezolid

• IV: 15mg/kg, dly
  (STG, Adult 2023)

Hospital-acquired pneumonia (Additional agent required)

• IV: 15mg/kg, dly; Treatment duration: 10 days
  (STG, Adult 2019)

Febrile neutropenia (Additional agent required)

• IV: 15mg/kg, dly
  (STG, Adult 2019)

Catheter-associated urinary tract infections

• IV: 15mg/kg, dly; Treatment duration: 7-14 days
  (STG, Adult 2019)

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South African registered indications and dosages

Serious nosocomial Gram-negative bacillary infections
Uncomplicated urinary tract infection (unless the causative organisms are not susceptible to antibiotics with less potential toxicity) 

• IV/IM: 15mg/kg/day, in 2-3 divided doses, 8-12hrly; as a slow injection over 2-3 mins OR as an infusion over 30-60mins; Max: 1.5g/24hrs; Treatment duration: 7-10 days

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Treatment should preferably not continue for longer than 10 days with the total treatment dosage not exceeding 15g for adults

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Should clinical response not occur in 3-5 days, alternate therapy should be considered

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The patient's pre-treatment body weight should be obtained for calculation of correct dosage

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Therapeutic concentration for amikacin should be in line with local laboratory practices. Prolonged peak (post-distributional) concentrations (measured 15-30 mins after injection) and trough concentrations (measured immediately prior to next dose) >30μg/ml and 10μg/ml respectively should be avoided. Dosage adjustments should be individualised and based on peak and trough serum concentrations

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Indications and dosages registered in other jurisdictions

Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP)
Complicated urogenital tract infections, including pyelonephritis
Complicated intra-abdominal infections
Endocarditis (additional agent(s) required)
Infected burns
Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above
Management of neutropenic patients with fever suspected to be due to a bacterial infection 

• IV/IM: 15mg/kg/day, as a single dose or in divided (equal) doses; Max: 1.5g/24hrs

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For endocarditis and febrile neutropenic patients, dosing should be twice a day as there is insufficient data for once daily dosing

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Life-threatening infections and/or those caused by Pseudomonas

• IV/IM: Max: 500mg, 8hrly; Max: 1.5g/24hrs; Treatment duration: ≤10 days

Urinary tract infections (other than pseudomonal infections)

• IV/IM: 7.5mg/kg/day, in 2 divided (equal) doses (equivalent to 250mg, 12hrly)

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As the activity of amikacin is enhanced by increasing the pH, a urinary alkalizing agent may be administered concurrently

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Irrigation solution in abscess cavities, the pleural space, the peritoneum and the cerebral ventricles 
- Following exploration for established peritonitis
- After peritoneal contamination due to faecal spill during surgery

• Sol: 0.25% (2.5mg/ml), after recovery from anaesthesia

- For instillation

• Sol: 500mg, as a single dose diluted in 20ml sterile distilled water; Instill through a polyethylene catheter sutured into the wound at closure

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If possible, instillation should be postponed until the patient has fully recovered from the effects of anaesthesia and muscle-relaxing drugs

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• General dosing range
• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enterica (enteritis salmonella), Serratia liquefaciens, Serratia marcescens, Shigella spp., Nocardia sp.

General dosing range

28 days and older
- Multiple daily dose

• IV/IM: 15-22.5mg/kg/day, in 3 divided doses, 8hrly

- Once daily dose

• IV/IM: 15-20mg/kg/day

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See additional prescribing points for dilution and administration directions

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Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Methicillin resistant S. aureus infection (Additional agent required)

Between 1 week-10 years

• IV: 25mg, immediately; THEN 18mg/kg, dly; Treatment duration: 5-14 days

Older than 10 years

• IV: 20mg, immediately; THEN 15mg/kg, dly; Treatment duration: 5-14 days
  (STG, Paed. 2017)

Aplastic anaemia with fever (Additional agent required)

Younger than 1 month

• IV: 25mg/kg immediately; THEN 18mg/kg, dly
  (STG, Paed. 2017)

Multidrug resistant tuberculosis (MDR TB) (Additional agent required)
- Intensive phase

• IV: 15-22.5mg/kg, dly; Treatment duration: ≥6 months (exact duration of therapy for the intensive phase is 4 months after the first date of sampling of a negative culture result) 
• (STG, Paed. 2017)

Pneumonia (Additional agent required)
- If poor response to first line empiric therapy and in the absence of positive cultures the possibility of infection with Methicillin-Resistant S. aureus (MRSA), or an extended spectrum beta lactamase (ESBL) producing organism, or atypical pathogen is suspected
Nosocomial pneumonia (Additional agent required)

• IV: 15mg/kg, dly
  (STG, Paed. 2023)

Septicaemia of the newborn (Additional agent required)
- Second line empiric treatment

• IV: 15mg/kg, dly; Treatment duration: 7 days
  (STG, Paed 2017)

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South African registered indications and dosages

Serious nosocomial Gram-negative bacillary infections
Uncomplicated urinary tract infection (unless the causative organisms are not susceptible to antibiotics with less potential toxicity) 

Neonates

• IV/IM: Loading dose: 10mg/kg; THEN 15mg/kg in 2 divided doses; Treatment duration: 7-10 days

Preterm neonates

- <30 weeks post-conceptional age

• IV: 9mg/kg, 18hrly; Treatment duration: 7-10 days

- >30 weeks post-conceptional age

• IV: 9mg/kg, 12hrly; Treatment duration: 7-10 days

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To ensure the accurate measurement of the appropriate dose in children and infants, the use of the 50mg/2ml, 100mg/2ml and 250mg/2ml formulations are recommended

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Indications and dosages registered in other jurisdictions

Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP)
Complicated urogenital tract infections, including pyelonephritis
Complicated intra-abdominal infections
Endocarditis (additional agent(s) required)
Infected burns
Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above
Management of neutropenic patients with fever suspected to be due to a bacterial infection 

Preterm infants

• IV/IM: 7.5mg/kg, 12hrly

Neonates

• IV/IM: Initial: 10mg/kg; THEN 7.5mg/kg, 12hrly

Between 4 weeks-12 years

• IV/IM: 15-20mg/kg/day, as a single dose OR as 7.5mg/kg, 12hrly

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When used in children, administer as IM or IV (as a slow IV infusion)₁₂

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For endocarditis and febrile neutropenic patients, dosing should be twice a day, as there is insufficient data for once daily dosing

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The amount of diluents used will depend on the amount of amikacin tolerated by the patient. The solution should normally be infused over 30-60mins. Infants should receive a 1-2 hour infusion

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Older than 12 years

• See adult dosage

Pregnancy

• Caution; positive evidence of risk
• Amikacin should be used in pregnant women and newborns only if clearly indicated and under medical supervision
• There is limited data on the use of aminoglycosides in pregnancy. Aminoglycosides can affect the development of the embryo/foetus in the womb. Aminoglycosides cross the placental barrier and there have been many reports of total, irreversible, bilateral congenital deafness in children whose mothers were treated with streptomycin during pregnancy
• Although adverse reactions to the unborn or neonate in pregnant women who have been treated with other aminoglycosides have not been reported, there is potential for harm
• If a pregnant patient is to be treated or becomes pregnant during treatment, medical advice should be provided on the risk of the potential hazard to the foetus

Breastfeeding

• Caution
• It is not known whether amikacin is excreted in the breastmilk. The decision should be made to either stop breastfeeding or stop the therapy

Fertility

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

Renal Impairment

• Caution; dose adjustment recommended 
  Recommended dose adjustments as per Sanford guidelines

CrCl (ml/min)	Maintenance Dose
No adjustment necessary for loading doses
>80	IV/IM: 15mg/kg/day
60-80	IV/IM: 12mg/kg/day
40-60	IV/IM: 7.5mg/kg/day
30-40	IV/IM: 4mg/kg/day
20-30	IV/IM: 7.5mg/kg, every 48 hours
10-20	IV/IM: 4mg/kg, every 48 hours
0-10	IV/IM: 3mg/kg, every 72 hours

* The above table is meant to act as a guide in renal impairment dose adjustments; dose adjustments may vary based on body weight, clinical condition, changes in renal function and amikacin plasma trough levels

Hepatic Impairment

• No dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Renal function should be taken into account in patients ≥65 years

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Tremor
• Paraesthesia
• Headache
• Balance disorders
• Paresis
• Neuromuscular blockade (may lead to respiratory arrest)

Cardiovascular Disorders 

• Hypotonia
• Thrombophlebitis
• Tachycardia
• Myocarditis

Respiratory Disorders 

• Apnoea
• Bronchopasm

Gastrointestinal Disorders 

• Nausea and vomiting

Hepatobiliary Disorders 

• Elevation of plasma hepatic enzymes
  - Aspartate transaminase
  - Alanine transaminase
  - Lactate dehydrogenase
  - Alkaline phosphatase
  - Bilirubin

Genitourinary Disorders 

• Nephrotoxicity
  - Increased excretion of tubule epithelia
  - Cylindruria
  - Increased β2-microglobulin excretion
  - Enzyme excretion via urine (e.g. alanine aminopeptidase, glutamine transferase, β-galactosidase, N-acetyl-
  glucosaminidase)
  - Azotemia
  - Decreased urine osmolarity
  - Increased blood urea nitrogen
  - Increased serum creatinine
  - Decreased creatinine clearance
• Oliguria
• Increased serum creatinine
• Albuminuria
• Azotemia
• Red blood cells in urine
• White blood cells in urine
• Cells in urine
• Acute renal failure

Endocrine and Metabolic Disorders 

• Hypomagnesemia

Musculoskeletal Disorders 

• Arthralgia
• Myokymia

Skin and Subcutaneous Tissue Disorders 

• Rash
• Pruritus
• Urticaria
• Pain in injection site

Immune, Blood and Lymphatic System Disorders 

• Super infection
• Colonisation with resistant bacteria or yeasts
• Anaemia
• Eosinophilia
• Granulocytopenia
• Thrombocytopenia
• Anaphylactic response
  - Anaphylactic reaction
  - Anaphylactic shock
• Hypersensitivity (due to sulphite content)
  - Vomiting
  - Diarrhoea
  - Wheezing
  - Acute asthma attack
  - Disturbance of consciousness
  - Shock
• Fever

Sensory Disorders 

• Blindness
• Retinal infarct
• Maculopathies, leading to loss of vision (if injected directly into the eye)
• Tinnitus
• Hypoacusis
• Ototoxic reactions involving the 8th cranial nerve (may involve vestibular or cochlear function)
• Cochlear damage
• Vestibular disorders
• Deafness
• Sensory deafness
• Pressure in the ears

• Neurotoxic agents
• Ototoxic agents
• Nephrotoxic agents
• Bacitracin
• Cisplatin
• Amphotericin B
• Cyclosporine
• Tacrolimus
• Cephaloridine
• Paromomycin
• Viomycin
• Colistimethate/colistin
• Vancomycin
• Aminoglycosides (topical and systemic)
• Cephalosporins
• Rapidly acting diuretic agents
• Furosemide
• Ethacrynic acid
• Platinum compounds
• Anaesthetics
• Muscle-relaxing agents
• Volatile anaesthetics
• d-tubocurarine
• Succinylcholine
• Decamethonium
• Atracurium
• Rocuronium
• Vecuronium
• Indomethacin
• Penicillin-type agents
• Penicillins
• Bisphosphonates
• Beta-lactam antibiotics (See additional prescribing points)
• Thiamine

Other

• Massive transfusions of citrate-anticoagulated blood
• Mixtures with other medicinal products (See additional prescribing points)

• Amikacin levels (peak and trough concentrations)

 Specific cases may require

• Renal function
• Urinalysis
• Blood urea nitrogen (BUN)
• Auditory and vestibular function (particularly if treatment duration is longer than 7-10 days)
• Hearing parameters
• Vital signs
• Temperature
• Weight

Administration directions

• The solution for IV use is prepared by adding the desired dose to 100ml or 200ml of sterile diluent such as normal saline or 5% dextrose in water or any other compatible solution
• The solution is administered to adults over a 30-60min period
• In paediatric patients the amount of diluents used will depend on the amount of amikacin tolerated by the patient. The solution should normally be infused over a 30-60min period. Infants should receive a 1-2hr infusion

Mixtures with other medicinal products

• Amikacin should not be physically premixed with other drugs, but should be administered separately according to the recommended dose and route
• Suitable solvents for intravenous infusion are
  - 0.9% NaCl solution for infusion
  - 5% glucose solution for infusion
  - Ringer's lactate solution without 5% glucose

Interaction with beta lactam antibiotics

• In vitro admixture of aminoglycosides with beta-lactam antibiotics (penicillins or cephalosporins) may result in significant mutual inactivation. A reduction in serum activity may also occur when an aminoglycoside or penicillin-type drug is administered in vivo by separate routes. Inactivation of the aminoglycoside is clinically significant only in patients with severely impaired renal function
• Inactivation may continue in specimens of body fluids collected for assay, resulting in inaccurate aminoglycoside readings. Such specimens should be properly handled (assayed promptly, frozen, or treated with beta-lactamase)

Amikacin is a kanamycin-derived semisynthetic aminoglycoside antibiotic. The mechanism of action of amikacin is due to a disruption of protein biosynthesis on the bacterial ribosome by interaction with the rRNA and subsequent inhibition of translation. This results in a bactericidal effect.

Spectrum of activity: Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enterica (enteritis salmonella), Serratia liquefaciens, Serratia marcescens, Shigella spp., Nocardia sp.

Injection (per 2ml) 100mg

• Amikacin-Fresenius (Fresenius Kabi)

Injection (per 2ml) 250mg

• Amikacin-Fresenius (Fresenius Kabi)
• Safeline-Amikacin Sulphate (Safeline)

Injection (per 2ml) 500mg

• Amikacin 500mg/2ml Pharma-Q (Pharma-Q)
• Amikacin-Fresenius (Fresenius Kabi)
• Safeline-Amikacin Sulphate (Safeline)

Injection (per 4ml) 1g

• Amikacin-Fresenius (Fresenius Kabi)