- amikacin sulfate
POM: Prescription only medicine
This information is intended for use by health professionals
Intramuscular and intravenous administrationAt the recommended dosage level, uncomplicated infections due to sensitive organisms should respond to therapy within 24 to 48 hours.If clinical response does not occur within three to five days, consideration should be given to alternative therapy.If required, suitable diluents for intravenous use are: Normal saline, 5% dextrose in water. Once the product has been diluted the solution must be used as soon as possible and NOT STORED.
Adults and Children over 12 yearsThe recommended intramuscular or intravenous dosage for adults and adolescents with normal renal function (creatinine clearance ≥50 ml/min) is 15 mg/kg/day which may be administered as a single daily dose or divided into 2 equal doses i.e. 7.5 mg/kg q 12 h. The total daily dose should not exceed 1.5 g. In endocarditis and in febrile neutropenic patients, dosing should be twice daily, as there is not enough data to support once daily dosing.
Children 4 weeks to 12 yearsThe recommended intramuscular or intravenous (slow intravenous infusion) dose in children with normal renal function is 15-20 mg/kg/day which may be administered as 15-20 mg/kg, once a day; or as 7.5 mg/kg q 12 h. In endocarditis and in febrile neutropenic patients dosing should be twice daily, as there is not enough data to support once daily dosing.
NeonatesAn initial loading dose of 10 mg/kg followed by 7.5 mg/kg q 12 h (see sections 4.4 and 5.2).
Premature InfantsThe recommended dose in prematures is 7.5 mg/kg in every 12 hours (see sections 4.4 and 5.2). The usual duration of treatment is 7 to 10 days. The total daily dose by all routes of administration should not exceed 15-20 mg/kg/day. In difficult and complicated infections where treatment beyond 10 days is considered, the use of amikacin sulphate injection should be re-evaluated and, if continued, renal, auditory, vestibular function should be monitored, as well as serum amikacin levels.If definite clinical response does not occur within 3 to 5 days, therapy should be stopped and the antibiotic susceptibility pattern of the invading organism should be rechecked. Failure of the infection to respond may be due to resistance of the organism or to the presence of septic foci requiring surgical drainage.
Intravenous administrationThe solution is administered to adults over a 30 to 60 minute period.
Specific recommendation for intravenous administrationIn 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 to 60 minute period. Infants should receive a 1 to 2 hour infusion.
ElderlyAmikacin is excreted by the renal route, renal function should be assessed whenever possible and dosage adjusted as described under impaired renal function.
Life-threatening infections and/or those caused by pseudomonasThe adult dose may be increased to 500 mg every eight hours but should never exceed 1.5 g/day nor be administered for a period longer than 10 days. A maximum total adult dose of 15 g should not be exceeded.
Urinary tract infections: (other than pseudomonas infections)7.5 mg/kg/day in two equally divided doses (equivalent to 250 mg b.i.d. in adults). As the activity of amikacin is enhanced by increasing the pH, a urinary alkalinising agent may be administered concurrently.
Impaired renal functionIn patients with renal impairment reflected by creatinine clearance less than 50 mL/min, administration of the recommended total daily dose of amikacin in single daily doses is not desirable since these patients will have protracted exposure to high trough concentrations. See below for dosage adjustments in patients with impaired renal function.For patients with impaired renal function receiving usual twice or three times daily dosing, whenever possible, serum amikacin concentrations should be monitored by appropriate assay procedures. Doses should be adjusted in patients with impaired renal function either by administering normal doses at prolonged intervals or by administering reduced doses at fixed intervals.Both methods are based on the patient's creatinine clearance or serum creatinine values since these have been found to correlate with aminoglycoside half-lives in patients with diminished renal function. These dosage schedules must be used in conjunction with careful clinical and laboratory observations of the patient and should be modified as necessary, including modification when dialysis is being performed.Normal Dose at Prolonged Intervals Between Dosing: If the creatinine clearance rate is not available and the patient's condition is stable, a dosage interval in hours for the normal single dose (ie, that which would be given to patients with normal renal function on a twice daily schedule, 7.5 mg/kg) can be calculated by multiplying the patient's serum creatinine by nine; eg, if the serum creatinine concentration is 2mg/100mL, the recommended single dose (7.5 mg/kg) should be administered every 18 hours.
|Serum Creatinine Concentration (mg/100 ml)||Interval between Amikacin doses of 7.5 mg/kg IM (hours)|
Intraperitoneal useFollowing exploration for established peritonitis, or after peritoneal contamination due to faecal spill during surgery, amikacin may be used as an irrigant after recovery from anaesthesia in concentrations of 0.25% (2.5 mg/ml). The intraperitoneal use of amikacin is not recommended in young children.
Other routes of administrationAmikacin in concentrations 0.25% (2.5 mg/ml) may be used satisfactorily as an irrigating solution in abscess cavities, the pleural space, the peritoneum and the cerebral ventricles.
Renal ToxicityAminoglycosides are potentially nephrotoxic. Renal toxicity is independent of plasma obtained at the peak (Cmax). The risk of nephrotoxicity is greater in patients with impaired renal function, and in those who receive higher doses, or in those whose therapy is prolonged.Patients should be well hydrated during treatment and renal function should be assessed by the usual methods prior to starting therapy and daily during the course of treatment. A reduction of dosage is required if evidence of renal dysfunction occurs, such as presence of urinary casts, white or red cells, albuminuria, decreased creatinine clearance, decreased urine specific gravity, increased BUN, serum creatinine, or oliguria. If azotemia increases, or if a progressive decrease in urinary output occurs, treatment should be stopped.Elderly patients may have reduced renal function which may not be evident in routine screening tests such as BUN or serum creatinine. A creatinine clearance determination may be more useful. Monitoring of renal function in elderly patients during treatment with aminoglycosides is particularly important.Renal and eighth-cranial nerve function should be closely monitored especially in patients with known or suspected renal impairment at the onset of therapy, and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. Urine should be examined for decreased specific gravity, increased excretion of proteins, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained where feasible in patients old enough to be tested, particularly high risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.Concurrent and/or sequential, oral, or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides, should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration.Patients suffering from pre-existing renal insufficiency should be assessed by the usual methods prior to therapy and periodically during therapy. Daily doses should be reduced and/or the interval between doses lengthened in accordance with serum creatinine concentrations to avoid accumulation of abnormally high blood levels and to minimise the risk of ototoxicity. Regular monitoring of serum drug concentration and of renal function is particularly important in elderly patients, who may have reduced renal function that may not be evident in the results of routine screening tests i.e. blood urea and serum creatinine.
Neuro/OtotoxicityNeurotoxicity, manifested as vestibular and/or bilateral ototoxicity, can occur in patients treated with aminoglycosides. The risk of aminoglycoside-induced ototoxicity is greater in patients with impaired renal function, and in those who receive high doses, or in those whose therapy is prolonged over 5-7 days of treatment, even in healthy patients. High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo may occur and may be evidence of vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions. The risk of ototoxicity due to aminoglycosides increases with the degree of exposure to either persistently high peak or high trough serum concentrations. Patients developing cochlear or vestibular damage may not have symptoms during therapy to warn them of developing eighth nerve toxicity, and total or partial irreversible bilateral deafness or disabling vertigo may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.
Neuromuscular ToxicityNeuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopaedic and abdominal irrigation or in local treatment of empyema), and following oral use of aminoglycosides. The possibility of respiratory paralysis should be considered if aminoglycosides are administered by any route, especially in patients receiving anaesthetics, neuromuscular blocking agents such as tubocurarine, succinylcholine, decamethonium, atracurium, rocuronium, vecuronium or in patients receiving massive transfusions of citrate-anticoagulated blood. If neuromuscular blockade occurs, calcium salts may reverse respiratory paralysis, but mechanical respiratory assistance may be necessary. Neuromuscular blockade and muscular paralysis have been demonstrated in laboratory animals given high doses of amikacin.Amikacin must not be used in patients with myasthenia gravis. Aminoglycosides 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 the neuromuscular junction.
Allergic reactionsThe use of amikacin in patients with a history of allergy to aminoglycosides or in patients who may have subclinical renal or eighth nerve damage induced by prior administration of nephrotoxic and/or ototoxic agents such as streptomycin, dihydrostreptomycin, gentamicin, tobramycin, kanamycin, neomycin, polymyxin B, colistin, cephaloridine or viomycin should be considered with caution, as toxicity may be additive. In these patients amikacin should be used only if, in the opinion of the physician, therapeutic advantages outweigh the potential risks. Large doses of amikacin administered during surgery have been responsible for a transient myasthenic syndrome.Amikacin sulfate injection in vials contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is uncommon and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic subjects.
Paediatric useAminoglycosides should be used with caution in premature and neonatal infants because of the renal immaturity of these patients and the resulting prolongation of serum half-life of these drugs.
OtherAminoglycosides 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.As with other antibiotics, the use of amikacin may result in overgrowth of non-susceptible organisms. If this occurs, appropriate therapy should be instituted.Macular infarction sometimes leading to permanent loss of vision has been reported following intravitreous administration (injection into the eye) of amikacin.
|System Organ Class||Frequency||MedDRA Term|
|Infections and Infestations||Uncommon||Superinfections or colonisation with resistant bacteria or yeasta|
|Blood and lymphatic system disorders||Rare||Anaemia, eosinophilia|
|Immune system disorders||Not known||Anaphylactic response (anaphylactic reaction, anaphylactic shock and anaphylactoid reaction), hypersensitivity|
|Metabolism and nutrition disorders||Rare||Hypomagnesaemia|
|Nervous system disorders||Not known||Paralysisa|
|Rare||Tremora, paresthesiaa, headache, balance disordera|
|Eye disorders||Rare||Blindnessb, retinal infarctionb|
|Ear and labyrinth Disorders||Rare||Tinnitusa, hypoacusisa|
|Not known||Deafnessa, deafness neurosensorya|
|Respiratory, thoracic and mediastinal disorders||Not known||Apnoea, bronchopasm|
|Gastrointestinal disorders||Uncommon||Nausea, vomiting|
|Skin and subcutaneous tissue disorders||Uncommon||Rash|
|Musculoskeletal, connective tissue and bone disorders||Rare||Arthralgia, muscle twitching a|
|Renal and urinary disorders||Not known||Renal failure acute, nephropathy toxic, cells in urinea|
|Rare||Oliguriaa, blood creatinine increaseda, albuminuriaa, azotemiaa, red blood cells urinea, white blood cells urinea|
|General disorders and administration site conditions||Rare||Pyrexia|
|a See section 4.4. bAmikacin is not formulated for intavitreal use. Blindness and retinal infarction have been reported following intravitreous admistrations (injection into the eye) of amikacin.|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation 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 via:Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard
Intramuscular and intravenous administrationIn neonates and particularly in premature babies, the renal elimination of amikacin is reduced. In a single study in newborns (1-6 days of post natal age) grouped according to birth weights (<2000, 2000-3000 and >3000g). Amikacin was administered intramuscularly and/or intravenously at a dose of 7.5 mg/kg. Clearance in neonates >3000 g was 0.84 ml/min/kg and terminal half-life was about 7 hours. In this group, the initial volume of distribution and volume of distribution at steady state was 0.3 ml/kg and 0.5 mg/kg, respectively. In the groups with lower birth weight clearance/kg was lower and half-life longer. Repeated dosing every 12 hours in all the above groups did not demonstrate accumulation after 5 days.
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