| Section 4.1 following text has been added:
Consideration should be given to official guidance on the appropriate use of antibacterial agents
Section 4.2 following text has been added:
Adults and children over 12 years:
The recommended intramuscular or intravenous dosage for adults and adolescents with normal renal function (creatinine clearance ³ 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 years:
The 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.
Neonates:
An initial loading dose of 10 mg/kg followed by 7.5 mg/kg q 12 h (see sections 4.4 and 5.2).
Premature infants:
The recommended dose in prematures is 7.5 mg/kg in every 12 hours (see sections 4.4 and 5.2).
Specific recommendation for intravenous administration
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 to 60 minute period. Infants should receive a 1 to 2 hour infusion.
Section 4.4 following text has been added:
Paediatric use
Aminoglycosides 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.
Section 4.6 following text has been added:
There are limited data on use of aminoglycosides in pregnancy. Aminoglycosides can cause foetal harm. Aminoglycosides cross the placenta and there have been reports of total, irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. Although adverse effects on the foetus or newborns have not been reported in pregnant women treated with other aminoglycosides, the potential for harm exists. In reproduction toxicity studies in mice and rats no effects on fertility or foetal toxicity were reported. If amikacin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the foetus.
It is not known whether amikacin is excreted in human milk. A decision should be made whether to discontinue breast-feeding or to discontinue therapy.
Amikacin should be administered to pregnant women and neonatal infants only when clearly needed and under medical supervision (see section 4.4).
Section 5.2 following text has been added:
Data from multiple daily dose trials show that spinal fluid levels in normal infants are approximately 10 to 20% of the serum concentrations and may reach 50% in meningitis.
Intramuscular and intravenous administration
In 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 birthweights (<2000, 2000-3000 and >intramuscularly 3000g). Amikacin was administered 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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