From the Guidelines
Amikacin dosing in neonates should be 15 mg/kg/dose IV q48h for those with gestational age <30 weeks and postnatal age <14 days, and 15 mg/kg/dose IV q24h for those with gestational age >34 weeks and postnatal age >7 days, with a maximum dose of 5-7.5 mg/kg/dose IV q8h. The dosing interval and frequency are determined by the neonate's gestational and postnatal age, as well as their renal function 1.
Key Considerations
- For premature neonates less than 30 weeks gestational age, dosing is typically every 48 hours, while term neonates usually receive the medication every 24 hours.
- Dosing should be adjusted based on therapeutic drug monitoring, aiming for peak concentrations of 20-30 mcg/mL and trough levels below 5-10 mcg/mL.
- Before administration, confirm the neonate's weight, gestational age, and renal function.
- Administer as an intravenous infusion over 30 minutes to avoid toxicity.
- Monitor renal function, hearing, and vestibular function during treatment as amikacin is an aminoglycoside antibiotic with potential nephrotoxicity and ototoxicity 1.
Mechanism of Action and Indications
- The drug works by binding to bacterial ribosomes and inhibiting protein synthesis, making it effective against many gram-negative organisms including Pseudomonas and some resistant Enterobacteriaceae.
- In neonatal sepsis, it's often combined with ampicillin or another beta-lactam for synergistic coverage of both gram-negative and gram-positive organisms 1.
Important Points to Note
- The recommended dosage is based on the most recent guidelines for the treatment of multidrug-resistant infections in pediatrics 1.
- It is essential to follow the recommended dosing guidelines and monitor the neonate's response to treatment to minimize the risk of adverse effects and ensure optimal outcomes 1.
From the FDA Drug Label
When amikacin is indicated in newborns (see BOXED WARNINGS), it is recommended that a loading dose of 10 mg/kg be administered initially to be followed with 7. 5 mg/kg every 12 hours. The recommended dosage of Amikacin in neonates is a loading dose of 10 mg/kg, followed by 7.5 mg/kg every 12 hours 2.
- The total daily dose should not exceed 15 mg/kg/day.
- It is desirable to limit the duration of treatment to short term whenever feasible.
From the Research
Amikacin Dosing in Neonates
- The Dutch Pediatric Formulary recommends a complex pharmacokinetic model-derived dosing regimen for amikacin in neonates, which consists of dosing categories based on postnatal age and weight 3.
- A simplified dosing regimen may be easier to apply in clinical practice, and both regimens have been shown to achieve target attainment of ≥90% for certain targets, such as Cmax ≥ 15 mg/L and Cmin ≤ 5 mg/L 3.
- Gestational and postnatal age, as well as clinical conditions like respiratory distress syndrome, can influence amikacin levels in neonates 4.
- Aminoglycosides, including amikacin, are concentration-dependent antibiotics, and their peak concentration to minimum inhibitory concentration ratio is the pharmacokinetic-pharmacodynamic index best linked to their antimicrobial activity and clinical efficacy 5.
- The recommended neonatal dosage regime for amikacin of 15 mg/kg/day may be unsatisfactory, and a higher dose of 20 mg/kg/day may be needed to achieve satisfactory levels 6.
- A modified neonatal amikacin dosage protocol based on postmenstrual and postnatal age has been shown to result in increased peak amikacin serum concentration compared with published dosage recommendations 7.
Key Findings
- Both simplified and complex dosing regimens can achieve target attainment for amikacin in neonates 3.
- Clinical conditions like respiratory distress syndrome can affect amikacin levels in neonates 4.
- Aminoglycosides require therapeutic drug monitoring due to their narrow therapeutic index 5.
- Higher doses of amikacin may be needed to achieve satisfactory levels in neonates 6.
- Modified dosage protocols can improve peak amikacin serum concentration in neonates 7.