Jonathan M. Klein, MD, Thomas N. George, MD, and Sarah B. Tierney, PharmD
Peer Review Status: Internally Peer Reviewed - 3/12/12

General guidelines

  • Antibiotic dosing and intervals for gentamicin and theophylline should be administered as described in the Iowa Neonatology Handbook. Vancomycin should be dosed at 15mg/kg, at the same intervals as described in the Handbook.
  • Antibiotics should be withheld until the level is known, and an order to that effect should be written. If the trough level is greater than acceptable, the drug should not be given and another level checked 6 hours later, and this should be repeated as needed until a safe level is obtained.
  • Peak levels are not necessary for patients being treated with a course of antibiotics without an identified organism.
  • If a blood culture is positive, and an organism and sensitivities are identified, both peak and trough levels should be obtained to ensure adequate dosing.
  • If 10 days of antibiotics are planned, and the first trough level obtained is acceptable, consider repeating the trough levels at 4 to 6 days into therapy to ensure non-toxic levels, especially if there is evidence or concern of impaired renal function.

Gentamicin

  • A gentamicin trough level should be obtained within 1 hour of the dose:
    Obtain level prior to the administration of the 2nd dose.
    If impaired renal function is a concern, a level should be obtained before the 2nd dose.
    An acceptable trough is < 2 mg/mL, with an optimal target ≤ 1.0.
  • Peak levels are not necessary for patients being treated with a course of antibiotics without an identified organism. If obtained, an acceptable peak is 5 – 12 mg/mL and should be obtained 30 minutes after the end of a 30 minute infusion or immediately after the end of a 1-hour infusion.

Vancomycin

  • A vancomycin trough level should be obtained within 1 hour of the dose:
    Gestational age ≥ 30 weeks, obtain level prior to the administration of the 3rd dose.
    Gestational age < 30 weeks, obtain level prior to the administration of the 2nd dose.
    If impaired renal function is a concern, a level should be obtained before the 2nd dose.
    An acceptable trough is < 10 mg/mL.
  • Peak levels are not necessary for patients being treated with a course of antibiotics without an identified organism. If obtained, an acceptable peak is 20 – 40 mg/mL and should be obtained 30 minutes after the infusion.

Theophylline

  • Either a trough or peak level will provide adequate information regarding dosing. A theophylline trough level should be obtained 0 - 2 hours before the scheduled dose, and the dose administered without awaiting the result. An acceptable theophylline trough level is 6 – 12 mg/ml. If obtained, an acceptable peak level is 10 - 20 mg/ml, and should be obtained between 2 and 4 hours after drug administration.
  • Consider writing the theophylline order to reflect times of administration to be at 4 am, 12 pm and 8 pm. This would allow the peak level to be drawn with morning labs if the patient is on a q 8 h schedule.
  • When initiating therapy or changing the dose serum theophylline levels should be obtained 48-72 hours the first dose or change in dose.  This will allow steady-state serum levels to be obtained.
  • If concern for toxicity, serum levels may be drawn prior to steady-state to assess the patient’s current progress or evaluate potential toxicity.

Phenobarbital

  • A serum concentration should be obtained 30-60 minutes after IV loading dose
  • Additional levels should be obtained:
    • 4-7 days into therapy (once steady state has been reached) on an unchanged dose
    • 2-3 weeks into therapy to verify the concentration is not continuing to increase slowly, leading to delayed toxicity.
    • As a control measurement after a change in dose.
    • After adding a second drug with a potential for interaction (i.e. valproic acid)
     
  • On-going levels can be drawn any time during dosing interval after steady state due to long half-life.
  • If concern for toxicity, serum levels may be drawn prior to steady-state to assess the patient’s current progress or evaluate potential toxicity
  • Therapeutic ranges for this drug should be a guide and a therapeutic concentration is one that stops seizure or decreases seizure frequency with acceptable side effects:
    • Therapeutic: 15-40 mcg/mL (SI: 65-172 micromoles/L)
    • Potentially toxic: >40 mcg/mL (SI: >172 micromoles/L)
     

Phenytoin/Fosphenytoin

  • A serum concentration should be obtained 2 hours after IV loading dose.
  • Additional levels should be obtained:
    • 1-5 days into therapy (once steady state has been reached) on an unchanged dose
    • 2-3 weeks into therapy to verify the concentration is not continuing to increase slowly, leading to delayed toxicity
    • As a control measurement after a change in dose
    • After adding a second drug with a potential for interaction (i.e. amiodarone, azole antifungals, benzodiazepines, calcium channel blockers, PPIs, theophylline derivatives, valproic acid),
     
  • On-going levels should be drawn as follows:
    • Oral: pre-dose
    • IV: 2 hours post dose
    • IM: 4 hours post dose
     
  • A “free-drug” concentration may be clinically useful in neonates with malnutrition, chronic renal failure, or hyperbilirubinemia as more free drug may be available and produce a greater effect than expected.
  • If concern for toxicity, serum levels may be drawn prior to steady-state to assess the patient’s current progress or evaluate potential toxicity
  • Therapeutic ranges for this drug should be a guide and a therapeutic concentration is one that stops seizure or decreases seizure frequency with acceptable side effects:
    • Therapeutic: neonates 8-15 mcg/mL; 10-20 mcg/mL (SI: 40-79 micromoles/L)
    • Free (unbound): 1-2 mcg/mL
     

References:

Lexi-Comp, Inc. Pediatric Drug Information.  Accessed online.  Updated annually.
Warner A, Privitera M, Bates D.  Standards of laboratory practice: antiepileptic drug monitoring.  Clinical Chemistry 44:5 (1998) 1085-1095.