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Pediatric Dosing Problems

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I had an interesting question from a student regarding guidelines for pediatric dosing. I thought you would benefit from my answer. Let’s start with the question:

“Hi Andrew,

How do you decide which concentration of a drug is appropriate when multiple concentrations are listed, and how do you decide which dose is appropriate when a dose range is given instead of a specific weight-based dose?  

For example: Cephalexin suspension is 125/ 5mL and 250/ 5mL and Amox comes in 125,200,250 and 400/ 5mL. 

Nitrofurantoin dosing is 50 to 100 mg po qid for uncomplicated UTI.  When do I dose 50mg and when do I dose 100mg?  Cipro dosing for complicated UTI or pyelonephritis in peds to 17 y/o says 6 to 10 mg/kg.  So when do I choose 6mg/ kg and when do I choose 10 mg/kg? 

I’ve asked a lot of preceptors about this and they don’t have a straight answer.  They say just choose whatever you think or whatever concentration the pharmacy has in stock.  Is there a more specific way to determine confidently which concentration or which dose is best for the patient?

PS:  All doses mentioned from pharmacopoeia 2016.  

Have a wicked good day!”

 

If you’re like most, you’ve also struggled with this dilemma. I’m going to share my thoughts on the matter – the short answer first and then i’ll provide more context.

Short answer: For antibiotics I go with the highest recommended dosing (not to exceed adult dosages). Anything else, I give the lowest recommended dose and then titrate up as needed.

Now, lets talk about this for a second.

The rate at which children metabolize a drug is different than that of an adult. Sometimes, children will need a higher dose because they metabolize the medication much faster. But, the rate differs in neonates (longer half lives) vs children vs adolescents vs adults.

Much of the children dosing recommendations (weight based) are not based on any real evidence – especially medications which are given off-label.

This is why you will see different recommendations by different sources and why you will see a recommended range. There’s just no data to back these numbers up.

An article titled, What is the right dosing for children, published in the BJCP stated:

“Given that children may not be subject to dose-finding studies similar to those carried out in the adult population, some initial estimation of the pediatric dose must be obtained via extrapolation approaches. As a consequence, the dose selected for a considerable number of drugs disseminates into clinical practice, irrespective of consensus about the appropriate dosing recommendation.”

Really, the core of this question is: what dose will cure the patient without causing harm?

Giving a higher than normal dose of nitrofurantoin, for example, probably won’t cause much harm. Compare that with giving a narcotic. Big difference, right?

Neonates and infants should not have dosing regimens extrapolated from adult dosing because the dosages are not linear. It very much has to do with the pharmacokinetics of the drug, age related changes in bioavailability, and the development of the patient’s liver/kidney function.

There’s not a lot of data supporting the recommendations of pediatric dosing. Like I said before, the goal is to treat your patients while minimizing the risk for harm. Most antibiotics can be dosed at the upper limit recommended dose (risk of harm is low but resistance is high) while all other drugs should take a conservative approach and started with the lowest recommended dose.

As with any recommendation or guideline – remember that is all they are – recommendations. Nothing is absolute and there will always be exceptions.

I’d love to hear your thoughts on the matter. What do you think?

Andrew