AmBisome with TPN

[Roger Rivera]

I would like to ask your opinion about the compatibility of AmBisome (Liposomal Amphotercin B) with the intralipd of the TPN. It has lipid content but I was not able to find the chaloric content per the vial. The only reference is the FDA guidance stating that “avoid concomitant therapy with intravenous fat emulsions, such as total parental nutrition (TPN), since that may change the pharmacokinetic (PK) profile of Amphotericin B Liposomal injection”

https://www.accessdata.fda.gov/drugsatfda_docs/psg/Amphotericin%20B_%20Liposomal%20injection_RLD%20050740_RV01-16.pdf

What is the best practice for the use of AmBisome concurrently with TPN for a baby patient in NICU 35 days old who was born preterm 35/52 with Major Omphalocele and Cholestiasis?

Considering that the fat emulsion was reduced to four days a week only.

Thank you very much in advance.

[Earl Jones]

Medications are not recommended to be mixed with TPN for many reasons:

– TPN-Drug interactions (chemical or physical).

– TPN or Drug may interfere in each others kinetics.

– And, most importantly medication or TPN may be asked to change their rate of infusion allover the day, which is kinda common in NICU, so it is difficult to keep both TPN and medicine rates on the optimum track.

Some hospitals are used to mixing Insulin, H2 antagonists, or Carnitine with TPN, even this practice is controversial and there is a big debate of its benefits.

Regarding the caloric contents of Ambisome, we neglect it for the next reason. If you sum all the lipid contents of Ambisome additives, they don’t exceed 350 mg for the whole vial (50mg), and given that the usual doses for ambisome varies from 1-6 mg/Kg/Day, so your baby is almost taking at maximum 35 mg/Kg of the lipid contents of the vial, which is an obsolete caloric value.

I recommend you use Ambisome totally apart from the TPN.

[Stephen Reed]

This study is a draft guidance invivo study that does not mandate change in practice. There is a study that shows precipitation when Ambisome is combined with intralipid. There are no studies that show safety of Ambisome when infused as Y site therefore Ambisome is not recommended to be infused with PN/Lipid. Pharmacokinetic derangement is a possibility.

If Ambisome is indicated, it should not be infused as Y site with neither PN or Lipid. The calorie intake from Ambisome is not significant and we should not dig further towards its consideration.

[Debra Stewart]

Liposomal amphotericin B is a “lonely” drug, it is strictly to be run alone in a dedicated line as per all references. As said before, it is preferable whenever possible (i know it gets really hard in intensive care settings!!) but drugs should not be added to PN – there’s a small number that is added like heparin at the time of compounding etc but in general no.

As for the caloric content of liposomal amphotericin B, the lipid portion contains 0.27kcal per 5mg. Hence you could argue that for patients receiving PN, adjustment to lipid content might be deemed necessary (Ref: Sacks 1997).

[Roger Alexander]

Studies showed that when the concentration of AmB in mixtures prepared with IL containing 20% soybean oil was reduced to 0.6 mg/ml, a precipitate was observed in all mixtures with more than 30 ml of IL/100 ml of the total volume.

With mixtures prepared with IL containing 10% soybean oil and having a final AmB concentration of 1.2 mg/ml, a precipitate was observed in all mixtures containing more than 30 ml of IL/100 ml of the total volume; when the concentration of AmB was 0.6 mg/ml, a precipitate occurred in mixtures with more than 40 ml of IL/100 ml of the total volume.

The observation by Trissel that the precipitate consists of particles greater than 10 μm in size suggests that even without centrifugation, certain AmB-IL mixtures might be unsafe for human administration. It has also been suggested that the formation of these aggregates might result in decreased antifungal activity.

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