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Reconstituting powder vials and risks of multi-dosing

The manufacturer of the EPO powder vials we usually sell recommends reconstituting the powder with 1ml sterile water for injection (WFI, 0.9% sodium chloride) and using the contents of the vial *immediately*. Any leftover EPO should be discarded. Likewise a sterile WFI vial or ampoule must never be re-used. Tips for reconstituting EPO powder vials can be found further down this post.

Recommended WFI product (supplier not affiliated to us)

The potency of any pharmaceutical EPO brand may vary significantly from the IU declared on the label. An EPO vial or syringe may in some cases contain 150%+ of the labelled IU (this was once reported for the brand of powder vials we usually sell). Likewise much lower than the labelled IU is possible. Even significant variations in labelled vs actual IU for different batches of the same product have previously been reported for more than one brand. Closely monitoring blood values including hemoglobin and hematocrit is always crucial for any person using EPO, even when repeating a past schedule of doses with the same brand…even if blood values were closely monitored on that past schedule!

Multi-dosing from a vial

– Vials could be multi-dosed for up to 21 days after reconstitution by instead using sterile bacteriostatic saline (contains 0.9% sodium chloride + 0.9% benzyl alcohol). However, doing this may lead to detrimental changes to the EPO protein, reducing potency and increasing health risks to an end user (e.g. increased chance of an immune response due to increased aggregation of the EPO). These changes may occur at the time when bacteriostatic saline is first introduced into the vial and/or during subsequent storage. The potency and safety profile of the liquid may be vastly reduced by the 20th day after reconstitution.*
– Between doses, keep liquid EPO refrigerated at a stable temperature (4-5 Celsius).
– Multi-dosing also greatly increases the risk of coring.**
– Multi-dosing without bacteriostatic saline would not be advisable due to the high risk of bacterial growth inside the vial (even if using up the vial over a short timespan).
– Medications containing benzyl alcohol are contraindicated in newborns and infants as fatal reactions have previously occurred. They are also contraindicated in pregnant or lactating women, as fetuses and infants exposed to benzyl alcohol in utero or in breast-fed milk are also at risk of fatal reaction.
– We only recommend using bacteriostatic saline drawn from vials made by Hospira. Available from here (supplier not affiliated to us).

*EPO produced in the USA (Epogen and Procrit brands) is available in multi-dose liquid vials containing 1.1% benzyl alcohol, however this does not mean that adding bacteriostatic saline to powder vials will have an equal or similar effect on the EPO as the benzyl alcohol does in Epogen/Procrit multi-dose vials. This is due to a different manufacturing process for the Epogen/Procrit multi-dose vials, which contain ready-to-use liquid. The patient instructions for Epogen/Procrit multi-dose vials state that the vials should be discarded within 21 days of initial needle entry.

**There is a longstanding recommended technique of needle insertion into a medication vial that reduces the risk of coring. The needle should be inserted at a 45–60° angle with the opening of the needle tip facing up (i.e., away from the stopper). A small amount of pressure is applied and the angle is gradually increased as the needle enters the vial. The needle should be at a 90° angle just as the needle bevel passes through the stopper.

Tips for reconstituting EPO powder vials:
(This is NOT a complete instructional)

– Always disinfect the vial rubber top with a sterile pre-injection wipe (70% isopropyl alcohol) and allow to dry completely before inserting needle.
– Reconstitute each vial with the exact volume specified by the manufacturer (1ml for our usual brand).
– Do not reconstitute a vial until ready to use it.
– Use the technique above** to minimize risk of coring.
– Add the sterile WFI or bacteriostatic saline to the powder vial very slowly (drop by drop down the vial wall rather than directly onto the powder). Then leave it to sit dissolving for several minutes before gently swirling and rotating/inverting the vial to *completely* dissolve the powder. Do NOT shake the vial.
– Draw the EPO liquid into syringe very slowly. Transferring the liquid quickly may damage the EPO.