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Re: Correcting for salt vs. base

From: Nancy Sambol <nancy.sambol>
Date: Wed, 26 Mar 2014 21:04:38 -0700

Hi Dennis,

Your main question is a straightforward one -- both the dose and =
concentration should be expressed w/respect to the same entity. When =
the concentration is expressed in terms of base (the norm), it makes =
sense to express the dose in terms of base for PK analysis.

What is in the label is another issue. There is a guidance (web site =
given below) from the FDA that says they will follow the USP Salt Policy =
which became effective in May 1, 2013. That policy states that, for =
newly approved drugs, "The strength also will be expressed in terms of =
the active moiety (e.g., "100 mg newdrug") rather than the salt strength =
equivalent (e.g., "123.7 mg newdrug hydrochloride")."

=
www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidan=
ces/UCM379753.pdf

So, for paroxetine mesylate, which was approved July 2013, the package =
insert says, 'BRISDELLE is available as 7.5 mg pink capsules printed =
with black edible ink with “NOVEN” and “7.5 mg” on the capsule. =
Each capsule contains 9.69 mg paroxetine mesylate equivalent to 7.5 mg =
paroxetine base.'

For mipomersen sodium, which was approved Jan 2013, the package insert =
says, 'Each vial or pre-filled string of KYNAMRO provides 200 mg of =
mipomersen sodium…'

With this policy, it seems prudent to look at the package insert and =
check what the dose amount refers to, salt or base, because there are =
exceptions (see guidance) and you would have to know with certainty when =
the drug was approved to make a determination.

Best regards,

Nancy

Nancy C Sambol, PharmD
Associate Clinical Professor
Dept of Bioengineering & Therapeutic Sciences
Schools of Pharmacy & Medicine
University of California San Francisco
San Francisco CA 94143-0912
415-476-8884
nancy.sambol


Received on Thu Mar 27 2014 - 00:04:38 EDT

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