Important: I've already consulted my doctor and am not seeking medical advice. I'm just curious here.

I've been prescribed and have taken Dextroamphetamine for some time (round orange pill). Recently my pharmacy has substituted a dextroamphetamine salt combo (elliptical blue pill) manufactured by a different company. These two pills seem to have dramatically different effects. It's my understanding the two medications must be chemically identical to be substituted. If this is in fact true, what are possible/common reasons for different effects?

  • can you give the proprietary names?
    – faustus
    Commented Jan 8, 2019 at 9:56
  • TEVA Generic Adderall and AURO Dextroamphetamine are all that I can find on the label Commented Jan 8, 2019 at 12:50
  • Thorough and thoughtful response, appreciate your time! Commented Feb 13, 2019 at 5:37

1 Answer 1


In order to substitute lawfully, the 2 drugs must be bioequivalent and in the same dosage form. Therefore the 2 drugs not only must be chemically equivalent, but also therapeutically equivalent. In your situation, dextroamphetamine and dextroamphetamine salts combo are 2 different drugs. The former is a single ingredient product while the latter is a mixture of salts. The basis of bioequivalence is determined by the kinetics of absorption, distribution, metabolism and elimination from the body. In general, a drug and its salt form will have different dissolution rates and therefore will be absorbed at dfferent rates, distributed differently, metabolized differently and eliminated differently from the body. So they have different effects on the body. In most cases, the drug itself and its salt are similar enough that there is no major therapeutic difference and are considered bioequivalent. However it’s not true in all cases.
A controlled release formulation (such as sustained release, extended release, delayed release, long-acting, etc.) releases the drug slower, get absorbed slower and reaches the peak plasma level slower than the regular formulation. Therefore the two formulations are not bioequivalent and are not substitutable. The d-amphetamine salts combo prescription you have now may be an extended release formulation and so the effects are very different from the single ingredient d-amphetamine that you had before. The prescriber might have changed it. Another example is the drug hydroxyzine. It is marketed as the hydrochloride salt under the trade name Atarax® and is also marketed as the pamoate ester under the trade name Vistaril®. The salt form cannot cross the blood brain barrier, so it is used peripherally as an anti-histamine. The ester can cross the blood brain barrier and acts centrally as a minor tranquilizer. These 2 drugs are not bioequivalent. In this case, the 2 drugs distribute dffferently and are not substitutable. For more information on bioequivalence, check out The Orange Book published by the FDA.

  • Generally, this is correct, but I'm not sure what "chemically equivalent" is supposed to mean. It's not a standard term when describing pharmaceuticals. Be assured that e.g., the tablet of two drugs from two different manufacturers, determined by a regulatory authority to be therapeutically equivalent, are most certainly NOT chemically identical.
    – De Novo
    Commented Feb 12, 2019 at 16:33
  • I would add that the standards for bioequivalence are relatively lax. Pharmacies often switch between generic manufacturers quite regularly, which can be a problem for medications where the effect depends on the time course. This is a reason for a prescriber to specify "no substitutions". It's not that generic drugs are worse than the brand name drugs, it's that drugs made by different manufacturers are all different.
    – De Novo
    Commented Feb 12, 2019 at 16:41
  • By "chemically equivalent", I mean the active ingredient to be chemically identical. The formulation may be different when comparing 2 products from 2 different manufacturers because they contain different additives such as binders, disintegrants, fillers, preservatives, dyes, etc., but the active ingredients must be identical.
    – Isaac Lai
    Commented Feb 12, 2019 at 18:38
  • You are absolutely correct in that the generic drug is not necessarily inferior to the brand name drug. The fact is the band name drug is approved first and therefore is used as the standard to which the generic is compared to for marketing approval by the FDA.
    – Isaac Lai
    Commented Feb 12, 2019 at 19:03
  • 3
    Welcome to MedicalSciences. This is a good answer, but we work differently than most SE sites in that we have a strict policy that all answers must be backed up with reliable references so that the answer can be verified regardless of the reader's background. See this list of reliable sources. If you have trouble with this, feel free to visit the help center or Medical Sciences Meta. Unreferenced claims can lead to answers being deleted.
    – Carey Gregory
    Commented Feb 12, 2019 at 22:03

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