Posted by Tomatheus on June 21, 2006, at 5:28:10
In reply to Re: Taking Nardil to the EXTREME!!!!!!!!!!!!!!!!!! » Tomatheus, posted by ace on June 20, 2006, at 23:08:27
Ace,
I guess I need to clarify some of my statements from my previous post:
** I am not claiming that the actual formulation of the Australian Nardil has changed. As far as I know, the medications' excipients are still as follows: mannitol, povidone, maize starch, magnesium stearate, and the film coating (Opadry 20A25096 Red).
** It was not my intention to make it seem like silica gel was an ingredient in the Australian Nardil. What I'm saying is that *each bottle* of Australian Nardil used to have a little gray cylindrical object filled with silica gel inside of it (along with the 100 tablets). The new bottles, with an expiration date of 12/2006 or (probably) later, only have the tablets inside of them -- no silica gel.
I know this because I used to order the Australian Nardil from an online pharmacy (I live in the U.S.) and take it using a special enteric capsule preparation method. Until I received the bottles with an expiration date of 12/2006 on them, they always had silica gel inside of them. And as I mentioned in my previous post, I started feeling drastically worse -- both physically and mentally -- within a few days of taking the Australian Nardil from one of the new silica gel-free bottles.
** When the tablets inside the new silica gel-free bottles of Australian Nardil leave the factory, they're probably not much different chemical-wise from the tablets that were in the older bottles that had silica gel inside of them. But the Nardil tablets inside the new silica gel-free bottles do not have the "protection" against moisture that the tablets in the older bottles had (and the "protection" that I'm referring to is, of course, the silica gel that was in the older bottles).
So, for example, if the bottles of Nardil that you received during your last visit to the pharmacy (assuming that you receive the original Link bottles with 100 tablets in them) were exposed to significant amounts of moisture at any point between when they left the factory and when you received them from your pharmacist, the tablets inside those bottles probably aren't "fresh." In other words, any hydrazine that might have formed from the phenelzine sulfate in the tablets probably underwent extensive chemical degradation as a result of being exposed to too much moisture.
In a study of time-dependent hydrazine levels in phenelzine and other hydrazine-derivative medications, Lovering et al. (1983) found that phenelzine tablets from one lot ("Lot C") contained an average of 47 micrograms of hydrazine and that the tablets from a second lot ("Lot D") contained an average of 40 micrograms of hydrazine. For both lots, the measurements that I referred to in the previous sentence were taken before the tablets were exposed to any experimental conditions. The authors of the study also found that hydrazine levels in phenelzine tablets dropped considerably after the tablets were stored at 80 or 100 percent relative humidity. They further went on to state that "the data obtained from the samples stored in sealed containers show that these decreases can be attributed to chemical degradation rather than evaporation of the hydrazine" (Lovering et al., 1983, 966).
I suppose it's theoretically possible that the Nardil bottles that you picked up on your last trip to the pharmacy *might* not have been exposed to enough moisture since arriving from the factory for the hydrazine inside the tablets to undergo significant chemical degradation. This possibility, however, is not very likely considering that the instructions on the bottle say to refrigerate the medication. If your pharmacists followed the instructions on the bottle and kept your Nardil refrigerated before dispensing it to you, then the tablets that you received were almost definitely exposed to more than enough moisture to potentiate the degradation of hydrazine.
Finally, regarding your question about the oxidization of aqueous hydrazine, the research reports that I've come across do suggest that the ammonium ion could result from the oxidization of aqueous hydrazine (N2H5+), depending on what the oxidizing agent is.
In reviewing the literature that had been published on the oxidization of hydrazine in solution up to that point, Cahn & Powell (1954) identified three oxidization reactions:
1) N2H5+ = 4e- + N2 + 5H+
2) N2H5+ = e- + NH4+ + 0.5N2 + H+
3) N2H5+ = 2e- + 0.5HN3 + 0.5NH4+ + 2.5H+
According to Cahn & Powell (1954), some oxidizing agents give one of the three reactions identified above, and others give reactions 1 and 2 together. (That's about the extent to which I can make sense of the article, given my limited knowledge of chemistry.)
As you can see, reactions 2 and 3 would both produce the ammonium ion (NH4+) as one of the byproducts. Other byproducts of the oxidization of hydrazine include nitrogen gas (N2), the hydronium ion (H+), and hydrazoic acid (HN3).
To be honest with you, I don't know enough about chemistry to tell you whether any of the excipients in the Australian Nardil could react with aqueous hydrazine to produce any of the oxidization reactions that Cahn & Powell (1954) identified.
But I can say the following:
* Ammonium has been confirmed to be a byproduct of the oxidization of hydrazine, at least in the presence of certain oxidizing agents.
* After I started taking the Australian Nardil from the new silica gel-free bottles, I experienced several signs of mild hyperammonemia: urinary retention (I had none when I was taking my specially prepared version of the Australian Nardil until I received the silica gel-free bottles), lethargy, poor coordination, agitation, and reduced appetite.
* Even if it's the case that ammonium is not produced as a result of the moisture-induced chemical degradation of hydrazine in Nardil tablets, the absence of silica gel inside the newer bottles of the Australian Nardil does allow for the accumulation of excessive moisture inside the bottles. And as Lovering et al. (1983) demonstrated, the hydrazine in phenelzine tablets that are stored in humid conditions undergoes rapid chemical degradation.
So, if nothing else, the silica gel that was inside the older bottles of the Australian Nardil (those with expiration dates older than 9/2006 -- and I'm not sure about 10/2006 or 11/2006) helped keep the chemical composition of the tablets intact between the time that the Nardil left the factory and the time that you picked it up from your pharmacy. And, considering that I began feeling mentally and physically awful within days of taking the Australian Nardil from the silica gel-free bottles (and the fact that over the past two or three months you've reported receiving a less robust response on Nardil than you had been receiving previously), I think that Link Pharmaceuticals and the TGA definitely need to be notified about the potential therapeutic consequences of shipping out Nardil bottles without any silica gel inside of them.
I hope this helps. Please let me know if you have any additional questions or if there's anything else that I can do to help make Link and/or the TGA aware of this situation.
(A very tired) Tomatheus (even with my screwed-up sleep schedule)
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REFERENCES
Cahn, J. W., & Powell, R. E. (1954). Oxidization of hydrazine in solution. Journal of the American Chemical Society, 76, 2568-2572.
Lovering, E. G., Matsui, F., Curran, N. M., Robertson, D. L., & Sears, R. W. (1983). Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine over a 2-year period. Journal of Pharmaceutical Sciences, 72, 965-967.
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> Hey friend!
>
> Now, the Nardil take, have always taken, since 5 yrs ago, has not and does not have silica gel inside them. Unless my eyes decieve me grossly.
>
> The Nardil I take has always been the same in terms of the lack of this silica gel issue.
>
> However, I am going to ring both Link and the TGA (equivalant governmental body to FDA in Australia) to see if any incipients have changed over time. However, I don't believe they have. I believe the Nardil which caused bliss 5 yrs ago is the same Nardil as I take now.
>
> My biggest mistake was to cease Nardil when it was providing an UNBELEAVABLE robust remission of my depressive illness, indeed, it was causing a 'healthy' euphoria, and start Clomipramine.
>
> This, I believe began the cycling in and out of healthy euphoria, and subsequent declining in theraputic effect. However Nardil still does provide significant help. But, in contrast to yrs ago, it does not seem to be able to "keep me going" with its euphoria even in the face of negative environmental factors. I believe enzyme induction provides a clue, but I have many theories.....
>
> Just a question, with regards to the oxidation of aqueous hydrazine, are you certain the ammonium ion is one (of many) by products????
> And what other byproducts can you ascertain?
>
> Thanks so much friend, pls respond!
>
> Ace
>
>
poster:Tomatheus
thread:658595
URL: http://www.dr-bob.org/babble/20060617/msgs/659611.html