Sandoz B12 Injection Reaction

[USmedsyssucks]

Well, I thought I had found the answer to my problem when I finally got my B12 injections from Canada thanks to the help of many wonderful people on this site. I am located in the US and have found my GPs to be less than helpful (still think I can take oral supplementation and won't prescribe enough injections to stop my neuro symptoms), so I was happy to have my health in my own hands. However, the Sandoz B12 I've received is giving me a terrible reaction that the US B12 (brand unknown for the moment - going to ask the pharmacist shortly) was not. Immediately upon depressing the plunger, I feel a strange sensation in the back of my throat and a burning at the injection site. The burning calms down with the remainder of the injection if I depress the plunger slowly, but the injection site throbs painfully for about 24 hours after injection. This, I could deal with, but I also have interstitial cystitis and find that my bladder symptoms are out of control the day after injection. I know it's the injection because when I stop injecting, the symptoms disappear again. With the injections I was getting in the US, the whole process was completely painless and I did not have a bladder reaction. Has anyone else had issues with Sandoz B12, specifically the multi-use vial? If so, is there another brand that worked better for you? Perhaps there is a difference between the stabilizers in the multi-use Sandoz vial I bought from Canada and the single-use vials I obtained in the US? Perhaps the single-use vials from Sandoz would be better? I'm pretty devastated because I was feeling so much better with every other day injections and now I'm back to square one.

To add some pertinent information,

- I am injecting deep subQ into my vastus lateralis and am medically-trained, so it's not an issue with the injection site itself. The negative reaction is reproducible regardless of injection site and has happened several times.

- The vial was completely sealed when I opened the package and the negative reaction happened upon the first injection, so it is not a sterility issue as far as I can tell. This feels like a sensitivity reaction to something in the formulation.

[Nackapan]

I cant relate to the brand or symptoms.However o e brand I've stopped using as I had a sensitivity to it and ir added to symptoms. It happened twice so it was clear what if was .

I had no pre conceptions.

So you may well be right

The doctor gave me another prescription. . The pharmacist

made a note not toh have that brand.

I'm fine on 4 other generic brands.

[fbirder]

The Sandoz cyanocobalamin contains benzyl alcohol as a preservative. But I was under the impression that was standard in American preparations. There is nothing else that might provoke any reaction, just the standard salt and vinegar.

[USmedsyssucks in reply to fbirder]

I've since learned that the preparations differ in 2 ingredients: sodium acetate and acetic acid. Both of these buffers are not present in the formulation I obtained in the US; all other inactive ingredients are identical. I know these are just buffers (and acetic acid is just vinegar), but as I'm intolerant of vinegar due to my interstitial cystitis, I wonder if this difference may be the problem. I'm currently searching for a formulation without these ingredients, since they seem to be the only logical reason I'm unable to tolerate the Sandoz solution.

[fbirder in reply to USmedsyssucks]

The preparations you use might not list them, but I'd be surprised if they didn't have something equivalent to use as a buffer.

Acetate is very, very common in the human body, so the tiny extra amount in an injection would make any difference. Your plasma alone contains about 3 mg/L sciencedirect.com/topics/ne....

[USmedsyssucks in reply to fbirder]

The formulation I've been using lists the ingredients as: cyanocobalamin, sterile water, sodium chloride, benzyl alcohol, and hydrochloric acid or sodium hydroxide as pH adjusters. I don't actually believe it is legal for a manufacturer to use additional reagents without disclosure or at least some indication that something additional may be added/substituted. The Sandoz preparation has all the same ingredients plus the acetic acid/sodium acetate. When combined to make a buffer, sodium acetate/acetic acid has a pKa of around 4.7, which is well below the normal pH of bodily fluids (~7.4), especially given that pH is a logarithmic scale. I'm wondering if the preparation is just too acidic for my body, causing the burning at the injection site. Later, the extra acid would be excreted in my urine. In a normal person, this wouldn't be an issue, but I'm exquisitely sensitive to acid because of my interstitial cystitis. This is the only hypothesis I can come up with, unless I got a chemically contaminated batch of the Sandoz cyanocobalamin. I honestly wasn't expecting this to happen, but I completely cannot tolerate the Sandoz formulation due to the bladder symptoms it produces, so I hope this hypothesis is correct or I won't know where to go from here.

[fbirder in reply to USmedsyssucks]

You're confusing pKa and pH.

When combining to make a buffer you vary the amounts of the acid and the conjugate base (acetic acid and sodium acetate) to achieve the desired pH. You can use the value of Ka (pKa is -log(ka)) to calculate the proportions required to achieve that pH.

chem.purdue.edu/gchelp/howt...

In solutions for injection that pH is going to be physiological pH - about 7.4.

[USmedsyssucks in reply to fbirder]

My intent was to say that due to the pKa of the buffer solution, it is possible, even likely, that the solution will be acidic. For instance, in the lab, I wouldn't use an acetic acid/sodium acetate solution to achieve a buffer that stabilizes the pH of a solution at 7.4. A phosphate buffer solution would be used instead. While one can achieve a wide range of solution pH values with any true buffer, the buffer will be most effective and stable when the pH of the solution is near the pKa of the buffer. This is because there are close to equal concentrations of conjugate acid and conjugate base, so the solution can accommodate decent additions of both H+ and OH- ions.

I didn't mean to imply that the pH of the Sandoz cyanocobalamin was actually 4.7 (it's obvious they are also adjusting the pH with the sodium hydroxide/hydrochloric acid I mentioned), but I was hypothesizing that the pH of the Sandoz preparation may be lower than the UBI Pharma brand I am getting in the US because the only difference is the addition of an acetic acidic/sodium acetate buffer solution to the Sandoz brand, and these are merely going to adjust the pH, not be antigenic. I'm unsure how much lower the pH may be, because Sandoz is simply mentioning adjusting the pH and not guaranteeing any specific pH value in any of the literature I can find. In this link for a different brand, it seems acceptable to have a pH anywhere between 4.5 and 7.0. dailymed.nlm.nih.gov/dailym...

I honestly wouldn't have even suspected there would be an issue with the Sandoz cyanocobalamin since the ingredients look fairly benign, but there is definitely an issue (for me) and those two ingredients are the only difference between the two formulations I've tried. That leads me to wonder if pH is the issue. Perhaps it is even the hydrochloric acid concentration that is higher and not the acetic acid at all. I do know that I just got my last prescription of the UBI brand yesterday and administered myself a completely painless injection that was not accompanied by an increase in bladder symptoms. The difference is immense. So if it isn't a pH issue, then something far worse is happening with this Sandoz B12 - either there are unlisted ingredients or the vial is bad.

[fbirder in reply to USmedsyssucks]

Sigma seem to think that acetate buffer is OK for pH7. Otherwise they wouldn't sell it. sigmaaldrich.com/catalog/pr...

[USmedsyssucks in reply to fbirder]

That's fine, and I'm not trying to argue with you. I did say that buffer solutions can be used in a relatively wide range around their pKa. In fact, if you are trying to resist the addition of specifically acid or base, it may be preferable to push your buffer solution to one end of the spectrum. So yes, if you are trying to do something specific, you may use a different buffer system. Overall though, a buffer will be most able to resist addition of either/both acid and base right around the pKa. Sigma also sells a sodium acetate buffer with pH 5.2: sigmaaldrich.com/catalog/pr...

I also mentioned that it may not be the acetate buffers at all and rather the pH adjustment with the hydrochloric acid/sodium hydroxide that could make one pH different than the other. The only reason I'm thinking pH is the issue is because the only ingredients that differ between the formulations are pH buffering ingredients that shouldn't be antigenic themselves.

But none of this is particularly helping me determine why one brand of cyanocobalamin is giving me side effects incompatible with living a normal (or even tolerable) life and another is completely side-effect free, when the only difference between the two is a relatively benign buffer solution. I hypothesized it may be a difference in the pH of each solution because of this. Nobody has been able to offer me any additional suggestions, so I will update after contacting the company.

[USmedsyssucks]

In case this helps anyone, I ended up ordering a vial of Sterimax B12 (same ingredients as Sandoz) and had zero adverse reaction. I went through the whole vial with no issues and just ordered more. I'm assuming there was a problem with the Sandoz vial I received (either with the formulation of that batch or with storage/handling. The company initially seemed interested in obtaining a sample for testing but then never followed up. I have not tried another Sandoz bottle since then, as it was easier to just stick with Sterimax since I haven't had an issue with that formulation.

[Litatamon]

Just want to add that I have used both companies. Neither has given me an adverse reaction; however, despite the same ingredients I do feel differently on them. That just goes to show that our bodies can be so sensitive because in theory to feel different makes no sense whatsoever.

And for months I used to buy whatever one was more handy and cheaper. So it was not a one and done for me.

[USmedsyssucks in reply to Litatamon]

That's really good information to know. Thank you for sharing!