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Combinations - Proton Pump Inhibitors (Omeprazole etc) and Benzodiazepines

Discussion in 'Benzodiazepines' started by Benzeneringz, May 25, 2006.

  1. Benzeneringz

    Benzeneringz Titanium Member

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    I'm kickin' myself for forgetting this: omeprazole (Prilosec) + a benzodiazepine = a significant reduction in benzodiazepine clearance. This means you're benzo will achieve a higher blood/plasma concentration and increase the half-life of the benzo. I'm including an article from Entrez Pubmed on the topic.

    The proton pump inhibitors (PPIs) are the most effective antisecretory agents used to treat acid-related disorders. As such, they are frequently prescribed for patients who are concurrently using other medications. PPIs may interact with other drugs through numerous mechanisms. The most important include competitive inhibition of hepatic cytochrome P (CYP) 450 enzymes involved in drug metabolism, and alteration of the absorption of other drugs via changes in gastric pH levels. Poor metabolizers, who lack CYP2C19, may be particularly predisposed to drug interactions. Although the potential for drug interactions is high, few clinically significant interactions have been reported for the PPIs. Nevertheless, caution is indicated when certain drugs are co-prescribed with these agents. The incidence of clinically significant drug interactions increases proportionately with the number of drugs taken and with the age of the patient. The drug interaction with the greatest clinical importance is the reduction in benzodiazepine clearance by omeprazole.

    --Division of Gastroenterology, Stanford University School of Medicine, CA, USA. MAY 13th, 2001

    Listen, SWIM has mixed temazepam and omeprazole on several different occasions and from what I can tell it is the perfect mixture.. and not with just temazepam, either! It appiles to all benzodiazepinesupercooldrugs. That's my two cents. There are many many other pharmacology issues that could be exploited with all sorts of drugs. Folks I'm making myself sound like a stuck-up ass when I say this, but...ALWAYS feel free to PM me in reguards to anything posessing pharmacologically active. Why? Because I garuntee I am MUCH more educated in the fields of pharmacology and organic chemistry than some of these idiots who make me shake my head.

    Sorry for the violent tone, it's DEFINATLY NOT from eating and sniffing anything.. ESPICALLY temazepam.
    -Benzene
     
  2. brook

    brook Newbie

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    Re: Benzo combos

    "I'm kickin' myself for forgetting this: omeprazole (Prilosec) + a benzodiazepine = a significant reduction in benzodiazepine clearance. This means you're benzo will achieve a higher blood/plasma concentration and increase the half-life of the benzo"

    This is VERY interesting indeed!! this will be tried by swim in the very near future i expect!!
     
  3. Pachanoid

    Pachanoid Silver Member

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    Omeprazole effect on benzos?

    Sorry if this is the wrong place to post this. Anyway SWIM came across this:

    There is not much info on Omeprazole, and I'm a total noob when it comes to pharmacology. Can any of SWIY elaborate on this, if it's true at all that it can potentiate benzodiazepines?

    Thanks
     
    Last edited by a moderator: Jul 30, 2009
  4. Jatelka

    Jatelka Psychedelic Shepherdess

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    Re: Omeprazole effect on benzos?

    Omeprazole is an hepatic enzyme inhibitor. Hepatic enzymes are also responsible for "First Pass" metabolism of certain benzodiazepines (Diazepam, Triazolam and Alprazolam spring to mind)

    By eliminating the effect of first pass metabolism, serum levels of benzodiazepines are higher

    It's essentially the same mechanism as with Grapefruit Juice and benzodiazepines

    Here's an abstract:

    Eur J Clin Pharmacol 1990;39(1):51-4

    Effect of omeprazole and cimetidine on plasma diazepam levels.
    Andersson T, Andrén K, Cederberg C, Edvardsson G, Heggelund A, Lundborg P.

    The effects of steady state dosing with omeprazole and cimetidine on plasma diazepam levels have been studied in 12 healthy males. Single doses of diazepam (0.1 mg.kg-1 i.v.) were administered after one week of treatment with omeprazole 20 mg once daily, cimetidine 400 mg b.d. or placebo, and the treatment was continued for a further 5 days. Blood was collected for 120 h after the dose of diazepam for the measurement of diazepam and its major metabolite desmethyl diazepam. The mean clearance of diazepam was decreased by 27% and 38% and its half-life was increased by 36% and 39% after omeprazole and cimetidine, respectively. Neither drug had any apparent effect on the volume of distribution of diazepam. Desmethyldiazepam appeared more slowly after both omeprazole and cimetidine. It is concluded that the decrease in diazepam clearance was associated with inhibition of hepatic metabolism both by omeprazole and cimetidine. However, since diazepam has a wide therapeutic range, it is unlikely that concomitant treatment with therapeutically recommended doses of either omeprazole or cimetidine will result in a clinically significant interaction with diazepam.
     
    Last edited: Dec 1, 2008
  5. Pachanoid

    Pachanoid Silver Member

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    Re: Omeprazole effect on benzos?

    Thank you very much. I wonder if SWYanyone else has tried this combination?
     
  6. tyranny4u

    tyranny4u

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    Re: Omeprazole effect on benzos?

    SWIM uses Omeprazole (regularly prescribed for gastric problems) for this
    reason. Means, he has to take it anyway to treat the stomach problems,
    but so it's a nice "side effect" that SWIM needs to take lower doses of benzo-
    diazepines and SWIM gets more out of his daily dose of Levomethadone.
     
  7. missrogue

    missrogue

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    Proton Pump Inhibitors and Benzodiazepines

    Does the effect describe by taking tagament with pills also work with other proton inhibitors, like rabeprazole {pariet}??
     
  8. Jatelka

    Jatelka Psychedelic Shepherdess

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    Re: Proton Pump Inhibitors and Benzodiazepines

    Tagamet is Cimetidine, which is not a Proton Pump Inhibitor (like rabeprazole), but an H2 receptor antagonist

    The data on PPI's and benzodiazepines is extremely mixed, and often contradictory

    Omeprazole is, certainly, a cytochrome inhibitor, and, as such, theoretically could be used to potentiate benzodiazepines such as diazepam, midazolam, and flunitrazepam

    see these...
    http://www.drugs-forum.com/forum/local_links.php?action=jump&catid=129&id=6842
    http://www.drugs-forum.com/forum/local_links.php?action=jump&catid=129&id=6828

    However, there is some debate as to whether this interaction results in clinically significant effects

    Long term Lansoprazole use does not effect the metabolism of diazepam

    (Influence of lansoprazole treatment on diazepam plasma concentrations. Clin Pharmacol Ther. 1992 Nov;52(5):458-63.
    Lefebvre RA, Flouvat B, Karolac-Tamisier S, Moerman E, Van Ganse E)


    Similarly, Pantoprazole does not interact with diazepam

    (Lack of pharmacokinetic interaction of pantoprazole with diazepam in man Gugler R, Hartmann M, Rudi J, Brod I, Huber R, Steinijans VW, Bliesath H, Wurst W, Klotz U. Br J Clin Pharmacol. 1996 Aug;42(2):249-52.)

    I have no information on Rabeprazole (and, neither, it seems, does pubmed, from a quick search this morning)