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Rifampin and food
By Norman Yarvin
Created 07/06/2008 - 10:04pm

  • Cpn-related research: Member-posted
  • Rifamcin
I recently went back on rifampin, after having been off it for a while due to liver function test issues. The instructions for rifampin are to take it on an empty stomach; but being the lazy guy that I am, I decided to test whether I could get away with taking it with a breakfast of cereal and skim milk. The reasoning was that drug instructions are written to err on the side of caution, that it's unlikely that absolutely every food absorbs rifampin, and that with rifampin in particular, one can test whether it's being absorbed by looking at the urine, to see whether it gets turned the appropriate shade of red. In my case, taking it with that breakfast didn't seem to make much difference.

Then I went to look at the scientific literature, to see if it said anything about what sorts of foods I really should be avoiding taking with it. I found the article Pharmacokinetics of Rifampin Under Fasting Conditions, With Food, and With Antacids [1] by Peloquin et al. The authors found that:

  • Antacids did nothing. So this isn't a drug that gets precipitated by calcium, magnesium, or such, like the tetracyclines are. One doesn't, for instance, have to worry about taking it too close in time to calcium pyruvate. (Strictly speaking, they didn't test calcium, only aluminum and magnesium; but aluminum, being in Group III of the periodic table, is usually a tougher test than calcium, so calcium probably isn't an issue either.)
  • Taking it with a high-fat meal reduced the maximum concentration (Cmax) by 36%, but reduced the area under the curve (AUC) by only 6%.

    The article also summarizes the results of four other studies:

    Siegler et al ... showed a 25% reduction in Cmax, 100% increase in Tmax, and 23% reduction in AUC when RIF[AMPIN] was administered with a high-fat meal. Zent and Smith administered RIF to 27 patients with active tuberculosis, and blood was collected at baseline and 12 time points over 8 h, plus a 24-h postdose. When RIF was given with a carbohydrate meal, a 15% reduction in Cmax, 19% increase in Tmax, and 4% reduction in AUC were shown. In contrast, when RIF was administered with a high-fat meal, these authors showed no significant effect of RIF's Cmax, Tmax, and AUC.

    Polasa and Krishnaswamy studied six healthy men, dosing them with 10 mg/kg of RIF. Blood was collected at seven time points over 8 h postdose. A wheat-based breakfast consisting of 565 calories, including 9 g protein, 109 g carbohydrate, and 11 g fat was administered on one of two occasions. Com- pared with the fasting treatment, food reduced the mean Cmax by 30%, doubled the Tmax to 4 h, and reduced the AUC by 26%. Finally, Hagelund et al studied six patients with tuberculosis, in addition to six gastrectomized patients, collecting blood at 1, 3, 5, and 7 h postdose. They compared fasting conditions with a breakfast of bread with butter and marmalade, meat, cheese, one egg, and coffee or tea with milk. This meal delayed absorption, but showed only minor effects on Cmax and AUC in the nongastrectomized patients.

    On the basis of all this, the authors recommend that rifampin be taken without food. This rather surprised me. Even a 25% reduction in area under the curve -- the worst number they cite -- isn't that much. As for the decrease in maximum concentration, that might be good or bad, depending on whether it is better to deliver a sudden shock to the pathogen, or to keep up the pressure on it steadily. In any case, I'll no longer be treating the instruction to take rifampin without food as an absolute rule, but rather as a rule I can bend according to the dictates of convenience.

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    Thanks for the detail and

    Submitted by Jim K on Sun, 2008-07-06 22:15.
    Thanks for the detail and the analysis, Norman. It's good to know there's some flex in this. I would have inaccurately misread the 25% reduction AUC as a straightforward one quarter reduction. So it's a boon to have someone around who can, literally, do the math. Keep us posted on how the Rifampin goes for you.

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    CAPi [2] for Cpni [3] 11/04. Dx: 25yrs CFSi [4] & FMSi [5]. Currently: 150mg BID Roxithromycin, Doxycycline 100mg BID, Tinii [6] 1000mg/day pulses; Vit D2000 units, T4 & T3

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    Norman, Thanks! I'm about

    Submitted by MacKintosh on Sun, 2008-07-06 23:49.
    Norman, Thanks! I'm about to join the rifampinauts, so this is good to know.

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    The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi

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    The 25% reduction in AUC

    Submitted by Norman Yarvin on Mon, 2008-07-07 00:54.
    The 25% reduction in AUC basically is a straightforward one-quarter reduction. It's not good, but that's the worst number reported. (It's the reduction in Cmax which is more ambiguous in its impact.) From the strong language in the warnings I'd seen, I'd figured they must be talking about a 50% or 75% reduction in AUC, at least; they made it sound like if you'd eaten, you might as well not even bother taking the stuff. With a possible 25% loss, it's still worth avoiding food, all other things being equal; but they often aren't equal. Going hungry imposes its own stresses on the body, which also are worth avoiding; so this is a tradeoff.
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    Thanks Norman the antacid

    Submitted by Michele on Mon, 2008-07-07 05:50.
    Thanks Norman the antacid information is particularly valuable to me as that is the main issue I have had with Rifampicin.

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    Michèle (UK) GFAi [7]: Wheldon CAPi [2] 1st May 2006. Daily Doxyi [8], Azi MWF, metroi [9] pulse. Zoo keeper for Ella, RRMSi [10], At worse EDSSi [11] 9, 3 months later 7 now 5.5 Wheldon CAP 16th March 2006

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