Cpnhelp.org

Jim - Thanks for sharing this article! Significant for any taking Rifampin.

Had actually lowered my husband's vitamin Di intake from 5000iu to 2000iu since he has been getting so much sun recently believe we will bump that right back up. 

Lessons learned so far on Rifampin

1) it interacts with a significant number of other medications.  Best to keep Rifampin dosed as far apart from other types of medications as possible. 

The well documented Rifampin drug/drug interactions is a usual scenario of  Rifampin level increased while level of other medications is decreased. 

This can and will effect efficacy to some degree of concommitant meds.  For example - prednisone, quinolones, macrolides, doxycycline, diflucan, mepron, birth control pills, narcotic pain meds, some seizure medications, some blood pressure meds just to mention a few. 

This occurs from the method Rifampin is metabolized thru the P450system where Rifampin is believed to induced certain P450 enzymes. 

From the PI - "Administration of rifampin with drugs that undergo biotransforation through these metabolic pathways (P450) may accelerate elimination of co administered drugs.."

To work around this I am trying to keep all medications with known or suspected Rifampin interactions adminstered at least several half life's away from Rifampin. 

From the PI

"In healthy adults, the mean biological half-life of rifampin in serum averages 3.35 ± 0.66 hours after a 600 mg oral dose, with increases up to 5.08 ± 2.45 hours reported after a 900 mg dose. With repeated administration, the half-life decreases and reaches average values of approximately 2 to 3 hours."

 If you use 3 hours as the mean half life, then at 5 hours and 15 minutes post Rifampin dosing you are through 3 half lives - to me personally - putting you in a theoretically safer range for getting the desirable effects of other co administered meds.  Probably 7 half lives would be optimal but with all of my husbands med and especially the Questran - not realistic.

The drug interaction issue with Rifampin - to me at least - makes a greater case for taking the full daily dose of Rifampin in a QD fashion vs BID.  Also Rifampin is 'cidal at higher concentrations and 'static at lower concentrations. 

Would be interested to look at Rifampin's 'cidal vs 'static activity at a lower 150mg bid dose for CPNi vs 600 QD.  It's probably in Dr. Strattons thorough patent.

Find it interesting that doctors are prescribing Rifampin BID.  Sometimes wonder if they have really examined the clinical pharmaco issues of this drug.  Just me though...  I am probably missing something that physicians are considering.  Just seems most people on Rifampin posting here are going to be taking quiet a number of other agents.

I would recommend that if you take Rifampin you discuss Rifampin drug/drug interactions with both your physician and pharmacist.

Also taking Rifampin with food can lower the Rifampin drug benefit by 30%.   This is significant.  Also why my husband takes all 600mg first thing in the AM when I KNOW his stomach is empty.  Then no food for at least 1 hour for drug to process.

2) it is well known and documented that Rifampin can induce porphyriai attacks.  Be prepared. 

Rifampin can induce delta-aminolaevulinic acid synthetase activity - porphyria.

The package insert indicates "Rifampin is rapidly eliminated in the bile and undergoes progressive enterohepatic circulation and deacetylation to the primary metabolite, 25 desacetyl-rifampin.  This metabolite is microbiologically active." 

Have been giving Questran about 4 hours post Rifampin AM dose.  In reviewing this I may be lowering the clinical effectiveness of Rifampin by binding it up from the bile as this prevents it from undergoing progressive enterohepatic circulation and deacetylation to the microbiologically active metabolite.  

It's also likely why using Questran so quickly arrested the porphyria attack.  Questran got to the Rifampin metabolizing through the bile quickly as well as porphyria triggering enzymes.

Is my husband loosing efficacy from this.  I will admit to thinking that he well might.  How significant - probably not.  Impossible to determine from home :)

3) From this article - might be wise to up your Vita D intake.

All just my personal thoughts.

^{Daisy - Husband on CAPi 5/07.   Roxyi, Diflucan round three 4-3, Rifampin, Bactrim DS, Mepron 4-7, Prednisone, Novantrone, Doxy, Azithromycin, Flagyli, Mino}

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Daisy - Husband on CAPi 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

Ok, crap!

Reading this article, I would have to conclude that for the last eight months I've been basically wasting both the Doxyi and Azi that I take always with 150mg of Rifampin at the same time.  Not good!  In addition, in the evening, I've been also taking the second dose of Rifampin with INHi, again at the same time.

So, in thinking about this, I'm left with one option that's potentially viable.  That option is to NOT take anything with Rifampin except perhaps NACi.  Instead, I should be taking those abxi at another time, probably late in the afternoon after lunch has settled for a couple of hours and still hours before I would take the second dose of Rifampin.

Still, there is not time enough in the day to do this.  The second dose would be merely 2 - 3 hours later and as such would then metabolize out the other abxi, regardless of the length of time I waited.

So essentially, the only course of action then is to discontinue Rifampin altogether.  Is it not? 

all my best

John

RRMSi/EDSSi was 4.5, was 4.???, now 5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily on 08/19/2007. Added INH 300mg/daily on 03/17/2008.

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all my best

John

RRMSi/EDSSi was 4.5, 5, now 6 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily 08/19/2007. Added INHi 300mg/daily 03/17/2008 stopped 05/08

John -

Taking Rifampin with azith and doxyi does lower some of their efficacy but not all of it.  Azith less than doxy because azith isn't as much of an issue with P450 compared to clarithromycin and doxycycline.  I wouldn't think you have been wasting your effort.

My post was just to say - not only is Vita D as reported above an issue with Rifampin - a lot of other things are as well and it's worthy of discussing with your physician and/or pharmacist - especially if you are taking other medications besides antibioticsi.

Since Rifampin is not a drug you can start and stop and restart very safely - you might want to stay on it. 

I am still giving my husband the Rifampin 600mg QD plus bactrim, roxyi, etc... all at once in the AM because it is so many agents and so much power - losing some from P450 shouldn't matter much.   If you start throwing other categories of meds in - then well - that's another story. 

^{Daisy - Husband on CAPi 5/07.   Roxy, Diflucan round three 4-3, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxy, Azithromycin, Flagyli, Minoi}

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Daisy - Husband on CAPi 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

As regards:

"If you use 3 hours as the mean half life, then at 5 hours and 15 minutes post Rifampin dosing you are through 3 half lives - to me personally"

Huh? That's more like two half-lives. (Not that the half-life is a great way to model that part of the curve, anyway -- at least with oral dosing, the levels rise for a while before falling.)

Also, the aim with most of the other antibioticsi is to keep blood levels high, continuously -- in which case rifampin will be an issue no matter when it's taken. One might even want to take it when blood levels of other antibiotics are at their highest, so that it would not lower their level to the point where bacteria could start growing again. But in general I'd think the right approach would just be to take more of the others, to keep up with the wastage, rather than to try to adjust timings. (When I looked at the numbers, the wastage didn't seem important enough to worry about changing dosages, but I didn't look at them for long, so could easily be wrong.)

Also, I thought doxycycline wasn't metabolized by the liver at all, so liver speedup wouldn't be an issue.

Norman -

As usual, you are technically sound!  You are absolutely right -it's in fact closer to 2 half lives. 

I was using an old trick I learned in school to approximate 75% clearance of the drug.  It's not exactly accurate (but close enough for me since I don't have the patience and exactness to work on the bench). I passed a lot of exams using it though   So glad you are the voice of technical reason !

Also you are correct - the general recommendation is to increase the amount of the other drug(s) you are taking (such as prednisone to compensate for the Rifampin effect) although many just try to space them further apart.

To bring this back around to the reason that I posted above - Rifampin can effect your other meds.  A good deal of them in fact - so be savvy and  speak with your doctor and/or your pharmacists regarding concommitant meds you are taking with Rifampin.  You may want to try to space them further apart (or increase the dose) and realize porphyriai may become a bigger issue.

Thanks for keeping me closer to the bright white line!

^{Daisy - Husband on CAPi 5/07.   Roxyi, Diflucan round three 4-3, Rifampin, Bactrim DS, Mepron, Prednisone, Novantrone, Doxyi, Azithromycin, Flagyli, Minoi}

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Daisy - Husband on CAPi 5/07.  "When Going Thru Hell, Just Keep Going", Winston Churchill

 Norman- I'm always so glad we have you checking on the technical logic of our discussions here. I rely on you for this, really. I'm pretty good about getting the broad implications of things, but once into the finer calculations I'm missing in action! 

We do have to put this single case study in perspective: this is an AIDS patient, and it's not just the Rifampin that's using up vitamin Di. I think it's importance is as a cautionary: I wouldn't necessarily have thought about vitaminsi being affected by liver metabolism. Short sighted in a way, and it's often our ignorance that kills us!

CAPi for Cpni 11/04. Dx: 25yrs CFSi & FMSi. Protocol: 200mg Doxyi, 250mg MWF Azith, Tinii 1000mg/day pulses; Vit D1000 units, Iodoral 50mg, T4 & T3

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

Another drug that Rifampicin affects the efficacy of is Levothyroxine.   This is signigicant to quite a few of the members of this site who suffer from hypothyroidism...

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

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Michèle (UK) GFAi: Wheldon CAPi 1st May 2006. Daily Doxyi, Azi MWF, metroi pulse. Zoo keeper for Ella, RRMSi, At worse EDSSi 9, 3 months later 7 now 6.5 Wheldon CAP 16th March 2006

Rifampin definitely affects Levothyroxine. I had to increase my dose from .88 mcg to .125 mcg and still was not able to keep TSH in normal band. After a month, my dr. recommended that I quit the Rifampin as the TSH just kept going up.Theoretically we should have been able to compensate for the increased metabolization of the Levothyroxine by continuing to up the dose, but my doc voted to discontinue the Rifampin and try other meds. If I had it to do over, I'd increase the Synthroid doseage more aggressively right off the bat and have hung in there a bit longer to see if it finally leveled out. Quite the nasty ride, total exhaustion and muscle cramping by the end. 

DX: Borrelia, Babesia, CP, suspected Bartonella CAPi: Omnicef, Minocycline, Tindamax, Roxithromycin

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DX: Borrelia, Babesia, CP, suspected Bartonella CAPi: Omnicef, Minocycline, Tindamax

Thanks Jim, this is a really important addition to the site and I want to keep track of this conversation.

 Louise

CFSi/ME.CPnPositive.BbPositive.WheldonCAPbegan6/24/07. NowNAC,Doxyi, Roxi, TiniPulse#4 Ended2/3/08. Cholestyramine at BedtimeforPhorphoria&liposacarideEndotoxinDie-OffExperiences.

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Louise  CFSi,CPNi+/Bb+(Lyme) Cholestyramine 1-2 pks @ HS for Porphyriai +fattyEndotoxins HS PRN, Wheldon CAPi 6/07,all supps, Doxyi 200QD, Roxi 300BID, Tinidazole 500 BIDx20day Pulses, VitD3-10,000IU,Iodoral25mg,SAM-e100mgQD+B-vits, Pyruvate3.75Gm at 1PM

For what it is worth, I took Rifampin and Doxyi together twice a day for sixteen months, leaving two hours before and two hours after without food. I was pretty much ok, beyond increasingly bad symptoms until I began flagyli three months later, then spent most of my time lying down in a mental and physical muddle. But John did several months of this without much impact. But John, you have had some "leg heaviness", I believe. I like that. Hope it gets heavier.

 

Rica PPMSi EDSSi 6.7 at beginning - now 2. Began CAPi Sept, 2004 with Rifampin 150 mg 2xd, Doxy 100 mg 2xd, added regular pulses Jan 2005. Jan 2006 switched to Doxy, Azith, cont. flagyl total 50 pulses NC USA

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Rica PPMSi EDSSi 6.7 at beginning - now 2. Began CAPi Sept, 2004 with Rifampin 150 mg 2xd, Doxyi 100 mg 2xd, added regular pulses Jan 2005. Jan 2006 switched to Doxy, Azith, cont. flagyli total 55 pulses LDNi Rifampin 8/08 again NC USA

Thanks Rica, me too.  My only concern about that is it makes going to work a chore at best but more commonly it's just that much harder to function as my symptoms have worsened over time and I'm really not sure what long term benefit I've gotten at all over the last 2 years, other then becoming more wise which will get me little.  But, being the glutton for punishment and having no other option that has any potential at all really to help me, I go on.

I understand from what Norman has said that regardless of when I take it, Rifampin is going to impact the metabolization on the other abxi.  As such, unless I discontinue Rifampin, my only choice is to try and minimalize that impact.  So, what I'm going to do is take them apart from one another, separated by 3 or 4 hours.  This will do little to reduce the impact of Rifampin although my hope is that the potency of the Rifampin in my blood will have diminished somewhat and that it's impact on the other drugs will have been reduced.

So here is my loose plan for all non pulse periods.

• 5:30 a.m. - NACi, CoQ10
• 6:30 a.m. - other supplementsi
• 9:30 a.m. - Rifampin and NAC
• 3:00 p.m. - Doxyi, Azi(MWF), and INHi.  May also do NAC or just do it later.
• 5:00 p.m. - Annato tocotrienols
• 6:00 p.m. - Rifampin and NAC

For pulse periods, here is the loose schedule for that...

• 5:30 a.m. - NAC, CoQ10, FLAGYL
• 6:30 a.m. - other supplementsi
• 9:30 a.m. - Rifampin and NAC
• 3:00 p.m. - Doxy, Azi(MWF), and INH.
• 3:30 p.m. - FLAGYL and NAC
• 5:00 p.m. - Annato tocotrienols
• 6:00 p.m. - Rifampin and NAC
• 9:30 p.m. - FLAGYL and NAC

I'm not at all sure that this schedule is best but will think about it some more and see what I come up with.  I know that on weekends, I tend not to follow the same schedule do to a desire to sleep more then during the week, but we'll see. 

all my best

John

RRMSi/EDSSi was 4.5, was 4.???, now 5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily on 08/19/2007. Added INH 300mg/daily on 03/17/2008.

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all my best

John

RRMSi/EDSSi was 4.5, 5, now 6 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily 08/19/2007. Added INHi 300mg/daily 03/17/2008 stopped 05/08

Holy crap....the anti-inflammatory nature of Doxyi and Azi sure make a difference.  I'm currently operating on a dose of Rifampin and it is really a big change over how I would feel before on everything.  We'll see what happens later when I eventually take the doxy and azi, and INHi. 

all my best

John

RRMSi/EDSSi was 4.5, was 4.???, now 5 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily on 08/19/2007. Added INH 300mg/daily on 03/17/2008.

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all my best

John

RRMSi/EDSSi was 4.5, 5, now 6 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily 08/19/2007. Added INHi 300mg/daily 03/17/2008 stopped 05/08

Maybe I missed something very important, but why can't you take NACi with the other supplementsi? We both do this EVERY am and pm.

 

Rica PPMSi EDSSi 6.7 at beginning - now 2. Began CAPi Sept, 2004 with Rifampin 150 mg 2xd, Doxyi 100 mg 2xd, added regular pulses Jan 2005. Jan 2006 switched to Doxy, Azith, cont. flagyli total 50 pulses NC USA

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Rica PPMSi EDSSi 6.7 at beginning - now 2. Began CAPi Sept, 2004 with Rifampin 150 mg 2xd, Doxyi 100 mg 2xd, added regular pulses Jan 2005. Jan 2006 switched to Doxy, Azith, cont. flagyli total 55 pulses LDNi Rifampin 8/08 again NC USA

Rica

Nobody said I couldn't take them all at once; however, given Rifampin's P450 Enzyme affect, I thought that spacing the time out so that the quantity of Rifampin in my system is lower when taking everything else would be in order.  That's my objective by not taking it all at once and why I've only taken Rifampin so far today.  I will be taking, Doxyi, Azi, and INHi in less then an hour from now.

all my best

John

RRMSi/EDSSi was 4.5, was 4.???, now 5 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily on 08/19/2007. Added INH 300mg/daily on 03/17/2008.

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all my best

John

RRMSi/EDSSi was 4.5, 5, now 6 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily 08/19/2007. Added INHi 300mg/daily 03/17/2008 stopped 05/08

The issue with thyroid medication is that it has to be precisely controlled: if you're on a dose of 112 micrograms/day, then 100 is too low and 125 is too large. (It's a noticeable effect: the former makes you too sluggish, and the latter too excited and nervous -- albeit not hugely so, at those levels.) Antibioticsi are not like that; instead the doses are chosen to include a generous safety margin. Also, when adding rifampin to other antibiotics, one expects a certain amount of synergy, which would probably permit having lower blood levels of the others. So it's really not something to worry about much, if at all. And if you want to worry anyway, the P450 stuff only applies to antibiotics that are metabolized (which in this case means destroyed) by the liver, which doxycycline isn't. Looking at the prescribing information from Pfizer, it seems like azithromycin isn't, either, although I can't tell for sure, and there's a line about metabolic studies not having been done. The liver does excrete it, in bile, but doesn't change it in doing so.

If I get it right, you are saying don't worry about Rif and other antibioticsi, but take care with the Thyroid medication....

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

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Michèle (UK) GFAi: Wheldon CAPi 1st May 2006. Daily Doxyi, Azi MWF, metroi pulse. Zoo keeper for Ella, RRMSi, At worse EDSSi 9, 3 months later 7 now 6.5 Wheldon CAP 16th March 2006

Yes, that's basically the upshot of what I was saying.

Interesting about the Thyroid medication.  I haven't taken it but have wondered if a reaction I've been having is due to something going wrong with my Thyroid.  Basically I get very sleepy after taking antibioticsi/NACi and could nap for a good hour when I do.  I don't generally nap but could.  I do sometimes on weekends but during the week I'm at work so it's just not an option.

Something else with respect to the differences between Herx'ing and inflamation, as well as other reactions is whether or not we've dilineated how to respond to things well enough?  My feeling is that we haven't due to the confusion a lot of times with knowing what's really happening.

For instance, Jim and others have talked about using a vitamin C flush in the past to deal with endotoxinsi.  I wonder if that is really actually addressing inflamation as well because don't they go hand in hand?

Case in point, when I started using Rifampin on it's own yesterday (taking it well apart from the other antibiotics) I noticed a much greater reaction from it then when I take it with Doxy/Azi.  It felt very inflammatory in nature and that also increased MSi symptoms.  I've dealt with that today by taking an extra gram of calcium ascorbate (mineral vitamin C) which seems to have made the reaction much less severe or at least did so today.

Just some thoughts...

all my best

John

RRMSi/EDSSi was 4.5, was 4.???, now 5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily on 08/19/2007. Added INHi 300mg/daily on 03/17/2008.

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all my best

John

RRMSi/EDSSi was 4.5, 5, now 6 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily 08/19/2007. Added INHi 300mg/daily 03/17/2008 stopped 05/08

I am one of those members. My TSH went up significantly just within 2 weeks of starting Rifampin and I am still in the process of balancing out my Synthroid since it takes a few weeks to see the final result of an increased dose. 

Nata.

Arthritis, muscle pain & twitching, sinusitis, hypertensioni, hypoT, restless legs, chronic cough, fatigue. Cpni IgGi (+), CMV IgG (+), HLA B27 (+), ANA (+), BB (Lyme) Western Blot (+).

Full CAPi since 02/29/08: RIF 600mg + Azith 300 mg/3 x wk. 

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Nata.

CAPi for arthritis, tendonitis, sinusitis, pelvic pain, fatigue and muscle pain. Hypertension, HypoT Hashi's. Lyme (+) and Cpnii (+

This discussion was linked in another post by someone so I came back and read it again, after over six months.  Due to what Norman was saying about where various abxi are metabolized, I didn't maintain the space between Rifampin and the other abxi.  I still take the abx together in the morning and just Rifampin in the evening. 

The good thing with this is that there is a reduction in symptoms taking it that way due to the anti-inflammatory effects of the other abx.  Taking Rifampin apart is more difficult then pairing it with doxyi and azi.  Since I take doxy every day and azi on MWF, my feeling is that doxy has a much more significant anti-inflammatory effect then azi.  Just my feeling / perception from experience, there may be studies somewhere that could be used to compare the two more objectively.

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all my best

John

RRMSi/EDSSi was 4.5, 5, now 6 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily 08/19/2007. Added INHi 300mg/daily 03/17/2008 stopped 05/08

John- a while back some of guessed that the more diminished immunei modulating effect of azithromycin, despite studies showing it as having that effect, was due to the less frequent dosing. Our hypothesis was that you only get the antiinflam effect while it is in your blood stream, and since it is taken up by cells and concentrates there, so you need take it less often for antibiotic effect, you would only get anti-inflam effect by taking it daily. I did this for a while and think there is something to it, but probably still not as much as the doxyi.

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

Thanks Jim  

It's good to have that general confirmation that my perception of doxyi and being more immunei modulating then azithromycin as generally correct.

On a related tangent to inflammationi, I discontinued taking curcumin yesterday.  It definitely makes a difference.  I'm surprised at the difference as I didn't realize that it was helping as much as it does/did.  I took this action based on the information that Red posted on COX and 5-LOX inhibitors, curcumin being one of them.  I'll be adding more moppers (vitamin  C) in hopes that it will offset things.

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all my best

John

RRMSi/EDSSi was 4.5, 5, now 6 on Wheldon Protocol (naci, doxycycline, azithromycin, metronidazolei) since 04/12/2006. Added Rifampin 2x150mg/daily 08/19/2007. Added INHi 300mg/daily 03/17/2008 stopped 05/08