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MyDeficiencies

Rifabutin

rifamycin antibacterial (antimycobacterial)

Also sold as Mycobutin.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Rifabutin has real but modest enzyme-induction machinery. The label states that multiple dosing induces hepatic CYP3A enzymes, that rifabutin "is a CYP3A inducer," and that it is "a weaker enzyme inducer than rifampin" [1]. It is extensively metabolized (25-O-desacetyl and 31-hydroxy metabolites predominate), about 53% of an oral dose leaves in urine, mostly as metabolites, and about 30% in feces, with a mean terminal half-life of 45 hours [1]. The rifabutin label contains no statement about vitamin D, vitamin K, folate, B12, iron or any other nutrient (read through a summarizing fetch tool) [1]. The only nutrient-adjacent text is that high-fat meals slow the rate but not the extent of absorption [1].

rifamycin antibacterial (antimycobacterial) · ATC J04AB04 (WHO ATC/DDD Index [3]) · also sold as Mycobutin [1]; Talicia (with omeprazole and amoxicillin) [2]; generic capsules · reviewed 2026-10-09. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Rifabutin in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Vitamin D (25-hydroxyvitamin D): possible faster catabolism by CYP3A induction; one osteomalacia case report, class data from rifampin only

Yellow — Low

See study details

One patient with HIV and prior vitamin D insufficiency developed worse deficiency, hypocalcaemia and an osteomalacic fracture on rifabutin; no cohort measured 25-hydroxyvitamin D in rifabutin users. Direction: depletion (functional catabolism), hypothesized.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: PubMed listing "rifabutin vitamin D" (12 records, both pages read): only [4] pairs rifabutin with vitamin D status in a patient; the rest are cell studies, reviews or a trial of ergocalciferol added to a rifabutin-substituted regimen [9] whose abstract reports no 25-hydroxyvitamin D values. PubMed listing "rifabutin 25-hydroxyvitamin D OR vitamin D deficiency rifamycin" (13 records, 10 viewed): no rifabutin cohort with 25-hydroxyvitamin D. A listing for rifabutin and osteomalacia, hypocalcemia or bone density returned unrelated records because the OR query was malformed; not repeated.
  • At-risk subgroups: Those with low baseline vitamin D (as in the case [4]), HIV, advanced disease or malabsorption; any long course such as MAC treatment. Confounding by indication is presumed: HIV and mycobacterial disease themselves lower or disturb vitamin D handling, and antiretroviral co-medication in the case is not described in the abstract.

Regulatory status

The rifabutin label read [1] contains no vitamin D, calcium or osteomalacia statement (summarizing fetch tool; the final 2,501 characters of the page were not read). It does state CYP3A induction and that rifabutin is weaker than rifampin [1].

Population evidence (Tier B)

Bolland et al., Ann Clin Microbiol Antimicrob 2008 [4]: a 59-year-old HIV-infected man with vitamin D insufficiency and secondary hyperparathyroidism before treatment; after rifabutin for recurrent Mycobacterium avium intracellulare infection his deficiency worsened, with hypocalcaemia, raised bone turnover markers and an osteomalacic vertebral fracture; high-dose cholecalciferol was needed to correct it. Read as an OpenAlex record plus a PubMed listing summary; full text and the numeric 25-hydroxyvitamin D values not opened. A further listed record (PMID 34786338, a MAC lung nodule with hypercalcemia in a patient given azithromycin, rifabutin and ethambutol) concerns a granuloma-type calcium disturbance and was not opened or used as evidence [8].

Class extrapolation (Tier C)

CLASS EXTRAPOLATION: rifampin was in these cohorts; rifabutin was NOT. Rifampicin 600 mg/day for 2 weeks lowered plasma 25-hydroxyvitamin D by about 70% in 8 healthy men [5] (abstract via OpenAlex, paraphrased). Short-term rifampin raised plasma 4beta,25-dihydroxyvitamin D3 by 60% (p < 0.01) and lowered 1,25-dihydroxyvitamin D3 by 10% (p = 0.03) in healthy volunteers, with a CYP3A4-dependent 4beta-hydroxylation pathway shown in hepatocytes [6] (abstract via OpenAlex, reconstructed). Neither study contains rifabutin. Capped at yellow.

Mechanism

Named but unproven for this drug: CYP3A induction (label [1]) increasing 25-hydroxyvitamin D 4beta-hydroxylation, shown for rifampin in [6]. Counterpoint: in PXR-humanized mice rifabutin is described as a "PXR-neutral analog of RIF" that did not potentiate cobicistat liver injury [7] (Tier B, mouse, summary of abstract only). Rifabutin therefore may induce vitamin D catabolism less than rifampin, or not through PXR, but this was not tested directly.

Why yellow, not orange

A single case report is Tier B; no Tier A rifabutin source measures a vitamin D metabolite. Near-orange: one rifabutin cohort with measured 25-hydroxyvitamin D.

Counter-evidence held on record

Counter-evidence Weaker induction (label [1]), PXR-neutral behavior in a mouse model [7], and the absence of any rifabutin cohort measurement all point to a smaller effect than the rifampin data; confounding by HIV and MAC disease is presumed for the single case. Framing caution A monitoring prompt about vitamin D turnover on long rifabutin courses, not a finding of rifabutin-caused bone disease. Do not supplement without a prescriber; no dose is given here.

Vitamin K: coagulopathy reported with rifampin; no rifabutin case or measurement found

Yellow — Low

See study details

CLASS EXTRAPOLATION: rifampin case reports describe vitamin K-responsive coagulopathy; rifabutin was not in them, and a consumer page rates rifabutin "Moderate Depletion" for vitamin K through an antibiotic gut-flora mechanism with no rifabutin source. Direction: functional depletion hypothesis.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: Vitamin K level was normal in the one class case that measured it [10]. No rifabutin study reports vitamin K, PIVKA or clotting factors.

Regulatory status

No vitamin K or coagulation statement in the rifabutin label text read [1]. The label does list thrombocytopenia (platelets <50,000/mm3 in 5% vs 4% on placebo) and one case of thrombotic thrombocytopenic purpura attributed to rifabutin in Study 023 [1]; that is a platelet outcome, not vitamin K.

Class extrapolation (Tier C)

Tiperneni et al., Eur J Case Rep Intern Med 2022 [10]: 88-year-old man with endocarditis, INR 11.6 on admission on rifampin (with cefazolin also given; Naranjo rated rifampin "probable"); vitamin K level measured on admission and reported normal; vitamin K given on admission and day 2 without INR improvement by day 3; INR 1.1 on day 4 after rifampin was withheld. Rifampin was the drug; rifabutin was NOT in the report. The authors list three possible mechanisms (vitamin K epoxide reductase inhibition, increased hepatic degradation, reduced gut-flora production). Article opened through a summarizing fetch tool.

Rifabutin-specific search

PubMed listing "rifabutin coagulopathy": 3 records, all index-tag artifacts (herbimycin and genistein cell studies), none a rifabutin coagulation report. A listing for rifabutin and vitamin K or prothrombin was rate limited and not repeated, so this is a partial search.

Mechanism

Hypothesized only. The enzyme-induction route would be weaker for rifabutin (label [1]); the gut-flora route is generic to antibacterials and is not measured in this dossier.

Why yellow, not ungraded

A circulating claim exists [11] and a class member (rifampin) has case-level data with a plausible mechanism, so ungraded and white are both excluded under the tightened boundary.

Counter-evidence held on record

Counter-evidence The consumer page rates all antibiotics together [11]; the rifampin case had co-administered cefazolin and normal measured vitamin K [10]; no rifabutin case was found. Framing caution A coagulation-monitoring prompt for people on anticoagulants or with bleeding, not a vitamin K deficiency claim. Vitamin K decisions belong to the prescriber.

High-fat food (nutrient-to-drug timing): slows absorption rate, not extent

Yellow — Low

See study details

Direction: nutrient affects drug (Hard Rule 4). High-fat meals slow the rate of rifabutin absorption without changing the extent, so this is not a depletion.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Regulatory status

"High-fat meals slow the rate without influencing the extent of absorption from the capsule dosage form"; capsules may be mixed with applesauce; 150 mg twice daily with food is an alternative for gastrointestinal intolerance [1]. Talicia is taken with food; in that product the high-fat meal changed omeprazole exposure (Cmax down 92%, AUC down 83%), which concerns omeprazole, not rifabutin [2].

Separation interval

None required by the rifabutin label text read. No mineral or antacid interaction is listed in the text read [1].

Counter-evidence held on record

Counter-evidence Extent of absorption is unchanged, so no clinically meaningful interaction is documented on the label. Framing caution Timing advice for the drug, not a nutrient deficiency or a supplement recommendation.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden: reactive-oxygen generation by sub-mitochondrial particles with rifabutin in vitro; class cell data; no human measurement

Yellow — Low

See study details

In a rat study, sub-mitochondrial particles generated hydroxyl radicals with NADH and rifabutin in the presence of iron; rifampicin lowers mitochondrial membrane potential and respiratory complex activity in cultured liver cells. No human or in vivo mitochondrial measurement was found for rifabutin.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • At-risk subgroups: None identified in human data.

Regulatory status

No mitochondrial statement in the label text read [1].

Drug-specific evidence (Tier B)

Rao and Cederbaum, Free Radic Biol Med 1997 [13]: rat liver microsomes and sub-mitochondrial particles; rifabutin (a quinonimine) redox cycles and, with added iron, generates hydroxyl radicals detected by DMPO spin trapping; with sub-mitochondrial particles NADH plus either drug produced the signal. Rifamycin S cycled about five times more efficiently than rifabutin. Abstract read through a PubMed listing page summarized by a fetch tool; full text not opened.

Class extrapolation (Tier C)

CLASS EXTRAPOLATION: rifampicin, isoniazid and pyrazinamide were in the HepG2 study [12]; rifabutin was NOT. Rifampicin lowered ATP dose-dependently at 4, 24 and 48 hours, reduced mitochondrial membrane potential and complex I and III activity at 24 hours (24-hour IC50 about 0.5 mM for rifampicin), and the authors suggest mitophagy. Repository page opened through a summarizing fetch tool; ROS not reported on the page.

Rifabutin-specific search

PubMed listing "rifabutin mitochondria" (14 hits, 10 viewed): none studies rifabutin for mitochondrial function; most are index-tag artifacts. One 1972 study found isolated rat liver mitochondrial RNA synthesis insensitive to rifampicin and rifamycin SV.

Mechanism

Named for the in vitro finding: quinonimine redox cycling with mitochondrial NADH dehydrogenase. Relevance to therapeutic exposure is not established.

Why yellow

Tier B drug-specific chemistry plus Tier C class data; no human or in vivo measurement.

Counter-evidence held on record

Counter-evidence The same rat study found that redox cycling caused no microsomal lipid peroxidation [13]; concentrations in the class cell study are in the millimolar range [12]; label hepatic enzyme elevations were not higher than placebo (SGOT >150 U/L 7% vs 12%; SGPT 9% vs 11%) [1]. Framing caution A mechanistic context flag. It does not show reduced mitochondrial function in people and does not support taking any supplement.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress: in vitro redox cycling with mixed pro-oxidant and antioxidant findings; no human marker

Yellow — Low

See study details

Rifabutin redox cycles to superoxide and hydrogen peroxide in rat liver microsomes and forms hydroxyl radicals with iron, yet it completely inhibited iron-ATP-induced lipid peroxidation in the same study. Direction: mixed/reverse, in vitro only.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Regulatory status

No oxidative stress or antioxidant statement in the label text read [1].

Drug-specific evidence (Tier B)

Rao and Cederbaum 1997 [13]: with NADPH or NADH, reduced rifabutin reoxidizes in air to superoxide and hydrogen peroxide; with iron and the Fenton reaction, hydroxyl radicals (DMPO-OH adduct about one fifth of that from rifamycin S); NADH was more effective than NADPH for rifabutin; redox cycling did not cause microsomal lipid peroxidation; both drugs completely inhibited Fe:ATP-induced lipid peroxidation. The authors speculate about a link to hepatotoxicity, which is a hypothesis.

Rifabutin-specific search

PubMed listing "rifabutin oxidative stress" (17 hits, 10 viewed): no record measures oxidative stress markers, ROS or antioxidant capacity in rifabutin-treated humans or animals; rifabutin appears as an antibiotic comparator in Mycobacterium abscessus stress-response papers and as index tags. No human MDA, glutathione or antioxidant-enzyme study with rifabutin was found. No class (rifampin) oxidative marker study was opened in this review.

Mechanism

Named: one-electron reduction of the quinonimine ring and redox cycling (in vitro).

Why yellow

Tier B only, direction conflicting between radical generation and protection from lipid peroxidation.

Counter-evidence held on record

Counter-evidence The study itself reports inhibition of lipid peroxidation by rifabutin [13]; microsomes are an acellular model; hepatic enzyme elevations were not higher than placebo on the label [1]. Framing caution Not evidence of oxidative damage or antioxidant depletion in people; do not read as a reason to take antioxidants.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Iron (status, absorption, stores)

Not graded — disclosed evidence gap

See study details

No evidence was found that rifabutin changes iron status, and no consumer list opened claims it does.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C evidence on iron status or handling for rifabutin, and no circulating claim to rebut. Mixed result: a genuine gap in the literature found, with tooling limits on further phrasings (repeated HTTP 429). Hematologic outcomes are covered in the Oxygen delivery entry and are not iron deficiency (Hard Rule 2).

What was searched

PubMed listing "rifabutin iron" (14 hits, 10 viewed): records on iron-limited culture media and Acinetobacter uptake, H. pylori eradication reviews that mention iron deficiency anemia as an indication, and one rat microsome study of rifabutin redox cycling with iron [13]. That study shows iron-dependent hydroxyl radical generation in a model and no Fe(II) complex with rifabutin; it does not test iron status, absorption or stores and is housed in the oxidative stress entry. PubMed "rifabutin ferritin" returned a fetch error; "rifabutin hemoglobin" and the label [1] show no iron effect (iron appears in the label only as red iron oxide colorant). Consumer checker page for rifabutin [11] lists seven nutrients, none iron.

Channel outcomes

Label via DailyMed (summarizing fetch tool); PubMed listings (spaced, partly rate limited); OpenAlex single record; consumer checker. WebSearch: no budget. Europe PMC, Semantic Scholar, Crossref (rate limited; irrelevant results): not productive.

Copper

Not graded — disclosed evidence gap

See study details

No evidence was found that rifabutin changes copper status, and no consumer list opened claims it does.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C evidence and no circulating claim. A disclosed evidence gap, not a finding of safety.

What was searched

PubMed listing "rifabutin copper" (4 records): a triclosan-Mannich synthesis paper using copper acetate as a reagent with rifabutin as a comparator, a kendomycin chelation study (rifabutin as an index tag only), a mis-indexed Hsp90 imaging paper, and a Mycobacterium species description measuring copper in lake water. None measures copper, ceruloplasmin or trace elements in rifabutin exposure. Consumer checker page for rifabutin [11]: no copper entry. Label [1]: no copper statement.

Channel outcomes

PubMed listing opened once; consumer checker opened; label read via summarizing fetch tool. WebSearch: no budget. Other databases blocked by network policy. Genuine gap for the phrasings tried; a "rifabutin zinc OR trace element serum" phrasing was not run (tooling-limited).

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk: C. difficile warning and case letters; no rifabutin microbiota measurement

Yellow — Low

See study details

The label carries the class C. difficile warning, two 1994 case letters link rifabutin to C. difficile diarrhea in AIDS patients, and rifamycin cohort data (rifampin, rifapentine) show composition change; no study sequenced stool in rifabutin users. Direction: disturbance (composition), not nutrient depletion.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Regulatory status

Mycobutin label: "Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents" [1]. Talicia label: antibacterial treatment "alters the normal flora of the colon leading to overgrowth of C. difficile," and CDAD may occur over two months after therapy [2]. About 30% of a dose is excreted in feces [1].

Population evidence (Tier A, Talicia trials)

Study 1 (active comparator amoxicillin plus omeprazole, so the arms differ by rifabutin): diarrhea 23/228 (10.1%) with Talicia vs 18/227 (7.9%); relative risk about 1.27 (95% CI about 0.71 to 2.29, computed here from the label counts). Study 2 (placebo): 11/77 (14.3%) vs 4/41 (9.8%) [2]. Regimen was 14 days. Diarrhea is a clinical outcome, not a microbiome measurement; read through a summarizing fetch tool.

Case evidence (Tier B, not opened)

Two Lancet 1994 letters, "Clostridium difficile diarrhoea and rifabutin" (PMID 7908385) and "Diarrhoea associated with Clostridium difficile in AIDS patients receiving rifabutin" (PMID 7905569), seen only as PubMed-listing records with no abstract; counts unknown [19].

Class extrapolation (Tier C)

CLASS EXTRAPOLATION: rifampin and rifapentine were in the cohort; rifabutin was NOT. Prospective cohort, Sci Rep 2023 [14]: 4 on daily rifampin for 4 months, 2 on weekly isoniazid plus rifapentine, 6 healthy controls, 16S sequencing; preventive therapy explained 17.0% of weighted UniFrac variance (PERMANOVA p = 0.001), alpha diversity fell but not significantly, and recovery 2 months after therapy was incomplete. Page opened through a summarizing fetch tool; the rifampin subgroup is inferred by subtraction.

Rifabutin-specific searches

PubMed listing "rifabutin Helicobacter pylori microbiome" (4 records) and "rifabutin microbiota" (4 records): registry, resistance and review papers; none reports microbiome composition after a rifabutin-based H. pylori regimen. "rifabutin Clostridioides difficile" (4 records): the two letters above, a 2008 rifamycin review that covers rifampin, rifaximin and rifalazil but not rifabutin, and a laboratory paper. One in vitro record shows a Bifidobacterium longum strain inhibited by rifabutin only at 512 ug/mL [20].

Mechanism

Antibacterial exposure of gut flora via fecal excretion and biliary or direct contact; unmeasured for rifabutin.

Why yellow, not orange

No Tier A source measures microbiome composition with rifabutin; the diarrhea difference is not significant by the computed interval.

Counter-evidence held on record

Counter-evidence The Talicia diarrhea difference includes a confidence interval spanning no effect, and a PPI plus amoxicillin background affects the gut itself; the class cohort has 4 rifampin participants and no rifabutin. Framing caution A disturbance risk (composition, C. difficile), not a nutrient deficiency; it does not imply taking probiotics or supplements.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization: rare labeled hemolysis; no excess anemia versus placebo; an adverse reaction, not a nutrient deficiency

Yellow — Low

See study details

The label lists hemolysis (<1%) as a likely rifabutin-caused event, but controlled data show no excess anemia and a prophylaxis trial found rifabutin delayed hemoglobin decline. Direction: neutral to reverse for population hemoglobin; rare idiosyncratic hemolysis.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Regulatory status

Label: rifabutin "appears to be a likely cause" of flu-like syndrome, hepatitis, hemolysis, arthralgia and myositis in under 1% of treated patients; anemia 1% vs 2% placebo (Table 3); hemoglobin <8.0 g/dL in 6% vs 7% (Table 4) [1].

Population evidence (Tier A)

Two randomized, double-blind trials of daily 300 mg rifabutin vs placebo in patients with AIDS and CD4 of 200 or less (n = 590 and 556): rifabutin significantly delayed a decline in hemoglobin of more than 10% (group rates not in the abstract); MAC bacteremia 8% vs 17% and 9% vs 18% [15]. The delay is best read as a disease-control effect (less MAC infection), not a pharmacologic effect on red cells. Abstract via OpenAlex, reconstructed.

Rifabutin-specific search

PubMed listing "rifabutin hemoglobin" (7 records): only [15] has rifabutin hemoglobin data. A listing for "rifabutin hemolytic anemia" was rate limited and not retrieved; the "rifabutin anemia" listing was also blocked, so the hemolysis case literature was not searched (tooling-limited).

Mechanism

Hemolysis, where it occurs, is an adverse reaction; no oxygen-carrying capacity or tissue oxygen measurement exists for rifabutin. Neutropenia and thrombocytopenia are separate hematologic outcomes in the Monitoring panel.

Why yellow

Tier A label statement of a rare event, contradicted at population level by controlled data; no oxygen delivery measure. Hard Rule 2: anemia or hemolysis is not iron deficiency and is not an oxygen-delivery nutrient finding.

Counter-evidence held on record

Counter-evidence Placebo-controlled anemia and hemoglobin rates were similar or lower with rifabutin [1][15]; HIV disease confounds hemoglobin. Framing caution An adverse-reaction note, not a deficiency claim; no iron or other supplement is implied.

ATP production: class extrapolation from rifampicin HepG2 data; rifabutin not tested

Yellow — Low

See study details

CLASS EXTRAPOLATION: rifampicin lowered cellular ATP dose-dependently in HepG2 cells; rifabutin was NOT tested, and no rifabutin ATP measurement exists.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Class extrapolation (Tier C)

Elmorsy et al., Hum Exp Toxicol 2016 [12]: rifampicin, isoniazid and pyrazinamide (alone and combined) decreased ATP in HepG2 cells in a dose- and time-dependent manner, with lower membrane potential and complex I and III activity; rifabutin was NOT among the drugs tested. Page opened through a summarizing fetch tool.

Drug-specific evidence

Rao and Cederbaum [13] did not report ATP or oxygen consumption (abstract). PubMed "rifabutin mitochondria" listing found no ATP data.

Mechanism

Plausible by the quinonimine redox cycling in the mitochondrial entry [13]; unmeasured.

Why yellow

At least one class member has real in vitro data and a mechanism is plausible; the tightened boundary excludes white and ungraded.

Counter-evidence held on record

Counter-evidence Millimolar concentrations in the class study [12]; the label shows no excess hepatic enzyme elevation versus placebo [1]. Framing caution An in vitro class signal, not a finding of low energy or fatigue in people. Rifabutin prophylaxis delayed fatigue in AIDS patients in the NEJM trials [15], a disease-control effect.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Biotin, riboflavin, thiamine and vitamin B6 "depleted by reduced gut bacteria"

    Where it comes from: Tier D consumer checker page for rifabutin, rating each "Insignificant Depletion" under the generic class "Antibiotic Drugs" [11].

    Why it fails: The page gives no rifabutin source and itself rates the effect insignificant. No opened study measured any of these vitamins in rifabutin users. The label is silent [1]. The Talicia riboflavin mention is a dosing choice to mask urine color in Study 1, not a depletion finding [2].

  • Folic acid and vitamin B12 depletion

    Where it comes from: Same checker page [11] ("Insignificant Depletion"; gut flora and enterohepatic recirculation mechanism).

    Why it fails: PubMed listing "rifabutin folate" (5 records) contains no folate, B12 or assay study with rifabutin (index tags, MAC reviews and an in vitro screen). The rifabutin label text read has no folate or B12 statement [1]. Hard Rule 2: no deficiency is established.

  • "Antibiotics destroy vitamin K-producing gut bacteria, giving Moderate vitamin K depletion on courses of 10 days or more"

    Where it comes from: Same checker page [11].

    Why it fails: Carried as a yellow class-extrapolation entry above, not as an established depletion: the only coagulopathy reports opened involve rifampin, one with a normal measured vitamin K [10], and no rifabutin case was found. The strength word "Moderate" and the duration cutoff have no rifabutin support.

How the body handles this medication

Metabolism and enzymes
Five metabolites are listed; 25-O-desacetyl (activity equal to parent, up to 10% of total antimicrobial activity) and 31-hydroxy predominate. Multiple dosing induces hepatic CYP3A enzymes; the label calls rifabutin a CYP3A inducer and "a weaker enzyme inducer than rifampin." No other CYP isoform is named as induced in the text read. Talicia label: rifabutin is a substrate and inducer of CYP3A.[1] Mycobutin (Greenstone/Mylan) label rev. 06/2026; [2] Talicia label
Elimination
53% of an oral dose appears in urine, primarily as metabolites; about 30% in feces. Renal and biliary clearance of unchanged drug each contribute about 5% of apparent clearance. Mean terminal half-life 45 hours (SD 17; range 16 to 69) in the Mycobutin label; the Talicia label gives a mean of 34 hours (SD 25).[1][2]
Absorption and food
Readily absorbed; Tmax about 3.3 hours; absolute bioavailability averaged 20% in five HIV-positive patients; capsule 85% relative to oral solution. "High-fat meals slow the rate without influencing the extent of absorption." Capsules may be mixed with applesauce. No named absorption transporter is given in the text read.[1]
Distribution
High propensity for intracellular tissue uptake; about 85% protein bound, not influenced by renal or hepatic dysfunction.[1][2]
Renal and hepatic impairment
AUC rose about 71% in severe renal impairment and about 41% at creatinine clearance 30 to 61 mL/min; the label advises a 50% dose reduction for creatinine clearance below 30 mL/min if toxicity is suspected. Mild hepatic impairment needs no change; pharmacokinetics in moderate and severe hepatic impairment are not known.[1]
Label statements touching nutrients
None for vitamins, minerals, folate, B12, vitamin D or vitamin K in the text read. Iron appears only as "red iron oxide," an inactive colorant. Brown-orange discoloration of urine, feces, saliva, sputum, perspiration, tears and skin is listed. Talicia: riboflavin was given in Study 1 only to prevent unblinding by urine color, and the product contains omeprazole magnesium (omeprazole can cause hypomagnesemia, an omeprazole label item, not attributed to rifabutin).[1][2] (both read through a summarizing fetch tool; paraphrased; tails of each page unread)

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

  • Outcome / lab

    Complete blood count with differential

    Neutropenia was more frequent than placebo on the label (25% vs 20%, p = 0.03; grade 3/4 criteria ANC below 750/mm3), and thrombocytopenia is rare (5% vs 4%; one TTP case) [1]. Small studies report grade 3 or 4 neutropenia in children on rifabutin with lopinavir/ritonavir (1 of 48 and 5 events in 15 children) and 13% neutropenia in a rifabutin-containing H. pylori rescue arm of a 360-patient trial (listing abstracts only) [16]. Label: consider periodic hematologic studies [1]. These are drug adverse reactions, not nutrient findings.

  • Outcome / symptoms

    Eyes: uveitis

    Uveitis is infrequent at 300 mg/day alone, and more frequent at higher doses combined with macrolides or fluconazole, or with raised rifabutin levels [1]. A case-control analysis reported incidence of 14%, 45% and 64% by body weight (above 65 kg, 55 to 65 kg, below 55 kg) at 600 mg daily with clarithromycin and ethambutol, falling at 300 mg daily [17] (listing abstract). Not a nutrient issue.

  • Outcome / lab

    Liver tests

    Label: jaundice and hepatitis under 1%; SGOT above 150 U/L in 7% vs 12% placebo and SGPT in 9% vs 11% [1]. A 2000 mouse report describes mild liver toxicity [18]. Hepatic effects are drug toxicity, not deficiency.

  • Lab / long courses

    25-hydroxyvitamin D, calcium, PTH

    A reasonable prompt only for long rifabutin courses in people with low sun exposure, HIV, malabsorption, or bone pain or low calcium, given one osteomalacia case [4] and rifampin class data [5][6]. A monitoring prompt, not a finding of rifabutin-caused bone disease.

  • Symptoms

    Diarrhea

    Persistent or severe diarrhea during or up to two months after therapy warrants evaluation for C. difficile [1][2].

  • Timing / interactions

    Meals, supplements and drug interactions

    Food slows absorption rate only [1]; no vitamin or mineral separation interval is listed in the label text read. Rifabutin induces CYP3A, and the label contraindicates voriconazole, delavirdine and cabotegravir/rilpivirine long-acting injection [1]. No supplement dose appears anywhere in this dossier, so no upper-limit check was needed.

  • Special populations

    Renal impairment, pregnancy, children

    AUC rises about 71% in severe renal impairment; the label allows a 50% dose reduction below creatinine clearance 30 mL/min if toxicity is suspected [1]. Pregnancy: use only if benefit justifies risk [1]. Pharmacokinetics under age 18 were not studied in the label; small pediatric tuberculosis and HIV cohorts exist [16].

  • Not a nutrient

    Discoloration

    Brown-orange discoloration of urine, feces, saliva, sputum, sweat, tears and skin is a pigment effect (urine discoloration 30% vs 6%), and soft contact lenses may be permanently stained [1]. Not blood or iron loss.

Overlap map, to prevent double counting

  • Mitochondrial burden

    Shares evidence with: Oxidative stress; ATP production; Iron (ungraded)

    Note: The rat microsome and sub-mitochondrial study [13] supports the mitochondrial and oxidative stress entries and is the only iron-related source. The HepG2 rifampicin study [12] supports mitochondrial burden and ATP production. One body of in vitro evidence viewed several times, not independent confirmation.

  • Oxidative stress

    Shares evidence with: Mitochondrial burden; Iron (ungraded)

    Note: Same [13]; the iron chemistry appears only here and is not an iron status finding.

  • ATP production

    Shares evidence with: Mitochondrial burden

    Note: [12] is the only ATP measurement and it is class evidence (rifampicin). Listed separately per the series rule.

  • Vitamin D

    Shares evidence with: Vitamin K

    Note: Both invoke hepatic enzyme induction, which is weaker for rifabutin [1]. The evidence is separate: vitamin D rests on a rifabutin case [4] and rifampin metabolite studies [5][6]; vitamin K rests on a rifampin case [10]. Not mutual confirmation.

  • Gut microbiome risk

    Shares evidence with: Vitamin K; Fails verification: B vitamins

    Note: The gut-flora hypothesis in the vitamin K entry and the checker claims [11] assume a microbiome mechanism that the microbiome entry (composition and C. difficile) does not test.

  • Oxygen delivery/utilization

    Shares evidence with: ATP production (fatigue note)

    Note: The NEJM prophylaxis trials [15] inform both only as disease-control outcomes (hemoglobin decline, fatigue). Two independent entries per the series rule.

  • Iron

    Shares evidence with: Copper

    Note: Both ungraded after the same no-signal searches; kept as separate entries per Hard Rule 7.

All references used above
  1. Mycobutin (rifabutin) capsules, prescribing information, Greenstone brand packaged by Mylan Pharmaceuticals; label revised 06/2026 (LAB-0721-9.0). — Regulatory label (Tier A). Read through a summarizing fetch tool (paraphrase, not verbatim) in two passes; the final 2,501 characters of the 102,501-character page were not read. Source of CYP3A induction and "weaker than rifampin" statement, pharmacokinetics, adverse-reaction tables, contraindications, and the absence of nutrient statements.
  2. Talicia (omeprazole magnesium, amoxicillin and rifabutin) delayed-release capsules, prescribing information, RedHill Biopharma. — Regulatory label (Tier A). Read through a summarizing fetch tool; the final 10,524 characters of the page were not read, so the clinical studies section and neutropenia frequencies were not seen. Source of the diarrhea counts in Studies 1 and 2, C. difficile text and the riboflavin and omeprazole magnesium notes.
  3. WHO Collaborating Centre, ATC/DDD Index: J04AB04 rifabutin. — Reference index. Page lists rifabutin, DDD 0.15 g oral, under J04AB antibiotics for tuberculosis.
  4. Bolland MJ, Grey AB, Horne AM, Thomas M. Osteomalacia in an HIV-infected man receiving rifabutin, a cytochrome P450 enzyme inducer: a case report. Ann Clin Microbiol Antimicrob 2008;7:3. — Tier B case report, 1 patient. PMID 18226256; DOI 10.1186/1476-0711-7-3. Abstract read through an OpenAlex record (paraphrased by the fetch tool) plus a PubMed listing summary; full text and numeric laboratory values not opened. A direct PubMed single-record fetch was blocked by a rate limit.
  5. Brodie MJ, Boobis AR, Dollery CT, et al. Rifampicin and vitamin D metabolism. Clin Pharmacol Ther 1980;27(6):810-4. — Tier C for rifabutin (rifampicin in the cohort; rifabutin NOT). 8 healthy men, rifampicin 600 mg/day for 2 weeks. PMID 7379450; DOI 10.1038/clpt.1980.115. Abstract via OpenAlex, paraphrased; full text not opened.CLASS EXTRAPOLATION: rifabutin was not in the cohort.
  6. Wang Z, Lin YS, Dickmann LJ, et al. Enhancement of hepatic 4-hydroxylation of 25-hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo: implications for drug-induced osteomalacia. J Bone Miner Res 2013;28(5):1101-16. — Tier C for rifabutin (rifampin among inducers; rifabutin NOT tested). Human hepatocytes and healthy volunteers on short-term rifampin. PMID 23212742. Abstract via OpenAlex, reconstructed; full text not opened.CLASS EXTRAPOLATION: rifabutin was not in the cohort.
  7. Shehu AI, Zhu J, Li J, et al. Targeting xenobiotic nuclear receptors PXR and CAR to prevent cobicistat hepatotoxicity. Toxicol Sci 2021;181(1):58-67. — Tier B (PXR-humanized mice). The rifabutin statement ("PXR-neutral analog of RIF") is a description in the OpenAlex summary of the abstract; the full paper was not opened and the assertion was not verified against its data. PMID 33629115; DOI 10.1093/toxsci/kfab023.
  8. PubMed listing "rifabutin vitamin D" (12 records; pages 1 and 2 read). Includes PMID 34786338 (MAC hypercalcemia case, IDCases 2021). — Seen only as PubMed-listing summaries; the records other than [4] are not opened. 13-record listing "rifabutin 25-hydroxyvitamin D OR vitamin D deficiency rifamycin" also viewed (10 shown).Listing summaries only; not opened.
  9. Wallis RS, Ginindza S, Beattie T, et al. Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial. Lancet Respir Med 2021;9(8):897-908. — Tier A trial with rifabutin in the background regimen (200 randomized, about 40 per arm, rifabutin substituted for rifampicin for 180 days). PMID 33740465; DOI 10.1016/s2213-2600(20)30448-3. Abstract via OpenAlex, reconstructed; no 25-hydroxyvitamin D results appear in the abstract. Used only to document that a candidate cohort exists.Vitamin D levels not reported in the abstract; full text and supplement not opened.
  10. Tiperneni R, Khalid F, Fichadiya H, Al-Alwan A, Mohan G, Heis F. Deranged haemostasis: rifampin-induced coagulopathy. Eur J Case Rep Intern Med 2022;9. DOI 10.12890/2022_003380. — Tier C for rifabutin (rifampin case report; rifabutin NOT). 88-year-old, INR 11.6, vitamin K level normal. Opened through a summarizing fetch tool.CLASS EXTRAPOLATION: rifabutin was not in the report.
  11. HelloPharmacist nutrient depletion checker, rifabutin page. — Tier D. Lists biotin, folic acid, riboflavin, thiamine, B12, B6 as "Insignificant Depletion" and vitamin K as "Moderate Depletion" under the class "Antibiotic Drugs." Claim origin only; not evidence.Tier D; not used as evidence.
  12. Elmorsy E, Attalla SM, Fikry E, et al. Adverse effects of anti-tuberculosis drugs on HepG2 cell bioenergetics. Hum Exp Toxicol 2016. — Tier C for rifabutin (rifampicin, isoniazid, pyrazinamide tested; rifabutin NOT). HepG2 cells. Repository page opened through a summarizing fetch tool; listed as in press (online July 2016).CLASS EXTRAPOLATION: rifabutin was not tested.
  13. Rao DN, Cederbaum AI. A comparative study of the redox-cycling of a quinone (rifamycin S) and a quinonimine (rifabutin) antibiotic by rat liver microsomes. Free Radic Biol Med 1997;22(3):439-46. — Tier B (rat liver microsomes and sub-mitochondrial particles; rifabutin tested). PMID 8981035; DOI 10.1016/s0891-5849(96)00335-8. Abstract read through a PubMed listing page summarized by a fetch tool (the OpenAlex record has no abstract); full text not opened.
  14. Seraphin MN, Bellot J, Klann E, et al. Gut microbiota composition and diversity before, during, and two months after rifamycin-based tuberculosis preventive therapy. Sci Rep 2023;13:18933. — Tier C for rifabutin (4 on rifampin, 2 on rifapentine plus isoniazid, 6 controls; rifabutin NOT in the text read). Page opened through a summarizing fetch tool; the rifampin subgroup size is inferred by subtraction.CLASS EXTRAPOLATION: rifabutin was not in the cohort.
  15. Nightingale SD, Cameron DW, Gordin FM, et al. Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS. N Engl J Med 1993;329(12):828-33. — Tier A (two randomized, double-blind trials, 590 and 556 patients, rifabutin 300 mg/day vs placebo). PMID 8179648; DOI 10.1056/NEJM199309163291202. Abstract via OpenAlex, reconstructed; neutropenia, uveitis and group hemoglobin rates not in the abstract.
  16. PubMed listing "rifabutin neutropenia" (36 hits, 10 viewed), including PMID 31139825 (48 children; 1 case of grade 3 neutropenia), PMID 33294914 (15 children; grade 3 in 4, grade 4 in 1) and PMID 41732217 (360-patient H. pylori rescue trial; neutropenia 16 [13%] in the rifabutin arm). — Seen only as listing-page abstract summaries; the records are not opened. Used for the Monitoring panel only.Listing summaries only; not opened.
  17. PubMed listing "rifabutin uveitis incidence" (10 records), including PMID 9419201 (J Infect Dis 1998, determinants of rifabutin-associated uveitis, multivariate analysis). — Seen only as listing-page abstract summaries; not opened. Incidence by body weight is as summarized by the fetch tool.Listing summaries only; not opened.
  18. PubMed listing "rifabutin hepatotoxicity" (25 hits, 10 viewed), including PMID 32479032 (NIEHS technical report, mouse zidovudine and rifabutin combinations, 2000). — Seen only as a listing-page summary; not opened. Qualitative mild liver toxicity in mice; no values.Listing summaries only; not opened.
  19. PubMed listing "rifabutin Clostridioides difficile" (4 records), including Lancet 1994 letters PMID 7908385 and PMID 7905569. — Letters without abstracts in the listing; counts unknown. Not opened.Listing summaries only; not opened.
  20. PubMed null-result listings run for this review: "rifabutin Helicobacter pylori microbiome" (4), "rifabutin microbiota" (4), "rifabutin mitochondria" (14 hits, 10 viewed), "rifabutin oxidative stress" (17 hits, 10 viewed), "rifabutin iron" (14 hits, 10 viewed), "rifabutin copper" (4), "rifabutin folate" (5), "rifabutin hemoglobin" (7), "rifabutin coagulopathy" (3). — Listing-page summaries only; no listed record was opened except where cited separately above. The Bifidobacterium longum W11 in vitro record (PMID 27741162) is from the microbiota listing.Listing summaries only; not opened.