Dicloxacillin

beta-lactamase resistant penicillin (isoxazolyl penicillin; beta-lactam antibacterial)

Also sold as Diclocil.

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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.

Dicloxacillin has little classical depletion machinery but one pharmacologic signal that is unusual for a penicillin. It is a rapidly absorbed, mostly renally excreted, 97.9% albumin-bound drug with a half-life near 0.7 hour, partly inactivated in the liver and excreted in bile, and the label names no CYP substrate role [1]. It is, however, an enzyme inducer: the label says it "may reduce the anticoagulant response to dicumarol and warfarin" through "hepatic enzyme induction," and a 2023 Danish register study (1,023 dicloxacillin users) found INR fell by 0.65 to 0.76 with over 90% of long-term users below INR 2, while a 2026 healthy-volunteer study showed warfarin clearance up 53 to 63% and phenytoin clearance up 42% with pregnane X receptor activation [1][8][9]. That is a drug-to-drug effect running opposite to the vitamin K depletion story told about antibiotics, so it is a yellow context flag and the vitamin K claim is rebutted in Fails verification.

beta-lactamase resistant penicillin (isoxazolyl penicillin; beta-lactam antibacterial) · ATC J01CF01 (WHO ATC/DDD Index [2]) · also sold as Diclocil (outside the US and per Wikipedia [3]); many US generic capsules [1] · 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 Dicloxacillin 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

Potassium: renal potassium loss with high-dose intravenous isoxazolyl penicillins; one dicloxacillin case, all cohorts are flucloxacillin (CLASS EXTRAPOLATION)

Yellow — Low

See study details

One older man developed severe hypokalaemia on intravenous dicloxacillin (case report, 2002); every cohort-level incidence figure (23.7% of 835 patients; 42% versus 14% against ceftriaxone) comes from flucloxacillin, a different drug.

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

At-risk subgroups: From the flucloxacillin cohort [17]: older age, female sex above 8 g per day, lower body weight, lower baseline potassium, concomitant antibiotics and longer treatment. The exposure in those cohorts (above 8 g per day intravenously) is roughly eight times or more the label oral maximum of 1 g per day, so those risks should not be transferred to oral use.

Direction

Disturbance of circulating potassium through renal loss (depletion of serum potassium by the drug, not a dietary shortfall). The dicloxacillin product is also a sodium salt, an excess-direction sodium load. Neither implies that potassium intake should be raised (Hard Rule 5).

Regulatory status

The label read describes a monosodium salt and gives no sodium content, no potassium statement and no hypokalemia warning; its adverse reactions note neurologic effects "with large intravenous doses of the penicillinase-resistant penicillins" [1]. Adult oral label dosing is 125 mg to 250 mg every 6 hours, which is 0.5 g to 1 g per day [1]. The intravenous use in the case report is outside the oral label read.

Population evidence

Dicloxacillin: Intern Med J 2002 [15], "Severe hypokalaemia secondary to dicloxacillin", case report, n = 1, male, intravenous (Johnson, Kay and Hawley, Princess Alexandra Hospital, Brisbane; a letter with no abstract. The PubMed single record and the OpenAlex record were opened on 2026-10-10: MeSH terms give intravenous dicloxacillin, an aged male patient, a staphylococcal infection and severity-of-illness monitoring, but neither record carries a dose, potassium nadir or course, and the journal text was not opened). Tier B. Flucloxacillin (not dicloxacillin): Br J Clin Pharmacol 2022 [17], retrospective single-centre cohort, 835 adults on intravenous flucloxacillin for more than 24 hours with baseline potassium of at least 3.5 mmol/L: hypokalaemia in 23.7% (28.4% of women, 20.4% of men); women above 8 g per 24 hours had odds 4.41 times those of men (95% CI 1.47 to 13.24). Br J Clin Pharmacol 2019 [16], 77 flucloxacillin versus 84 ceftriaxone patients: 42% versus 14% (p below 0.0001). A 2024 narrative review [18] states incidence "may be as high as 40%" for beta-lactam associated hypokalaemia and names flucloxacillin, ticarcillin and azlocillin; its abstract does not name dicloxacillin. Abstracts only, read through OpenAlex reconstructions summarized by a fetch tool.

Mechanism

Proposed, not shown for dicloxacillin: a non-reabsorbable penicillin anion delivered to the distal nephron promotes renal potassium excretion; the 2019 authors describe flucloxacillin as a "non-reabsorbable anion" [16]. Dicloxacillin is an isoxazolyl penicillin of the same class and is given as a sodium salt [1], so the mechanism is plausible but untested for it.

Cohort test

CLASS EXTRAPOLATION. Dicloxacillin was not in any of the flucloxacillin cohorts [16][17] or the review abstract [18]. Dicloxacillin appears only in one case report. The grade is capped at yellow (Hard Rule 6).

Counter-evidence held on record

Counter-evidence on record PubMed "dicloxacillin AND (hypokalemia OR hypokalaemia OR potassium)" (17 results, 10 read) returned the one case above and no cohort, trial or series [15]. The pediatric azithromycin safety analysis with dicloxacillin or flucloxacillin comparators (PMID 8396082, listing line only, not opened) reported potassium abnormalities for the azithromycin arm and does not isolate dicloxacillin. Hypokalaemia is not a label warning for dicloxacillin [1]. Repair re-check (2026-10-10): a 2020 Dutch pharmacovigilance signal on flucloxacillin hypokalaemia (10 reports, 7 analysed) calls the effect a class effect of penicillinase-resistant penicillins and cites the dicloxacillin case [15] as its only dicloxacillin item, so it is not an independent dicloxacillin source [40]. A 2009 conference abstract of one flucloxacillin patient with severe hypokalaemia and hypomagnesaemia says a literature review found dicloxacillin reported to cause hypokalaemia, again without new data [39]. A 2023 Indian cross-sectional study of 60 hypokalaemia reactions lists dicloxacillin among known causes in its introduction only, and its own cases do not name it [41]. No second dicloxacillin report, cohort or series was found, so the entry stays yellow. Framing caution for the consumer surface This is a renal-loss disturbance linked mainly to very high intravenous doses of a related drug. It is not a reason to take potassium, and the dicloxacillin evidence is a single case.

PubMed search log (listing level, all queries run 2026-10-09 through the proxy): "dicloxacillin" (992 results, first 18 lines seen); "dicloxacillin warfarin" (17); "dicloxacillin AND (hypokalemia OR hypokalaemia OR potassium)" (17, 10 read); "dicloxacillin pyroglutamic" (1); "dicloxacillin microbiota" (5); "dicloxacillin Escherichia coli mice" (6); "dicloxacillin hemolysis" (3); "dicloxacillin vitamin" (4); "dicloxacillin iron" (4); "dicloxacillin copper" (3); "dicloxacillin glutathione" (1); "dicloxacillin ATP" (7); "dicloxacillin oxidative stress" (2); "dicloxacillin carnitine" (0); "dicloxacillin mitochondria" (0); "dicloxacillin hypophosphatemia" (0); "flucloxacillin hypophosphatemia" and "flucloxacillin hypophosphataemia" (0); "flucloxacillin hypokalaemia" (9). — Search results only (titles and one-line summaries from a summarizing fetch tool). The 992-result listing also contained items that the tool marked as paraphrased (for example a 2026 Lancet Microbe item and a PBPK transporter paper); none was opened or used. Records seen only in listings and not opened include PMID 8396082 (azithromycin pediatric safety, dicloxacillin or flucloxacillin comparators), PMID 41630535 and PMID 41278897 (hepatic transporter inhibition by dicloxacillin and flucloxacillin).Listing level only.

Warfarin and other vitamin K antagonists: dicloxacillin lowers INR by enzyme induction (drug-to-drug, reverse direction; not a vitamin K status finding)

Yellow — Low

See study details

In warfarin users, dicloxacillin lowers INR and raises stroke risk because it induces CYP-mediated warfarin clearance; the measured quantities are INR and drug clearance, not vitamin K, so this is a context flag and not a nutrient depletion.

Full detail and limits

Direction

Reverse of the vitamin K depletion route proposed for antibiotics: INR falls. The interaction runs drug to drug (dicloxacillin to warfarin clearance). It is not a depletion of vitamin K and not a vitamin K to drug interaction (Hard Rules 2 and 4).

Regulatory status

Label: "Dicloxacillin may reduce the anticoagulant response to dicumarol and warfarin" and the effect "may be due to hepatic enzyme induction" [1].

Population evidence

Danish register study [8] (Tier A, warfarin users; dicloxacillin n = 1,023, flucloxacillin n = 123): INR fell by 0.65 (95% CI 0.57 to 0.74) with short-term and 0.76 (95% CI 0.50 to 1.02) with long-term dicloxacillin, over 90% of long-term users fell below INR 2, and flucloxacillin lowered INR by 0.37 (95% CI 0.14 to 0.60); in 3D primary human hepatocytes dicloxacillin induced CYP3A4 up to 4.9-fold (mRNA), 2.9-fold (protein), 2.4-fold (activity) and CYP2C9 mRNA 1.7-fold. Healthy-volunteer study [9] (Tier A, 28 non-smokers, warfarin 20 mg and phenytoin 300 mg before and during 21 days of dicloxacillin 500 mg four times daily, abstract states dicloxacillin is a potent pregnane X receptor activator): oral clearance of (S)-warfarin rose 53.2% and (R)-warfarin 63.2%, INR-time AUC fell 15.5% (p below 0.001), phenytoin clearance rose 42.4%. Danish propensity-matched cohort [10] (Tier A, about 50,000 episodes, days 7 to 28): ischemic stroke or systemic embolism HR 2.09 (95% CI 1.51 to 2.90) for dicloxacillin or flucloxacillin versus phenoxymethylpenicillin, 2.17 (1.56 to 3.02) for dicloxacillin alone, 2.84 (1.97 to 4.09) versus no antibiotic. JAMA 2015 research letter [11] on INR change with dicloxacillin and vitamin K antagonists (OpenAlex gives only a one-sentence abstract, no figures). A 2026 systematic review of isoxazolyl penicillin interactions [12] (51 articles, 33 victim drugs) points to induction of CYP, UGT and P-glycoprotein as the most plausible mechanism. Case-level reports [13][14] agree in direction.

Mechanism

Named: pregnane X receptor activation with induction of CYP3A4, CYP2C9 and CYP2C19 [8][9]. Vitamin K status was not measured in any of these studies.

Independence

The Danish register [8], the JAMA letter [11] and the stroke cohort [10] draw on Danish national registers and may share patients (overlap not verified from the abstracts). The healthy-volunteer trial [9] is independent.

Why yellow

Red and orange need a directly measured nutrient. None is measured here. The evidence is strong for the drug-drug effect, and it is graded yellow only as a context flag that readers will meet next to the vitamin K claim (see Fails verification).

Counter-evidence held on record

Counter-evidence on record No dicloxacillin source found contradicts the direction of the effect. Flucloxacillin lowered INR less than dicloxacillin in the Danish study (0.37 versus 0.65) [8], and the stroke cohort [10] pools the two drugs for its headline estimate, so the flucloxacillin share cannot be separated there. Framing caution for the consumer surface The finding is about anticoagulation control, which belongs to the prescriber. It gives no instruction about vitamin K intake and is not a vitamin K deficiency.

Vitamin D: pregnane X receptor activation by dicloxacillin could in theory raise vitamin D catabolism; contested mechanism, no vitamin D measurement (CLASS EXTRAPOLATION)

Yellow — Low

See study details

Dicloxacillin is a potent pregnane X receptor activator and CYP inducer, and PXR agonists such as rifampicin have been linked to vitamin D catabolism in cells, but a second study disputed that link and no study measured vitamin D in dicloxacillin users.

Full detail and limits

Direction

Possible depletion of active vitamin D through enzyme induction (theoretical).

Regulatory status

Label states hepatic enzyme induction as a possible explanation for the warfarin effect and names no vitamin D statement [1].

Population evidence

PXR activation and CYP induction by dicloxacillin: [8][9] (see the warfarin entry). Vitamin D link for PXR agonists: Pascussi 2005 [29] (rifampicin and phenobarbital raised CYP24 expression through PXR in mice and human hepatocytes; abstract via PubMed listing summary) versus Zhou 2006 [30] (SXR activation did not induce CYP24 in vitro or in vivo, SXR inhibited VDR-mediated CYP24 promoter activity, and rifampicin did not change intestinal CYP24 in humans despite strong CYP3A4 induction; abstract via PubMed listing summary). Neither names dicloxacillin. Repair addition (2026-10-10): a Newcastle University PhD thesis on flucloxacillin liver injury by Chamberlain [38] (opened; year given as 2013 in the text read) reports that dicloxacillin was a stronger PXR agonist than flucloxacillin in a HepG2 reporter assay, a further Tier B confirmation of PXR activation by dicloxacillin; no vitamin D endpoint and no numbers were in the text read.

Cohort test

CLASS EXTRAPOLATION (PXR-activating drugs). Dicloxacillin was not in [29] or [30]. No 25-hydroxyvitamin D, PTH or bone endpoint exists for dicloxacillin. Capped at yellow.

Counter-evidence held on record

Counter-evidence on record The two PXR studies point in opposite directions [29][30]. PubMed "dicloxacillin vitamin" (4 results, all read as listing lines) returned no vitamin D or K measurement. Framing caution for the consumer surface A mechanistic hypothesis only. It does not show low vitamin D in people taking dicloxacillin and implies no supplement.

Food and mineral timing: food delays dicloxacillin absorption (nutrient-to-drug direction; separation interval from the label)

Yellow — Low

See study details

Meals delay oral dicloxacillin absorption, so the label directs it be taken at least 1 hour before or 2 hours after meals with at least 4 fluid ounces of water; this is a timing interaction and not a nutrient depletion.

Full detail and limits

Direction

Nutrient (food) to drug. Hard Rule 4: filed as a timing interaction with a separation interval, not as a depletion.

Regulatory status

Label: "Oral absorption of dicloxacillin is delayed when the drugs are administered after meals"; "best absorbed when taken on an empty stomach"; "should be administered at least 1 hour before or 2 hours after meals"; take with "at least 4 fluid ounces (120 mL) of water" and not in the supine position or immediately before bed [1].

Population evidence

Label only for the food effect. A Tier D reproduction (Drugs.com) repeats the statement and adds that penicillin V and amoxicillin "are not affected by food" [33]. Peak concentrations occur at 1 to 1.5 hours; bioavailability figures quoted via PubChem are 48.8% (serum AUC) and 74.1% (urinary recovery) after a 2 g oral dose in healthy volunteers [5]. No iron, calcium, magnesium or antacid separation interval is stated in the label read.

Mechanism

Delayed gastric emptying and absorption with food; the label gives no transporter or chelation mechanism.

Counter-evidence held on record

Counter-evidence on record The in vitro metal-binding work [27][28] suggests metal ions could bind dicloxacillin, but no clinical mineral interaction was found and the label lists none. Framing caution for the consumer surface A dosing-timing instruction for the prescriber and pharmacist, not a nutrient finding.

Carnitine

Not graded — disclosed evidence gap

See study details

No evidence was found that dicloxacillin lowers carnitine, and no circulating claim about dicloxacillin and carnitine was found.

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 source and no circulating claim found. Not a statement that carnitine is unaffected.

What was searched

PubMed "dicloxacillin carnitine": no results (first attempt returned a client error, second attempt read as zero results). The label describes the drug as the monosodium salt of the free acid, 250 mg or 500 mg capsules [1]; no pivalate-releasing ester prodrug is present in that description, so the pivalate mechanism that links some other penicillin and cephalosporin prodrugs to carnitine loss does not apply on the label as read. Repair 2026-10-10: web searches 'dicloxacillin carnitine deficiency' and 'dicloxacillin acylcarnitine OR carnitine OR fatty acid oxidation penicillin metabolomics' returned general carnitine reviews and one pivampicillin carnitine paper (title only, not opened; a different drug) and no dicloxacillin item [44].

Channel outcomes

Label read through a summarizing fetch tool. Web search for consumer claims was unavailable (budget exhausted), so the no-claim finding is tooling-limited. The PubMed zero is a genuine gap. Repair update: the first page of web results for the dicloxacillin carnitine query held only general carnitine deficiency pages, so no consumer claim linking dicloxacillin to carnitine was seen; the web-search budget ran out after the second query, so this remains a two-phrasing check.

Phosphate (hypophosphatemia)

Not graded — disclosed evidence gap

See study details

No dicloxacillin report of low phosphate was found, and the flucloxacillin phosphate search also returned nothing.

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 source and no circulating claim found. A disclosed gap, not a finding of safety.

What was searched

PubMed "dicloxacillin hypophosphatemia": no results. PubMed "flucloxacillin hypophosphatemia" and "flucloxacillin hypophosphataemia": no results (two spellings). No phosphate statement in the label read [1]. Two spellings were tried for flucloxacillin and one for dicloxacillin; no further phrasings (for example "serum phosphate" or "phosphorus") were possible within the rate limits.

Channel outcomes

Mixed: PubMed returned clean zeros (a genuine gap on those phrasings) but the narrower phrasing set and the unavailable web search for circulating claims make this partly tooling-limited. Repair update (2026-10-10): web searches 'dicloxacillin hypophosphatemia serum phosphate' and 'dicloxacillin flucloxacillin hypophosphataemia OR low phosphate OR serum phosphate case report' returned a 1980 Acta Paediatrica study of serum phosphate as a neonatal sepsis marker [43] (opened; names neither dicloxacillin nor flucloxacillin), the Liamis QJM 2010 review of medication-induced hypophosphatemia [37] (record opened; names diuretics, bisphosphonates and alkylating agents, no penicillin) and a 2009 flucloxacillin case of hypokalaemia with hypomagnesaemia [39] with no phosphate statement. No dicloxacillin or flucloxacillin phosphate report was found and no consumer claim appeared. No PubMed 'serum phosphate' or 'phosphorus' phrasing was run, so the entry stays partly tooling-limited.

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: beta-lactam class signal in cells and mice only; no dicloxacillin mitochondrial study found (CLASS EXTRAPOLATION)

Yellow — Low

See study details

Bactericidal antibiotic classes including beta-lactams caused mitochondrial dysfunction in mammalian cells and mice in one study that does not name dicloxacillin, and nothing mitochondrial has been found for dicloxacillin itself.

Full detail and limits

Direction

Possible mitochondrial dysfunction (a risk signal, not a nutrient deficiency).

Regulatory status

Label silent [1].

Population evidence

Kalghatgi 2013, Sci Transl Med [22] (Tier C): quinolones, aminoglycosides and beta-lactams at clinically relevant doses caused mitochondrial dysfunction and excess reactive oxygen species in mammalian cells, with oxidative damage and higher oxidative markers in treated mice; effects were reduced by N-acetyl-L-cysteine and avoided with bacteriostatic antibiotics. Abstract only, as an OpenAlex paraphrase; named drugs and doses not retrieved. No human data.

Mechanism

Named by the class study: mitochondrial dysfunction with ROS overproduction; unconfirmed for dicloxacillin.

Cohort test

CLASS EXTRAPOLATION. The abstract names classes only, so dicloxacillin is not confirmed in the cohort. Capped at yellow.

Counter-evidence held on record

Counter-evidence on record PubMed "dicloxacillin mitochondria" returned no results. A bacteriostatic-versus-bactericidal contrast in [22] cannot be applied to a specific penicillin without the drug-level data. Repair re-check (2026-10-10): the PubMed record of [22] names no individual drugs and lists ATP only as an indexing term. A 2025 respirometry study in permeabilized human HEK293T cells [36] tested gentamicin, ciprofloxacin and amoxicillin; amoxicillin (0.01 to 2 mg/mL) had no significant effect on leak respiration or OXPHOS capacity and only a slight, non-significant inhibition of electron transfer and complex IV (text read; figures and supplementary tables not seen). Dicloxacillin was not tested, so this is a Tier C class null for a different penicillin; it leaves the grade at yellow and is not a dicloxacillin result. Framing caution for the consumer surface A theoretical class-level signal. It is not evidence that dicloxacillin damages mitochondria in people.

Oxidative Stress

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

Oxidative stress: glutathione-cycle disturbance with 5-oxoproline accumulation in dicloxacillin plus paracetamol case reporting, in vitro glutathione S-transferase inhibition; outcome-level and class evidence

Yellow — Low

See study details

A confirmed pyroglutamic (5-oxoproline) acidosis occurred in a patient on long-term dicloxacillin and regular paracetamol, and dicloxacillin was among the strongest penicillin inhibitors of purified human glutathione S-transferase in vitro; no antioxidant or redox marker has been measured in people taking dicloxacillin alone.

Full detail, limits and 1 references

Limits on what this shows

Confounding: Paracetamol, chronic kidney disease, malignancy, sepsis and malnutrition are each named contributors in the case and review [19][20]. The dicloxacillin contribution cannot be separated.

Direction

Possible functional loss of glutathione-cycle capacity in the presence of paracetamol and illness. High anion gap acidosis is a clinical outcome and not a nutrient deficiency (Hard Rule 2); glutathione or cysteine status was not reported measured in the case.

Regulatory status

Label silent on acidosis, glutathione and oxidative stress [1].

Population evidence

Case (Tier B): BMJ Case Rep 2020 [19]: 85-year-old man with transfusion-dependent chronic myelomonocytic leukaemia, stage III chronic kidney disease, acute kidney injury and sepsis; persistent high anion gap acidosis, long-term dicloxacillin for endocarditis prophylaxis plus regular paracetamol, pyroglutamic acidosis "confirmed with elevated serum levels," resolved after both drugs were stopped; authors state it may be the second reported dicloxacillin case (OpenAlex-reconstructed abstract). In vitro (Tier B): PMID 6515130 [21]: of seven penicillins tested against purified human placenta glutathione S-transferase, the dihalogenated dicloxacillin and flucloxacillin were the strongest inhibitors; no inhibition percentage, Ki or concentration is in the abstract (PubMed listing text and OpenAlex summary; the two records disagree on the journal). Flucloxacillin (not dicloxacillin): a 2024 review of 100 pyroglutamic acidosis cases [20] found paracetamol in most and flucloxacillin co-prescribed in about a third, with hypokalaemia in about a third; its abstract does not name dicloxacillin and calls the clinical evidence "anecdotal." Class (Tier C): Kalghatgi 2013 [22] reports mitochondrial dysfunction and oxidative damage with clinically relevant doses of quinolones, aminoglycosides and beta-lactams in cells and mice, reduced by N-acetyl-L-cysteine; the abstract names classes, not drugs, so dicloxacillin is not confirmed in the cohort: CLASS EXTRAPOLATION.

Mechanism

Named for the acidosis: paracetamol and illness divert the glutathione cycle, overproducing pyroglutamate [20]; isoxazolyl penicillins have been proposed to contribute, but the mechanism for dicloxacillin is unestablished. In vitro GST inhibition [21] is a plausibility signal only.

Counter-evidence held on record

Counter-evidence on record No dicloxacillin study measured malondialdehyde, glutathione, antioxidant enzymes or reactive oxygen species (PubMed "dicloxacillin oxidative stress" returned two unrelated records; "dicloxacillin glutathione" returned the GST record). The 2024 review [20] concerns flucloxacillin. Framing caution for the consumer surface Pyroglutamic acidosis is a rare clinical outcome tied mostly to paracetamol. It is not a glutathione or antioxidant deficiency claim and no antioxidant supplement is implied.

In vitro interaction of penicillins and cephalosporins with human placenta GSH S-transferase. Res Commun Chem Pathol Pharmacol 1984;46(3):411-423. PMID 6515130. — Tier B in vitro. PubMed listing summary plus OpenAlex summary; OpenAlex attributes the record to J Urol 1985 (DOI 10.1016/s0022-5347(17)49400-6), so the journal metadata is inconsistent. No numbers in the abstract.

Copper and Iron Balance

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

Copper: dicloxacillin binds Cu(II) more strongly than Co(II) or Ni(II) in vitro; copper-to-drug direction, no human copper data

Yellow — Low

See study details

In aqueous solution dicloxacillin forms stable complexes with Cu(II) (more stable than Co(II) and Ni(II) and more stable than the analogous cloxacillin complexes); no study measured copper status in people on dicloxacillin.

Full detail and limits

Direction

Drug-metal binding in vitro. Neither copper depletion nor retention in the body is shown. If anything, a copper or other metal-ion effect would run from the metal to the drug (reduced free drug), which is a timing question and not a depletion (Hard Rule 4).

Regulatory status

Label names no copper or mineral interaction [1].

Population evidence

Sci Rep 2026 [27] (Tier B, potentiometric and spectroscopic study of cloxacillin and dicloxacillin with Co(II), Ni(II), Cu(II) and Nd(III), Eu(III), Tb(III)): stability order Co(II) approximately Ni(II) below Cu(II); dicloxacillin gave consistently more stable complexes than cloxacillin; coordination mainly through the carboxylate group (abstract via OpenAlex reconstruction summarized by a fetch tool; stability constants not retrieved). Earlier solid-complex work is listed under Iron [28].

Mechanism

Named: metal coordination at the penicillin carboxylate and amide groups. Physiological relevance at body concentrations is not shown.

Counter-evidence held on record

Counter-evidence on record PubMed "dicloxacillin copper" (3 results, all read as listing lines) returned no human copper measurement. The label and the 2026 abstract report no effect on copper absorption, status or loss. Framing caution for the consumer surface An in vitro chemistry finding. It does not show copper loss or a need for copper.

Iron: dicloxacillin Fe(II) and Fe(III) coordination complexes in a 2001 chemistry paper only (title and metadata read; no iron status data)

Yellow — Low

See study details

The only drug-specific iron-related record is a 2001 spectroscopic paper on synthetic dicloxacillin complexes of Fe(II), Fe(III) and other metals; no study measured iron absorption or status in people on dicloxacillin.

Full detail and limits

Direction

In vitro metal binding only. No iron depletion or excess is shown. Hard Rule 7: kept independent of Copper.

Regulatory status

Label names no iron interaction [1].

Population evidence

Spectrochim Acta A 2001 [28] (Tier B by title, "Metal complexes of antibiotic drugs. Studies on dicluxacillin complexes of FeII, FeIII, CoII, NiII and CuII"): the OpenAlex record has no abstract and the article is closed access, so only the title and topic metadata (carboxylate coordination, thermal decomposition, magnetic properties) were read. Content, doses and any biological testing are unknown.

Mechanism

Named by the title only: coordination chemistry. No physiological mechanism is established.

Counter-evidence held on record

Counter-evidence on record PubMed "dicloxacillin iron" (4 results, all read as listing lines) returned no iron absorption, ferritin or iron-status study with dicloxacillin; the only clinical record excluded iron deficiency in a red-cell aplasia patient [31]. Graded yellow rather than ungraded only because a drug-specific in vitro source exists; it is weak. Framing caution for the consumer surface A chemistry title. It gives no basis for a claim about iron levels.

Gut Microbiome Risk

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

Gut microbiome risk: marked community shifts and E. coli expansion in mice; no dicloxacillin-stratified human data (bounded to short courses)

Yellow — Low

See study details

In mice dicloxacillin shifted the dominant gut phyla and promoted overgrowth of ESBL-producing E. coli; in people, dicloxacillin sits unstratified inside a 7-patient narrow-spectrum arm that showed higher, not lower, richness.

Full detail and limits

Direction

Disturbance of the gut microbial community and resistance carriage (a risk entry). It is not a nutrient deficiency and implies no supplementation or probiotic.

Regulatory status

Label: CDAD "has been reported with use of nearly all antibacterial agents, including dicloxacillin sodium," "may range in severity from mild diarrhea to fatal colitis" and "has been reported to occur over two months after the administration of antibacterial agents"; pseudomembranous colitis is listed as an adverse reaction [1].

Population evidence

Mouse (Tier B): Hertz 2014 [25]: nine antimicrobials, 8 mice per group (PubMed listing text), CTX-M-15 E. coli ST131 colonization; cefotaxime, dicloxacillin and clindamycin promoted ST131 overgrowth (P below 0.05), dicloxacillin did not suppress Bacteroides or Gram-positive aerobes and did not prolong colonization (listing summary and OpenAlex summary). Antibiotics 2020 [24]: five mice per drug, daily subcutaneous injection on days 1 to 3, stool days 1, 3 and 5, IS-pro profiling; dicloxacillin and clindamycin "induced major shifts among all phyla," Bacteroidetes were inhibited in 3 of 5 dicloxacillin mice, E. coli proliferated, diversity rose and total load fell (journal page read through a summarizing tool; P values are in tables not seen). Human (cohort includes dicloxacillin, not stratified): Microorganisms 2021 [23]: 34 antibiotic-naive neurointensive care patients, rectal swabs before and after 5 to 7 days, shotgun metagenomics; narrow-spectrum arm n = 7 (ciprofloxacin, cefuroxime, vancomycin and dicloxacillin as a group), richness increased (Wilcoxon p = 0.016), Shannon index trend p = 0.078, no per-drug numbers; the number on dicloxacillin is not stated.

Mechanism

Named: killing of susceptible gut bacteria with loss of colonization resistance (the 2020 mouse authors suggest abundant anaerobes, especially Bacteroidetes, are affected [24]).

Cohort test

Mouse studies use dicloxacillin itself (Tier B). The human study [23] has dicloxacillin in an unquantified part of a 7-patient arm and cannot isolate it. The Swedish prescription-to-metagenome cohort of 14,979 adults [26] analysed flucloxacillin and did not name dicloxacillin: CLASS EXTRAPOLATION, dicloxacillin not in that cohort, flucloxacillin was linked to 203 of 1,340 species for use under 1 year before sampling and lower diversity. No grade is raised on [26]. Repair re-check (2026-10-10): the MDPI page of [23] mentions dicloxacillin once, in the abstract, with no patient count or per-drug result (arms: broad n = 27, narrow n = 7). The Nature Medicine paper [26], opened on nature.com, names only flucloxacillin (about 21 fewer species per course in the previous year, q = 1.4e-6; 203 associated species); dicloxacillin is not named. A 2026 exploratory study of 16 hospitalized Staphylococcus aureus patients and 10 controls (16S rRNA; 15 of 16 on antimicrobials) [42] does not name dicloxacillin in the text read and cannot separate drug from infection, so it adds nothing for this drug.

Counter-evidence held on record

Counter-evidence on record The human arm that included dicloxacillin showed rising richness [23], and the 2020 mouse authors note that a previous case-control study did not reproduce the ESBL link in patients with urinary tract infection [24]. Mouse dose and route differ from human oral use. The Hertz result is a short-lived overgrowth, not a prolonged effect [25]. Framing caution for the consumer surface A risk of microbial disturbance and C. difficile disease, not a nutrient deficiency. No supplement or probiotic is implied.

Oxygen and ATP Output

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

Oxygen delivery/utilization: label-listed hemolytic anemia and one red-cell aplasia case (outcome only; no oxygen-carrying measurement)

Yellow — Low

See study details

The label lists hemolytic anemia and other blood-count reactions as dicloxacillin adverse reactions, and one man developed pure red cell aplasia months after a course; these are clinical outcomes, not measures of oxygen delivery or an iron or vitamin deficiency.

Full detail and limits

Direction

Outcome only: a drug adverse reaction (hematologic toxicity). It is not an oxygen-delivery deficiency and not iron deficiency (Hard Rule 2).

Regulatory status

Label adverse reactions (hematologic): "Eosinophilia, hemolytic anemia, agranulocytosis, neutropenia, leukopenia, granulocytopenia, thrombocytopenia"; precautions advise blood counts before and periodic hematopoietic assessment during prolonged therapy [1].

Population evidence

Case report, Tidsskr Nor Laegeforen 2023 [31] (Tier B, n = 1): man in his forties, hemoglobin 5.4 g/dL a few months after dicloxacillin for a skin abscess, diagnosed with pure red cell aplasia, improved with ciclosporin; iron and vitamin deficiency anemia were excluded on testing; the authors could not determine whether the cause was idiopathic or drug-related (PubMed listing text only; the record was not opened further). No hemoglobin, methemoglobin or hemolysis cohort for dicloxacillin was found.

Mechanism

Hemolysis, marrow suppression and immune cytopenias are immunologic or toxic reactions; no mechanism is named for dicloxacillin in the sources read.

Counter-evidence held on record

Counter-evidence on record PubMed "dicloxacillin hemolysis" returned three records: the case above and two chemistry papers using dicloxacillin as a comparator. The case authors could not attribute the aplasia to the drug. Framing caution for the consumer surface Rare label-listed blood reactions are outcomes. They are not evidence of impaired oxygen delivery from a nutrient shortfall.

ATP production

Not graded — disclosed evidence gap

See study details

No ATP, oxidative phosphorylation or respiration measurement with dicloxacillin was found, and no circulating claim linking dicloxacillin to low cellular energy was located.

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 on reachable evidence: no Tier B or C source measures ATP, respiration or membrane potential for dicloxacillin, and no circulating claim was found to rebut. Kept independent of Mitochondrial burden and Oxygen delivery/utilization (Hard Rule 7). A disclosed gap, not a finding of safety; re-check when web search is available. After the repair the dual condition still holds: the only new Tier C item [36] is a null for amoxicillin and does not support a yellow grade.

What was searched

PubMed "dicloxacillin ATP": 7 results, none measuring cellular ATP with dicloxacillin (P-glycoprotein, pharmacokinetic and microbiology records; one aminoglycoside bioluminescence assay). PubMed "dicloxacillin mitochondria": no results. PubMed "dicloxacillin oxidative stress": 2 unrelated records. The class study [22] reports no ATP endpoint in its abstract. Label: no statement [1]. Full query log in [35]. Repair 2026-10-10 (web search worked for these queries): 'dicloxacillin mitochondria ATP respiration oxidative phosphorylation' returned a 2025 respirometry paper [36] (gentamicin, ciprofloxacin and amoxicillin only; dicloxacillin not tested; amoxicillin no significant OXPHOS effect), the Kalghatgi record [22] re-read (no drug names; ATP only as an indexing term), a rapid HepG2 glucose-galactose ATP assay paper (J Toxicol Sci 2017, abstract page only; it lists no compounds, so dicloxacillin could be neither confirmed nor excluded) and a Newcastle thesis [38] showing dicloxacillin PXR activation but no ATP endpoint. PubMed 'dicloxacillin respiration' (HTTP 429) and the PubChem Tox21 assay summary (refused by robots.txt) could not be read.

Channel outcomes

The open-web search budget was exhausted, so circulating consumer claims about "low energy" or ATP could not be searched; the absence of a claim is tooling-limited. The Drugs.com patient and food pages read make no depletion claim [33][34]. The absence of drug-specific ATP data on PubMed is a genuine gap on the channels that worked. Repair update: the first page of web results for the ATP query held research papers and a vendor blog on antibiotics and energy metabolism (blog not opened) and no consumer or retail page asserting that dicloxacillin lowers energy or ATP, so the no-claim finding is now partly verified, but the web-search budget then ran out and only one phrasing was run. Remaining lead: Tox21 mitochondrial membrane potential or HepG2 ATP data for dicloxacillin sodium, if a reachable data host is found.

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.

Vitamin K deficiency and raised INR or bleeding from loss of vitamin K-producing gut bacteria
Where it comes from: General antibiotic statement in the NIH Office of Dietary Supplements vitamin K sheet: "Antibiotics can destroy vitamin K-producing bacteria in the gut, potentially decreasing vitamin K status," more pronounced "with cephalosporin antibiotics, such as cefoperazone" [32]. Dicloxacillin is not named. Consumer pages repeat the idea for antibiotics broadly; no dicloxacillin-specific page was found (web search unavailable).
Why it fails: Dicloxacillin's own Tier A data run the other way: INR falls (by 0.65 to 0.76) because the drug induces warfarin clearance, and stroke risk rises, not bleeding [8][9][10]. No study measured vitamin K in dicloxacillin users. The claimed direction is reversed by this drug's data (Hard Rule 2 and the white boundary). Vitamin K supplementation would not be a remedy for the interaction.
B vitamins (folate, B12, biotin) lost through reduced gut-flora synthesis (provisional, tooling-limited)
Where it comes from: General consumer and supplement-retail framing that antibiotics deplete B vitamins. No page asserting this for dicloxacillin was found and the claim was not traced to a specific origin because the web-search budget was exhausted. The Drugs.com pages read make no such claim [33][34].
Why it fails: Dicloxacillin disturbs the gut community in mice [24][25] but no study measured any B vitamin in dicloxacillin users, and the one human arm that included it showed higher richness [23]. The mechanism is not impossible but is unmeasured; held out of publication as a deficiency claim pending a re-check that could convert it to yellow.

How the body handles this medication

Metabolism and enzymes: About 10% of the absorbed dose is hydrolyzed to inactive penicilloic acids and a small amount is hydroxylated to a slightly less active metabolite (HSDB via PubChem). The label names only "hepatic inactivation" and no CYP isoenzyme as a metabolic route. As a perpetrator, dicloxacillin activates the pregnane X receptor and induces CYP2C9, CYP2C19 and CYP3A4 activity per a 2026 abstract; hepatocyte CYP3A4 mRNA rose up to 4.9-fold.[1] label; [4] PubChem/HSDB; [8][9]
Elimination: "Rapidly excreted, primarily as unchanged drug in the urine by glomerular filtration and active tubular secretion"; nonrenal elimination includes hepatic inactivation and biliary excretion; not dialyzable. Half-life about 0.7 hour (label), 42 minutes in healthy volunteers and 129 minutes in hemodialysis patients (Nauta and Mattie 1976, quoted by PubChem). Urinary recovery 38.65 to 50.10% in a 2015 volunteer study (quoted by PubChem).[1] label; [5] PubChem/DrugBank/HSDB
Absorption: "Rapid but incomplete," peak blood levels at 1 to 1.5 hours, delayed after meals. Bioavailability 48.8% by serum AUC and 74.1% by urinary excretion after a 2 g oral dose in healthy volunteers (quoted by PubChem). No absorption transporter is named in the label.[1] label; [5]
Distribution and binding: 97.9 +/- 0.6% bound to serum protein, mainly albumin. Placental transfer is incomplete (Pacifici 2006, quoted by PubChem).[1] label; [5]
Renal tubular handling and electrolytes: Actively secreted by the renal tubule; supplied as the monosodium salt with no sodium or potassium content stated in the label read. Hypokalaemia with related penicillins is attributed to a non-reabsorbable anion effect at high intravenous doses; label oral dosing is 125 mg to 250 mg every 6 hours. Reduce total dose if renal impairment is suspected; not recommended for newborns.[1] label; [16] flucloxacillin cohort
Food, mineral and drug interactions: Food delays absorption: take at least 1 hour before or 2 hours after meals with at least 4 fluid ounces of water. Tetracycline "may antagonize the bactericidal effect"; probenecid increases and prolongs penicillin levels; warfarin response may be reduced. No iron, calcium, antacid or other mineral interaction appears in the label read.[1] label (summarized by a fetch tool)

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.

Lab / anticoagulated patients
INR when starting or stopping
Dicloxacillin lowers warfarin effect and one 1996 case series (listing line only) reports recovery taking up to 3 weeks after stopping [14]; INR checks and any dose change belong to the prescriber [1][8][9]. Phenytoin and other narrow-window CYP2C9 or CYP3A4 substrates are also affected [9][12]. Vitamin K is not a remedy to add.
Lab / high-dose intravenous courses
Serum potassium
Hypokalaemia is documented with high-dose intravenous flucloxacillin and in one intravenous dicloxacillin case [15][16][17]. Checking potassium is reasonable for prolonged intravenous isoxazolyl penicillin courses in older or low-weight patients; it is not supported as routine for label-dose oral use.
Lab / liver
AST, ALT and symptoms
The label calls for AST and ALT periodically during therapy; LiverTox describes rare cholestatic hepatitis, onset typically 1 to 6 weeks, with jaundice and pruritus [1][6][7]. This is a clinical outcome and not a nutrient finding.
Lab / unusual symptoms
Complete blood count
The label lists hemolytic anemia, agranulocytosis, neutropenia and thrombocytopenia and advises blood counts before and during prolonged therapy [1]. Iron indices are not the first test for these reactions.
Timing / every course
Empty stomach and water
Take at least 1 hour before or 2 hours after meals with at least 4 fluid ounces of water, and not lying down or just before bed (esophageal injury is label-listed) [1]. No mineral separation interval is stated in the label read.
Symptoms / during and after a course
Severe or persistent diarrhea
New watery or bloody diarrhea during or up to two months after a course warrants assessment for C. difficile; the label states CDAD can occur over two months after antibacterial therapy [1].
Lab / prolonged courses with paracetamol
Unexplained acidosis
Persistent high anion gap acidosis in a patient on long-term dicloxacillin and regular paracetamol, especially with kidney disease or poor nutrition, should prompt a clinician to consider pyroglutamic acidosis [19][20]. Not a routine screen.
Renal, pregnancy and pediatric
Kidney function and special groups
The label advises considering dose reduction if renal impairment is suspected, notes incompletely developed renal function in newborns (no newborn dose is recommended), and advises starting at the low end of dosing in the elderly [1]. Sodium content may matter in sodium-restricted patients per a Tier D page [33].

Overlap map, to prevent double counting

Warfarin/vitamin K antagonist response
Shares evidence with: Vitamin D; Fails verification: vitamin K
Note: The same PXR and CYP induction finding [8][9] underlies the INR entry, the theoretical vitamin D entry and the rebuttal of the vitamin K claim. The INR result is measured; vitamin D is inferred. Treat as one mechanism, not several confirmations.
Oxidative stress
Shares evidence with: Mitochondrial burden
Note: Kalghatgi 2013 [22] supports both entries; the case report [19] and GST work [21] support only oxidative stress. Not independent confirmation of mitochondrial injury.
Oxidative stress
Shares evidence with: Potassium
Note: The 2024 pyroglutamic acidosis review [20] reports hypokalaemia in about a third of cases alongside flucloxacillin, and the potassium entry draws on flucloxacillin cohorts [16][17]; the case in [19] is dicloxacillin. These are different drugs and different endpoints; do not count one as the other.
Gut microbiome risk
Shares evidence with: Fails verification: vitamin K; B vitamins
Note: The same loss-of-susceptible-bacteria mechanism underlies the microbiome entry and both rebutted flora-based claims. Mouse studies [24][25] are from related work (the 2020 study builds on the Hertz study) and are not fully independent.
Copper
Shares evidence with: Iron; Food and mineral timing
Note: Copper rests on [27] and Iron on [28]; they are different papers and different metals, kept as separate entries. Both are in vitro complexation and neither is clinical evidence for the food-timing entry.
Oxygen delivery/utilization
Shares evidence with: Iron
Note: The red-cell aplasia case [31] excluded iron deficiency; the hemolytic anemia label entry is a drug adverse reaction and not an iron finding. Iron has no clinical evidence of its own.
ATP production
Shares evidence with: Mitochondrial burden; Oxygen delivery/utilization
Note: ATP has no evidence of its own; it is ungraded and independent of the other two (Hard Rule 7). The 2025 amoxicillin respirometry null [36] is Tier C for a different penicillin and bears on both Mitochondrial burden and ATP production; it is one source, not two.

All references used above

Dicloxacillin

Findings for this medication

What the research found

Potassium: renal potassium loss with high-dose intravenous isoxazolyl penicillins; one dicloxacillin case, all cohorts are flucloxacillin (CLASS EXTRAPOLATION)

Warfarin and other vitamin K antagonists: dicloxacillin lowers INR by enzyme induction (drug-to-drug, reverse direction; not a vitamin K status finding)

Vitamin D: pregnane X receptor activation by dicloxacillin could in theory raise vitamin D catabolism; contested mechanism, no vitamin D measurement (CLASS EXTRAPOLATION)

Food and mineral timing: food delays dicloxacillin absorption (nutrient-to-drug direction; separation interval from the label)

Carnitine

Phosphate (hypophosphatemia)

The five body-system areas

⚡Mitochondrial Burden

Mitochondrial burden: beta-lactam class signal in cells and mice only; no dicloxacillin mitochondrial study found (CLASS EXTRAPOLATION)

💥Oxidative Stress

Oxidative stress: glutathione-cycle disturbance with 5-oxoproline accumulation in dicloxacillin plus paracetamol case reporting, in vitro glutathione S-transferase inhibition; outcome-level and class evidence

⚖️Copper and Iron Balance

Copper: dicloxacillin binds Cu(II) more strongly than Co(II) or Ni(II) in vitro; copper-to-drug direction, no human copper data

Iron: dicloxacillin Fe(II) and Fe(III) coordination complexes in a 2001 chemistry paper only (title and metadata read; no iron status data)

🌿Gut Microbiome Risk

Gut microbiome risk: marked community shifts and E. coli expansion in mice; no dicloxacillin-stratified human data (bounded to short courses)

💨Oxygen and ATP Output

Oxygen delivery/utilization: label-listed hemolytic anemia and one red-cell aplasia case (outcome only; no oxygen-carrying measurement)

ATP production

Claims checked and not supported

Vitamin K deficiency and raised INR or bleeding from loss of vitamin K-producing gut bacteria

B vitamins (folate, B12, biotin) lost through reduced gut-flora synthesis (provisional, tooling-limited)

How the body handles this medication

What the research says is worth watching

Overlap map, to prevent double counting

Mitochondrial Burden

Oxidative Stress

Copper and Iron Balance

Gut Microbiome Risk

Oxygen and ATP Output