Penicillin V

beta-lactamase sensitive penicillin (beta-lactam antibacterial)

Also sold as Veetids.

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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.

Penicillin V has almost no classical depletion machinery. It is a poorly and variably absorbed oral penicillin (about 25% of the dose recovered in urine per the label, 25 to 60% bioavailability per DrugBank, 60 to 73% in fasting adults per AHFS), about 80% protein bound, with a serum half-life of about 0.5 hour that lengthens to up to 4 hours in renal impairment [1][6]. About 35 to 70% of an oral dose is converted to inactive penicilloic acid, no CYP450 enzyme is named in the label, and the label lists no nutrient, mineral or antacid interaction [1][6]. The one mechanism that applies is the one the drug is built to produce: antibacterial action on susceptible bacteria, including colon flora, which the label says alters the normal colon flora [1].

beta-lactamase sensitive penicillin (beta-lactam antibacterial) · ATC J01CE02 (WHO ATC/DDD Index [4]) · also sold as Veetids and Apocillin; also called penicillin VK; many generics [5] · 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 Penicillin V 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 K and prothrombin: label silent; INR did not rise in warfarin users starting penicillin V (negative-control arm); vitamin K never measured; high-dose hypoprothrombinemia literature concerns other beta-lactams (CLASS EXTRAPOLATION)

Yellow — Low

See study details

No source measured vitamin K status in penicillin V users, the label has no coagulation or vitamin K statement, and in a 21,000-patient Swedish register study of warfarin users INR moved from 2.49 to 2.52 after starting penicillin V.

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: Mannheimer: no INR fall and a 0.03 rise in the mean after starting penicillin V [14]. No randomized study of penicillin V on INR or vitamin K markers was found.

Direction

Possible drug-induced coagulopathy or anticoagulant potentiation if gut vitamin K-producing flora were lost. Not a dietary vitamin K deficiency and not an indication to supplement (Hard Rules 2 and 4); vitamin K supplements oppose warfarin.

Regulatory status

The label text read has no warning on coagulation, bleeding, INR or vitamin K and no drug-interaction section [1][2].

Population evidence

Mannheimer 2019 [14] (Tier A for this drug as a negative-control arm; Swedish register cohort, warfarin users dispensed flucloxacillin or phenoxymethylpenicillin 2005 to 2012, 10 week follow-up): phenoxymethylpenicillin n = 21,430 in the text and 21,626 in Table 1 (the two disagree). INR "increased slightly from 2.49 (95% CI 2.48; 2.50) at baseline to 2.52 (95% CI 2.51; 2.53) during the first week"; the proportion with INR below 2 "remained stable at approximately 15%". Flucloxacillin, by contrast, lowered INR. Read through a summarizing fetch tool of a copy of the paper. This tests the functional vitamin K-dependent clotting marker in anticoagulated patients; it does not measure vitamin K, PIVKA or menaquinone, and the design used penicillin V only as a comparator, so the supratherapeutic fraction and bleeding were not reported in the text read. Class (Tier C, CLASS EXTRAPOLATION): NIH Office of Dietary Supplements [15]: "Antibiotics can destroy vitamin K-producing bacteria in the gut, potentially decreasing vitamin K status", with cephalosporins (cefoperazone) singled out; penicillin is not named. PubMed listing "penicillin hypoprothrombinemia" [24]: hypoprothrombinemia reports concern cephalosporins (cefoperazone, cefamandole), moxalactam plus ticarcillin, and mezlocillin; a 1988 review lists antipseudomonal penicillin platelet dysfunction as a separate, non-vitamin K route (Sattler); an amoxicillin case is also listed. Penicillin V is not named in any listing line, and the records were not opened.

Mechanism

Proposed for broad-spectrum beta-lactams (loss of menaquinone-producing flora; N-methylthiotetrazole side chains in some cephalosporins), not shown for penicillin V. The penicillin V gut data show minor change in total flora [7][8], which weakens the route.

Cohort test

Penicillin V was in Mannheimer's cohort. The NIH sheet and the hypoprothrombinemia listing lines did not name penicillin V: class extrapolation, capped at yellow.

Counter-evidence held on record

Counter-evidence and confounding A 0.03 INR rise in a large warfarin cohort argues against a clinically meaningful vitamin K-flora effect at oral doses, but a mean change can hide rare extreme values, and the comparator-design paper was not built to detect it. Infection and reduced intake are competing explanations for any INR change. Framing caution A monitoring prompt only. No vitamin K deficiency claim is supported for penicillin V, and vitamin K supplements should not be added by this entry because they would oppose warfarin therapy.

Potassium: label-identified potassium salt contributes a small potassium load; hypokalemia is not label-listed and no penicillin V case was found (excess/retention direction, context flag)

Yellow — Low

See study details

One 500 mg tablet of penicillin V potassium contains 1.43 mEq (55.8 mg) of potassium per one label, the label text for oral products lists no hypokalemia, and no hypokalemia report with penicillin V was found.

Full detail and limits

Limits on what this shows

Null findings: The label text read lists no potassium disturbance.

Direction

Excess/retention context: a small potassium load from the salt, not depletion. Neither a potassium load of this size nor the absence of a hypokalemia statement implies a change in intake (Hard Rule 5); supplementation is not suggested.

Regulatory status

Chartwell RX label reproduced on Drugs.com Professional [3]: 250 mg tablet "contains 0.71 mEq (27.9 mg) of potassium", 500 mg tablet "contains 1.43 mEq (55.8 mg)", oral solution 0.36 mEq (13.9 mg) per 5 mL at 125 mg/5 mL and 0.71 mEq (27.9 mg) per 5 mL at 250 mg/5 mL; no sodium figure is given (sodium citrate, saccharin sodium and sodium benzoate appear as excipients). The RemedyRepack label identifies the potassium salt without a mEq value; the Sandoz label page read has no potassium or hypokalemia statement [1][2][3]. By arithmetic only, four 500 mg tablets contain 5.72 mEq (about 223 mg) of potassium.

Population evidence

No cohort. A PubMed listing "penicillin V hypokalemia" [24] returned one record, a 1998 case of cervical actinomycosis with lupus-related distal renal tubular acidosis in which penicillin V was the treatment given, not a hypokalemia report (listing line only). Hypokalemia with high-dose intravenous penicillins was not retrieved and is not claimed here.

Mechanism

None read for penicillin V and potassium.

Cohort test

No study exists, so no class extrapolation is made.

Counter-evidence held on record

Counter-evidence and confounding The potassium figures come from a reproduction of one manufacturer's label on a Tier D site and differ in presence across label copies; renal impairment delays penicillin V excretion (label), but a potassium consequence was not studied. Framing caution No potassium change is expected from oral penicillin V on this evidence, and potassium supplements are not recommended. Potassium supplements have their own safety limits; none is recommended here.

Dietary intake and GI loss: label-listed nausea, vomiting, epigastric distress, diarrhea and black hairy tongue (context flag, no nutrient measured)

Yellow — Low

See study details

The most common oral penicillin reactions are gastrointestinal, which could reduce intake or raise fluid and electrolyte loss during a course, but no study measured intake or nutrient status in penicillin V users.

Full detail and limits

Limits on what this shows

Null findings: None located; the question has not been studied for penicillin V.

Direction

Transient intake or loss effect of the illness and drug adverse reactions. Not a nutrient deficiency (Hard Rule 2); confounded by the infection being treated (Hard Rule 6).

Regulatory status

Label: "The most common reactions to oral penicillin are nausea, vomiting, epigastric distress, diarrhea, and black hairy tongue" [1][2].

Population evidence

No source measured dietary intake, weight, hydration or nutrient levels in penicillin V users.

Mechanism

Present (mechanism H, changed intake; and microbiome disruption for the diarrhea component).

Counter-evidence held on record

Counter-evidence and confounding Acute infection itself reduces appetite and raises fluid loss, so any association with the drug is confounded by indication. Framing caution Hydration and persistent diarrhea are clinical matters, not a nutrient-supplement prompt. Nothing here supports adding a vitamin or mineral.

Food and milk: timing interaction in which food lowers or delays penicillin V absorption (nutrient affecting the drug, not drug depleting a nutrient)

Yellow — Low

See study details

The label says penicillin V may be given with meals but blood levels are slightly higher on an empty stomach, and a pharmacy reference states food delays and lowers peak levels without changing total absorbed amount, except with milk in young children.

Full detail and limits

Limits on what this shows

Null findings: No separation interval from any mineral, calcium product or antacid is given in the label text read.

Direction

Food or milk affecting the drug (Hard Rule 4): a timing interaction, not a depletion. Nothing here changes what a person should eat.

Regulatory status

Label: "It may be given with meals; however, blood levels are slightly higher when the drug is given on an empty stomach." Only about 25% of the dose is recovered in urine; penicillin V is about 80% bound to serum protein [1][2].

Population evidence

AHFS 1995 as quoted in the HSDB record on PubChem [6]: food usually lowers and delays peak levels but total absorbed amount is unchanged; in children aged 2 months to 5 years both peak level and AUC decrease when given with or just before milk or food. Absorption is 60 to 73% in healthy fasting adults. Read through a summarizing fetch tool; the primary studies were not opened.

Mechanism

Delayed gastric emptying and dilution (not named in the sources read).

Counter-evidence held on record

Counter-evidence and confounding The pediatric milk statement comes from a 1995 reference summary of older studies; the label itself does not require an empty stomach. Framing caution Follow the dispensed label directions. This entry creates no dietary restriction and recommends no supplement.

Vitamin B12: older microbiological serum assay can read falsely low on penicillin therapy (assay interference, not depletion)

Yellow — Low

See study details

A 1969 study found that serum from two patients taking phenoxymethyl penicillin or phenethicillin inhibited the Lactobacillus leichmanii B12 microbiological assay, while radioisotope and Euglena methods were unaffected; this is a laboratory artifact, not a loss of B12.

Full detail and limits

Limits on what this shows

Null findings: The abstract does not test phenoxymethylpenicillin in vitro. Whether current B12 assays are affected was not assessed.

Direction

Measurement artifact (reverse of a depletion claim): a low reading on one historic method with the drug present. B12 itself was not shown to fall.

Regulatory status

B12 is not mentioned in the label text read [1][2].

Population evidence

Powell 1969 [22] (Tier B, case-level for penicillin V; OpenAlex abstract paraphrase only): of 750 consecutive serum B12 assays by L. leichmanii, 25 (3.3%) showed inhibition; 17 of 23 with a drug history were taking ampicillin; two were taking phenoxymethyl penicillin or phenethicillin (the only penicillin V statement in the abstract); in 11 prospectively studied patients inhibition appeared in 7 during ampicillin. B12 by the radioisotope and Euglena gracilis methods was not affected. Ampicillin at serum concentrations reproduced the inhibition in vitro, whereas benzylpenicillin did not. The authors suggest other methods may be needed to distinguish it from true B12 depletion.

Mechanism

In vitro inhibition of the assay organism by drug in the serum sample.

Counter-evidence held on record

Counter-evidence and confounding Two patients, a 1969 method and an abstract-level read. It does not show any change in true B12 status. Framing caution Not a B12 deficiency claim and not a reason to take B12. If a result is unexpectedly low during a course, the prescriber can ask which assay method was used.

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: no human measurement; one rodent abstract reports mitochondrial dysfunction in brain after perinatal penicillin V; beta-lactam class study (CLASS EXTRAPOLATION)

Yellow — Low

See study details

The only drug-specific mitochondrial statement is a rodent abstract (altered mitochondrial complex activity in hippocampus and prefrontal cortex after perinatal penicillin V), and a PubMed search for phenoxymethylpenicillin with mitochondria returned no records.

Full detail and limits

Limits on what this shows

Null findings: No human null on mitochondrial function exists for penicillin V. The human urinary oxidative-marker null [18] is an oxidative stress surrogate, shared with the Oxidative stress entry, not a mitochondrial test.

Direction

Possible drug toxicity (excess burden) in an animal model. Not a nutrient deficiency.

Regulatory status

Not mentioned in the label text read [1][2].

Population evidence

None in humans. Shekhar 2025 [19] (Tier B, abstract via OpenAlex only): perinatal penicillin V 31 mg/kg orally in rodents increased oxidative stress, mitochondrial dysfunction (altered complex activity) and neuroinflammation in brain regions; complexes assayed, directions, group sizes and magnitudes were not retrieved (the Wiley page did not open). Kalghatgi 2013 [20] (Tier C for this drug): the abstract states that quinolones, aminoglycosides and beta-lactams caused mitochondrial dysfunction and ROS overproduction in mammalian cells; no drug names appear in the abstract record and ampicillin-level data were not read. The 2025 Sailer respirometry study of gentamicin, ciprofloxacin and amoxicillin in human cells (read for the amoxicillin dossier) did not include penicillin V and is not used.

Mechanism

Named only at pathway level in the abstract (oxidative stress and complex activity changes in brain tissue). Not shown in human tissue.

Cohort test

CLASS EXTRAPOLATION (beta-lactams) for Kalghatgi: penicillin V not confirmed in the cohort. Shekhar is penicillin V itself (Tier B). No grade above yellow is possible without human data.

Counter-evidence held on record

Counter-evidence and confounding A single rodent abstract at a perinatal-exposure design does not describe a human course of a few days. Cell-level mitochondrial effects reported for bactericidal antibiotics occurred in cultured cells at doses whose human relevance was not assessed here. Framing caution Theoretical and non-human. Do not present penicillin V as mitochondrially toxic in people and do not recommend mitochondrial or antioxidant supplements from this entry.

Oxidative Stress

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

Oxidative stress: no change in urinary oxidized nucleic acids or plasma malondialdehyde in a placebo-controlled human trial of penicillin V; oxidative stress and mitochondrial dysfunction in perinatally exposed rodent brain

Yellow — Low

See study details

In healthy men, one week of penicillin V 330 mg twice daily did not change urinary 8-oxodG (P = 0.63) or 8-oxoGuo (P = 0.90) versus placebo, while a rodent study reports higher oxidative stress in hippocampus and prefrontal cortex after perinatal penicillin V.

Full detail and limits

Limits on what this shows

Null findings: Larsen 2017: penicillin V had no effect on oxidative nucleic acid modifications [18].

Direction

Neutral in humans (null); excess oxidative burden in an animal model. No antioxidant nutrient was measured, so this is not a depletion, and supplementation is not supported by this entry.

Regulatory status

Not mentioned in the label text read [1][2].

Population evidence

Larsen 2017 [18] (Tier A, PENTRIOX trial, double-blind randomized placebo-controlled, three parallel groups; 90 randomized, baseline group sizes 28 placebo, 29 penicillin V, 30 trimethoprim; healthy Caucasian non-smoking men; penicillin V 330 mg twice daily with meals for 1 week): urinary 24 h 8-oxodG, penicillin V versus placebo P = 0.63; 8-oxoGuo P = 0.90; plasma malondialdehyde not changed by any antibiotic (P > 0.05, pooled). No confidence intervals were given for penicillin V; clarithromycin in the companion trial raised 8-oxodG by 22.0% (95% CI 3.6 to 40.4%) and 8-oxoGuo by 14.9% (3.7 to 26.1%), and trimethoprim lowered 8-oxodG by 21.7% (5.8 to 37.6%), which shows the assay could detect changes. Read from the PMC full text through a summarizing fetch tool plus the PubMed record. The authors note small sample sizes and whole-body (not tissue) measurement. Shekhar 2025 [19] (Tier B, rodents, penicillin V 31 mg/kg orally in the perinatal period; abstract via OpenAlex only): gut dysbiosis by 16S sequencing, social and cognitive deficits, and "increased oxidative stress, mitochondrial dysfunction, and neuroinflammation" in hippocampus and prefrontal cortex, reversed by capric acid. The specific oxidative markers, species, group sizes and effect sizes were not available. Class (Tier C, CLASS EXTRAPOLATION): Kalghatgi 2013 [20] reports that clinically relevant doses of quinolones, aminoglycosides and beta-lactams caused mitochondrial dysfunction and oxidative damage in mammalian cells and mice; the abstract names classes, not drugs, and penicillin V was not confirmed to be tested.

Mechanism

Proposed for bactericidal antibiotics (mitochondrial reactive oxygen species); not shown for penicillin V in humans. The rodent abstract links the effect to dysbiosis and mitochondria.

Cohort test

Penicillin V was in Larsen [18] and Shekhar [19]. Kalghatgi [20] is class extrapolation with penicillin V not confirmed in the cohort.

Counter-evidence held on record

Counter-evidence and confounding The only human measurement is null, at a low dose (660 mg/day) for 1 week in healthy young men, which does not address long courses, children, or tissue-level effects. The rodent dose is per kg body weight in the perinatal window and is not a human treatment exposure. Framing caution Theoretical animal and class signal against a null human trial. Do not present as an expected effect in people and do not recommend antioxidant supplements.

Copper and Iron Balance

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

Copper: in vitro hydrolysis of penicillin V by cupric ion (copper acting on the drug); no human copper measurement

Yellow — Low

See study details

Laboratory studies cited in a 2023 review show cupric ion hydrolyzing penicillin G and V to penicilloic acids under mild acidic conditions, a nutrient acting on the drug, and no study measured copper status in penicillin V users.

Full detail and limits

Limits on what this shows

Null findings: No human study of penicillin V with a copper outcome was located in the PubMed listings tried [24].

Direction

Nutrient affecting the drug (in vitro), not the drug depleting the nutrient (Hard Rule 4).

Regulatory status

Copper is not mentioned in the label text read [1][2].

Population evidence

None in humans. A 2023 review of in vitro work [21] (read through a summarizing fetch tool; primary studies not opened) states: "Under mild acidic conditions, both penicillin G and V were hydrolysed by the cupric ion into penicilloic acids", from earlier studies at non-physiological pH. A 2018 study cited in the same review found that penicillin G "does not form a complex with Cu2+ under physiological conditions" and that penicillin G showed decreased activity against S. aureus in the presence of copper, possibly from slow copper-induced degradation. The review does not mention phenoxymethylpenicillin by that name and gives no concentrations.

Mechanism

Copper-catalyzed hydrolysis of the beta-lactam ring in vitro. Physiological relevance (plasma copper, ceruloplasmin, absorption or excretion) is not shown.

Cohort test

In vitro (Tier B) for penicillin V as the substrate; no human cohort exists. The aminopenicillin results in the same review are not applied to penicillin V.

Counter-evidence held on record

Counter-evidence and confounding The primary studies were not opened and the review itself describes results as inconsistent for the other penicillins it covers. Copper status was not measured in anyone. Framing caution Not a depletion claim and not a reason to take copper. No copper dose appears in this dossier.

Iron

Not graded — disclosed evidence gap

See study details

No evidence was found that penicillin V alters iron absorption, status or loss, and no circulating claim about iron and penicillin V 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 on the channels reachable: no Tier B or C source supports even a yellow grade, and no circulating consumer claim on iron and penicillin V was found to rebut. Not a finding of safety; re-check with PubMed access restored.

What was searched

Label text: no iron statement, no interaction section [1][2][3]. PubMed "penicillin V ferritin OR iron absorption" and "penicillin V iron deficiency OR ferrous": ten records, all about oral iron products or unrelated topics, none a human study of penicillin V with an iron or ferritin outcome [24]. PubMed "phenoxymethylpenicillin vitamin" listing: no iron study. Hemolytic anemia reports are carried under Oxygen delivery/utilization, not here. Pharmacy reference (PubChem HSDB/DrugBank text) mentions no iron interaction [6].

Channel outcomes

The PubMed phrasings "phenoxymethylpenicillin iron OR copper OR ferritin", "phenoxymethylpenicillin ferritin" and "penicillin V hemoglobin OR anaemia" returned 429 and were not read; the Europe PMC search endpoint also returned 429. Open-web search budget was exhausted, so no consumer-claim search for iron was possible. A thin literature is likely but not established; mixed genuine gap and tooling-limited.

Gut Microbiome Risk

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

Gut microbiome risk: transient rise in ampicillin-resistant Enterobacterales and new Gram-negative colonization after a 5 to 10 day course, with small change in total flora; bounded to short courses in healthy adults and pharyngitis patients

Orange — Moderate

See study details

Penicillin V raised carriage of ampicillin-resistant Enterobacterales from 52% to 86% in 31 pharyngotonsillitis patients (statistically lost 7 to 9 days after the course, though new resistant and non-E. coli Gram-negative colonization persisted), while healthy-volunteer and population data show only minor shifts in total intestinal flora and few species associations.

Full detail and limits

What the grade means here: 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. Orange

Limits on what this shows

Null findings: Adamsson and the Elvers stratum found minor or no change in total intestinal flora [7][8]. Baldanzi found no diversity association for penicillin V in the text read and only 29 species associations, against hundreds for clindamycin [10].
At-risk subgroups: Patients on 10 day rather than 5 day courses were not separated in the records read. Neonates, young infants and renal impairment have delayed penicillin V excretion (label), which was not linked to microbiome outcomes. No infant gut microbiome cohort for penicillin V was found.

Direction

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

Regulatory status

Label: "Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile"; CDAD "has been reported with use of nearly all antibacterial agents" and "may range in severity from mild diarrhea to fatal colitis"; "Prolonged use of antibiotics may promote the overgrowth of nonsusceptible organisms, including fungi." A second label copy adds that CDAD "has been reported to occur over two months after the administration of antibacterial agents" [1][2]. Diarrhea is among the most common oral penicillin reactions [1].

Population evidence

Rystedt 2023 [9] (Tier A, observational pre/post, penicillin V only): 31 primary care patients with group A streptococcal pharyngotonsillitis, penicillin V for 5 days (800 mg four times daily) or 10 days (1000 mg three times daily); 29 gave three faecal swabs (start, last dose, follow-up 7 to 9 days after). Ampicillin-resistant Enterobacterales colonization rose from 52% to 86% between first and second samples (P = 0.007); Enterobacterales with decreased third-generation cephalosporin susceptibility rose from 32% to 52% (P = 0.034); "no longer significant at follow-up". New colonization with ampicillin-resistant Enterobacterales species and non-Enterobacterales Gram-negative species appeared and persisted at follow-up. No confidence intervals, no diversity measure and no per-arm (5 versus 10 day) split were available in the records read (abstract and OpenAlex summary only). Adamsson 1997 [8] (Tier A, randomized comparison of cefadroxil and phenoxymethylpenicillin, 20 healthy volunteers across the two drugs; penicillin V 1 g twice daily for 10 days per the abstract): "caused a strong decrease in the number of viridans streptococci" in the oropharynx with Neisseria overgrowth; changes in intestinal aerobic and anaerobic counts were minor; flora "became normalised 2 weeks after withdrawal". Per-arm n and count data not retrieved (abstract through a summarizer). Elvers 2020 systematic review [7] (Tier A, stratified by drug): two phenoxymethylpenicillin studies, both healthy volunteers. The very early study found no effect on aerobic and anaerobic faecal counts. The later study (likely Adamsson 1997, not confirmed from the page read) found no significant change in total aerobic and anaerobic flora, three volunteers newly colonised with Klebsiella sp, one with high numbers of a non-fermentative Gram-negative rod, E. coli minor alterations, median Clostridium counts up during treatment, Bacteroides unaffected, normalised two weeks after withdrawal. Review conclusion: "did not have much effect on gut microbiome". Sample sizes and doses were not in the text retrieved. Baldanzi 2026 [10] (Tier A, Swedish register-linked cohort, 14,979 adults, metagenomes versus prescriptions in the prior 8 years): clindamycin, fluoroquinolones and flucloxacillin drove most associations (richness 47, 20 and 21 fewer species per course for use under 1 year before sampling); penicillin V was associated with 29 species and no diversity effect is reported for it in the text read (figure values not available). Read through a summarizing fetch tool and an OpenAlex abstract. Case report [11] (Tier B): one 1-year-old child with otitis media on penicillin V; faecal resistance genes 7 at baseline, 5 at day 5 and 21 at day 30 (oral genes mostly back to baseline by day 30). n = 1; abstract only.

Mechanism

Present and named in the label: antibacterial action against susceptible commensals with overgrowth of resistant organisms (resistant Enterobacterales and Klebsiella in the cohorts above) [1][7][9].

Cohort test

Penicillin V was in the cohort of Rystedt [9], Adamsson [8], Baldanzi [10], the Elvers stratum [7] and the child case [11]. Korpela 2016 [12] (142 Finnish children aged 2 to 7) states that penicillins left a weaker mark than macrolides; the abstract does not name penicillin V, so it is Tier C for this drug (CLASS EXTRAPOLATION, not used for the grade). McDonnell 2021 and Reyman 2022 (pediatric and neonatal listing lines) concern unspecified or intravenous penicillins and were not used [24]. Raju 2020 [13] (808 Finnish children, saliva rather than gut, penicillin V associated with a decrease in one genus; listing summary only) is an oral microbiome study and was not used for the grade. No amoxicillin-cohort result or class grade was carried over from the amoxicillin dossier.

Why orange, not red

At least one Tier A source with penicillin V (Rystedt) shows a real shift, but it is a culture and colonization endpoint with no CI and no diversity index, the resistant-carriage rise was not significant at 7 to 9 days, and the other Tier A sources report minor or no change in total flora. Red needs consistent direction and clinically meaningful magnitude across two independent sources; Adamsson and Baldanzi are not a second consistent, quantified source.

Counter-evidence held on record

Counter-evidence and confounding Rystedt had no untreated comparator and patients had an acute infection; Adamsson's volunteers numbered 20 across two drugs; Baldanzi is an association study of dispensing records, not a course-by-course trial. Prescription-register exposure and culture endpoints are not equivalent to metagenomic diversity. Framing caution This is a disturbance risk, not a deficiency. No probiotic, fiber or vitamin supplement is recommended by this entry, and nothing here says a short course causes lasting harm. New severe or persistent diarrhea during or up to two months after a course needs clinical assessment for C. difficile (label warning).

Oxygen and ATP Output

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

Oxygen delivery/utilization: label-listed hemolytic anemia (infrequent, usually high-dose parenteral) and oral penicillin V immune hemolysis case reports; adverse outcome, not a nutrient deficiency

Yellow — Low

See study details

The label lists hemolytic anemia as infrequent and usually tied to high-dose parenteral penicillin, and two case reports describe immune hemolysis on oral penicillin V, but no incidence figure or hemoglobin cohort exists for oral penicillin V.

Full detail and limits

Limits on what this shows

Null findings: None located; absence of a cohort is a gap, not reassurance.

Direction

Drug toxicity (idiosyncratic immune red-cell destruction). Not iron deficiency and not an oxygen-carrying nutrient deficit (Hard Rule 2). Kept separate from Iron and ATP production (Hard Rule 7).

Regulatory status

Label: "Hemolytic anemia, leukopenia, thrombocytopenia, neuropathy, and nephropathy are infrequent reactions" and are "usually associated with high doses of parenteral penicillin" [1][2].

Population evidence

Case level only (Tier B), seen as PubMed listing lines and a metadata record [17]: Jelic 1977, a healthy man with Coombs-positive hemolytic anemia and thrombocytopenia on oral phenoxymethylpenicillin with a drug-dependent IgG antibody (listing summary; article not opened); Schlatterer 2023, a 28-year-old man with penicillin V-induced immune hemolysis presenting as macrohematuria that resolved after stopping (listing summary; the OpenAlex record had no abstract, and no hemoglobin values were retrieved); Dove 1975, a short report of penicillin hemolytic anemia in an adult woman (penicillin type not specified in the listing). No cohort comparing hemoglobin or hematocrit in penicillin V users with non-users was located.

Mechanism

Immune, drug-dependent antibody (named in the Jelic listing summary); not tested beyond case level.

Counter-evidence held on record

Counter-evidence and confounding Single cases cannot give a frequency; the label itself places most events with parenteral high doses. The case reports were read only as listing summaries. Framing caution Report new jaundice, dark urine or unexplained pallor and fatigue during a course to a clinician. Do not read this as an iron or oxygen-delivery deficiency; iron supplements are not indicated by this entry.

ATP production

Not graded — disclosed evidence gap

See study details

No ATP, oxidative phosphorylation or respiration measurement with penicillin V in any model was found, and no circulating claim on penicillin V and 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 the evidence reachable: no Tier B or C source measures ATP, respiration or membrane potential for penicillin V, and no circulating claim was found to rebut as white. Kept independent of Mitochondrial burden and Oxygen delivery/utilization (Hard Rule 7). This is a disclosed gap, not a finding of safety; re-check with the Shekhar full text and PubMed access.

What was searched

PubMed "phenoxymethylpenicillin mitochondria": No results found [24]. PubMed "penicillin V mitochondrial", "penicillin V mitochondrial respiration", "phenoxymethylpenicillin mitochondrial toxicity" and "penicillin V mitochondria antibiotic": 429, bot-check or client errors; not read. PubMed "phenoxymethylpenicillin oxidative stress" returned Larsen 2017 [18] and Shekhar 2025 [19]; neither reports ATP. The Shekhar abstract mentions altered mitochondrial complex activity (carried under Mitochondrial burden); complex activity is not an ATP or respiration measurement. Kalghatgi 2013 [20] abstract names no ATP endpoint. Label: no statement [1][2].

Channel outcomes

Open-web search budget was exhausted before consumer-claim searches for energy or ATP could be run, so the absence of a circulating claim is tooling-limited. The Shekhar full text (Wiley) did not open, so an ATP endpoint in its methods is not excluded. This is a mixed result: a genuine absence on the channels that worked, plus tooling limits.

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.

B vitamins (B12, folate, biotin, vitamin K2) 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 penicillin V was found, and the claim was not traced to a specific origin because the web-search budget was exhausted.
Why it fails: The NIH folate fact sheet says colonic folate synthesis exists but its contribution to status is "unclear" and lists methotrexate, antiepileptics and sulfasalazine as interacting drugs, not antibiotics; the biotin sheet does not mention antibiotics or gut synthesis [23]. Penicillin V's own Tier A data show only minor change in total intestinal flora [7][8], and no study measured any B vitamin in penicillin V users. The only B12 finding is a laboratory artifact on an old assay, carried as its own yellow entry [22]. The mechanism is not impossible (resistant-carriage changes occur [9]) but is unmeasured; held out of publication as a deficiency claim pending a re-check that could convert it to yellow.
"Penicillin V causes vitamin K deficiency or bleeding" as a stated fact
Where it comes from: Reference statements about antibiotics in general [15] and the hypoprothrombinemia literature on cephalosporins and extended-spectrum penicillins [24].
Why it fails: The NIH sheet names cephalosporins and uses hedged wording ("potentially") and does not name penicillin. In warfarin users, INR rose only from 2.49 to 2.52 after starting penicillin V and the proportion below INR 2 stayed near 15% [14]. No vitamin K level was measured. Carried as yellow with the drug-interaction direction explicit, not as a deficiency.
Penicillin V "wipes out" or permanently destroys gut flora
Where it comes from: Generic consumer and probiotic-marketing framing; not traced to a single page.
Why it fails: Total intestinal counts changed little and normalised two weeks after the drug in healthy volunteers [7][8], and the rise in resistant Enterobacterales was not significant 7 to 9 days after the course [9]. "Permanent" fails as stated. It is not a reassurance either: new ampicillin-resistant Enterobacterales and non-E. coli Gram-negative colonization persisted at follow-up [9] and one child's faecal resistance genes rose from 7 to 21 at day 30 (n = 1) [11].
Penicillin V creates oxidative stress or mitochondrial damage in people
Where it comes from: The bactericidal-antibiotic mitochondrial toxicity literature [20] and rodent exposure work [19].
Why it fails: In the one randomized placebo-controlled human trial, penicillin V did not change urinary 8-oxodG (P = 0.63) or 8-oxoGuo (P = 0.90), and none of the antibiotics changed plasma malondialdehyde [18]. The Kalghatgi abstract names classes, not penicillin V. The positive finding is a perinatal rodent abstract. Stated as a human effect it fails; the animal and class signals are carried as yellow entries with these limits shown.
Low serum B12 on a penicillin course means a true B12 deficiency
Where it comes from: Inference from a low reading by the L. leichmanii microbiological method [22].
Why it fails: Radioisotope and Euglena gracilis assays were unaffected in that study and the authors say other methods may be needed to separate artifact from true depletion [22]. Carried as a yellow assay-interference entry; no true B12 change was shown.

How the body handles this medication

Metabolism and enzymes: About 35 to 70% of an oral dose is metabolized to penicilloic acid (inactive); small amounts of 6-aminopenicillanic acid and a hydroxylated active metabolite are reported. No CYP450 enzyme is named in the label or in the PubChem metabolism text.[1] label (CYP: absent); [6] PubChem/DrugBank/HSDB
Elimination: "The drug is excreted as rapidly as it is absorbed in individuals with normal kidney function"; excretion is "considerably delayed" in neonates, young infants and impaired kidney function. Serum half-life about 0.5 hour in normal renal function, up to 4 hours in renal impairment.[1] label; [6] HSDB/DrugBank
Absorption: Only about 25% of the dose given is recovered in urine, which the label reads as the absorbed fraction; DrugBank gives 25 to 60% bioavailability and AHFS 60 to 73% in fasting adults. The potassium salt is absorbed slightly better than the free acid. No absorption transporter is named in the sources read.[1][6]
Distribution: About 80% bound to serum protein; volume of distribution 35.4 L at steady state after IV administration; highest tissue levels in kidney, then liver, skin and intestine.[1][6]
Interactions of nutritional interest: Food: "may be given with meals; however, blood levels are slightly higher when the drug is given on an empty stomach". No iron, calcium, antacid or other mineral interaction and no probenecid, neomycin, anticoagulant or oral contraceptive statement appears in the label copies read.[1][2]
Electrolyte content: Potassium salt: 500 mg tablet contains 1.43 mEq (55.8 mg) of potassium and 250 mg tablet 0.71 mEq (27.9 mg) on the Chartwell label; no sodium figure is stated and hypokalemia is not mentioned in any label copy read.[3] (Tier D reproduction of a label); [1][2]

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.

Symptoms / during and after a course
Severe or persistent diarrhea
New watery or bloody diarrhea with cramping or fever, during or after a course, warrants clinical assessment for C. difficile infection; the label warns that CDAD has been reported with nearly all antibacterial agents and may occur more than two months after treatment [1][2]. This is a clinical outcome, not a nutrient finding.
Lab / anticoagulated patients
INR
The label read has no INR statement, and warfarin users did not show a fall or meaningful rise in mean INR after starting penicillin V in one large register cohort [14]. Routine extra INR checks are not supported by this evidence; any anticoagulant adjustment belongs to the prescriber. Vitamin K is not a remedy to add.
Lab / unusual symptoms
Complete blood count
Jaundice, dark urine, new pallor or unexplained fatigue during a course justify a blood count and review for hemolysis (label-listed, infrequent) [1]. Iron indices are not the first test for this problem.
Renal
Kidney function
Excretion is considerably delayed in neonates, young infants and impaired kidney function (label), and the half-life can extend to about 4 hours [1][6]. Dose selection is a prescriber matter.
Electrolytes
Potassium
Not routinely indicated for oral penicillin V on this evidence: the potassium in the salt is small (1.43 mEq per 500 mg tablet on one label) and no hypokalemia report was found [3][24]. Consider only if renal impairment, high cumulative tablet counts, potassium-affecting drugs or prolonged vomiting or diarrhea are also present.
Lab method
Vitamin B12 testing
An unexpectedly low B12 on a penicillin course may reflect the older microbiological assay rather than true depletion; the prescriber or laboratory can confirm the method [22].
Timing
Food, milk and supplement separation
The label allows dosing with meals; blood levels are slightly higher on an empty stomach, and young children dosed with milk had lower peak and AUC in older studies [1][6]. No separation interval from any vitamin, mineral or antacid is given in the label text read. No supplement dose is recommended or appears anywhere in this dossier, so no upper-limit comparison was needed.
Special populations
Pregnancy, infants, older adults
Pregnancy and pediatric nutrient considerations were not assessed from the label sections read. No infant gut microbiome cohort for penicillin V was found; the only child data are one 1-year-old with otitis media and a Finnish pre-school cohort that did not name penicillin V [11][12].

Overlap map, to prevent double counting

Gut microbiome risk
Shares evidence with: Vitamin K and prothrombin; Dietary intake and GI loss; Fails verification: B vitamins
Note: The same mechanism (loss of susceptible gut bacteria) underlies the proposed vitamin K route, the diarrhea component and the B-vitamin claim, and the label CDAD and flora statements support all of them. Treat as one mechanism, not several confirmations.
Oxidative stress
Shares evidence with: Mitochondrial burden; ATP production (ungraded)
Note: Shekhar 2025 (rodent brain: oxidative stress and mitochondrial dysfunction in one abstract) and Kalghatgi 2013 support both yellow entries; Larsen 2017 is an oxidative-marker null that does not test mitochondria. ATP production has no evidence of its own.
Oxidative stress
Shares evidence with: Gut microbiome risk
Note: The Shekhar abstract reports dysbiosis and oxidative stress together in the same animals. It is not independent confirmation of either entry.
Oxygen delivery/utilization
Shares evidence with: Iron (ungraded)
Note: Hemolytic anemia is a drug-toxicity outcome and is not an iron finding. Iron has no evidence of its own here.
Copper
Shares evidence with: Iron; Oxidative stress
Note: No shared source with Iron. The copper evidence is one review of in vitro studies; it does not support the oxidative stress entry. The pair is graded separately per Hard Rule 7.
Potassium
Shares evidence with: Dietary intake and GI loss
Note: Both rest on label wording; no shared study. Diarrhea could lower potassium without any penicillin-specific mechanism, so the two cannot be added together.
Food and milk
Shares evidence with: Dietary intake and GI loss
Note: Both involve meals, but the food entry is a nutrient-to-drug absorption timing interaction and the other is an adverse-reaction context flag. They share no study.
Vitamin B12 (assay interference)
Shares evidence with: Fails verification: B vitamins
Note: Powell 1969 is the only B-vitamin-related source and is an assay artifact; it is cited in both places and is not independent evidence of a depletion.
Gut microbiome risk (cross-dossier)
Shares evidence with: Amoxicillin dossier (b016)
Note: The amoxicillin dossier grades its gut microbiome entry orange on amoxicillin-only cohorts. No amoxicillin cohort included penicillin V, so none of its sources or its grade were carried over. The Elvers 2020 systematic review appears in both because its penicillin V stratum was read separately here.

All references used above

Penicillin V

Findings for this medication

What the research found

Vitamin K and prothrombin: label silent; INR did not rise in warfarin users starting penicillin V (negative-control arm); vitamin K never measured; high-dose hypoprothrombinemia literature concerns other beta-lactams (CLASS EXTRAPOLATION)

Potassium: label-identified potassium salt contributes a small potassium load; hypokalemia is not label-listed and no penicillin V case was found (excess/retention direction, context flag)

Dietary intake and GI loss: label-listed nausea, vomiting, epigastric distress, diarrhea and black hairy tongue (context flag, no nutrient measured)

Food and milk: timing interaction in which food lowers or delays penicillin V absorption (nutrient affecting the drug, not drug depleting a nutrient)

Vitamin B12: older microbiological serum assay can read falsely low on penicillin therapy (assay interference, not depletion)

The five body-system areas

⚡Mitochondrial Burden

Mitochondrial burden: no human measurement; one rodent abstract reports mitochondrial dysfunction in brain after perinatal penicillin V; beta-lactam class study (CLASS EXTRAPOLATION)

💥Oxidative Stress

Oxidative stress: no change in urinary oxidized nucleic acids or plasma malondialdehyde in a placebo-controlled human trial of penicillin V; oxidative stress and mitochondrial dysfunction in perinatally exposed rodent brain

⚖️Copper and Iron Balance

Copper: in vitro hydrolysis of penicillin V by cupric ion (copper acting on the drug); no human copper measurement

Iron

🌿Gut Microbiome Risk

Gut microbiome risk: transient rise in ampicillin-resistant Enterobacterales and new Gram-negative colonization after a 5 to 10 day course, with small change in total flora; bounded to short courses in healthy adults and pharyngitis patients

💨Oxygen and ATP Output

Oxygen delivery/utilization: label-listed hemolytic anemia (infrequent, usually high-dose parenteral) and oral penicillin V immune hemolysis case reports; adverse outcome, not a nutrient deficiency

ATP production

Claims checked and not supported

B vitamins (B12, folate, biotin, vitamin K2) lost through reduced gut-flora synthesis (provisional, tooling-limited)

"Penicillin V causes vitamin K deficiency or bleeding" as a stated fact

Penicillin V "wipes out" or permanently destroys gut flora

Penicillin V creates oxidative stress or mitochondrial damage in people

Low serum B12 on a penicillin course means a true B12 deficiency

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