Penicillin V

What it is

Penicillin V is a natural penicillin made by fermentation, the phenoxymethyl analogue of penicillin G. It is dispensed as the potassium salt, penicillin V potassium, in 250 mg (400,000 unit) and 500 mg (800,000 unit) tablets and as a powder for oral solution. The potassium salt resists stomach acid, which is what makes it usable by mouth, and gives blood levels two to five times higher than the same dose of oral penicillin G. Absorption is incomplete and variable: urine recovery suggests only about 25% of a dose is absorbed.

What the research says

It kills bacteria that have no penicillinase, chiefly group A, C, G, H, L and M streptococci and pneumococci, by stopping them building a cell wall. What that buys a patient depends entirely on the condition. For strep throat the pooled trial evidence is a real but modest symptom benefit, with most people recovering within a week without any antibiotic, plus a clearer reduction in local complications such as quinsy and middle-ear infection. For preventing repeat episodes of leg cellulitis the evidence is good and the absolute benefit large. For preventing recurrent rheumatic fever the oral form is the weaker option: injected penicillin beat it in every head-to-head trial. For endocarditis prophylaxis there is no controlled efficacy trial at all. Harms are mostly gut upset and rash, with rare but potentially fatal anaphylaxis and the antibiotic-class risk of C. difficile colitis.

Evidence grade: Well established.

How it works

Drug class: Narrow-spectrum beta-lactam antibiotic (natural penicillin), acid-stable oral form

Penicillin V kills bacteria rather than merely slowing them, and only while they are actively dividing. It blocks the final cross-linking step in building the bacterial cell wall (the wall peptide, or mucopeptide), so the growing wall fails and the cell bursts. Human cells have no such wall, which is why the drug is selective. It is the acid-stable version of penicillin G, so it survives the stomach and can be swallowed, and it has no activity against bacteria that make penicillinase, which includes most staphylococci today. (Source 1)

What it is used for

• Antibiotics for sore throat work, modestly. Cochrane's 2021 review of 29 trials and 15,337 cases found sore throat at day three reduced (RR 0.70) with a number needed to treat under six, but 82% of untreated people were better within a week anyway, and fever was not reduced. Most of those trials were run in the 1950s when rheumatic fever was far commoner, so the complication-prevention numbers do not transfer cleanly to high-income countries today. A 2019 Swedish trial showed five days of penicillin V four times daily was non-inferior to the standard ten-day course for clinical cure, though bacterial eradication was lower. Evidence: established. (Source 2)
• The label says continuous oral penicillin “has proven effective”, but the trial evidence puts oral penicillin second. Cochrane's 2002 review found that in all four head-to-head trials (1,098 patients) intramuscular penicillin beat oral penicillin at preventing both rheumatic fever recurrence and streptococcal throat infection, and judged the overall quality of the trials poor. Evidence: disputed. (Source 3)
• Approved on long clinical use rather than on modern placebo-controlled trials. The label restricts it to mild to moderately severe infection caused by penicillin G-sensitive organisms, and explicitly excludes the acute stage of severe pneumonia, empyema, bacteraemia, pericarditis, meningitis and arthritis. Evidence: limited. (Source 4)
• The strongest single piece of evidence for penicillin V. In the PATCH I double-blind randomised trial (274 patients, 28 hospitals), 250 mg twice daily for 12 months cut recurrence from 37% to 22% during prophylaxis, hazard ratio 0.55, number needed to treat 5. Adverse events did not differ from placebo. The benefit faded once the drug stopped. Evidence: established. (Source 5)
• The label itself concedes there is no efficacy trial: it states that “no controlled clinical efficacy studies have been conducted” and that the regimen was suggested by the American Heart Association and American Dental Association, citing a 1984 statement. It also says oral penicillin should not be used in those at particularly high risk, such as people with prosthetic valves. Evidence: not-supported. (Source 6)
• An approved indication resting on clinical experience; no controlled trial for this use was found in the literature we could reach. Evidence: limited. (Source 4)

Interactions

• Food and milk (label): Penicillin V can be taken with meals, but food lowers blood levels; the label states levels are slightly higher on an empty stomach. This is a pharmacokinetic effect, and the practical point is consistency rather than avoidance. (Source 7)
• Methotrexate (pharmacokinetic study): Penicillin competes with methotrexate for the same tubular secretion pathway in the kidney, so methotrexate is cleared more slowly and its blood levels rise. The direct evidence is an animal experiment in monkeys plus human case reports of methotrexate toxicity and pancytopenia after penicillin was added; there is no human pharmacokinetic trial. (Source 8)
• Hormonal contraceptives (combined pill, progestogen-only, vaginal ring) (clinical trial): Contrary to long-standing advice, the systematic review evidence does not support an interaction. Across 29 studies no antibiotic other than the rifamycins reduced progestin levels, suppressed ovulation less, or caused breakthrough bleeding, and two studies found no difference in pregnancy rates. (Source 9)
• Potassium supplements, potassium-sparing diuretics and salt substitutes (theoretical): Penicillin V is dispensed as the potassium salt, so each dose carries a small potassium load. The literature we reached does not quantify a clinically important effect at normal doses, and this is a theoretical concern that matters only for people with impaired potassium handling, such as advanced kidney disease. (Source 1)
• Alcohol (label): No interaction between alcohol and penicillin V was found in the literature we searched, and the label records none. The relevant label caution about the oral route is unrelated to alcohol: it is that the oral route should not be relied on in people who are severely ill or vomiting - which heavy drinking can cause. (Source 10)
• Any oral drug in a person with poor absorption (label): Not a drug-drug interaction but worth recording alongside them: the label states some patients simply do not absorb therapeutic amounts of oral penicillin, which is one reason injected penicillin outperformed oral penicillin in the rheumatic fever prophylaxis trials. (Source 10)

Stopping it

• Penicillin V causes no dependence and no withdrawal syndrome; stopping it is about relapse of infection, not about the drug. The label takes the traditional position that a streptococcal course must run a 10-day minimum or the sequelae of streptococcal disease may follow. (Source 10)
• The trial evidence now partly contradicts that position. In a 433-patient randomised non-inferiority trial, stopping at five days (with four-times-daily dosing) gave the same clinical cure, shorter time to symptom relief and fewer, shorter adverse events than the ten-day course, although bacterial eradication was lower. (Source 11)
• Where penicillin V is taken long term as prophylaxis, stopping removes the benefit rather than causing withdrawal. In PATCH I, recurrence of leg cellulitis returned to the placebo rate once the 12 months of penicillin ended. (Source 12)
• Antibiotic-associated diarrhoea usually settles when the drug is stopped, but the label warns that watery or bloody stools can begin two or more months after the last dose, which is the C. difficile risk and needs medical attention rather than simple reassurance. (Source 13)

What goes wrong

Cochrane could not quantify the harms of antibiotics for sore throat because the trials reported them poorly. (Source 14)

• Systematic review, Certainty not rated.
• Size: 29 trials, 15,337 cases.
• Who: children and adults with sore throat.
• How long: varied.
• Result: no pooled harm estimate was possible; harms were poorly or inconsistently reported.
• Funding: not stated in the review record we read.

Harms from antibiotics were poorly or inconsistently reported, and were thus not quantified for this review.

Adverse events on penicillin V were mainly diarrhoea, nausea and vaginal discharge or itching, and were more frequent and longer-lasting on the ten-day course. (Source 15)

• Randomized trial, Moderate certainty.
• Size: 433 randomised; 132 physician-recorded events in the five-day group and 170 in the ten-day group.
• Who: patients with group A streptococcal pharyngotonsillitis.
• How long: five or ten days of treatment.
• Result: no serious adverse events; 73% (97/132) of five-day events and 61% (104/170) of ten-day events rated mild; higher incidence and longer duration in the ten-day group in all three categories.
• Funding: independent: Public Health Agency of Sweden.

The adverse events recorded by physicians were mainly diarrhoea, nausea, and vaginal discharge or itching. In all three categories, the 10 day group had higher incidence and longer duration of adverse events

Penicillin prophylaxis for cellulitis caused no more adverse events than placebo over a year. (Source 12)

• Randomized trial, High certainty.
• Size: 274 patients.
• Who: patients with recurrent leg cellulitis.
• How long: 12 months.
• Result: adverse events in 37 patients on penicillin versus 48 on placebo, P=0.50.
• Funding: independent: Action Medical Research.

There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50).

The label records fatal anaphylaxis as a reported harm of oral penicillin, and previous penicillin hypersensitivity as an absolute contraindication. (Source 16)

• Official position, Certainty not rated.
• Size: postmarketing reports; frequency not quantified.
• Who: anyone taking penicillin.
• How long: any duration.
• Result: no rate given; the label states reactions are reported with much less frequency after oral than parenteral therapy but that all degrees of hypersensitivity, including fatal anaphylaxis, have been reported with oral penicillin.
• Funding: label holder Hikma Pharmaceuticals USA; regulatory position revised January 2024.

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (anaphylactic) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY.

Clostridioides difficile associated diarrhoea, which can progress to fatal colitis, is a recognised harm of penicillin as of all antibacterials. (Source 17)

• Official position, Certainty not rated.
• Size: postmarketing reports; frequency not quantified.
• Who: anyone taking penicillin.
• How long: can begin more than two months after the last dose.
• Result: no rate given; severity ranges from mild diarrhoea to fatal colitis.
• Funding: label holder Hikma Pharmaceuticals USA; position revised January 2024.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including penicillin and may range in severity from mild diarrhea to fatal colitis.

The common, mild harms of oral penicillin are gastrointestinal, plus rash and other hypersensitivity reactions. (Source 13)

• Official position, Certainty not rated.
• Size: not quantified.
• Who: anyone taking oral penicillin.
• How long: any duration.
• Result: nausea, vomiting, epigastric distress, diarrhoea and black hairy tongue listed as the most common; fever and eosinophilia may be the only sign; haemolytic anaemia, leukopenia, thrombocytopenia, neuropathy and nephropathy listed as infrequent and usually associated with high parenteral doses.
• Funding: label holder Hikma Pharmaceuticals USA; position revised January 2024.

The most common reactions to oral penicillin are nausea, vomiting, epigastric distress, diarrhea, and black hairy tongue.

Prescribing penicillin V without a proven or strongly suspected bacterial infection gives no benefit and increases drug resistance. (Source 10)

• Official position, Certainty not rated.
• Size: not quantified.
• Who: anyone prescribed penicillin V.
• How long: any duration.
• Result: no rate given; stated as a labelling warning about antibacterial resistance.
• Funding: label holder Hikma Pharmaceuticals USA; position revised January 2024.

Prescribing penicillin V potassium tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

What the evidence supports

Antibiotics reduced sore throat at day three, but most untreated people recovered within a week regardless. (Source 2)

• Systematic review, Moderate certainty.
• Size: 29 trials, 15,337 cases of sore throat.
• Who: children and adults presenting to medical care with sore throat; most participants adults.
• How long: symptoms assessed at day three and one week.
• Result: sore throat at day three RR 0.70 (95% CI 0.60 to 0.80; 16 studies, 3,730 participants); at one week RR 0.50 (95% CI 0.34 to 0.75); NNTB under six at day three and 18 at one week; 82% of the placebo or no-treatment group were symptom-free by one week.
• Funding: not stated in the review record we read.

The number needed to treat for an additional beneficial outcome (NNTB) to prevent one sore throat at day three was less than six; at week one it was 18.

Antibiotics reduced suppurative complications of sore throat - acute otitis media and quinsy - but not acute sinusitis. (Source 2)

• Systematic review, High certainty.
• Size: 10 studies, 3,646 participants (otitis media); 8 studies, 2,433 (quinsy)
• Who: children and adults with sore throat.
• How long: 14 days to two months.
• Result: acute otitis media Peto OR 0.21 (95% CI 0.11 to 0.40); quinsy Peto OR 0.16 (95% CI 0.07 to 0.35); acute sinusitis Peto OR 0.46 (95% CI 0.10 to 2.05, not significant)
• Funding: not stated in the review record we read.

antibiotics reduced the incidence of acute otitis media within 14 days (Peto odds ratio (OR) 0.21, 95% CI 0.11 to 0.40; 10 studies, 3646 participants; high-certainty evidence) and quinsy within two months (Peto OR 0.16, 95% CI 0.07 to 0.35; 8 studies, 2433 participants; high-certainty evidence)

Five days of penicillin V four times daily was non-inferior to ten days three times daily for clinical cure in streptococcal pharyngotonsillitis. (Source 18)

• Randomized trial, Moderate certainty.
• Size: 433 randomised (215 five-day, 218 ten-day)
• Who: patients aged 6 and over with group A streptococcal pharyngotonsillitis and three or four Centor criteria, 17 Swedish primary care centres.
• How long: treatment five or ten days, follow-up to three months.
• Result: clinical cure 89.6% (181/202) on five days versus 93.3% (182/195) on ten days, 95% CI of the difference -9.7 to 2.2, within the prespecified 10 percentage point non-inferiority margin.
• Funding: independent: funded by the Public Health Agency of Sweden and the Healthcare Committee, Region Vastra Gotaland; authors declared no financial relationships with interested organisations.

Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval -9.7 to 2.2).

Low-dose penicillin V cut recurrence of leg cellulitis during prophylaxis, with a number needed to treat of five. (Source 5)

• Randomized trial, High certainty.
• Size: 274 patients recruited in 28 hospitals in the UK and Ireland.
• Who: patients with two or more previous episodes of cellulitis of the leg.
• How long: 12 months of treatment, followed up to three years.
• Result: recurrence during prophylaxis 30/136 (22%) on penicillin versus 51/138 (37%) on placebo; hazard ratio 0.55 (95% CI 0.35 to 0.86), P=0.01; NNT 5 (95% CI 4 to 9); median time to first recurrence 626 versus 532 days.
• Funding: independent: funded by Action Medical Research.

During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9).

Treatment-related adverse events were markedly less frequent on penicillin V than on azithromycin in children. (Source 19)

• Randomized trial, Moderate certainty.
• Size: 500 children assessable for safety (167 penicillin V)
• Who: children aged 2 to 12 with group A streptococcal tonsillopharyngitis.
• How long: penicillin V for 10 days versus azithromycin for 3 days.
• Result: treatment-related adverse events 5/166 (3%) on penicillin V versus 31/169 (18.3%) and 37/164 (23%) on the two azithromycin doses.
• Funding: not stated in the record we read.

The incidence of treatment-related adverse events was similar in the two azithromycin groups [AZM 10 mg, 31 of 169 (18.3%); AZM 20 mg, 37 of 164 (23%)] but significantly higher than those observed in the penicillin V group [5 of 166 (3%)

What the evidence does not support

Antibiotics did not reduce fever at day three in sore throat, on high-certainty evidence. (Source 2)

• Systematic review, High certainty.
• Size: 8 studies, 1,443 participants.
• Who: children and adults with sore throat.
• How long: day three.
• Result: fever at day three RR 0.75 (95% CI 0.53 to 1.07)
• Funding: not stated in the review record we read.

Compared with placebo or no treatment, antibiotics did not significantly reduce fever at day three (RR 0.75, 95% CI 0.53 to 1.07; 8 studies, 1443 participants; high-certainty evidence)

The shorter penicillin V course cleared the bacteria less well, even though patients recovered just as often. (Source 18)

• Randomized trial, Moderate certainty.
• Size: 376 with culture data.
• Who: patients with group A streptococcal pharyngotonsillitis.
• How long: five or ten days.
• Result: bacteriological eradication 80.4% (156/194) on five days versus 90.7% (165/182) on ten days.
• Funding: independent: Public Health Agency of Sweden.

Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group.

Once penicillin prophylaxis stopped, the protection disappeared - recurrence rates were identical to placebo. (Source 5)

• Randomized trial, High certainty.
• Size: 274 patients.
• Who: patients with recurrent leg cellulitis.
• How long: no-intervention follow-up after 12 months of treatment.
• Result: first recurrence 27% in both groups during the no-intervention period.
• Funding: independent: Action Medical Research.

During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups).

For preventing recurrent rheumatic fever, every head-to-head trial found injected penicillin better than oral penicillin. (Source 3)

• Systematic review, Low certainty.
• Size: 4 trials, 1,098 patients (9 studies, 3,008 patients in the whole review)
• Who: people with previous rheumatic fever.
• How long: varied.
• Result: all four trials favoured intramuscular over oral penicillin for both rheumatic fever recurrence and streptococcal throat infection; data were not pooled because of heterogeneity.
• Funding: not stated in the review record we read.

Four trials (n=1098) compared intramuscular with oral penicillin and all showed that intramuscular penicillin reduced rheumatic fever recurrence and streptococcal throat infections compared to oral penicillin.

In a large paediatric trial, penicillin VK eradicated the streptococcus in only 68% of children, below the threshold regulators normally expect of a first-line drug. (Source 20)

• Randomized trial, Moderate certainty.
• Size: 579 children randomised; 194 evaluable in the penicillin VK arm.
• Who: children aged 6 months to 12 years with acute streptococcal tonsillopharyngitis.
• How long: penicillin VK four times daily for 10 days versus once-daily amoxicillin sprinkle for 7 days.
• Result: bacteriological eradication 68.0% (132/194) for penicillin VK versus 65.3% (132/202) for amoxicillin sprinkle (95% CI -12.0% to 6.6%); clinical cure 91.9% (204/222) versus 86.1% (216/251)
• Funding: not stated in the record we read; the trial tested a manufacturer's modified-release amoxicillin formulation, so industry sponsorship should be assumed until checked.

Thus, neither antibiotic regimen met the minimum criterion of > or =85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes.

Where the evidence is mixed

Antibiotics reduced acute rheumatic fever after sore throat, but the trials were old and the baseline risk far higher than today. (Source 21)

• Systematic review, Moderate certainty.
• Size: 18 studies, 12,249 participants.
• Who: children and adults with sore throat, mostly in 1950s trials.
• How long: two months.
• Result: acute rheumatic fever Peto OR 0.36 (95% CI 0.26 to 0.50); the review notes the overall prevalence of acute rheumatic fever was very low, particularly in the later studies.
• Funding: not stated in the review record we read.

Antibiotics reduced acute rheumatic fever within two months when compared to the control group (Peto OR 0.36, 95% CI 0.26 to 0.50; 18 studies, 12,249 participants; moderate-certainty evidence).

The rheumatic fever prophylaxis trial evidence is of poor methodological quality, and only one of three placebo comparisons was positive. (Source 3)

• Systematic review, Very low certainty.
• Size: 9 studies, 3,008 patients; 3 trials (1,301 patients) against control.
• Who: people with previous rheumatic fever.
• How long: varied.
• Result: one of three trials showed penicillin reduced recurrence (RR 0.45, 95% CI 0.22 to 0.92) and streptococcal throat infection (RR 0.84, 95% CI 0.72 to 0.97); the reviewers judged overall methodological quality poor.
• Funding: not stated in the review record we read.

Only one of three studies showed that penicillin reduced rheumatic fever recurrence (RR 0.45, 95% CI 0.22 to 0.92) and streptococcal throat infection (RR 0.84, 95% CI 0.72 to 0.97).

Where the research disagrees

Whether a ten-day course is necessary for streptococcal pharyngitis

• The US penicillin V potassium label (Hikma Pharmaceuticals USA, revised January 2024), regulatory position, carried forward in labelling for decades and not supported in the label by a cited trial: In streptococcal infections, therapy must be sufficient to eliminate the organism (10-day minimum); otherwise the sequelae of streptococcal disease may occur. (Source 10)
• Skoog Stahlgren and colleagues, randomised open-label non-inferiority trial (BMJ 2019), 433-patient randomised controlled non-inferiority trial funded by the Public Health Agency of Sweden: Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval -9.7 to 2.2). (Source 18)

Whether oral penicillin is adequate for preventing recurrent rheumatic fever

• The US penicillin V potassium label, regulatory position; the label cites no controlled trial for this claim: Prophylaxis with oral penicillin on a continuing basis has proven effective in preventing recurrence of these conditions. (Source 6)
• Manyemba and Mayosi, Cochrane review (2002), systematic review of 9 randomised and quasi-randomised trials, 3,008 patients, judged of poor methodological quality: Four trials (n=1098) compared intramuscular with oral penicillin and all showed that intramuscular penicillin reduced rheumatic fever recurrence and streptococcal throat infections compared to oral penicillin. (Source 3)

How much

• Reference intake: There is no reference intake: penicillin V is a prescription antibiotic and the dose is set by the prescriber according to the organism's sensitivity and the severity of infection. As a position, the US label (revised January 2024) gives, for mild to moderately severe upper respiratory streptococcal infection including scarlet fever and erysipelas, 125 to 250 mg (200,000 to 400,000 units) every 6 to 8 hours for 10 days. (Source 22)
• Upper limit: No upper limit in the nutritional sense exists. The largest single amount in the label is the endocarditis prophylaxis regimen: 2 g of penicillin V one hour before the procedure (1 g for children under 60 lb), then 1 g six hours later. That is a position of the label holder citing a 1984 American Heart Association statement, not a toxicological ceiling. (Source 23)
• Studied: Streptococcal pharyngotonsillitis: penicillin V 800 mg four times daily for five days (total 16 g) versus 1000 mg three times daily for 10 days (total 30 g) in 433 patients. (Source 11)
• Studied: Prevention of recurrent leg cellulitis: penicillin 250 mg twice a day, or placebo, for 12 months in 274 patients. (Source 5)
• Studied: Children with streptococcal tonsillopharyngitis: penicillin VK 10 mg/kg four times daily for 10 days, up to a maximum of 250 mg four times daily, in 579 children. (Source 20)
• Studied: Rheumatic fever secondary prophylaxis as the label positions it: 125 to 250 mg (200,000 to 400,000 units) twice daily on a continuing basis. (Source 22)

A common belief, and what the research shows

The belief: Antibiotics such as penicillin V will interfere with the contraceptive pill, so you need backup contraception while taking them.

What the research shows: The systematic review evidence says no, for every antibiotic except the rifamycins. Simmons and colleagues searched four databases and included 29 studies; they report that “No differences in ovulation suppression or breakthrough bleeding were observed in any study that combined hormonal contraceptives with any antibiotic.” and conclude “Evidence from clinical and pharmacokinetic outcomes studies does not support the existence of drug interactions between hormonal contraception and non-rifamycin antibiotics.” The caveat the authors give themselves is that the data are limited in quantity and quality for some drug classes, and that only oral pills, emergency contraception and the vaginal ring were studied.

Questions and answers

What is it?

Penicillin V is an oral antibiotic - the phenoxymethyl form of penicillin G, dispensed as its potassium salt. Tablets contain the equivalent of 250 mg (400,000 units) or 500 mg (800,000 units) of penicillin V. Being acid-stable, it survives the stomach, which is what makes it swallowable where penicillin G has to be injected. (Source 1)

What does it do in the body?

It stops bacteria building their cell wall, and only while they are actively multiplying, which kills them. Human cells have no cell wall, so the drug is selective. It covers streptococci (groups A, C, G, H, L, M), pneumococci and some other organisms, but not bacteria that produce penicillinase, which today includes most staphylococci. (Source 1)

Is it good or bad for you?

Good for specific infections and useless, or worse than useless, outside them. For strep throat it shortens symptoms modestly - number needed to treat under six at day three - and cuts quinsy and ear infection, but most people recover in a week without it. For preventing repeat leg cellulitis the benefit is clear and large. Where there is no proven or strongly suspected bacterial infection the label states plainly that it is unlikely to help and increases resistance. The bad side is allergy, up to fatal anaphylaxis, gut upset, and C. difficile colitis. (Source 10)

How do you get more of it?

The question does not apply in the way it would for a nutrient: penicillin V is a prescription medicine, taken for a defined course for a defined infection, and the label states that therapy should be guided by bacteriological studies including sensitivity tests and by clinical response. No food, supplement or behaviour increases it. Taking it on an empty stomach gives slightly higher blood levels than taking it with meals. (Source 4)

If it is harmful, what reduces it?

It leaves the body quickly by itself. In people with normal kidney function the drug is excreted as fast as it is absorbed, so levels fall within hours of the last dose; in newborns, young infants and people with impaired kidneys excretion is considerably delayed. If the problem is an allergic reaction rather than the drug itself, the label's instruction is to discontinue it and treat the reaction, with epinephrine for anaphylaxis. (Source 7)

Why might someone be low in it or missing it?

Not applicable as a deficiency - but the related real phenomenon is treatment failure from not getting enough of it into the blood. Only about 25% of an oral dose is absorbed, food lowers levels further, and the label records that occasional patients will not absorb therapeutic amounts at all. That is part of why injected penicillin outperformed the oral form in every head-to-head rheumatic fever prophylaxis trial. (Source 10)

Which whole foods contain it or feed it?

No food contains penicillin V; it is made by fermentation and formulated as a salt. Food is relevant only to absorption: the label states it may be given with meals but that blood levels are slightly higher when it is given on an empty stomach. (Source 7)

What happens if you do not have it?

Nothing happens from not having the drug itself. The question is what untreated infection does. In the pooled sore-throat trials, withholding antibiotics left more people with symptoms at day three and more suppurative complications: acute otitis media and quinsy were both several times commoner without antibiotics. Against that, 82% of untreated people were symptom-free within a week, and the rheumatic fever figures come mostly from 1950s trials when that complication was far more common than it is in high-income countries today. (Source 2)

How can you test for it?

You do not test for penicillin V in the body; you test what it is aimed at and what it might do to you. The label directs that therapy be guided by bacteriological studies including sensitivity tests, and that cultures be taken after treatment to confirm the streptococci have been eradicated - which matters because in one 579-child trial only 68% of children on penicillin VK were cleared of the organism. For allergy, skin testing and drug provocation testing are used by allergy specialists to confirm or remove a penicillin allergy label; the reliability of those tests is outside the sources we read here. (Source 10)

References

1. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
2. Cochrane Database of Systematic Reviews. Antibiotics for treatment of sore throat in children and adults. 2021. PMID 34881426, DOI 10.1002/14651858.CD000023.pub5. Read the source
3. Cochrane Database of Systematic Reviews. Penicillin for secondary prevention of rheumatic fever. 2002. PMID 12137650, DOI 10.1002/14651858.CD002227. Read the source
4. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
5. New England Journal of Medicine. Penicillin to prevent recurrent leg cellulitis. 2013. PMID 23635049, DOI 10.1056/NEJMoa1206300. Read the source
6. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
7. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
8. Cancer Research. Effect of penicillin on the renal tubular secretion of methotrexate in the monkey. 1984. PMID 6713392. Read the source
9. American Journal of Obstetrics and Gynecology. Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review. 2018. PMID 28694152, DOI 10.1016/j.ajog.2017.07.003. Read the source
10. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
11. BMJ. Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study. 2019. PMID 31585944, DOI 10.1136/bmj.l5337. Read the source
12. New England Journal of Medicine. Penicillin to prevent recurrent leg cellulitis. 2013. PMID 23635049, DOI 10.1056/NEJMoa1206300. Read the source
13. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
14. Cochrane Database of Systematic Reviews. Antibiotics for treatment of sore throat in children and adults. 2021. PMID 34881426, DOI 10.1002/14651858.CD000023.pub5. Read the source
15. BMJ. Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study. 2019. PMID 31585944, DOI 10.1136/bmj.l5337. Read the source
16. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
17. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
18. BMJ. Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study. 2019. PMID 31585944, DOI 10.1136/bmj.l5337. Read the source
19. The Pediatric Infectious Disease Journal. Comparison of two dosages of azithromycin for three days versus penicillin V for ten days in acute group A streptococcal tonsillopharyngitis. 2002. PMID 12075760, DOI 10.1097/00006454-200204000-00008. Read the source
20. Antimicrobial Agents and Chemotherapy. Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered once daily for 7 days compared to penicillin V potassium administered four times daily for 10 days in the treatment of tonsillopharyngitis due to Streptococcus pyogenes in children. 2008. PMID 18332170, DOI 10.1128/AAC.00132-07. Read the source
21. Cochrane Database of Systematic Reviews. Antibiotics for treatment of sore throat in children and adults. 2021. PMID 34881426, DOI 10.1002/14651858.CD000023.pub5. Read the source
22. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source
23. DailyMed / US National Library of Medicine (Hikma Pharmaceuticals USA; repackaged by Preferred Pharmaceuticals). Penicillin V Potassium Tablets, USP - US prescribing information, revised January 2024. 2024. Read the source