Penicillin V

350.39

350.39

201-722-0

Z61I075U2W

DTXSID3023429

C62064

white, crystalline powder

J01CE02|J - Antiinfectives for systemic use

3003101300

121.24000

1.88

Penicillin v is a white crystalline powder. (NTP, 1992)

1.5±0.1 g/cm3

148-149 °C

681.4±55.0 °C at 760 mmHg

365.9±31.5 °C

1.651

Very slightly soluble in water, soluble in ethanol (96 per cent).

−20°C

LD50 oral in rat: > 2220mg/kg

The biologically active form is the dextrorotatory D-form; the DL-form is half as active. L-Penicillin V has little, if any, antibiotic activity. Maximum absorption: 268, 274 nm (E= 1330, 1100).

Odorless

2.5-4.0 (saturated solution)

2.79None

2.79|pKa 2.73

182.6 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|186.7 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

120-128 °C (decomp)

Insoluble in water.

Acids, Carboxylic

Stable in air up to 37%; relatively stable to acid. This compound is incompatible with acids, oxidizing agents (especially in the presence of trace metals), heavy metal ions such as copper, lead, zinc and mercury; glycerol, sympathomimetic amines, thiomersal, wood alcohols, cetostearyl alcohol, hard paraffins, macrogols, cocoa butter and many ionic an nonionic surface-active agents. It is also incompatible with alkalis, compounds leached from vulcanized rubber, hydrochlorides of tetracyclines and organic peroxides. Other incompatibilities include reducing agents, alcohols, other hydroxy compounds, self-emulsifying stearyl alcohol, emulsifying wax, lanolin, crude cholinesterated bases, glycol, sugars, amines, aminacrine hydrochloride, ephedrine, procaine, rubber tubing, thiamine hydrochloride, zinc oxide, oxidized cellulose, iodine, iodides, thiols, chlorocresol and resorcinol. It may also be incompatible with naphthalene oils and vitamin B. (NTP, 1992)

NONH for all modes of transport

42/43

22-36

RY4025000

Xn

Stable. Combustible. Incompatible with strong oxidizing agents.

P261, P264, P270, P272, P280, P285, P301+P312, P302+P352, P304+P341, P321, P330, P333+P313, P342+P311, P363, P501

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Oral Dosage Form New Animal Drugs. Specifications and conditions of use provided for dogs and cats. /Penicillin V potassium for oral solution/|Oral Dosage Form New Animal Drugs. Specifications and conditions of use provided for dogs and cats. /Penicillin V potassium tablets/|Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Flash point data for this chemical are not available; however it is probably combustible. (NTP, 1992)

|Danger|H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P280, P285, P302+P352, P304+P341, P321, P333+P313, P342+P311, P363, and P501|Aggregated GHS information provided by 2 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302 (97.87%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P280, P285, P301+P312, P302+P352, P304+P341, P321, P330, P333+P313, P342+P311, P363, and P501|Aggregated GHS information provided by 95 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. You should then dampen the solid spill material with ethanol, and transfer the dampened material to a suitable container. Use absorbent paper dampened with ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material under freezer conditions. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

The oral LD50 is >1040 mg/kg in rats. Nausea, vomiting, black hairy tongue, and epigastric distress are common reactions to oral penicillins. In rare cases, neuromuscular sensitivity and seizures may be seen with antibiotics and supportive treatments are advised and further drug absorption should be limited through induced emesis or gastric lavage, followed by administration of activated charcoal. Severe hypersensitivity reactions, often leading to death, have been reported with penicillin therapies. Although phenoxymethylpenicillin was shown to be excreted in human breast milk, the use of this drug in pregnant or nursing women is regarded generally safe.

Rare instances of idiosyncratic liver injury have been reported in persons receiving the first generation penicillins. Many case reports predated availability of serologic testing for viral hepatitis and many described patients with multiple reasons for having liver disease (such as sepsis) and who were receiving other potentially hepatotoxic agents. Three distinct forms of liver injury can occur with the first generation penicillins: (1) transient, asymptomatic elevations in serum aminotransferase levels with prolonged high doses of parenteral penicillin, (2) minor liver injury associated with severe hypersensitivity reactions, and (3) idiosyncratic, delayed cholestatic hepatitis. These three forms of injury probably occur with all four generations of penicillin, some being more common with one form of penicillin than another.

Oral neomycin has been shown to decrease the absorption of penicillin V ... .|Since penicillin acts by inhibiting cell wall synthesis, agents which inhibit protein synthesis (eg, chloramphenicol) could ... mask the bactericidal effect of penicillin. /Penicillin/|Since penicillin acts by inhibiting cell wall synthesis, agents which inhibit protein synthesis (eg, erythromycin) could ... mask the bactericidal effect of penicillin. ... Clinical evidence exists for erythromycin-penicillin antagonism in patients with group A hemolytic streptococcal pharyngitis. ... The possibility of antagonism exists, but it has not been sufficiently documented in clinical studies. /Penicillin/|Tetracyclines ... may interfere with a bactericidal agent such as penicillin. /Penicillin/|For more Interactions (Complete) data for PENICILLIN V (16 total), please visit the HSDB record page.

Upon oral administration, about 50-80% of the drug is bound to plasma proteins.

Veterinarians, physicians, nurses, and pharmacists have occasionally experienced contact dermatitis after handling penicillin preparations.

Indicated for the treatment of mild to moderately severe infections due to penicillin G­-sensitive microorganisms, with the use of bacteriological studies (including sensitivity tests) and clinical response. Phenoxymethylpenicillin may be used for the treatment of: - mild to moderate infections of the upper respiratory tract, scarlet fever, and mild erysipelas caused by Streptococcus without bacteremia - mild to moderately severe infections of the respiratory tract caused by Pneumococcus - mild infections of the skin and soft tissues caused by penicillin G-sensitive Staphylococcus - mild to moderately severe infections of the oropharynx caused by Fusospirochetosis, including Vincent’s gingivitis and pharyngitis, usually respond to oral penicillin therapy **Off-label** Indicated for use as prophylaxis against bacterial endocarditis in patients with congenital heart disease or rheumatic or other acquired valvular heart disease when they undergo dental procedures and surgical procedures of the upper respiratory tract.|FDA Label

Penicillin G and V are first generation penicillins that are used widely to treat infections due to susceptible organisms and have been linked rarely and only weakly with idiosyncratic liver injury.

Antiinfective Agents

Penicillins|Penicillin V is used for the treatment of mild to moderately severe infections caused by organisms susceptible to low concentrations of the drug or for prophylaxis of certain streptococcal infections.|Penicillin V /is/ indicated in the treatment of acute otitis media caused by susceptible organisms. /Included in US product labeling/|Penicillin V /is/ indicated in the treatment of bacterial pharyngitis cuased by susceptible organisms. /Included in US product labeling/|For more Therapeutic Uses (Complete) data for PENICILLIN V (21 total), please visit the HSDB record page.

The most important biological effect of penicillin, unrelated to hypersensitivity or to "toxic" reaction, is alteration of bacterial flora in areas of the body to which it gains access. Regardless of the route by which the drug is administered, but most strikingly when it is given by mouth, penicillin changes the composition of the microflora by eliminating sensitive microorganisms. ... In some persons ... suprainfection results from the changes in flora. /Penicillin/|Fever and even vascular collapse and death may follow the use of penicillin in syphilis. This is one manifestation of the Jarisch-Herxheimer reaction. It is thought to be due to hypersensitivity to antigens released during rapid and massive lysis of spirochetes. /Penicillin/|Contraceptive failure and pregnancies attributed to the concurrent use of penicillins ... have been reported on a number of occasions. ... Mechanism /is/ not understood. It has been observed that ampicillin given to women in latter wk of pregnancy decreases urinary oestriol levels ... & phenoxymethylpenicillin behaves in a similar way ...|Individual with phenylketonuria (ie, homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that Warner Chilcott's penicillin V potassium powder for oral soln contains aspartame ... which is metabolized in the GI tract to phenylalanine following oral administration.|For more Drug Warnings (Complete) data for PENICILLIN V (16 total), please visit the HSDB record page.

Phenoxymethylpenicillin works against penicillin-sensitive microorganisms with bactericidal effects. It targets the bacteria during its active multiplication stage by interfering with bacterial cell wall peptidoglycan synthesis. _In vitro_, phenoxymethylpenicillin was shown to be active against staphylococci (except penicillinase-producing strains), streptococci (groups A, C, G, H, L and M), and pneumococci, as well as _Corynebacterium diphtheriae_, _Bacillus anthracis_, Clostridia, _Actinomyces bovis_, _Streptobacillus moniliformis_, _Listeria monocytogenes_, _Leptospira_, _Neisseria gonorrhoeae_, and _Treponema pallidum_.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Upon oral administration, phenoxymethylpenicillin is rapidly but incompletely absorbed. The bioavailability of phenoxymethylpenicillin ranges from 25 to 60%. Compared to the free acid form of the drug, the calcium or potassium salts of phenoxymethylpenicillin displays better absorption profiles. It is reported that fasting state enhances the drug absorption. The peak plasma concentrations of 200 to 700 ng/mL are achieved in 2 hours following an oral dose of 125 mg. Following an oral dose of 500 mg, the peak plasma concentrations of 3 to 5 μg/mL are reached in 30 to 60 minutes post-dose.|While the drug is rapidly excreted, only 25% of the total dose is detected in the urine. Renal excretion may be delayed in neonates, young infants, and patients with renal impairment.|Following intravenous administration, the volume of distribution at steady state was 35.4 L. Small amounts of the drug can be found in various tissues, with the highest amount found in the kidneys, with lesser amounts in the liver, skin, and intes­ tines. Phenoxymethylpenicillin was found in the cerebrospinal fluid. Phenoxymethylpenicillin was detectable in the placenta and human breast milk.|A dose of 1,000,000 units of the acid gives peak plasma levels of about 2 to 3 ug/ml ...|Approx 60-73% of an oral dose of penicillin V or penicillin V potassium is absorbed from the GI tract in healthy, fasting adults. Following oral administration of a single dose of penicillin V or penicillin V potassium in fasting children or adults, peak serum concn of penicillin V are generally attained within 30-60 min. Peak serum penicillin V concn are attained sooner and are slightly higher following administration of the potassium salt than the free acid.|Following oral administration of a single 125-mg tablet of penicillin V potassium in healthy, fasting adults in one study, serum penicillin V concn averaged 1.2, 1.2, 0.5, and 0.1 ug/ml @ 30 min, 1 hr, 2 hr, and 4 hr, respectively, after the dose. Oral administration of a single 250-mg tablet of the drug in healthy, fasting adults results in serum penicillin V concn averaging 2.1-2.8, 2.3-2.7, 0.8-0.9, and 0.1-0.2 ug/ml @ 30 min, 1 hr, 2 hr, and 4 hr, respectively, after the dose. Following oral administration of a single 500-mg tablet of penicillin V potassium in healthy, fasting adults, serum penicillin V concn average 4.7-5, 4.9-6.3, 2.3-3, and 0.04-0.1 ug/ml @ 30 min, 1 hr, 2 hr, and 6 hr, respectively, after the dose.|Variable results have been obtained in studies evaluating the effect of food on GI absorption of penicillin V and penicillin V potassium. In most studies, presence of food in the GI tract resulted in lower and delayed peak serum concn of penicillin V, although the total amt of drug absorbed was unaffected. However, results of several studies in children 2 mo to 5 yr of age indicate that both the peak serum concn and the area under the serum concn-time curve (AUC) are decreased when penicillin V potassium is administered with or immediately prior to milk or food.|For more Absorption, Distribution and Excretion (Complete) data for PENICILLIN V (8 total), please visit the HSDB record page.

About 35-70% of an oral dose is metabolized to penicilloic acid, an inactive metabolite. Small amounts of 6-aminopenicillanic acid have been recovered in the urine of patients on penicillin G. A small percentage of the drug appears to be hydroxylated into one or more active metabolites, which are also excreted via urine.|Approximately 35-70% of an oral dose of penicillin V or penicillin V potassium is metabolized to penicilloic acid which is microbiologically inactive. Small amt of 6-aminopenicillanic acid (6-APA) have also been found in urine of patients receiving penicillin V. In addition, the drug appears to be hydroxylated to a small extent to one or more microbiologically active metabolites which are also excreted in urine.

Upon oral administration, the half-life is about 30 minutes. It can last up to 4 hours in patients with renal impairment.|The serum half-life of penicillin V in adults with normal renal function is reportedly 0.5 hr.

Phenoxymethylpenicillin inhibits the biosynthesis of cell wall mucopeptide by binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, which are critical in the cell wall synthesis and maintenance, as well as cell division. This disrupts the third and last stage of bacterial cell wall synthesis. This subsequently leads to cell lysis.|Penicillins and breakdown products of penicillins act as haptens after their covalent reaction with proteins. The most important antigenic intermediate of penicillin appears to be the penicilloyl moiety, which is formed when the beta-lactam ring is opened. This is considered to be the major (predominant) determinant of penicillin allergy. /Penicillins/|Penicillin is known to interfere with synthesis of N-acetylmuramic acid mucopeptides and teichoic acids which are part of cell-wall material. ... Under favorable conditions penicillin exerts direct bactericidal action, & successful penicillin therapy may be relatively independent of immunity mechanisms of the host. /Penicillins/|The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/|Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/

Commercially available penicillin ... V preparations may contain small amounts of high molecular weight protein impurities that originate from the fermentation process used to produce the drugs.

SYMPTOMS: Symptoms of exposure to this compound include hypersensitization, skin rashes, contact dermatitis, oral lesions, fever, eosinophilia, interstitial nephritis, angioedema, serum sickness, anaphylaxis, "Arthus" phenomenon; irritation of the Gastrointestinal tract; phlebitis; bronchoconstriction with severe asthma, or abdominal pain, nausea, vomiting, extreme weakness and fall in blood pressure, diarrhea, and purpuric skin eruptions. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Hypersensitivity reactions are one of the most frequent adverse reactions to penicillin G & penicillin V. In addition ... oral admin ... is frequently associated with adverse GI effects.|In addition to eosinophilia & hemolytic anemia ... other adverse hematologic effects including transient neutropenia, leukopenia, thrombocytopenia, & thrombocytopenic purpura have occurred rarely in patients receiving penicillin G or penicillin V. These hematologic reactions occur most frequently when high doses of penicillin G are admin IV & are generally reversible following discontinuance of the drugs. ... Some or the most frequent adverse reactions to orally admin penicillin ... V are GI effects including nausea, vomiting, epigastric distress & diarrhea.|Skin rashes of all types may be caused by allergy to penicillin. Scarlatiniform, morbilliform, urticarial, vesicular, and bullous eruptions may develop. Purpuric lesions are uncommon & are usually the result of a vasculitis ... Henoch-Schoenlein purpura with renal involvement has been a rare complication. ... The most serious hypersensitivity reactions produced by the penicillins are angioedema and anaphylaxis. Angioedema with marked swelling of the lips, tongue, face, & periorbital tissues, frequently accompanied by asthmatic breathing & "giant hives" ... observed after topical, oral or systemic admin of penicillins of various types. ... Anaphylactoid reactions may occur at any age. ... About 0.002% of patients treated with these agents die from anaphylaxis. It has been estimated that there are at least 300 deaths per yr due to this complication of therapy. /Penicillins/|Anaphylaxis has most often followed the injection of penicillin, although it has also been observed after oral ingestion of the drug, & has even resulted from the intradermal instillation of a very small quantity for the purpose of testing for the presence of hypersensitivity. ... The most dramatic /clinical picture/ is sudden, severe hypotension & rapid death. ... Bronchoconstriction with severe asthma, or abdominal pain, nausea, and vomiting, or extreme weakness & fall in blood pressure, or diarrhea & purpuric skin eruptions have characterized the anaphylactic episodes. Serum sickness varies from mild fever, rash, and leukopenia to severe arthralgia or arthritis, purpura, lymphadenopathy, splenomegaly, mental changes, ECG abnormalities suggestive of myocarditis, generalized edema, albuminuria, and hematuria. It is mediated by IgG antibodies. /Penicillins/|For more Human Toxicity Excerpts (Complete) data for PENICILLIN V (45 total), please visit the HSDB record page.

Apocillin

... Penicillin V is commercially available as the acid and its potassium salt.|Generic: Powder for oral solution (plain, buffered) and oral suspension 125 and 250 mg/5 ml; tablets 250 and 500 mg.

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-[(2-phenoxyacetyl)amino]-, potassium salt (1:1), (2S,5R,6R)-: ACTIVE|Grade: NF|Although potency of penicillin V ... is generally expressed in terms of the weight of penicillin V, potency of the drugs may be expressed in terms of USP penicillin V units. For labeling purposes, each mg of penicillin V contained in penicillin V ... prepn is considered equivalent to 1695 penicillin V units.|The problem of antibiotic contamination of milk requires that the dairy operator, veterinarian, and milk processor be aware of the sensitizing ability of penicillin and the importance of adherence to drug withdrawal times. /Penicillins/

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients