Phenoxymethylpenicillin

J01C - Beta-lactam antibacterials, penicillins ATC J01CE02 Small molecule approved 1958 Oral Natural product

🧬 Cross-allergy: Penicillins

JFDA label: Ospen 1500mg tablet

Mechanism of Action

Inhibitor of Bacterial penicillin-binding protein — Bacterial penicillin-binding protein inhibitor

Target	Action	Gene / class
Bacterial penicillin-binding protein efficacy	INHIBITOR

Indications

Approved

Fusospirochetosis (Vincent gingivitis and pharyngitis)
Pneumococcal infections
Rheumatic fever and/or chorea prophylaxis
Staphylococcal infections (penicillin G-sensitive)
Streptococcal infections (without bacteremia)

Off-label

Actinomycosis
Bite wounds (animal)
Chronic antimicrobial suppression of prosthetic joint infection
Cutaneous anthrax
Cutaneous erysipeloid
GAS chronic carrier
Pneumococcal prophylaxis in asplenia/sickle cell
Pneumococcal prophylaxis in hematopoietic cell transplant
Pneumonia, community-acquired (children)

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: openfda-label.

Bacteria

Organism	Activity	MIC
Bacillus anthracis	Active	—
Listeria monocytogenes	Active	—
Neisseria gonorrhoeae	Active	—
Staphylococcus aureus	Active	—
Streptococcus pneumoniae	Active	—
Treponema pallidum	Active	—

Class profile

gramStatus	Gram+
spectrumBreadth	Narrow
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (beta-lactam, PBP binding)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	0
resistanceMechanisms	Beta-lactamase production,PBP mutations

Contraindications

Source: Lexicomp

Hypersensitivity to penicillin or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Other (5)

Very Common Gastrointestinal: Melanoglossia · mild diarrhea · nausea · oral candidiasis · vomiting

Dosing

Source: Lexicomp

Usual dosage range: Oral: 125 to 500 mg every 6 to 8 hours Actinomycosis (off-label use): Oral: Note: Duration is dependent upon disease location and patient-specific factors; complicated infections requiring surgical intervention usually initiate IV therapy with penicillin G until disease subsidence followed by long term oral therapy (Hsieh 1993, Sudhakar 2004): 2 to 4 g/day in divided doses every 6 hours (Smego 1998) Bite wounds (animal) (off-label use): Oral: 500 mg 4 times daily in combination with dicloxacillin (IDSA [Stevens 2014]) Cutaneous anthrax, community-acquired (off-label use): Oral: 500 mg 4 times daily for 7 to 10 days (IDSA [Stevens 2014]) Cutaneous erysipeloid (off-label use): Oral: 500 mg 4 times daily for 7 to 10 days (IDSA [Stevens 2014]) Erysipelas: Oral: Manufacturer’s labeling: 125 to 250 mg every 6 to 8 hours for 10 days Alternate dosing: 500 mg 4 times daily (IDSA [Stevens 2014]) Fusospirochetosis (Vincent infection): Oral: 250 to 500 mg every 6 to 8 hours Pharyngitis (streptococcal): Oral: Acute treatment, group A streptococci: Manufacturer’s labeling: Acute treatment, group A streptococci: 125 to 250 mg every 6 to 8 hours for 10 days Alternate dosing: 500 mg 2 to 3 times daily for 10 days (Gerber 2009) or 250 mg 4 times daily or 500 mg twice daily for 10 days (Shulman 2012) Chronic carrier treatment, group A streptococcal: 500 mg 4 times daily (maximum: 2,000 mg daily) for 10 days in combination with oral rifampin (Shulman 2012) Pneumococcal prophylaxis in hematopoietic cell transplant (off-label use): Oral: 250 to 500 mg twice daily. Note: Use only in areas where incidence of penicillin-resistant S. pneumoniae is low (Tomblyn 2009) Prophylaxis of recurrent rheumatic fever infections: Oral: 250 mg twice daily (Gerber 2009) Prosthetic joint infection (off-label use): Chronic oral antimicrobial suppression (Enterococcus spp [penicillin-susceptible], streptococci [beta-hemolytic], Cutibacterium spp): Oral: 500 mg 2 to 4 times daily (Osmon 2013) Streptococcal skin infection (off-label dose): Oral: 250 to 500 mg every 6 hours (IDSA [Stevens 2014])

(For additional information see "Penicillin V potassium (oral): Pediatric drug information") General dosing, susceptible infections: Infants and Children day) (Red Book [AAP 2015]) Children ≥12 years and Adolescents: Oral: Manufacturer’s labeling (fixed dosing): 125 to 500 mg every 6 to 8 hours Alternate dosing (weight-based): Mild to moderate infection: 25 to 75 mg/kg/day in divided doses every 6 to 8 hours (maximum daily dose: 2,000 mg/day [Red Book (AAP 2015)]) Indication-specific dosing: Anthrax (cutaneous), community-acquired (off-label use): Infants, Children, and Adolescents: Oral: 25 to 50 mg/kg/day in divided doses 2 or 4 times daily; maximum single dose: 500 mg (Stevens 2005) Fusospirochetosis (Vincent infection), mild to moderately severe infections: Children ≥12 years and Adolescents: Oral: Refer to adult dosing. Tonsillopharyngitis; Group A streptococcal infection, treatment and primary prevention of rheumatic fever: Acute treatment (Gerber 2009; Shulman 2012; WHO 2004): Children ≤27 kg: Oral: 250 mg 2 to 3 times daily for 10 days Children >27 kg and Adolescents: Oral: 500 mg 2 to 3 times daily for 10 days; in adolescents, 250 mg 4 times daily has also been suggested Chronic carrier treatment (Group A streptococci) (off-label use): Children and Adolescents: 50 mg/kg/day in 4 divided doses for 10 days in combination with oral rifampin; maximum daily dose: 2,000 mg/day (Shulman 2012) Recurrent rheumatic fever, prophylaxis (off-label): Children and Adolescents: 250 mg twice daily (Gerber 2009) Pneumococcal infection prophylaxis for anatomic or functional asplenia (eg, sickle cell disease [SCD]) (off-label use) (AAP 2002; Kavanagh 2011; NHLBI 2014): Infants (as soon as SCD diagnosed or asplenic) and Children Children ≥3 years: Oral: 250 mg twice daily; the decision to discontinue penicillin prophylaxis after 5 years of age in children who have not experienced invasive pneumococcal infection and have received recommended pneumococcal immunizations is patient and clinician dependent Pneumonia, community-acquired; Group A Streptococcus, mild infection or step-down therapy (off-label use): Infants ≥3 months, Children, and Adolescents: Oral: 50 to 75 mg/kg/day in 3 to 4 divided doses (Bradley 2011); maximum daily dose: 2,000 mg/day

Refer to adult dosing.

There are no dosage adjustments provided in manufacturer’s labeling. Use with caution; excretion is prolonged in patients with renal impairment.

There are no dosage adjustments provided in manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Anaphylactic/hypersensitivity reactions

Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity or history of sensitivity to multiple allergens.). Use with caution in asthmatic patients. If a serious reaction occurs, treatment with supportive care measures and airway protection should be instituted immediately.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Renal impairment

Use with caution in patients with severe renal impairment.

Seizure disorders

Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures. Concurrent drug therapy related issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Benzyl alcohol and derivatives

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling. Other warnings/precautions:

Prolonged use

Extended duration of therapy or use associated with high serum concentrations (eg, in renal insufficiency) may be associated with an increased risk for some adverse reactions (neutropenia, hemolytic anemia, serum sickness).

Pregnancy & Lactation

Pregnancy

Penicillin crosses the placenta. Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects. Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of penicillin V may be altered in the second and third trimester (Heikkilä 1993). If treatment for the management of Bacillus anthracis is needed in pregnant women, other agents are preferred (Meaney-Delman 2014)

Lactation

Penicillin V is excreted into breast milk and may be detected in the urine of some breast-feeding infants. Loose stools and rash have been reported in nursing infants (Matheson 1988).

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C16H18N2O5S
Molecular weight	350.4 g/mol
IUPAC name	(2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenoxyacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
CAS	87-08-1
PubChem CID	6869
InChIKey	`BPLBGHOLXOTWMN-MBNYWOFBSA-N`
logP	0.7 (XLogP 2.1)
Polar surface area	95.94 Å²
H-bond acceptors / donors	5 / 2
Drug-likeness (QED)	0.76
Lipinski violations	0

SMILES

CC1(C)S[C@@H]2[C@H](NC(=O)COc3ccccc3)C(=O)N2[C@H]1C(=O)O

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—
CYP2D6	Inhibitor	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (18, DDInter)

Interacting drug	Severity	Management
Methotrexate	major
Balsalazide	moderate
Demeclocycline	moderate
Dicoumarol	moderate
Doxycycline	moderate
Ethinylestradiol	moderate
Iodide I-123	moderate
Iodide I-131	moderate
Minocycline	moderate
Mycophenolic acid	moderate
Neomycin	moderate
Oxytetracycline	moderate
Pemetrexed	moderate
Picosulfuric acid	moderate
Tetracycline	moderate
Warfarin	moderate
Clarithromycin	minor
Erythromycin	minor

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Orvek 125 Syrup	Syrup 125 mg/5 ml	60 ml pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	0.750
Orvek 125 Syrup	Syrup 125 mg/5 ml	100 ml pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	1.170
Ospen	Tablet 1.5 MIU	12 tab	Nabulsi Drug Store	3.550