Phenoxymethyl Penicillin [Penicillin V]

Approved Medical Uses:

• Upper Respiratory Tract Infections (caused by susceptible streptococci):
• Streptococcal pharyngitis
• Tonsillitis
• Mild sinusitis and otitis media
• Skin and Soft Tissue Infections:
• Erysipelas
• Impetigo (due to Streptococcus pyogenes)
• Rheumatic Fever Prophylaxis:
• Long-term prevention of recurrent attacks in patients with prior rheumatic fever or rheumatic heart disease
• Dental Infections:
• Treatment of mild odontogenic infections
• Prophylaxis of infective endocarditis in at-risk patients undergoing dental procedures (when appropriate)

Important Off-label or Clinically Accepted Uses:

• Post-splenectomy Infection Prophylaxis (especially in children)
• Treatment of mild anaerobic infections when caused by susceptible organisms
• Secondary prophylaxis in pediatric populations with certain congenital heart defects

Route of Administration: Oral
Available Forms: Tablets, Oral Suspension (after reconstitution)

Adults:

• Streptococcal infections (e.g., pharyngitis, tonsillitis):
  250 mg to 500 mg orally every 6 to 8 hours for 10 days
• Skin or dental infections:
  500 mg orally every 6 to 8 hours for 5–10 days
• Rheumatic fever prophylaxis:
  250 mg orally twice daily, indefinitely or as per guideline

Pediatric Patients:

• Streptococcal infections:
  25–50 mg/kg/day orally, divided every 6–8 hours (maximum: 3 g/day)
• Rheumatic fever prophylaxis:
• Children <27 kg: 125 mg orally twice daily
• Children ≥27 kg: 250 mg orally twice daily

Elderly:

• Same as adult dose
• Monitor renal function to avoid accumulation in renal impairment

Renal Impairment:

• Mild to moderate impairment (CrCl >10 mL/min): No adjustment usually required
• Severe impairment (CrCl <10 mL/min): Extend dosing interval or reduce dose cautiously; monitor closely

Hepatic Impairment:

• No adjustment required; use with caution in severe liver dysfunction

Phenoxymethyl Penicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) located inside the bacterial cell wall. These proteins are essential for the final stages of peptidoglycan synthesis. By blocking this process, the drug prevents proper cell wall formation, leading to bacterial cell lysis and death. It is a bactericidal antibiotic, most effective against non–β-lactamase-producing Gram-positive cocci, especially Streptococcus pyogenes.

• Absorption: Rapid and adequate oral absorption; food may reduce peak levels
• Bioavailability: Approximately 60%
• Time to Peak Plasma Concentration: 30 to 60 minutes post-dose
• Protein Binding: 60–80%
• Distribution: Well distributed in body fluids and tissues; limited central nervous system (CNS) penetration unless meninges are inflamed
• Metabolism: Minimal hepatic metabolism
• Half-life: 30 minutes to 1 hour in healthy individuals
• Elimination: Primarily renal (glomerular filtration and tubular secretion); 30–40% excreted unchanged in urine

• Pregnancy:
  Safe to use in pregnancy. Previously classified as FDA Category B. No evidence of teratogenicity or adverse fetal outcomes in humans.
• Lactation:
  Excreted in small quantities into breast milk. Generally safe during breastfeeding, but may cause gastrointestinal upset or oral thrush in the infant. Monitoring is advised.

• Primary Class: Beta-lactam Antibiotic
• Subclass: Natural Penicillin
• Generation: First-generation penicillin (penicillin V group)

• Known hypersensitivity to penicillin or other β-lactam antibiotics
• Previous anaphylactic reactions to any penicillin
• History of severe allergic reactions to cephalosporins or carbapenems
• Infectious mononucleosis (increased risk of rash)

• Severe Allergic Reactions: Risk of anaphylaxis; discontinue immediately if signs of hypersensitivity appear
• Superinfections: Prolonged use may lead to overgrowth of non-susceptible organisms including Candida and Clostridioides difficile
• Renal Impairment: Dose adjustments may be necessary; monitor renal function in elderly or at-risk patients
• Hematological Effects: Rare occurrences of leukopenia, anemia, and thrombocytopenia with prolonged use
• Neurological Effects: High doses may cause seizures, particularly in patients with renal failure

Common (≥1%):

• Gastrointestinal: Nausea, vomiting, diarrhea, epigastric discomfort
• Skin: Rash, urticaria

Less Common (<1%):

• Hematologic: Eosinophilia, leukopenia
• Neurological: Dizziness, headache

Serious/Rare:

• Anaphylaxis
• Stevens-Johnson Syndrome
• Serum sickness-like reactions
• Pseudomembranous colitis
• Hemolytic anemia
• Seizures (especially in overdose or renal failure)

• Probenecid: Inhibits renal tubular secretion, increasing serum levels of penicillin
• Bacteriostatic antibiotics (e.g., tetracyclines): May antagonize bactericidal effects
• Oral contraceptives: May reduce efficacy; additional contraception may be necessary
• Methotrexate: Decreased clearance of methotrexate may increase toxicity

Enzyme Involvement:

• No involvement of CYP450 enzymes; metabolism-independent drug interactions

• AHA 2024 Rheumatic Fever Guidelines: Continues to recommend Penicillin V for long-term secondary prophylaxis
• NICE 2023 Infective Endocarditis Guidance: Limits prophylactic use of antibiotics including Penicillin V to high-risk patients undergoing dental procedures
• EMA/FDA: No recent changes to core dosing or safety recommendations

• Tablets: Store at 15°C to 25°C (59°F to 77°F). Protect from moisture and heat
• Oral Suspension (after reconstitution):
• Store at 2°C to 8°C (refrigerated)
• Use within 14 days
• Shake well before each use
• Handling: Do not freeze the suspension. Keep all forms tightly closed and out of reach of children.