Benzylpenicillin

J - Antiinfectives for Systemic Use ATC JO1CE01 Small molecule approved 1947 Oral Parenteral Natural product Black-box warning

🧬 Cross-allergy: Penicillins

JFDA label: Injpen

⚠ Black-Box Warning

Appropriate administration:

Mechanism of Action

Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria

Indications

Approved

Acute glomerulonephritis
Respiratory tract infections
Rheumatic fever and chorea
Rheumatic heart disease
Syphilis and other venereal diseases

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16.

Bacteria

Organism	Activity	MIC
Anaerobes	Susceptible	0.51 mg/L
Corynebacterium spp.	Susceptible	0.001 mg/L
Neisseria gonorrhoeae	Susceptible	0.061 mg/L
Neisseria meningitidis	Susceptible	0.25 mg/L
Pasteurella multocida	Susceptible	0.5 mg/L
Viridans group streptococci	Susceptible	0.251 mg/L

Contraindications

Source: Lexicomp

Hypersensitivity to penicillin(s) 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

Cardiac disorders (8)

Not Known Cerebrovascular accident · hypotension · palpitations · syncope · tachycardia · vasodepressor syncope · vasodilatation · vasospasm

Nervous system disorders (15)

Not Known Anxiety · coma · confusion · dizziness · drowsiness · euphoria · fatigue · headache · localized warm feeling · nervousness · neurologic abnormality (neurogenic bladder) · numbness · pain · seizure · transverse myelitis

Hepatobiliary disorders (1)

Not Known Increased serum AST

Renal and urinary disorders (8)

Not Known Hematuria · impotence · Increased blood urea nitrogen · increased serum creatinine · myoglobinuria · priapism · proteinuria · renal failure

Blood and lymphatic system disorders (2)

Not Known Local hemorrhage (at injection site) · lymphadenopathy

Immune system disorders (2)

Not Known Hypersensitivity reaction · Jarisch-Herxheimer reaction

Gastrointestinal disorders (4)

Not Known Bloody stools · intestinal necrosis · nausea · vomiting

Skin and subcutaneous tissue disorders (5)

Not Known Diaphoresis · gangrene of skin or other tissue · pallor · skin mottling · skin ulceration at injection site

Musculoskeletal and connective tissue disorders (6)

Not Known Arthropathy · exacerbation of arthritis · periosteal disease (periostitis) · rhabdomyolysis · tremor · weakness

Eye disorders (2)

Not Known Blindness · blurred vision

General disorders and administration site conditions (10)

Not Known Abscess at injection site · atrophy at injection site · bruising at injection site · cellulitis at injection site · inflammation at injection site · injection site reaction (neurovascular damage) · localized edema (at injection site) · pain at injection site · residual mass at injection site · tissue necrosis at injection site

Respiratory, thoracic and mediastinal disorders (1)

Not Known Cyanosis

Dosing

Source: Lexicomp

Usual dosage range: IM: 1.2 to 2.4 million units as a single dose Upper respiratory infection, group A streptococci: IM: 1.2 million units as a single dose Secondary prevention of glomerulonephritis: 1.2 million units every 4 weeks or 600,000 units twice monthly Secondary prevention of rheumatic fever: 1.2 million units every 3 to 4 weeks or 600,000 units twice monthly (Gerber, 2009) Pharyngitis, group A streptococci (IDSA guidelines): IM: Acute treatment: 1.2 million units as a single dose (Shulman, 2012) Chronic carrier treatment: 1.2 million units as a single dose in combination with oral rifampin (Shulman, 2012) Syphilis (CDC [Workowski 2015]): IM: Primary, Secondary, Early Latent ( 2.4 million units as a single dose Late Latent, Latent with unknown duration, or Tertiary Syphilis (with normal CSF examination): 2.4 million units once weekly for 3 doses Neurosyphilis (including Ocular Syphilis): Not indicated for use; aqueous penicillin G IV is preferred initial therapy (refer to Penicillin G Parenteral/Aqueous monograph for dosing) but consideration may be given to administering 2.4 million units IM once weekly for 3 weeks following IV treatment to provide a comparable total duration of therapy as latent syphilis Yaws, bejel, and pinta: IM: 1.2 million units as a single dose

(For additional information see "Penicillin G benzathine (long-acting intramuscular): Pediatric drug information") Usual dosage range: IM: 50,000 units/kg as a single dose (maximum: 2.4 million units) Upper respiratory infection, group A streptococci (eg, pharyngitis): Infants and Children: IM: Manufacturer's labeling: For older children, a dose of 900,000 units as a single dose is recommended. Primary prevention of rheumatic fever: Infants and Children: IM: ≤27 kg: 600,000 units as a single dose; >27 kg: 1.2 million units as a single dose (Gerber, 2009) Secondary prevention of rheumatic fever: Infants and Children: IM: ≤27 kg: 600,000 units every 3-4 weeks; >27 kg: 1.2 million units every 3 to 4 weeks (Gerber, 2009) Pharyngitis, group A streptococci (IDSA guidelines): Infants and Children: IM: Acute treatment: Chronic carrier treatment: Syphilis (off-label population; CDC [Workowski 2015]): IM: Primary, Secondary, and Early Latent ( Infants and Children: 50,000 units/kg/dose as a single injection (maximum: 2.4 million units/dose) Late Latent: Infants and Children: 50,000 units/kg/dose every week for 3 doses (maximum: 2.4 million units/dose)

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

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

Warnings & Precautions

Source: Lexicomp

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 (including cephalosporins), history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids and airway management (including intubation) as indicated.

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 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.

Syphilis/neurosyphilis use

CDC and AAP do not currently recommend the use of penicillin G benzathine for the initial treatment regimen for congenital syphilis or neurosyphilis due to reported treatment failures and lack of published clinical data on its efficacy (CDC [Workowski 2015]). Other warnings/precautions:

Appropriate administration

Not for intravenous use; cardiopulmonary arrest and death have occurred from inadvertent IV administration. Administer by deep IM injection only. Quadriceps femoris fibrosis and atrophy have been reported after repeated IM injections of penicillin preparations into the anterolateral thigh. Injection into or near an artery or nerve could result in severe neurovascular damage or permanent neurological damage.

Appropriate use

Use only for treatment of infections due to penicillin G sensitive gram positive organisms, few gram-negative organisms such as Neisseria gonorrhoeae, and some anaerobes and spirochetes. Use only for infections susceptible to the low and very prolonged serum concentrations of benzathine penicillin G.

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

Adverse events have not been observed in animal reproduction studies. Penicillin G benzathine crosses the placenta (Nathan 1993; Weeks 1997). Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects. Penicillin G is the drug of choice for treatment of syphilis during pregnancy (CDC [Workowski 2015]).

Lactation

Soluble penicillin G is excreted in breast milk. The manufacturer recommends that caution be exercised when administering penicillin to nursing women. Nondose-related effects could include modification of bowel flora and allergic sensitization.

Monitoring

Clinical pearl	Observe for signs and symptoms of anaphylaxis during first dose

Chemistry & Properties

Formula	C16H18N2O4S
Molecular weight	334.4 g/mol
IUPAC name	(2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
CAS	61-33-6
PubChem CID	5904
InChIKey	`JGSARLDLIJGVTE-MBNYWOFBSA-N`
logP	0.86 (XLogP 1.8)
Polar surface area	86.71 Å²
H-bond acceptors / donors	4 / 2
Drug-likeness (QED)	0.80
Lipinski violations	0

SMILES

CC1(C)S[C@@H]2[C@H](NC(=O)Cc3ccccc3)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)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)OAT1 (Inhibitor)OAT3 (Inhibitor)OAT4 (Inhibitor)OATP1A2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCTN1 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)PEPT1 (Inhibitor)PEPT2 (Inhibitor)MDR1 (Substrate)OAT1 (Substrate)OAT3 (Substrate)OATP1A2 (Substrate)OATP2B1 (Substrate)P-gp (Substrate)PEPT1 (Substrate)

Drug–drug interactions (17, DDInter)

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

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Retarpen 6:3:3 Vial	Vial 300000 IU, 600000 IU, 300000 IU	5 ml	Nabulsi Drug Store	1.220
Injpen	Vial 1 mega	10 vial	Oasis of Hope	5.630