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Penicillin G Benzathine


General


Pronunciation

(pen i SIL in jee BENZ a theen)


Brand Names: U.S.

  • Bicillin L-A

Indications


Use: Labeled Indications

Acute glomerulonephritis: Prophylaxis (secondary) in patients with a history of acute glomerulonephritis

Respiratory tract infections: Treatment of mild to moderate upper respiratory tract infections caused by streptococci susceptible to low, prolonged serum concentrations of penicillin G

Rheumatic fever and chorea: Prophylaxis (secondary) of rheumatic fever and/or chorea

Rheumatic heart disease: Prophylaxis (secondary) in patients with rheumatic heart disease

Syphilis and other venereal diseases: Treatment of syphilis, yaws, bejel, and pinta


Contraindications


Hypersensitivity to penicillin(s) or any component of the formulation


ALERT: U.S. Boxed Warning

Appropriate administration:

Not for intravenous (IV) use. Do not inject IV or admix with other IV solutions. There have been reports of inadvertent IV administration of penicillin G benzathine that has been associated with cardiorespiratory arrest and death. Prior to administration of this drug, carefully read the Administration and Dosage section.


Dosing and Administration


Dosing: Adult

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 (<1 year duration): 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


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

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: Manufacturers labeling:

<27.3 kg: 300,000 to 600,000 units as a single dose. Manufacturer labeling does not provide specific recommendation for children ≥27.3 kg.

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: <27 kg: 600,000 units as a single dose; ≥27 kg: 1.2 million units as a single dose (Shulman, 2012)

Chronic carrier treatment: <27 kg: 600,000 units as a single dose (in combination with oral rifampin); ≥27 kg: 1.2 million units as a single dose (in combination with oral rifampin) (Shulman, 2012)

Syphilis (off-label population; CDC [Workowski 2015]): IM:

Primary, Secondary, and Early Latent (<1 year duration): 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)


Dosing: Renal Impairment

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


Dosing: Hepatic Impairment

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


Administration

IM: Warm to room temperature before administration to lessen the pain associated with injection. Administer by deep IM injection in the upper outer quadrant of the buttock; in children <2 years of age, IM injections should be made into the midlateral muscle of the thigh, not the gluteal region. Do not inject near an artery or a nerve; permanent neurological damage or gangrene may result. When doses are repeated, rotate the injection site. Do not administer IV, intra-arterially, or SubQ.


Storage

Store at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F); do not freeze. The following stability information has also been reported: May be stored at 25 ‚ °C (77 ‚ °F) for 7 days (Cohen, 2007).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intramuscular:

Bicillin L-A: 600,000 units/mL (1 mL); 1,200,000 units/2 mL (2 mL); 2,400,000 units/4 mL (4 mL) [contains methylparaben, propylparaben]


Drug Interactions

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy


Monitoring Parameters

Observe for signs and symptoms of anaphylaxis during first dose


Lab Test Interferences


Test Interactions

Positive Coombs [direct], false-positive urinary and/or serum proteins; false-positive or negative urinary glucose using Clinitest ‚ ®


Adverse Reactions


Frequency not defined.

Cardiovascular: Cardiac arrest, cerebral vascular accident, cyanosis, gangrene, hypotension, pallor, palpitations, syncope, tachycardia, vasodilation, vasospasm, vasovagal reaction

Central nervous system: Anxiety, coma, confusion, dizziness, euphoria, fatigue, headache, nervousness, pain, seizure, somnolence

In addition, a syndrome of CNS symptoms has been reported which includes: Severe agitation with confusion, hallucinations (auditory and visual), and fear of death (Hoigne 's syndrome); other symptoms include cyanosis, dizziness, palpitations, psychosis, seizures, tachycardia, taste disturbance, tinnitus

Gastrointestinal: Bloody stool, intestinal necrosis, nausea, vomiting

Genitourinary: Impotence, priapism

Hepatic: AST increased

Local: Injection site reactions: Abscess, atrophy, bruising, cellulitis, edema, hemorrhage, inflammation, lump, necrosis, pain, skin ulcer

Neuromuscular & skeletal: Arthritis exacerbation, joint disorder, neurovascular damage, numbness, periostitis, rhabdomyolysis, transverse myelitis, tremor, weakness

Ocular: Blindness, blurred vision

Renal: BUN increased, creatinine increased, hematuria, myoglobinuria, neurogenic bladder, proteinuria, renal failure

Miscellaneous: Diaphoresis, hypersensitivity reactions, Jarisch-Herxheimer reaction, lymphadenopathy, mottling, warmth


Warnings/Precautions


Concerns related to adverse effects:

- 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: [US Boxed Warning]: 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 Risk Factor

B


Pregnancy Considerations

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]).


Actions


Pharmacology

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


Absorption

IM: Slow


Distribution

Minimal concentrations attained in CSF with inflamed or uninflamed meninges; highest levels in the kidney; lesser amounts in liver, skin, intestines


Excretion

Excreted by renal tubular excretion; penicillin G is detected in urine for up to 12 weeks after a single IM injection; renal clearance is delayed in neonates, young infants, and patients with impaired renal function


Time to Peak

Serum: Within 12 to 24 hours; serum levels are usually detectable for 1 to 4 weeks depending on the dose; larger doses result in more sustained levels rather than higher levels


Duration of Action

Dose dependent: 1 to 4 weeks; larger doses result in more sustained levels


Protein Binding

~60%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea, vomiting, or diarrhea. Have patient report immediately to prescriber bruising, bleeding, severe injection site irritation, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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