Penicillin G benzathine (Penidure LA) is a long-acting formulation of penicillin for intramuscular use in the prevention of rheumatic fever and treatment of a variety of infections including syphilis.

Penicillin G benzathine Uses:

• Acute glomerulonephritis:

  • Secondary prophylaxis with a history of acute glomerulonephritis

• Respiratory tract infections:

  • Treatment for streptococcal upper respiratory tract infections (including pharyngitis) that are mild to moderate and responsive to low, prolonged serum penicillin G concentrations.

• Rheumatic fever and chorea:

  • Secondary prophylaxis of rheumatic fever and/or chorea

• Rheumatic heart disease:

  • Secondary prophylaxis in patients with rheumatic heart disease

• Syphilis and other venereal diseases:

  • Treatment of syphilis, yaws, bejel, and pinta

• Off-Label Use of Penicillin G benzathine in Adults:

  • Streptococcal (group A) chronic carriage

Penicillin G benzathine Dose in Adults

Penicillin G benzathine Usual dosage range:

• IM: Single dose of 1.2 to 2.4 million units

Streptococcus (group A):

Penicillin G benzathine Dose in the treatment of acute Pharyngitis:

• IM: 1.2 million units as a stat single dose

Penicillin G benzathine Dose in the Secondary prophylaxis for rheumatic fever (prevention of recurrent attacks):

• IM: 1.2 million units once every 21 to 28 days.
• The duration of prophylaxis depends on risk factors and the presence of valvular heart disease.

• Manufacturer's labeling:

  • The dosing recommended in drug literature could not correspond to current clinical guidelines.
  • IM: 600,000 units every 2 weeks

Penicillin G benzathine Dose in the Secondary prophylaxis of glomerulonephritis:

• IM: 1.2 million units every 4 weeks or 600,000 units twice monthly

Penicillin G benzathine Dose in the treatment of Chronic carriage (off-label):

• IM: 1.2 million units as a stat single dose in combination with oral rifampin.
• Note: Most individuals with chronic carriage do not require antibiotics.

Penicillin G benzathine Dose in the treatment of Syphilis:

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

  • IM: 2.4 million units as a single dose

• Late Latent, Latent with unknown duration, or Tertiary Syphilis (with normal CSF examination):

  • IM: 3 doses of 2.4 million units once a week

Penicillin G benzathine Dose in the treatment of Neurosyphilis (including Ocular Syphilis):

• Not indicated for initial treatment;
• aqueous penicillin G IV is preferred initial therapy (refer to Penicillin G Parenteral/Aqueous monograph for dosing).
• To offer a comparable overall duration of therapy to that for latent syphilis after penicillin G IV first treatment, one may consider administering penicillin G benzathine 2.4 million units IM once weekly for 3 weeks.

Penicillin G benzathine Dose in the treatment of Yaws, bejel, and pinta:

• IM: 1.2 million units as a single dose

Penicillin G benzathine Dose in Children

Penicillin G benzathine dose in Group A streptococcal upper respiratory infection:

• Infants, Children, and Adolescents: IM:

  • Primary prevention of Rheumatic fever:

    • ≤27 kg: 600,000 units as a single dose
    • >27 kg: 1.2 million units as a single dose

  • Secondary prevention of Rheumatic fever:

Note:

• Duration of secondary rheumatic fever prophylaxis varies:
  • Rheumatic fever with carditis and residual heart disease:
    • 10 years, sometimes lifelong prophylaxis, or until age 40, whichever comes first;
  • rheumatic fever with carditis but no residual heart disease:
    • 10 years, or for the duration of 21 years, whichever comes first;
  • rheumatic fever without carditis:
    • Until the older of five years or 21. (whichever is longer)
    • ≤27 kg: For 3-4 weeks, 600,000 units 
    • >27 kg: For 3-4 weeks, 1.2 million units 

Penicillin G benzathine Dose in the treatment of Syphilis:

• Infants, Children, and Adolescents: IM

  • Primary, Secondary, or Early Latent (< 1-year duration):

    • 50,000 units/kg once;
    • The maximum dose: 2.4 million units

  • Late Latent or Latent with unknown duration:

    • 50,000 units/kg once weekly for 3 doses;
    • The maximum dose: 2.4 million units

Penicillin G benzathine Pregnancy Risk Category: B

• Animal reproduction studies have not shown any adverse events.
• Penicillin G benzathine crosses over to the placenta.
• Penicillins used by mothers have not been shown to increase the risk of adverse effects on fetus. Penicillin G is the preferred drug for the treatment of syphilis in pregnancy.

Penicillin G benzathine use during breastfeeding:

• Breast milk contains soluble penicillin G.
• The manufacturer suggests that nursing mothers exercise caution when using penicillin.
• Other effects that are not related to the dose include altered bowel flora or allergic sensitization.

Penicillin G benzathine Dose in Kidney Disease:

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

Penicillin G benzathine Dose in Liver Disease:

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

Side effects of Penicillin G benzathine:

• Cardiovascular:

  • Cerebrovascular Accident
  • Hypotension
  • Palpitations
  • Syncope
  • Tachycardia
  • Vasodilation
  • Vasospasm
  • Vasodepressor Syncope

• Central Nervous System:

  • Anxiety
  • Coma
  • Confusion
  • Dizziness
  • Drowsiness
  • Euphoria
  • Fatigue
  • Headache
  • Localized Warm Feeling
  • Nervousness
  • Neurologic Abnormality (Neurogenic Bladder)
  • Numbness
  • Pain
  • Seizure
  • Transverse Myelitis

• Dermatologic:

  • Diaphoresis
  • Gangrene Of Skin Or Other Tissue
  • Pallor
  • Skin Mottling
  • Skin Ulceration At Injection Site

• Gastrointestinal:

  • Bloody Stools
  • Intestinal Necrosis
  • Nausea
  • Vomiting

• Genitourinary:

  • Hematuria
  • Impotence
  • Priapism
  • Proteinuria

• Hematologic & Oncologic:

  • Local Hemorrhage (At Injection Site)
  • Lymphadenopathy

• Hepatic:

  • Increased Serum AST

• Hypersensitivity:

  • Hypersensitivity Reaction

• Immunologic:

  • Jarisch-Herxheimer Reaction

• Local:

  • Abscess At Injection Site
  • Atrophy At Injection Site
  • Bruising At Injection Site
  • Cellulitis At Injection Site
  • Localized Edema (At Injection Site)
  • Inflammation At Injection Site
  • Injection Site Reaction (Neurovascular Damage)
  • Pain At Injection Site
  • Residual Mass At Injection Site
  • Tissue Necrosis At Injection Site

• Neuromuscular & Skeletal:

  • Arthropathy
  • Exacerbation Of Arthritis
  • Periosteal Disease (Periostitis)
  • Rhabdomyolysis
  • Tremor
  • Weakness

• Ophthalmic:

  • Blindness
  • Blurred Vision

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine
  • Myoglobinuria
  • Renal Failure

• Respiratory:

  • Cyanosis

Contraindications to Penicillin G benzathine:

• Hypersensitivity/ Allergy To Penicillins Or Any Component of The Formula

Warnings and precautions

• Hypersensitivity reactions

  • Patients on penicillin have experienced severe and sometimes fatal hypersensitivity/ anaphylactic reactions.
  • This is especially true if patients have a history beta-lactam hypersensitivity (including cephalosporins), sensitivity to numerous allergens or IgE-mediated responses such as anaphylaxis or angioedema.
  • Serious allergic or anaphylactic reactions necessitate immediate emergency care, including the delivery of oxygen, epinephrine, steroids intravenously, and airway control, including intubation as needed.

• Superinfection

  • Extended use can result in fungal and bacterial superinfections including pseudo-membranous collitis and C. difficile-associated diarrhoea (CDAD).
  • After more than two months of post-antibiotic therapy, CDAD was noticed.

• Renal impairment

  • Patients with impaired renal function should be cautious.

• Seizure disorders:

  • Patients who have a history of epilepsy should take extra care.
  • High uric acid levels can make people more likely to have seizures, especially if they have renal impairment.

• Use of Syphilis or Neurosyphilis:

  • AAP and CDC don't recommend penicillin G benzathine as a first treatment for neurosyphilis and congenital syphilis. This is due to treatment failures, lack of published data and insufficient clinical evidence.

Penicillin G benzathine (long-acting intramuscular): Drug Interaction

Monitoring Parameters:

• Observe for signs and symptoms of anaphylaxis during the first dose of administration.

How to administer Penicillin G benzathine?

• Warm to room temperature before IM administration to lessen the pain associated with the injection.
• Deep IM injection administration is done at a slow, steady rate in the dorso-gluteal region (upper outer quadrant of the buttock) or the ventro-gluteal region.
• Do not inject near an artery or a nerve;
• It can cause permanent neurological damage or gangrene.
• When doses are repeated, rotate the injection site.
• Do not administer IV, intra-arterially, or SubQ.

Mechanism of action of Penicillin G benzathine:

• Interferes in the synthesis and maintenance of the bacterial cell walls during active multiplication, resulting in cell death and bactericidal activity.

Duration:

• 1 to 4 weeks (dose-dependent); larger doses result in more sustained levels

Absorption:

• IM: Slow

Distribution:

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

Protein Binding:

• ~60%

Time to peak serum concentration:

• Within 12 to 24 hours;
• serum levels are usually detectable for 7 to 28 days depending on the dose; larger doses result in more sustained levels rather than higher levels

Excretion:

• Excreted by renal tubular excretion;
• penicillin G can be found 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

International Brands of Penicillin G benzathine:

• Bicillin L-A
• Bencelin
• Benzapen
• Benzetacil
• Benzetacil L.A.
• Benzibiotic
• Bepeben
• Bicillin G
• Bicillin L-A
• Debecylina
• Deposilin
• Extencilline
• Indopen
• Lentocilin-S
• Leomypen
• Longacillin
• Mycin
• Noraben
• Pebenzatil
• Pen Di Ben
• Penadur
• Penadur - LA
• Penadur LA
• Pencom
• Pendepon
• Pendiben L-A
• Pendysin
• Penidure
• Penilente
• Penilente LA
• Penzathine
• Retarpen
• Retarpen LA
• Tardocillin
• Terbocyl
• Ultracillin LA
• Unicil L-A
• Zalpen

Penicillin G benzathine Brands Names in Pakistan: