penicillin G procaine

Penicillin G procaine is a medication used to treat infections caused by susceptible bacteria. Penicillin G procaine is a combination of penicillin G, a narrow-spectrum antibiotic, and procaine, a local anesthetic used to relieve pain. Penicillin G is administered as a deep intramuscular injection which can cause significant pain, and procaine is added to the formulation to reduce the pain. Penicillin G has low solubility and is slowly released from the injection site, which keeps the drug levels in the blood low but prolongs its activity.

Penicillin G is a natural penicillin that kills susceptible bacteria (bactericidal). Natural penicillins are produced from the mold Penicillium chrysogenum. Penicillin G is primarily active against Gram-positive aerobic bacteria but is effective against a few Gram-negative bacteria. The two main classes of bacteria are structurally different and are identified by the Gram stain lab test. Penicillin G is ineffective against strains that produce penicillinase or beta-lactamase, enzymes that some bacteria produce to inactivate the antibiotic, and develop resistance.

Penicillin G is a beta-lactam antibiotic that has a beta-lactam ring in its chemical structure. Beta-lactam is a compound that targets and blocks penicillin-binding proteins, enzymes that are essential for the biosynthesis of peptidoglycan. Penicillin G procaine inhibits the synthesis of mucopeptides (peptidoglycans), which provide structure and strength to the bacterial cell wall. This weakens the bacterial cell wall, leading to leakage of cell contents and bacterial death. 

Penicillin G procaine is approved by the FDA for the treatment of infections caused by susceptible microorganisms that respond to low and persistent penicillin G serum levels. If high, sustained serum levels are required, aqueous penicillin G is administered as an intravenous or intramuscular injection. The uses of penicillin G procaine include:

Adult and Pediatric:

• Streptococci Groups A, C, G, H, L, and M are sensitive (Group D, that is, enterococcus is resistant). Aqueous penicillin is G recommended for streptococcal bacteremia.
• Moderate/severe respiratory tract infection caused by pneumococci. Aqueous penicillin G is recommended for the acute stage of severe pneumonia, empyema, bacteremia, pericarditis, meningitis, peritonitis, or arthritis.
• Moderate/severe skin infections caused by susceptible staphylococci
• Susceptible fusiform bacilli and spirochetes (fusospirochetosis/Vincent’s infection)
• Syphilis (all stages) caused by susceptible Treponema pallidum
• Yaws, Bejel, and Pinta
• C. diphtheriae carrier stage
• Anthrax
• Rat-bite fever caused by Streptobacillus moniliformis and Spirillum minus

Adult:

• Erysipeloid caused by Erysipelothrix rhusiopathiae
• Subacute bacterial endocarditis, only in extremely sensitive infections caused by susceptible Group A streptococci
• Whipple’s disease caused by Tropheryma whipplei

Organisms susceptible to penicillin G procaine include:

• Staphylococci (except penicillinase-producing strains)
• Streptococci (Groups A, C, G, H, L, and M)
• Pneumococci
• Bacillus anthracis
• Corynebacterium diphtheriae
• Erysipelothrix rhusiopathiae
• Clostridia species
• Actinomyces bovis
• Streptobacillus moniliformis
• Listeria monocytogenes
• Leptospira species
• Treponema pallidum

• Do not administer penicillin G procaine to patients with a history of hypersensitivity reactions to any of the penicillins or any component of the formulation.
• Penicillin G procaine should be administered only as an intramuscular injection. Do not administer through any other route including intravenous (IV), subcutaneous (SC) or intrathecally (IT) into the spinal canal.
• Do not inject penicillin into or near a major peripheral nerve or artery, it can result in permanent neurological and/or neurovascular injury.
• Penicillin G is no longer used to treat gonorrhea, because most strains of Neisseria gonorrhoeae produce beta-lactamase which inactivates penicillin G.
• Avoid use of penicillin G procaine in newborns, there is an increased risk for sterile abscess development and procaine toxicity.
• Use penicillin G procaine with caution in patients with histories of significant allergies and/or asthma.
• There have been reports of serious allergic reactions including anaphylaxis in patients treated with penicillin.
  • The likelihood of serious reactions is higher in patients with a history of hypersensitivity to any penicillin or a history of sensitivity to multiple allergens.
  • Patients with hypersensitivity to penicillin may also experience severe reactions to cephalosporin class of antibiotics.
  • Carefully review the patient’s history of hypersensitivity reactions to penicillins, cephalosporins and other allergens before initiating treatment with penicillin G procaine.
  • If a patient develops hypersensitivity reactions, discontinue penicillin G procaine immediately, unless the treatment is for a life-threatening condition that is only amenable to penicillin therapy. Manage hypersensitivity with appropriate treatment.
  • Treat serious anaphylactic reactions immediately with epinephrine, oxygen, intravenous steroids, and airway management including intubation, if required.
• There have been reports of severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome following treatment with penicillin. Monitor patient for signs of such reactions, discontinue penicillin and use alternate therapy if they occur.
• As with most antibacterial agents, treatment with penicillin G procaine can alter the gut flora and lead to Clostridium difficile overgrowth that can cause pseudomembranous colitis and C. difficile associated diarrhea (CDAD), even up to two months after discontinuation.
  • Monitor patients for signs of colon inflammation (colitis) and diarrhea, and treat promptly.
  • If CDAD is suspected or confirmed during antibiotic treatment, all antibiotics other than those directed against C. difficile should be discontinued, and CDAD should be treated with fluid and electrolyte management and protein supplementation.
• Use of penicillin G procaine in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to be beneficial and increases the risk of development of drug-resistant bacteria.
• Prolonged use of antibiotics may promote overgrowth of non-susceptible organisms, including fungi. Fungal or bacterial superinfections should be treated promptly.
• A few patients may be sensitive to procaine. Perform a skin test in patients with a history of procaine sensitivity and if a patient shows signs of sensitivity, do not use procaine penicillin preparations. Procaine sensitivity reactions may be treated with barbiturates and antihistamines.
• Local anesthetics, including procaine, have been reported to cause methemoglobinemia, a condition with a high blood level of methemoglobin, a form of hemoglobin that cannot deliver oxygen to the tissues. 
  • Methemoglobinemia risk increases in patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, and infants younger than 6 months, and with concurrent use of oxidizing agents or their metabolites.
  • Monitor patients for signs and symptoms of methemoglobinemia, and if patient shows symptoms, discontinue procaine and any oxidizing drug, if used. Based on severity of symptoms, institute treatment such as oxygen therapy and hydration, or if required, methylene blue, exchange transfusion, or hyperbaric oxygen.
• Procaine may cause transient immediate toxic reactions, particularly with large doses. Symptoms include mental disturbances, anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness, and a sense of impending death.

Common side effects of penicillin G procaine include:

• Injection site reactions including:
  • Pain
  • Swelling (edema)
  • Lump
  • Skin peeling and blistering
  • Bruising and bleeding
  • Discoloration
  • Numbness
• Hypersensitivity reactions including:
  • Rashes
  • Hives (urticaria)
  • Exfoliative dermatitis
  • Itching (pruritus)
  • Difficulty breathing and swallowing
  • Swelling of face, throat, lips, tongue, eyes, ankle and/or feet
• Severe skin reactions including:
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Acute generalized exanthematous pustulosis
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Serum sickness-like reactions including:
  • Fever
  • Chills
  • Edema
  • Joint pain (arthralgia)
  • Weakness
• Jarisch Herxheimer reaction (JHR), a type of sensitivity reaction common with treatment of syphilis with symptoms that can include:
  • Fever
  • Chills
  • Rigors
  • Nausea
  • Vomiting
  • Headache
  • Rapid heart rate (tachycardia)
  • Low blood pressure (hypotension)
  • Rapid breathing (hyperventilation)
  • Flushing
  • Muscle pain (myalgia)
  • Exacerbation of skin lesions
• Colon inflammation (pseudomembranous colitis) due to Clostridium difficile bacteria overgrowth
• C. difficile-associated diarrhea (CDAD)
• Transient symptoms of procaine toxicity including:
  • Anxiety
  • Confusion
  • Agitation
  • Depression
  • Weakness
  • Seizures
  • Hallucinations
  • Combativeness
  • Sense of impending death
• Fungal or bacterial superinfection
• Kidney infection (interstitial nephritis)
• Low red blood cell count due to premature destruction (hemolytic anemia)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable suspension

• 600,000 units/1 mL syringe
• 1.2 million units/2 mL syringe

Adult:

Pneumonia

• Indicated for moderately severe uncomplicated pneumococcal pneumonia
• 600,000-1,000,000 units intramuscular (IM) once daily

Streptococcal Infections (Group A)

• Indicated for moderately severe-to-severe tonsillitis, erysipelas, scarlet fever, upper respiratory tract, skin and soft tissue infections
• 600,000-1,000,000 units IM once daily for at least 10 days

Staphylococcal Infections

• 600,000-1,000,000 units IM once daily

Bacterial Endocarditis

• Indicated only for treatment of extremely sensitive infections; not indicated for prophylaxis
• 600,000 -1,000,000 units IM once daily

Syphilis

• Primary, secondary, and latent: 600,000 units IM once daily for 8 days
• Late (tertiary and latent syphilis with positive spinal fluid): 600,000 units IM once daily for 10-15 days (total 6-9 million units)
• Neurosyphilis: 2.4 million units IM once daily for 10-14 days; administer with probenecid 500 mg oral 4 times a day (penicillin G aqueous preferred)

Anthrax

• Cutaneous: 600,000-1,000,000 units IM once daily
• Inhaled (post-exposure): 1.2 million units IM once every 12 hours for up to 2 weeks, THEN switch to oral treatment (total treatment 60 days)

Diphtheria

• Adjunct with antitoxin: 300,000-600,000 units IM once daily
• Carrier state: 300,000 units IM once daily

Vincent’s Infection (fusospirochetosis)

• 600,000-1,000,000 units IM once daily

Erysipeloid

• 600,000-1,000,000 units IM once daily

Rat-Bite Fever

• Indicated for Streptobacillus moniliformis and Spirillum minus (rat-bite fever)
• 600,000-1,000,000 units IM once daily

Whipple’s disease

• 1.2 million units IM once daily for 10-14 days; co-administer with streptomycin, THEN
• Trimethoprim/sulfamethoxazole or doxycycline oral for 1 year

Renal Impairment

• Creatinine clearance (CrCl) 10-50 mL/minute: Decrease dose by 25%
• CrCl below 10 mL/minute: Decrease dose by 50-70%
• Hemodialysis: Removed by hemodialysis; administer after dialysis

Other Indications and Uses

• Indicated for susceptible microorganisms that respond to low and persistent penicillin G serum levels (if high, sustained serum levels required, use aqueous penicillin G IV/IM)

Pediatric:

General Dosing for Infections

• Infants/children: 25,000-50,000 units/kg/day IM
• Avoid use in neonates; higher risk of abscess and procaine toxicity

Pneumonia

• Indicated for pneumonia caused by streptococcal Group A and staphylococcal infections
• Children weighing below 60 pounds: 300,000 units IM once daily
• Children weighing 60 pounds or greater: As adults; 600,000 units IM once daily

Syphilis

• Congenital Syphilis: children weighing below 70 pounds: 50,000 units/kg IM once daily for 10 days
• Primary, secondary, and latent (children 12 years or older): As adults; 600,000 units IM once daily for 8 days

Anthrax

• Inhaled (post-exposure): 25,000 units/kg IM once every 12 hours for up to 2 weeks; not to exceed 1.2 million units once every 12 hours, THEN switch to PO treatment (total treatment 60 days)

Renal Impairment

• Not defined in children; see adult recommendations

Overdose

• Penicillin G overdose can cause muscle twitching and seizures. Procaine overdose can cause methemoglobinemia, a condition with high blood levels of methemoglobin, a form of hemoglobin that does not deliver oxygen to tissues.
• Penicillin G overdose may be treated with supportive care, including anticonvulsants. Based on the severity of symptoms, methemoglobinemia may be treated with oxygen therapy and hydration, or if required, methylene blue, exchange transfusion, or hyperbaric oxygen.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Penicillin G procaine has no listed severe interactions with other drugs
• Serious interactions of penicillin G procaine include:
  • typhoid vaccine
  • methotrexate
  • tetracycline
  • probenecid
• Penicillin G procaine has no listed moderate or mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Studies with use of penicillin G procaine in pregnant animals did not reveal fetal harm or fertility impairment. Human experience with use of penicillins during pregnancy has not shown evidence of fetal harm.
• There are no adequate and well-controlled studies of penicillin G procaine in pregnant women that conclusively prove that there is no fetal harm. The drug should be used during pregnancy only if clearly needed.
• Penicillins are excreted in breastmilk. Use with caution in nursing mothers.

• Complete your prescribed course of penicillin G procaine injections. Do not miss your appointment for injections or discontinue therapy if you feel better, it can decrease effectiveness of treatment and can also lead to development of drug-resistant bacteria.
• Inform your physician of your history of hypersensitivity to antibiotics and allergens and notify immediately if you experience hypersensitivity reactions to penicillin G procaine.
• Report to your physician immediately if you develop:
  • Severe injection site reactions
  • Severe skin reactions
  • Nausea and vomiting
• Inform your physician if you experience symptoms of methemoglobinemia such as pale or bluish skin, breathing difficulty, headache, racing heart, dizziness and fatigue.
• Notify your physician if you experience signs of mental disturbances following the injection, which can include anxiety, confusion, agitation, depression, hallucinations, combativeness, and a sense of impending death, and weakness and seizures.
• Diarrhea is a common problem with antibiotic treatments which should resolve with the completion of the therapy. Seek medical help if you have watery or bloody stools, with or without stomach cramps and fever. Symptoms can develop even up to two months after the last dose of antibiotic.