CDC Recommendation

BICILLIN L-A (penicillin G benzathine injectable suspension)
INDICATIONS

Intramuscular penicillin G benzathine is indicated in the treatment of infections due to penicillin-G-sensitive microorganisms that are susceptible to the low and very prolonged serum levels common to this particular dosage form. Therapy should be guided by bacteriological studies (including sensitivity tests) and by clinical response.

The following infections will usually respond to adequate dosage of intramuscular penicillin G benzathine:

Mild-to-moderate infections of the upper-respiratory tract due to susceptible streptococci.

Venereal infections—Syphilis, yaws, bejel, and pinta.

Medical Conditions in which Penicillin G Benzathine Therapy is indicated as Prophylaxis:

Rheumatic fever and/or chorea—Prophylaxis with penicillin G benzathine has proven effective in preventing recurrence of these conditions. It has also been used as follow-up prophylactic therapy for rheumatic heart disease and acute glomerulonephritis.

IMPORTANT SAFETY INFORMATION

WARNING NOT FOR INTRAVENOUS USE. DO NOT INJECT INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS. THERE HAVE BEEN REPORTS OF INADVERTENT INTRAVENOUS ADMINISTRATION OF PENICILLIN G BENZATHINE WHICH HAS BEEN ASSOCIATED WITH CARDIORESPIRATORY ARREST AND DEATH. Prior to administration of this drug, carefully read the WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections of the labeling.

Contraindication

History of a previous hypersensitivity reaction to any of the penicillins.

Warnings and Precautions

Anaphylaxis 
SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH BICILLIN L-A, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, BICILLIN L-A SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Serious cutaneous adverse reactions 
Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in patients taking penicillin G (the active moiety in BICILLIN L-A). When SCAR is suspected, BICILLIN L-A should be discontinued immediately and an alternative treatment should be considered.

Clostridioides difficile associated diarrhea 
Clostridioides difficile associated-diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including BICILLIN L-A, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Do not inject into or near an artery or nerve. See administration instructions. 
Injection into or near a nerve may result in permanent neurological damage.

FOR DEEP INTRAMUSCULAR INJECTION ONLY. There have been reports of inadvertent intravenous administration of penicillin G benzathine which has been associated with cardiorespiratory arrest and death. Therefore, do not inject intravenously or admix with other intravenous solutions.

Prescribing BICILLIN L-A in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of a development of drug-resistant bacteria.

Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma.

With streptococcal infections, cultures should be taken following completion of treatment to determine whether streptococci have been eradicated.

Tetracycline may antagonize the bactericidal effect of penicillin, and concurrent use of these drugs should be avoided.

Concurrent administration of penicillin and probenecid increases and prolongs serum penicillin levels.

Pregnancy: Use during pregnancy only if clearly needed.

Nursing mothers: Caution should be exercised when penicillin G benzathine is administered to a nursing mother.

Geriatric patients: Use caution during dose selection, starting at the low end of the dosing range while carefully monitoring for side effects.

Adverse Reactions

As with other treatments for syphilis, the Jarisch-Herxheimer reaction has been reported.

The following adverse reactions have been reported with BICILLIN L-A during post-marketing experience:
Skin and Appendages: Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS).  
Immune System Disorders: Acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction (Kounis syndrome).

The following have been reported with parenteral penicillin G (the active moiety in BICILLIN L-A):
General: Hypersensitivity reactions including the following: skin eruptions (maculopapular to exfoliative dermatitis), urticaria, laryngeal edema, fever, eosinophilia; other serum sickness-like reactions (including chills, fever, edema, arthralgia, and prostration); and anaphylaxis including shock and death: severe cutaneous adverse reactions (SCAR), such as toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). Note: Urticaria, other skin rashes, and serum sickness-like reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, penicillin G should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to therapy with penicillin G. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be administered as indicated. 
Gastrointestinal: Pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. 
Hematologic: Hemolytic anemia, leukopenia, thrombocytopenia. 
Neurologic: Neuropathy. 
Urogenital: Nephropathy.

The following adverse events have been temporally associated with parenteral administration of penicillin G benzathine (a component of BICILLIN L-A):
Body as a Whole: Hypersensitivity reactions including allergic vasculitis, pruritus, fatigue, asthenia, and pain; aggravation of existing disorder; headache, Nicolau syndrome. 
Cardiovascular: Cardiac arrest; hypotension; tachycardia; palpitations; pulmonary hypertension; pulmonary embolism; vasodilation; vasovagal reaction; cerebrovascular accident; syncope. 
Gastrointestinal: Nausea, vomiting; blood in stool; intestinal necrosis. 
Hemic and Lymphatic: Lymphadenopathy. 
Injection Site: Injection site reactions including pain, inflammation, lump, abscess, necrosis, edema, hemorrhage, cellulitis, hypersensitivity, atrophy, ecchymosis, and skin ulcer. Neurovascular reactions including warmth, vasospasm, pallor, mottling, gangrene, numbness of the extremities, cyanosis of the extremities, and neurovascular damage. 
Metabolic: Elevated BUN, creatinine, and SGOT. 
Musculoskeletal: Joint disorder; periostitis; exacerbation of arthritis; myoglobinuria; rhabdomyolysis. 
Nervous System: Nervousness; tremors; dizziness; somnolence; confusion; anxiety; euphoria; transverse myelitis; seizures; coma. A syndrome manifested by a variety of CNS symptoms such as severe agitation with confusion, visual and auditory hallucinations, and a fear of impending death (Hoigne’s syndrome), has been reported after administration of penicillin G procaine and, less commonly, after injection of the combination of penicillin G benzathine and penicillin G procaine. Other symptoms associated with this syndrome, such as psychosis, seizures, dizziness, tinnitus, cyanosis, palpitations, tachycardia, and/or abnormal perception in taste, also may occur. 
Respiratory: Hypoxia; apnea; dyspnea. 
Skin: Diaphoresis. 
Special Senses: Blurred vision; blindness. 
Urogenital: Neurogenic bladder; hematuria; proteinuria; renal failure; impotence; priapism. 
Overdosage: Penicillin in overdosage has the potential to cause neuromuscular hyperirritability or convulsive seizures.

INDICATIONS

Intramuscular penicillin G benzathine is indicated in the treatment of infections due to penicillin-G-sensitive microorganisms that are susceptible to the low and very prolonged serum levels common to this particular dosage form. Therapy should be guided by bacteriological studies (including sensitivity tests) and by clinical response.

The following infections will usually respond to adequate dosage of intramuscular penicillin G benzathine:

Mild-to-moderate infections of the upper-respiratory tract due to susceptible streptococci.

Venereal infections—Syphilis, yaws, bejel, and pinta.

Medical Conditions in which Penicillin G Benzathine Therapy is indicated as Prophylaxis:

Rheumatic fever and/or chorea—Prophylaxis with penicillin G benzathine has proven effective in preventing recurrence of these conditions. It has also been used as follow-up prophylactic therapy for rheumatic heart disease and acute glomerulonephritis.