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Bicillin L-A Side Effects

Generic name: penicillin g benzathine

Medically reviewed by Last updated on Sep 21, 2020.

Note: This document contains side effect information about penicillin g benzathine. Some of the dosage forms listed on this page may not apply to the brand name Bicillin L-A.

For the Consumer

Applies to penicillin g benzathine: parenteral injection, parenteral powder for im or iv use, parenteral suspension for im injection


  • Penicillin G benzathine (Bicillin® L-A, Permapen®)2 3 penicillin G procaine,7 and fixed combination of penicillin G benzathine and penicillin G procaine (Bicillin® C-R, Bicillin® C-R 900/300),4 5 are administered by deep IM injection only2 4 5 7 and should not be injected IV or admixed with other IV solutions.2 4 5

  • Inadvertent IV administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.2 4 5

  • Prior to administration of penicillin G benzathine, penicillin G procaine, or fixed combination of penicillin G benzathine and penicillin G procaine, carefully read the warnings, adverse reactions, and dosage and administration sections of the prescribing information.2 4 5 7

Side effects include:

Hypersensitivity reactions (rash, urticaria, serum sickness); local effects.

For Healthcare Professionals

Applies to penicillin g benzathine: intramuscular suspension


Frequency not reported: Injection site reactions (including pain, inflammation, lump, abscess, necrosis, edema, hemorrhage, cellulitis, hypersensitivity, atrophy, ecchymosis, skin ulcer), neurovascular reactions (including warmth, vasospasm, pallor, mottling, gangrene, numbness of the extremities, cyanosis of the extremities, neurovascular damage)[Ref]


Frequency not reported: Hypersensitivity reactions (including skin eruptions [maculopapular to exfoliative dermatitis], urticaria, laryngeal edema, fever, eosinophilia, hypersensitivity myocarditis, other serum sickness-like reactions [including chills, fever, edema, arthralgia, prostration], anaphylactic/anaphylactoid reaction [including shock, death], allergic vasculitis, pruritus, fatigue, asthenia, pain)[Ref]


Frequency not reported: Cardiac arrest, hypotension, tachycardia, palpitations, pulmonary hypertension, pulmonary embolism, vasodilation, vasovagal reaction, cerebrovascular accident, cyanosis[Ref]

Nervous system

Severe reactions (including myoclonus, seizures, auditory and visual hallucinations, decreased mentation) have been reported with high-dose penicillin therapy or in patients with renal dysfunction. Severe neurologic reactions were most often seen with penicillin doses of 18 million to 80 million units daily. These reactions frequently abated after discontinuation of penicillin. In several cases, penicillin was restarted at a lower dose with no further sequelae. In 1 review, the authors found that cerebral spinal fluid (CSF) penicillin levels were higher in patients with seizures than in those without. CSF penicillin levels ranged from 12 to 61 units/mL in the seizure group with the highest CSF concentrations, compared to 7.8 units/mL in the group without seizures. Neurologic reactions occurred frequently in patients with renal dysfunction.

A syndrome characterized by various central nervous system symptoms (e.g., severe agitation with confusion, visual and auditory hallucinations, fear of impending death [Hoigne's syndrome]) has been reported after administration of this drug. Other symptoms associated with this syndrome have included psychosis, seizures, dizziness, tinnitus, cyanosis, palpitations, tachycardia, and abnormal taste perception.[Ref]

Frequency not reported: Syncope, neuropathy, headache, tremors, dizziness, somnolence, abnormal taste perception, tinnitus, transverse myelitis, seizures, aseptic meningitis, coma, neurovascular reactions (including warmth, vasospasm, pallor, mottling, gangrene, numbness of the extremities, cyanosis of the extremities, neurovascular damage), myoclonus, decreased mentation, neurologic reactions[Ref]


Frequency not reported: Clostridium difficile-associated diarrhea, pseudomembranous colitis, nausea, vomiting, intestinal necrosis, blood in the stool[Ref]

Onset of pseudomembranous colitis symptoms have been reported during or after antibacterial therapy.[Ref]


Frequency not reported: Hemolytic anemia, leukopenia, thrombocytopenia, lymphadenopathy[Ref]


A 28-year-old female developed jaundice, fever, epidermolysis, abnormal liver function tests, and cholestasis several days after receiving a single dose of penicillin IM. Her liver dysfunction continued for up to 18 months. She had taken acetaminophen concurrently but denied alcohol use.[Ref]

Frequency not reported: Increased AST, jaundice, cholestasis, abnormal liver function tests[Ref]


Frequency not reported: Joint disorder, periostitis, myoglobinuria, rhabdomyolysis, exacerbation of arthritis, quadriceps femoris fibrosis and atrophy[Ref]

Quadriceps femoris fibrosis and atrophy have been reported after repeated IM injections into the anterolateral thigh.[Ref]


Frequency not reported: Increased BUN, increased creatinine, renal failure, nephropathy, acute interstitial nephritis[Ref]


Frequency not reported: Hypoxia, apnea, dyspnea[Ref]


Frequency not reported: Nervousness, confusion, anxiety, euphoria, auditory and visual hallucinations, agitation, fear of impending death, psychosis[Ref]


Frequency not reported: Blurred vision, blindness[Ref]


Frequency not reported: Neurogenic bladder, hematuria, proteinuria, impotence, priapism[Ref]


Frequency not reported: Diaphoresis, rash, peeling, mucosal ulceration, urticaria, epidermolysis

Beta-lactam antibiotics:

-Frequency not reported: Severe cutaneous adverse reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms [DRESS syndrome], acute generalized exanthematous pustulosis)[Ref]


Frequency not reported: Fatigue, asthenia, pain, aggravation of existing disorder, Hoigne's syndrome[Ref]


The Jarisch-Herxheimer reaction has been reported during syphilis treatment.

Frequency not reported: Jarisch-Herxheimer reaction


1. "Product Information. Bicillin L-A (penicillin)." Monarch Pharmaceuticals Inc, Bristol, TN.

2. Cerner Multum, Inc. "Australian Product Information." O 0

3. International Rheumatic Fever Study Group "Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever." Lancet 337 (1991): 1308-10

4. Barrons RW, Murray KM, Richey RM "Populations at risk for penicillin-induced seizures." Ann Pharmacother 26 (1992): 26-9

5. Andrade RJ, Guilarte J, Salmeron FJ, Lucena MI, Bellot V "Benzylpenicillin-induced prolonged cholestasis." Ann Pharmacother 35 (2001): 783-4

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.