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Penicillin g benzathine Side Effects

For the Consumer

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

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]


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

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

Some side effects of penicillin g benzathine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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