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Penicillin g sodium Side Effects

Applies to penicillin g sodium: injectable powder for injection.


Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Get emergency medical help if you have signs of an allergic reaction: hives, itching; feeling like you might pass out; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

Common side effects may include:

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to penicillin g sodium: injectable powder for injection.


Allergic reactions have been reported with all penicillins and the incidence ranged from 0.7% to 10% in studies. Hypersensitivity reactions with penicillin were more common and more serious with IV therapy, but have also been reported with oral therapy. An initial sensitizing exposure is required to stimulate the production of antigen-specific IgE before clinical manifestations of hypersensitivity are seen on the second exposure. There are numerous "hidden" environmental or occupational exposures to penicillin including in utero exposure, breast milk exposure, and occupational exposure.

Immediate and delayed allergic reactions were more likely to occur in patients with history of sensitivity to multiple allergens. Immediate allergic reactions generally occurred within 20 minutes of use; accelerated immediate reactions have occurred 20 minutes to 45 hours after use. Immediate anaphylactic reactions generally occurred after parenteral therapy; however, a few cases of anaphylaxis have been reported after oral therapy. Delayed allergic reactions to penicillin have been reported within 1 to 2 weeks after therapy was started.[Ref]

Common (1% to 10%): Hypersensitivity (rashes [all types], fever, serum sickness)

Rare (0.01% to 0.1%): Anaphylactic reactions

Frequency not reported: Hypersensitivity reactions (including rash, pruritus, bullous eruptions, exfoliative dermatitis, edema, bronchospasm, anaphylactic shock, hypotension, syncope, other anaphylactoid reactions), allergic reactions, immediate allergic reactions (ranged from urticaria, pruritus to angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse, death), accelerated immediate allergic reaction (included urticaria, pruritus, fever; occasionally, laryngeal edema), delayed allergic reactions (manifestations included serum sickness-like symptoms, i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain, various skin rashes [ranging from maculopapular eruptions to exfoliative dermatitis]), hypersensitivity myocarditis, eosinophilia, allergic vasculitis, asthenia, pain, reactions resembling serum sickness (including chills, fever, edema, arthralgia, prostration), anaphylaxis (severe and occasionally fatal)[Ref]


Very common (10% or more): Jarisch-Herxheimer reaction (characterized by malaise, fever, chills, sore throat, myalgia, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, mild hypertension)

Frequency not reported: Sensitization[Ref]

The Jarisch-Herxheimer reaction has been reported during penicillin treatment in patients with syphilis or other spirochetal infections. It has started 1 to 2 hours after initiation of therapy and has stopped within 12 to 24 hours. The Herxheimer reaction may be due to the release of heat-stable pyrogen from spirochetes.[Ref]

Nervous system

CNS toxicity has been reported with massive doses over 60 g/day and in patients with severe renal dysfunction. Neurotoxic reactions have been reported after administration of massive IV doses, and were more likely in patients with renal dysfunction. Severe reactions (including myoclonus, seizures, auditory and visual hallucinations, and decreased mentation) have been reported with high dose penicillin therapy or in patients with renal dysfunction. Neurologic reactions occurred frequently in patients with renal dysfunction.

Encephalopathy occurred after IV doses greater than 60 g. As the blood brain barrier became more permeable in meningitis, toxic symptoms were precipitated by lower doses of penicillin in patients with meningitis.

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 levels, compared to 7.8 units/mL in the group without seizures.[Ref]

Rare (0.01% to 0.1%): Central nervous system (CNS) toxicity (including convulsions)

Frequency not reported: Encephalopathy, neurotoxic reactions (including hyperreflexia, myoclonic twitches, seizures, coma), severe reactions (including myoclonus, seizures, decreased mentation), neuropathy, headache, tremor, aseptic meningitis, coma, neurologic reactions, vasovagal reaction, syncope, cerebrovascular accident, dizziness, somnolence, abnormal taste perception, tinnitus[Ref]


Hemolytic anemia, granulocytopenia (neutropenia), agranulocytosis, leukopenia, and thrombocytopenia have been reported with prolonged high doses of this drug.

Neutropenia generally resolved after penicillin was discontinued.

Coombs-positive hemolytic anemia (an uncommon reaction) was reported in patients treated with more than 10 million units/day of IV penicillin G (benzylpenicillin) and who previously received large doses of the drug.

A bleeding diathesis secondary to platelet dysfunction has been associated with large doses of penicillin.[Ref]

Rare (0.01% to 0.1%): Hemolytic anemia, granulocytopenia, neutropenia, agranulocytosis, leukopenia, thrombocytopenia

Frequency not reported: Eosinophilia, coagulation disorders, Coombs-positive hemolytic anemia, bleeding diathesis (secondary to platelet dysfunction), anemia, lymphadenopathy[Ref]


Rare (0.01% to 0.1%): Interstitial nephritis

Frequency not reported: Abnormal renal function, renal tubular damage, increased BUN/serum urea nitrogen, increased creatinine, renal failure, nephropathy[Ref]

Interstitial nephritis has occurred after IV use of this drug at doses higher than 12 g/day.

Renal tubular damage and interstitial nephritis have been reported with large IV doses of penicillin G; symptoms of this reaction included fever, rash, eosinophilia, proteinuria, eosinophiluria, hematuria, and increased serum urea nitrogen and resolved in most patients after penicillin G was discontinued.

Nephropathy has been reported in patients administered 12 to 36 g of penicillin G for several days.[Ref]


High doses of this drug have resulted in congestive heart failure due to high sodium intake.[Ref]

Frequency not reported: Congestive heart failure, cardiac arrest, hypotension, tachycardia, palpitations, vasodilatation[Ref]


Frequency not reported: Clostridium difficile-associated diarrhea, pseudomembranous colitis, abdominal pain, nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, other symptoms of gastrointestinal (GI) irritation, pancreatitis, intestinal necrosis, blood in the stool, oral moniliasis (thrush)[Ref]

Onset of pseudomembranous colitis symptoms has been reported during or after antibacterial therapy.

Nausea, vomiting, stomatitis, black or hairy tongue, and other symptoms of GI irritation have been reported, especially during oral therapy.[Ref]


Frequency not reported: Rash, urticaria, contact dermatitis, epidermolysis, diaphoresis, peeling, skin eruptions (maculopapular to exfoliative dermatitis), pruritus[Ref]

Contact dermatitis has been reported in those who prepared penicillin solutions.

Skin eruptions (maculopapular to exfoliative dermatitis), pruritus, and urticaria have been associated with hypersensitivity reactions.[Ref]


Frequency not reported: Electrolyte disturbances (e.g., hypokalemia, hypernatremia)[Ref]

Serious and sometimes fatal electrolyte disturbances have been reported with large IV doses; 1 million units of this drug contains 1.68 mEq of sodium ion.[Ref]


Frequency not reported: Hematuria, proteinuria, eosinophiluria, neurogenic bladder, impotence, priapism, vaginal moniliasis (thrush)[Ref]


Frequency not reported: Hepatitis, cholestatic jaundice, increased AST, reversible hepatotoxicity, jaundice, cholestasis (including prolonged), liver dysfunction, abnormal liver function tests[Ref]

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


Frequency not reported: Phlebitis at site of IV injection, thrombophlebitis with IV administration, thrombophlebitis at IM injection site, pain at IM injection site[Ref]


Frequency not reported: Fever, fatigue, asthenia, pain, aggravation of existing disorders, mucosal ulceration[Ref]


Frequency not reported: Confusion, agitation, severe reactions (including auditory and visual hallucinations), nervousness, anxiety, euphoria,[Ref]


Frequency not reported: Pulmonary hypertension, pulmonary embolism


Blurred vision and blindness have been associated with parenteral administration.[Ref]

Frequency not reported: Blurred vision, blindness[Ref]


1. Cerner Multum, Inc. UK Summary of Product Characteristics.

2. Cerner Multum, Inc. Australian Product Information.

3. Product Information. Penicillin G Sodium (penicillin G sodium). Sandoz Inc. 2022.

4. Blake PS, eds., Sweetman SC, McGlashan JM, et al. Martindale: the Complete Drug Reference. Grayslake, IL: Pharmaceutical Press. 2005.

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.