Penicillin G Potassium (Page 3 of 5)

Hypersensitivity reactions

The reported incidence of allergic reactions to all penicillins ranges from 0.7 to 10 percent in different studies (see WARNINGS). Sensitization is usually the result of previous treatment with a penicillin, but some individuals have had immediate reactions when first treated. In such cases, it is postulated that prior exposure to penicillin may have occurred via trace amounts present in milk or vaccines.

Two types of allergic reactions to penicillin are noted clinically – Immediate and delayed.

Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angloneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse and death (see WARNINGS). Such immediate anaphylactic reactions are very rare and usually occur after parenteral therapy, but a few cases of anaphylaxis have been reported following oral therapy. Another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus, fever and, occasionally, laryngeal edema.

Delayed reactions to penicillin therapy usually occur within 1 to 2 weeks after initiation of therapy. Manifestations include serum sickness-like symptoms, i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain and various skin rashes, ranging from maculopapular eruptions to exfoliative dermatitis.

Contact dermatitis has been observed in individuals who prepare penicillin solutions.

Gastrointestinal system

Pseudomembranous colitis has been reported with the onset occurring during or after penicillin G treatment. Nausea, vomiting, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral therapy.

Hematologic system

Reactions include neutropenia, which resolves after penicillin therapy is discontinued; Coombspositive hemolytic anemia, an uncommon reaction, occurs in patients treated with intravenous penicillin G in doses greater than 10 million units/day and who have previously received large doses of the drug; and with large doses of penicillin, a bleeding diathesis, can occur secondary to platelet dysfunction.


Buffered penicillin G potassium for injection (1 million units contains 0.3 mEq of sodium and 1.68 mEq of potassium) may cause serious and even fatal electrolyte disturbances, i.e., hyperkalemia, when given intravenously in large doses.

Nervous system

Neurotoxic reactions including hyperreflexia, myoclonic twitches, seizures and coma have been reported following the administration of massive intravenous doses, and are more likely in patients with impaired renal function.

Urogenital system

Renal tubular damage and interstitial nephritis have been associated with large intravenous doses of penicillin G. Manifestations of this reaction may include fever, rash, eosinophilia, proteinuria, eosinophiluria, hematuria and a rise in serum urea nitrogen. Discontinuation of penicillin G results in resolution in the majority of patients.

Local reactions

Phlebitis and thrombophlebitis may occur with intravenous administration.


Dose related toxicity may arise with the use of massive doses of intravenous penicillins (40 to 100 million units per day), particularly in patients with severe renal impairment (see PRECAUTIONS). The manifestations may include agitation, confusion, asterixis, hallucinations, stupor, coma, multifocal myoclonus, seizures and encephalopathy. Hyperkalemia is also possible (see ADVERSE REACTIONS – Metabolic).

In case of overdosage, discontinue penicillin, treat symptomatically and institute supportive measures as required. If necessary, hemodialysis may be used to reduce blood levels of penicillin G, although the degree of effectiveness of this procedure is questionable.


Buffered penicillin G potassium for injection may be given intravenously or intramuscularly. The usual dose recommendations are as follows:


Serious infections due to susceptible strains of streptococci (including S. pneumoniae) and staphylococci-septicemia , empyema, pneumonia, pericarditis, endocarditis and meningitis

5 to 24 million units/day depending on the infection and its severity administered in equally divided doses every 4 to 6 hours


Minimum of 8 million units/day in divided doses every 6 hours. Higher doses may be required depending on susceptibility of organism.


Cervicofacial disease

1 to 6 million units/day

Thoracic and abdominal disease

10 to 20 million units/day

Clostridial infections

Botulism (adjunctive therapy to antitoxin)

20 million units/day

Gas gangrene (debridement and/or surgery as

Tetanus (adjunctive therapy to human tetanus
immune globulin)

Diphtheria (adjunctive therapy to antitoxin and for the prevention of the carrier state)

2 to 3 million units/day in divided doses for 10 to 12 days

Erysipelothrix endocarditis

12 to 20 million units/day for 4 to 6 weeks

Fusospirochetosis (severe infections of the oropharnyx [Vincent’s], lower respiratory tract and genital area)

5 to 10 million units/day

Listeria infections


15 to 20 million units/day for 2 weeks


15 to 20 million units/day for 4 weeks

Pasteurella infections including bacteremia and meningitis

4 to 6 million units/day for 2 weeks

Haverhill fever, Rat-bite fever

12 to 20 million units/day
for 3 to 4 weeks

Disseminated gonococcal infections, such as meningitis endocarditis, arthritis, etc., caused by penicillin-susceptible organisms

10 million units/day; duration depends on the type of infection

Syphilis (neurosyphilis)

12 to 24 million units/day, as 2 to 4 MU every 4 hours for 10 to 14 days; many experts recommend additional therapy with Benzathine PCN G 2.4 MU intramuscular weekly for 3 doses after completion of intravenous therapy

Meningococcal meningitis and/or septicemia

24 million units/day as 2 million units every 2 hours

* Because of its short half-life, penicillin G is administered in divided doses, usually every 4 to 6 hours with the exception of meningococcal meningitis/septicemia, i.e., every 2 hours.

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