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Penicillin g potassium Side Effects

Medically reviewed by Last updated on Sep 21, 2023.

Applies to penicillin g potassium: injection solution reconstituted.

Serious side effects

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

For all uses of this drug:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of a high potassium level like a heartbeat that does not feel normal; change in thinking clearly and with logic; feeling weak, lightheaded, or dizzy; feel like passing out; numbness or tingling; or shortness of breath.
  • Signs of a very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes.
  • Very bad dizziness or passing out.
  • Fever, chills, or sore throat; any unexplained bruising or bleeding; or feeling very tired or weak.
  • Headache.
  • A fast heartbeat.
  • Fast breathing.
  • Flushing.
  • Yellow skin or eyes.
  • Muscle or joint pain.
  • Stomach pain.
  • Twitching.
  • Seizures.
  • Not able to pass urine or change in how much urine is passed.
  • Diarrhea is common with antibiotics. Rarely, a severe form called C diff–associated diarrhea (CDAD) may happen. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen during or a few months after taking antibiotics. Call your doctor right away if you have stomach pain, cramps, or very loose, watery, or bloody stools. Check with your doctor before treating diarrhea.

Injection (if given in the muscle):

  • Nerve damage can happen if this drug is given into or near a nerve. This could be long-lasting. Call your doctor right away if you have any numbness, tingling, or weakness.

Other side effects

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Diarrhea.
  • Upset stomach or throwing up.
  • Mouth irritation or mouth sores.
  • Change in tongue color.
  • Irritation where the shot is given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at

For Healthcare Professionals

Applies to penicillin g potassium: injectable powder for injection, intravenous solution.


Allergic reactions have been reported with all penicillins and the incidence ranged from 0.7% to 10% in various 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 was 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 allergic reactions generally occurred within 20 minutes of use; accelerated immediate reactions have occurred 20 minutes to 48 hours after use. Immediate anaphylactic reactions were very rare and 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]

Frequency not reported: 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]


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

Frequency not reported: Rash, urticaria, contact dermatitis

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]


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

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

Frequency not reported: Clostridioides difficile-associated diarrhea, pseudomembranous colitis, nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, other symptoms of gastrointestinal (GI) irritation[Ref]


Serious and even fatal electrolyte disturbances (i.e., hyperkalemia) have been reported with large IV doses since 1 million units of this drug contains 1.68 mEq of potassium ion.

Severe or fatal potassium poisoning has been reported in patients receiving continuous IV therapy in high doses (10 million to 100 million units/day), especially when renal insufficiency was present.[Ref]

Frequency not reported: Electrolyte disturbances (hyperkalemia), potassium poisoning (signs included hyperreflexia, convulsions, coma)[Ref]

Nervous system

Neurotoxic reactions have been reported after massive IV doses were administered and were more likely in patients with renal dysfunction.

Neuropathy, which was usually associated with high IV dosage, has been reported.

Severe neurologic reactions have been reported with high dose penicillin therapy or in patients with renal dysfunction; such reactions were most often seen with penicillin doses of 18 million to 80 million units daily. Neurologic reactions occurred frequently in patients with renal dysfunction. 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]

Frequency not reported: Neurotoxic reactions (including hyperreflexia, myoclonic twitches, seizures, coma), neuropathy, severe neurologic reactions (including myoclonus, seizures, auditory and visual hallucinations, decreased mentation), neurovascular damage, headache, tremor, confusion, agitation, aseptic meningitis, coma[Ref]


Frequency not reported: Neutropenia, Coombs-positive hemolytic anemia, bleeding diathesis secondary to platelet dysfunction, eosinophilia, thrombocytopenia, hemolytic anemia, anemia, leukopenia[Ref]

Neutropenia resolved after penicillin was discontinued.

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

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

Hemolytic anemia, leukopenia, and thrombocytopenia have been reported and were usually associated with high IV dosage.[Ref]


Frequency not reported: Injection site pain with IV administration, phlebitis, thrombophlebitis[Ref]


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

Frequency not reported: Jarisch-Herxheimer reaction (characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, mild hypertension)[Ref]


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 and was usually associated with high IV dosage.[Ref]

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


Frequency not reported: Hematuria, proteinuria, eosinophiluria[Ref]


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


Frequency not reported: Cardiac arrhythmias, cardiac arrest[Ref]


1. Product Information. Pfizerpen (penicillin). Roerig Division. 2001.

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.