Penicillin Side Effects

It is possible that some side effects of penicillin may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to penicillin: capsule, powder for solution, powder for suspension, solution, suspension, syrup, tablet, tablet for suspension, tablet chewable, tablet extended release

As well as its needed effects, penicillin may cause unwanted side effects that require medical attention.

Stop taking penicillin and get emergency help immediately if any of the following effects occur:

Less common
  • Fast or irregular breathing
  • fever
  • joint pain
  • lightheadedness or fainting (sudden)
  • puffiness or swelling around the face
  • red, scaly skin
  • shortness of breath
  • skin rash, hives, itching

If any of the following side effects occur while taking penicillin, check with your doctor immediately:

  • Abdominal or stomach cramps and pain (severe)
  • abdominal tenderness
  • convulsions (seizures)
  • decreased amount of urine
  • diarrhea (watery and severe), which may also be bloody
  • mental depression
  • nausea and vomiting
  • pain at place of injection
  • sore throat and fever
  • unusual bleeding or bruising
  • yellow eyes or skin
Rare - For penicillin G procaine only
  • Agitation or combativeness
  • anxiety
  • confusion
  • fear of impending death
  • feeling, hearing, or seeing things that are not real

Some penicillin side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common
  • Diarrhea (mild)
  • headache
  • sore mouth or tongue
  • vaginal itching and discharge
  • white patches in the mouth and/or on the tongue

For Healthcare Professionals

Applies to penicillin: injectable powder for injection, intramuscular suspension, intravenous solution, oral powder for reconstitution, oral tablet


Hypersensitivity reactions with penicillin are more common and more serious with intravenous 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.

Hypersensitivity side effects have included rash, maculopapular rash, exfoliative dermatitis, pruritus, urticaria, laryngeal edema, fever, eosinophilia, hypersensitivity myocarditis, serum sickness-like reactions (chills, fever, edema, arthralgia, and prostration), severe or fatal anaphylaxis, shock, and death. Parenteral administration has been associated with allergic vasculitis, asthenia and pain. Hypersensitivity reactions including allergic vasculitis, pruritus, fatigue, asthenia, and pain have been temporally associated with parenteral penicillin G benzathine use. The Jarisch-Herxheimer reaction has been reported during syphilis treatment.

Nervous system

Severe neurologic reactions are most often seen with penicillin doses of 18 to 80 million units daily. These reactions frequently abate after discontinuation of penicillin. In several cases, penicillin was restarted at a lower dose with no further sequelae. In one 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 side effects have included severe reactions with high dose penicillin therapy or in patients with renal dysfunction. These reactions include myoclonus, seizures, auditory and visual hallucinations, and decreased mentation. Neurologic reactions occur frequently in patients with renal dysfunction. Parenteral administration has also been associated with neurovascular reactions (including warmth, vasospasm, pallor, mottling, gangrene, numbness of the extremities, cyanosis of the extremities, and neurovascular damage), nervousness, neuropathy, headache, tremors, dizziness, somnolence, transverse myelitis, severe agitation, and coma. Aseptic meningitis has been reported.


Gastrointestinal side effects have included nausea, vomiting, and diarrhea. These side effects are more common with oral therapy. Pseudomembranous colitis may occur during or after therapy. Pancreatitis, intestinal necrosis, and blood in the stool have also been reported.


Psychiatric side effects temporally associated with parenteral penicillin G benzathine have included nervousness, confusion, anxiety, and euphoria.


Hematologic side effects have included hemolytic anemia, anemia, leukopenia, thrombocytopenia, and lymphadenopathy.


Renal side effects associated with parenteral administration have included increased BUN and creatinine, renal failure, and nephropathy.


Cardiovascular side effects associated with parenteral administration have included cardiac arrest, hypotension, tachycardia, palpitations, pulmonary hypertension, pulmonary embolism, vasodilatation, vasovagal reaction, cerebrovascular accident, and syncope.


Local side effects have included injection site reactions, including pain, inflammation, lump, abscess, necrosis, edema, hemorrhage, cellulitis, hypersensitivity, atrophy, ecchymosis, and skin ulcer. Neurovascular reactions including warmth, vasospasm, pallor, mottling, gangrene, numbness or cyanosis of the extremities, and neurovascular damage have also been reported.


Hepatic side effects have included increased SGOT, reversible hepatotoxicity, jaundice, and prolonged cholestasis.

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


Musculoskeletal side effects associated with parenteral administration have included joint disorder, periostitis, exacerbation of arthritis, myoglobinuria, and rhabdomyolysis. Fibrosis of the quadriceps femoris and atrophy have been reported following repeated intramuscular injections into the thigh.


Respiratory side effects have included hypoxia, apnea, and dyspnea.


Ocular side effects associated with parenteral administration have included blurred vision and blindness.


Genitourinary side effects associated with parenteral administration have included neurogenic bladder, hematuria, proteinuria, impotence, and priapism.


Other side effects have included fatigue, asthenia, pain, abnormal taste perception, tinnitus, and aggravation of existing disorders.


Metabolic side effects associated with intravenous penicillin G have included hypernatremia and hyperkalemia, especially in the presence of renal insufficiency. Severe or fatal hyperkalemia has occurred in patients receiving high doses (10 to 100 million units/day).


Dermatologic side effects have included rash, peeling, mucosal ulceration, and urticaria. Diaphoresis has been associated with parenteral administration.

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