Applies to penicillin g potassium: injection solution reconstituted

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.
• Very bad dizziness or passing out.
• Fever or chills.
• Headache.
• A fast heartbeat.
• Fast breathing.
• Flushing.
• Feeling very tired or weak.
• Yellow skin or eyes.
• Muscle or joint pain.
• Stomach pain.
• Any unexplained bruising or bleeding.
• 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.

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-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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 studies.

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.

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 reactions to penicillin have been reported within 1 to 2 weeks after therapy was started.

The Jarisch-Herxheimer reaction 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.

Hypersensitivity side effects have included immediate and delayed allergic reactions. Immediate reactions generally occurred within 20 minutes of use and the severity ranged from urticaria and pruritus to angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse, and death. A different type of immediate reaction, an accelerated reaction, occurred 20 minutes to 48 hours after use and included urticaria, pruritus, fever, and, occasionally, laryngeal edema. Manifestations of delayed reactions to penicillin included serum sickness-like symptoms, i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain, and 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, and prostration), and anaphylaxis (severe and occasionally fatal) have been reported. The Jarisch-Herxheimer reaction (characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypertension) has been reported during penicillin treatment of patients with syphilis or other spirochaetal infections.

Cardiovascular side effects have included cardiac arrhythmias and cardiac arrest.

Gastrointestinal side effects have included Clostridium difficile associated diarrhea and pseudomembranous colitis; onset has occurred during or after therapy. Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation have been reported, especially during oral therapy.

Metabolic side effects have included serious and even fatal electrolyte disturbances (i.e., hyperkalemia) with large intravenous doses since 1 million units of penicillin G potassium contains 1.68 mEq of potassium ion. Severe or fatal potassium poisoning (signs included hyperreflexia, convulsions, and coma) has been reported in patients receiving continuous intravenous therapy in high doses (10 million to 100 million units/day), especially in the presence of renal insufficiency.

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 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.

Nervous system side effects have rarely included neuropathy, which was usually associated with high intravenous dosage. Neurotoxic reactions (including hyperreflexia, myoclonic twitches, seizures, and coma) have been reported after massive intravenous doses were administered, 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. Neurovascular damage, headache, tremor, confusion, agitation, aseptic meningitis, and coma have been reported.

Renal tubular damage and interstitial nephritis resolved in most patients after penicillin G was discontinued.

Nephropathy has been reported rarely and was usually associated with high intravenous dosage.

Renal side effects associated with large intravenous doses of penicillin G have included renal tubular damage and interstitial nephritis. Symptoms of this reaction included fever, rash, eosinophilia, proteinuria, eosinophiluria, hematuria, and a rise in serum urea nitrogen. Increased BUN and creatinine, renal failure, and nephropathy have been reported.

Hematologic side effects have included hemolytic anemia, anemia, leukopenia, neutropenia, thrombocytopenia, Coombs-positive hemolytic anemia, and a bleeding diathesis secondary to platelet dysfunction.

Hemolytic anemia, leukopenia, and thrombocytopenia have been reported rarely and were usually associated with high intravenous dosage.

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 intravenous 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.

Local side effects have included injection site pain with intravenous administration, phlebitis, thrombophlebitis, and neurovascular damage.

Genitourinary side effects have included hematuria, proteinuria, and eosinophiluria.

Dermatologic side effects have included rash and urticaria. Contact dermatitis has been reported in those who prepared penicillin solutions.

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.

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