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Penicillin G Procaine Side Effects

Generic name: procaine penicillin

Note: This document contains side effect information about procaine penicillin. Some dosage forms listed on this page may not apply to the brand name Penicillin G Procaine.

Applies to procaine penicillin: intramuscular suspension.


You should not use this medication if you are allergic to penicillin. Tell your doctor if you have ever had an allergic reaction to a cephalosporin antibiotic such as Ceftin, Cefzil, Omnicef, Keflex, and others.

Before using procaine penicillin, tell your doctor if you have asthma or a history of allergies, or kidney disease.

Do not inject this medication into a vein or life-threatening side effects may result.

Use this medication for the full prescribed length of time. Call your doctor if your infection does not improve, or if it gets worse while using procaine penicillin.

Tell your doctor about all other medications you use, especially gout medication, a blood thinner, a diuretic, a tetracycline antibiotic, or a non-steroidal anti-inflammatory drug (NSAID).

Procaine penicillin can make birth control pills less effective. Ask your doctor about using a non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while using procaine penicillin. Hormonal forms of contraception (such as birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment.

After you have finished your treatment with procaine penicillin, your doctor may want to do tests to make sure your infection has completely cleared up.

Get emergency medical help if you have any of these signs of an allergic reaction while taking procaine penicillin (the active ingredient contained in Penicillin G Procaine) hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • diarrhea that is watery or bloody;

  • peeling skin , severe pain, or changes in skin color where the medicine was injected;

  • dizziness, joint or muscle pain;

  • fast or pounding heartbeats;

  • numbness, tingling, pain, swelling, or redness in your arms or legs;

  • confusion, agitation, depression, unusual thoughts or behavior;

  • chest pain, problems with vision or speech;

  • feeling like you might pass out;

  • fever, chills, dizziness, muscle pain, rapid breathing or heart rate;

  • uncontrolled muscle movements, problems with balance or walking;

  • pale skin, easy bruising or bleeding, unusual weakness;

  • sore throat, flu symptoms;

  • urinating less than usual or not at all;

  • rash or itching with swollen glands, joint pain, or general ill feeling; or

  • slow heart rate, weak pulse, fainting, slow breathing.

Less serious side effects of procaine penicillin may include:

  • pain where the injection was given;

  • vaginal itching or discharge;

  • white patches in your mouth or throat;

  • nausea, vomiting;

  • blurred vision, ringing in your ears;

  • headache, dizziness; or

  • mild skin rash,

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 procaine penicillin: intramuscular suspension.


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

Very common (10% or more): Gastrointestinal effects (like diarrhea, nausea, vomiting)

Penicillin G (benzylpenicillin):

-Frequency not reported: Pseudomembranous colitis/Clostridioides difficile-associated diarrhea[Ref]


Very common (10% or more): Skin rash

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)


Very common (10% or more): Difficulty in breathing


Severe and often fatal anaphylaxis has been reported.[Ref]

Common (1% to 10%): Hypersensitivity reactions (including skin rashes/eruptions [maculopapular eruptions to exfoliative dermatitis], urticaria, laryngeal edema, fever, eosinophilia, other serum sickness-like reactions [including chills, fever, edema, arthralgia, prostration])

Rare (0.01% to 0.1%): Anaphylactic shock

Frequency not reported: Anaphylaxis[Ref]


Frequency not reported: Procaine toxicity manifestations of mental disturbance (including anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness, fear of impending death), extreme anxiety, sensation of impending death, hallucinations, disorientation, acute depersonalization, frank psychotic behavior[Ref]

Immediate toxic reactions to procaine have occurred in some patients, especially when a large single dose (4.8 million units) was administered; such reactions were demonstrated by mental disturbances (including anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness, fear of impending death) and were transient, generally lasting 15 to 30 minutes. In controlled studies, the incidence was about 1 in 500 patients who received large doses of this drug.

Extreme anxiety and a sensation of impending death have been reported after IM injection of this drug but showed no major abnormal physical signs. Some have developed hallucinations, disorientation, tachycardia, acute depersonalization, or frank psychotic behavior. Patients have been regarded as hysterical by those unaware of this reaction. According to some authorities, these attacks were due to procaine and were generally self-limiting (subsiding in 15 to 30 minutes); these reactions have been attributed to accidental intravascular administration.[Ref]


Frequency not reported: Nicolau syndrome, weakness


Frequency not reported: Jarisch-Herxheimer reaction

A Jarisch-Herxheimer reaction has been reported in some patients shortly after starting this drug to treat syphilis.


Frequency not reported: Tachycardia

Nervous system

Frequency not reported: Seizures

Penicillin G:

-Rare (0.01% to 0.1%): Neuropathy[Ref]

Neuropathy has generally been associated with large IV doses (more than 10 million units/day) of penicillin G; this reaction typically only occurred with large doses.[Ref]


Penicillin G:

-Rare (0.01% to 0.1%): Hemolytic anemia, leukopenia, thrombocytopenia

Local anesthetic:

-Frequency not reported: Methemoglobinemia[Ref]

Hemolytic anemia, leukopenia, and thrombocytopenia have generally been associated with large IV doses (more than 10 million units/day) of penicillin G; these reactions typically only occurred with large doses.[Ref]


Nephropathy has generally been associated with large IV doses (more than 10 million units/day) of penicillin G; this reaction typically only occurred with large doses.[Ref]

Penicillin G:

-Rare (0.01% to 0.1%): Nephropathy[Ref]


1. Cerner Multum, Inc. Australian Product Information.

2. Product Information. Penicillin G Procaine (procaine penicillin). Monarch Pharmaceuticals Inc. 2009.

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.