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Penicillin g benzathine Side Effects

Medically reviewed by Last updated on Oct 5, 2022.

Applies to penicillin g benzathine: intramuscular suspension.


Intramuscular route (Suspension)

Not for intravenous use. Do not inject intravenously or admix with other intravenous solutions. There have been reports of inadvertent intravenous administration of penicillin G benzathine which has been associated with cardiorespiratory arrest and death.

Serious side effects

Along with its needed effects, penicillin g benzathine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking penicillin g benzathine:

Incidence not known

  • Agitation
  • anxiety
  • back pain, sudden and severe
  • back, leg, or stomach pains
  • black, tarry stools
  • bleeding gums
  • blindness
  • bloating
  • bloody or cloudy urine
  • bluish color of the fingernails, lips, skin, palms, or nail beds
  • blurred vision
  • burning, tingling, numbness, or pain in the hands, arms, feet, or legs
  • chest pain or discomfort
  • chills
  • confusion
  • continuing ringing or buzzing or other unexplained noise in the ears
  • cough
  • dark urine
  • decreased frequency or amount of urine
  • diarrhea, watery and severe, which may also be bloody
  • difficult or painful urination
  • difficulty breathing
  • difficulty swallowing
  • dizziness or lightheadedness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • euphoria
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • fever
  • general body swelling
  • general feeling of illness or discomfort
  • headache
  • hearing loss
  • hives, itching, skin rash
  • increased blood pressure
  • increased thirst
  • joint swelling loss of appetite
  • lower back or side pain
  • muscle cramps, pain, stiffness, or spasms
  • muscle weakness, sudden and progressing
  • nausea
  • nosebleeds
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • rigidity
  • seeing or hearing things that are not there
  • seizures
  • sensation of pins and needles
  • skin blisters
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • stabbing pain
  • stomach cramps or tenderness
  • sudden decrease in the amount of urine
  • sweating
  • swelling of the face, fingers, or lower legs
  • swollen, painful, or tender lymph glands in the neck, armpit, or groin
  • swollen glands
  • tightness in the chest
  • tremors
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • unusual weight loss
  • vomiting
  • weight gain
  • yellowing of the eyes or skin

Other side effects

Some side effects of penicillin g benzathine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

  • Bad unusual or unpleasant (after)taste
  • bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
  • change in taste
  • decreased interest in sexual intercourse
  • inability to have or keep an erection
  • loss in sexual ability, desire, drive, or performance
  • painful or prolonged erection of the penis
  • sleepiness or unusual drowsiness

For Healthcare Professionals

Applies to penicillin g benzathine: intramuscular suspension.


Frequency not reported: Injection site reactions (including pain, inflammation, lump, abscess, necrosis, edema, hemorrhage, cellulitis, hypersensitivity, atrophy, ecchymosis, skin ulcer), neurovascular reactions (including warmth, vasospasm, pallor, mottling, gangrene, numbness of the extremities, cyanosis of the extremities, neurovascular damage)[Ref]


Frequency not reported: Hypersensitivity reactions (including skin eruptions [maculopapular to exfoliative dermatitis], urticaria, laryngeal edema, fever, eosinophilia, hypersensitivity myocarditis, other serum sickness-like reactions [including chills, fever, edema, arthralgia, prostration], anaphylactic/anaphylactoid reaction [including shock, death], allergic vasculitis, pruritus, fatigue, asthenia, pain)[Ref]


Frequency not reported: Cardiac arrest, hypotension, tachycardia, palpitations, pulmonary hypertension, pulmonary embolism, vasodilation, vasovagal reaction, cerebrovascular accident, cyanosis[Ref]

Nervous system

Severe reactions (including myoclonus, seizures, auditory and visual hallucinations, decreased mentation) have been reported with high-dose penicillin therapy or in patients with renal dysfunction. 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 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 concentrations, compared to 7.8 units/mL in the group without seizures. Neurologic reactions occurred frequently in patients with renal dysfunction.

A syndrome characterized by various central nervous system symptoms (e.g., severe agitation with confusion, visual and auditory hallucinations, fear of impending death [Hoigne's syndrome]) has been reported after administration of this drug. Other symptoms associated with this syndrome have included psychosis, seizures, dizziness, tinnitus, cyanosis, palpitations, tachycardia, and abnormal taste perception.[Ref]

Frequency not reported: Syncope, neuropathy, headache, tremors, dizziness, somnolence, abnormal taste perception, tinnitus, transverse myelitis, seizures, aseptic meningitis, coma, neurovascular reactions (including warmth, vasospasm, pallor, mottling, gangrene, numbness of the extremities, cyanosis of the extremities, neurovascular damage), myoclonus, decreased mentation, neurologic reactions[Ref]


Frequency not reported: Clostridium difficile-associated diarrhea, pseudomembranous colitis, nausea, vomiting, intestinal necrosis, blood in the stool[Ref]

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


Frequency not reported: Hemolytic anemia, leukopenia, thrombocytopenia, lymphadenopathy[Ref]


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

Frequency not reported: Increased AST, jaundice, cholestasis, abnormal liver function tests[Ref]


Frequency not reported: Joint disorder, periostitis, myoglobinuria, rhabdomyolysis, exacerbation of arthritis, quadriceps femoris fibrosis and atrophy[Ref]

Quadriceps femoris fibrosis and atrophy have been reported after repeated IM injections into the anterolateral thigh.[Ref]


Frequency not reported: Increased BUN, increased creatinine, renal failure, nephropathy, acute interstitial nephritis[Ref]


Frequency not reported: Hypoxia, apnea, dyspnea[Ref]


Frequency not reported: Nervousness, confusion, anxiety, euphoria, auditory and visual hallucinations, agitation, fear of impending death, psychosis[Ref]


Frequency not reported: Blurred vision, blindness[Ref]


Frequency not reported: Neurogenic bladder, hematuria, proteinuria, impotence, priapism[Ref]


Frequency not reported: Diaphoresis, rash, peeling, mucosal ulceration, urticaria, epidermolysis

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]


Frequency not reported: Fatigue, asthenia, pain, aggravation of existing disorder, Hoigne's syndrome[Ref]


The Jarisch-Herxheimer reaction has been reported during syphilis treatment.

Frequency not reported: Jarisch-Herxheimer reaction


1. Product Information. Bicillin L-A (penicillin). Monarch Pharmaceuticals Inc. 2003.

2. Cerner Multum, Inc. Australian Product Information.

3. International Rheumatic Fever Study Group. Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever. Lancet. 1991;337:1308-10.

4. Barrons RW, Murray KM, Richey RM. Populations at risk for penicillin-induced seizures. Ann Pharmacother. 1992;26:26-9.

5. Andrade RJ, Guilarte J, Salmeron FJ, Lucena MI, Bellot V. Benzylpenicillin-induced prolonged cholestasis. Ann Pharmacother. 2001;35:783-4.

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.