Safety of Benzathine Penicillin

Video by Dr. Aidan Long MD, Massachusetts General Hospital, Harvard Medical School

Benzathine penicillin is also used for primary and secondary prevention of rheumatic heart disease (THD). The safety evaluation by Dr. Long also applies to the use of benzathine penicillin for treatment of other conditions such as congenital syphilis.


Benzathine penicillin is a safe medication to use, and an allergic reaction of benzathine penicillin is rare.

Prevalence and symptoms of penicillin allergy

Allergy is one type of an adverse reaction that can be caused by a medication. An allergy is a hypersensitivity disorder of the immune system. An allergic reaction occurs when a person’s immune system “over-reacts” to normally harmless substances, such as a medication.

While penicillin allergy is commonly self-reported by patients, it occurs in only one per 10,000 injections. In the case of allergic reactions to penicillin, most are very mild and involve only skin rashes. Other symptoms to penicillin allergy include shortness of breath, swelling of the skin (angioedema), low blood pressure (hypotension) and swelling of the epiglottis and vocal cords (laryngeal edema). Anaphylaxis, a severe and potentially life-threatening allergic reaction, is an extremely rare event that happens in only 0 to 3 per 100,000 injections. When anaphylaxis does occur, it is recognized by dizziness and fainting.

Penicillin allergy is likely to be less frequent in younger populations or populations without significant prior exposure to penicillin or related antibiotics. All penicillins are the same core structure, because of this, if a patient has tolerated penicillin G by injection, Pen VK by mouth, or synthetic penicillin such as ampicillin or amoxicillin then they are not allergic to BPG, and no allergic reaction will occur when injected. To find out whether a patient has an antibiotic allergy, ask them if they have had any adverse reactions to penicillin, or other penicillin-based drugs.

Recognizing an allergic reaction to penicillin includes a sudden onset of skin reactions such as itching around the eyes, development of hives, and other types of skin flushing or rash. On some occasions, a sudden onset of swollen lips, tongue, and face may occur. Sudden respiratory symptoms manifest in wheezing, difficulty breathing, or hoarse or change in character of the voice. Acute onset of gastrointestinal symptoms may also be seen and manifest as cramping abdominal pain, diarrhea, nausea, or vomiting. In more severe cases, sudden cardiovascular symptoms such as faintness, dizziness, confusion, rapid heartrate or pulse, or heart palpitations may occur.

Most importantly, if a patient has had an allergic reaction to penicillin, no further penicillin should be administered without further evaluation.

Diagnosing penicillin allergy

Penicillin allergy is tested by skin using a special testing solution. Most patients will be referred to an immunology clinic for skin testing. Skin testing should be done with a purified protein derivative, rather than with a diluted injection formulation. A small amount of penicillin is injected into the skin as an intradermal injection to raise a bleb. A positive reaction will cause a red, itchy, raised bump.

If facilities for penicillin allergy skin testing are not available or there is a risk of losing the patient if referred, it is safe to take a graded oral challenge with oral amoxicillin. This is particularly critical for pregnant women, as penicillin is the only mean to prevent congenital syphilis. The soonest the treatment is administered in pregnancy, it is less likely that the baby gets infected. Patients who have no history or knowledge of penicillin allergy can also be tested with oral amoxicillin. It could also be used for patients with a history of mild allergic reactions, or skin-only reactions in past instances of injection.

Give the patient 50 mg of amoxicillin orally, and then wait for 30 minutes. If patient has no symptoms, then administer 450 mg of amoxicillin orally. Wait another 30 minutes and check for symptoms. Let the patient know the times, procedures, and its importance beforehand. If there are none, proceed with the injection.

Treatment of penicillin allergy

It is vital to always keep an anaphylaxis kit on standby with several medications. Components of such a kit include:

  • Epinephrine (at concentration of 1:1000=1mg/ml) which can be stored as pre-drawn syringes (adult dose 0.3cc and 0.15cc for children) or autoinjectors if available
  • Antihistamines, such as: Benadryl 25mg (20 tabs), Cetirizine 10mg (25 tabs), Fexofenadine 180mg, or Loratadine 10mg
  • Rapidly acting bronchodilator (inhaler) such as an Albuterol/Salbutamol MDI (90ug/actuation)
  • Package of oral steroids such as Methylprednisolone dose pack (6-day blister pack)

Treatment of severe penicillin allergic reaction is as follows: lie the patient down flat, and elevate their feet; administer epinephrine; then, seek help and give supplemental oxygen (if available and if required). Consider other medications such as antihistamines like Benadryl or inhaled albuterol, but always give epinephrine first. Observe the patient for several hours and give oral steroids at the time of discharge. Do not give penicillin again to this patient.