penicillin G procaine (Rx)

Frequency Not Defined

Skin rashes including maculopapular eruptions and exfoliative dermatitis

Urticaria

Serum-sicknesslike reactions (eg, chills, fever, edema, arthralgia, prostration)

Jarisch-Herxheimer reaction reported when treating syphilis

Pseudomembranous colitis

Contraindications

Hypersensitivity to drug or excipients

Cautions

For deep IM administration only; do not administer IV, SC, or IT

No longer indicated for gonorrhea; should not be used for beta-lactamase producing organisms which include most strains of Neisseria gonorrhea

Avoid use in neonates; increased risk for sterile abscess development and procaine toxicity

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) reported in patients taking penicillin G (the active moiety in penicillin G procaine); when SCAR suspected, discontinue therapy immediately and consider alternative treatment

Prescribing penicillin G procaine in absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria

Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma

Care should be taken to avoid intravenous or intra-arterial administration, or injection into or near major peripheral nerves or blood vessels, since such injections may produce neurovascular damage

A small percentage of patients are sensitive to procaine; if there is a history of sensitivity, make the usual test: inject intradermally 0.1 mL of a 1 to 2 percent procaine solution; development of erythema, wheal, flare, or eruption indicates procaine sensitivity; sensitivity should be treated by usual methods, including barbiturates, and the procaine penicillin preparations not used; antihistaminics appear beneficial in treatment of procaine reactions

The use of antibiotics may result in overgrowth of nonsusceptible organisms; constant observation of patient is essential; if new infections due to bacteria or fungi appear during therapy, the drug should be discontinued and appropriate measures taken

Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy

Anaphylaxis

• Serious and fatal hypersensitivity (anaphylactic reactions) have been reported in patients receiving penicillin therapy; reactions are likely occur in individuals with history of sensitivity to multiple allergens
• Some individuals with hypersensitivity to penicillin have experienced severe reactions when treated with cephalosporins; carefully inquire about previous hypersensitivity reactions before initiating therapy with any penicillin, cephalosporins, or other allergens
• If allergic reaction occurs, discontinue therapy and institute appropriate therapy; serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management, including intubation as indicated

Methemoglobinemia

• Cases of methemoglobinemia reported in association with local anesthetic use; although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition; if local anesthetics must be used, monitor for symptoms and signs of methemoglobinemia closely
• Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure and are characterized by cyanotic skin discoloration and/or abnormal coloration of the blood; methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system (CNS) and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death
• Discontinue this drug and any other oxidizing agents; depending on severity of signs and symptoms, patients may respond to supportive care, eg, oxygen therapy, hydration; a more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen

Pseudomembranous colitis

• Pseudomembranous colitis reported with nearly all antibacterial agents, including penicillin G, and may range in severity from mild to life-threatening; it is important to consider this diagnosis in patients who present with diarrhea subsequent to administration of antibacterial agents
• Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridioides; studies indicate that a toxin produced by Clostridioides difficile is one primary cause of "antibiotic-associated colitis"
• After diagnosis of pseudomembranous colitis established, therapeutic measures should be initiated; mild cases of pseudomembranous colitis usually respond to drug discontinuation alone
• In moderate to severe cases, consideration should be given to management of fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis

Procaine reactions

• Immediate toxic reactions to procaine may occur; these reactions may be manifested by mental disturbances, including anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness, and expressed "fear of impending death"
• Reactions have been reported primarily in some patients who have received large doses of penicillin G procaine (4.8 million units); reactions are transient, lasting from 15 to 30 minutes

Pregnancy

Reproduction studies performed on the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to fetus due to penicillin G

Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus

There are no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed

Lactation

Penicillins are excreted in human milk; exercise caution when penicillins are administered to a nursing woman

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Half-Life: 20-30 minutes

Absorption: IM, slow absorption for up to 24 hr

Vd: 0.3-0.47 L/kg

Peak Plasma Time: 2-4 hr

Peak Plasma Concentration: 1.5 units/mL

Protein Bound: 60%

Metabolism: ~30% in liver

Excretion: urine (60-90% within 24-36 hr)

Mechanism of Action

Interferes with cell wall mucopeptide synthesis during active multiplication, resulting in bactericidal activity against susceptible microorganisms

IM Administration

Do not inject near artery or nerve (may result in permanent neurologic damage)

Neonates, infants, small children: Midlateral aspect of thigh preferable

Older children and adults: Deep IM injection in upper outer quadrant of buttock

Because of high concentration of suspended matter, needle may be blocked if injection is not made at slow, steady rate

Storage

Store refrigerated at 2-8 degrees C (36-46 degrees F)

Do not freeze