Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillin, cephalosporins, and other allergens. If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management–including intubation, should be administered as indicated.
Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma.
Intramuscular therapy: Care should be taken to avoid intravenous administration, accidental intraarterial administration, or injection into or near major peripheral nerves or blood vessels, since many injections may produce neurovascular damage.
As with all intramuscular preparations, penicillin G benzathine should be injected well within the body of a relatively large muscle.
ADULTS: The preferred site is the upper outer quadrant of the buttock (i.e., gluteus maximus), or the mid-lateral thigh.
CHILDREN: It is recommended that intramuscular injections be given preferably in the mid-lateral muscles of the thigh. In infants and small children the periphery of the upper outer quadrant of the gluteal region should be used only when necessary, such as in burn patients, in order to minimize the possibility of damage to the sciatic nerve.
The deltoid area should be used only if well developed such as in certain adults and older children, and then only with caution to avoid radial nerve injury. Intramuscular injections should not be made into the lower and mid-third of the upper arm. As with all intramuscular injections, aspiration is necessary to help avoid inadvertent injection into a blood vessel.
Irritation at the site of injection may occur. In addition, subcutaneous and fat–layer injections should be avoided since they may cause pain and induration. If these occur, they may be relieved by the application of an ice pack.
In streptococcal infections, therapy must be sufficient to eliminate the organism (10 days minimum), otherwise the sequelae of streptococcal disease may occur. Cultures should be taken following completion of treatment to determine whether streptococci have been eradicated.
The use of antibiotics may result in overgrowth of nonsusceptible organisms. Constant observation of the 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.
In prolonged therapy with penicillin, periodic evaluation of the renal, hepatic and hematopoietic systems for organ dysfunction is recommended. This is particularly important in prematures, neonates and other infants, and when high doses are used.
When treating gonococcal infections in which primary and secondary syphilis are suspected, proper diagnostic procedures, including dark field examinations, should be done before receiving penicillin and monthly serological tests made for at least four months. All cases of penicillin-treated syphilis should receive clinical and serological examinations every six months for two to three years.
In streptococcal infections, cultures should be taken following completion of treatment to determine whether streptococci have been eradicated.
Concurrent administration of bacteriostatic antibiotics (e.g., erythromycin, tetracycline) may diminish the bactericidal effects of penicillins by slowing the rate of bacterial growth. Bactericidal agents work most effectively against the immature cell wall of rapidly proliferating microorganisms. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented. There are few clinical situations in which the concurrent use of "static" and "cidal" antibiotics are indicated. However, in selected circumstances in which such therapy is appropriate, using adequate doses of antibacterial agents and beginning penicillin therapy first, should minimize the potential for interaction.
Penicillin blood levels may be prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins.
Displacement of penicillins from plasma protein binding sites will elevate the level of free penicillin in the serum.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No information or long term studies are available on the carcinogenesis, mutagenesis, or impairment of fertility with the use of penicillins.
Pregnancy Category B – Teratogenic Effects
Reproduction studies in the mouse, rat and rabbit have revealed no evidence of impaired fertility or harm to the 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, however, 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.
Pencillin G benzathine has been reported in milk. Caution should be exercised when penicillin G benzathine is administered to a nursing woman.
Pencillins are excreted largely unchanged by the kidney. Because of incompletely developed renal function in infants, the rate of elimination will be slow. Use caution in administering to newborns and evaluate organ system function frequently.