Classifications: beta-lactam antibiotic; natural penicillin;
Therapeutic: antibiotic
; beta-lactam
Pregnancy Category: B


1,000,000 units, 5,000,000 units, 10,000,000 units, 20,000,000 units vials; 1,000,000 units/50 mL, 2,000,000 units/50 mL 3,000,000 units/50 mL injection


Acid-labile, penicillinase-sensitive, natural penicillin. Antimicrobial spectrum is relatively narrow compared to that of the semisynthetic penicillins. Acts by interfering with synthesis of mucopeptides essential to formation and integrity of bacterial cell wall. Action is inhibited by penicillinase.

Therapeutic Effect

Highly active against gram-positive cocci (e.g., non-penicillinase-producing Staphylococcus, Streptococcus groups) and gram-negative cocci. Also effective against gram-positive bacilli and gram-negative bacilli. Penicillin G is effective against some strains of Salmonella and Shigella and spirochetes.


Moderate to severe systemic infections caused by penicillin-sensitive microorganisms. Certain staphylococcal infections; streptococcal infections. Also used as prophylaxis in patients with rheumatic or congenital heart disease. Since oral preparations are absorbed erratically and thus must be given in comparatively high doses, this route is generally used only for mild or stabilized infections or long-term prophylaxis.


Hypersensitivity to any of the penicillins or cephalosporins; administration of oral drug to patients with severe infections; nausea, vomiting, hypermotility, gastric dilatation; cardiospasm. Use of penicillin G sodium in patients on sodium restriction.

Cautious Use

History of or suspected allergy (asthma, eczema, hay fever, hives); history of allergy to cephalosporins; GI disorders; kidney or liver dysfunction, myasthenia gravis, epilepsy, neonates, young infants; pregnancy (category B). Use during lactation may lead to sensitization of infants.

Route & Dosage

Moderate to Severe Infections
Adult: IV/IM 2–24 million U divided q4h
Child: IV/IM 250,000–400,000 U/kg divided q4h


Note: Check whether physician has prescribed penicillin G potassium or sodium.

  • Do not use the 20,000,000 unit dosage form for IM injection.
  • Reconstitute for IM: Loosen powder by shaking bottle before adding diluent (sterile water for injection or sterile NS). Keep the total volume to be injected small. Solutions containing up to 100,000 units/mL cause the least discomfort. Adding 10 mL diluent to the 1,000,000 unit vial = 100,000 units/mL. Shake well to dissolve.
  • Select IM site carefully. IM injection is made deep into a large muscle mass. Inject slowly. Rotate injection sites.

PREPARE: Intermittent/Continuous: Reconstitute as for IM injection then withdraw the required dose and add to 100–1000 mL of D5W or NS IV solution, depending on length of each infusion.  

ADMINISTER: Intermittent/Continuous: Give intermittent infusion over at least 1 h and continuous infusion at a rate required to infuse the daily dose in 24 h. With high doses, IV penicillin G should be administered slowly to avoid electrolyte imbalance from potassium or sodium content. Physician will often prescribe specific flow rate.  

INCOMPATIBILITIES Solution/additive: Dextran 40, fat emulsion, aminophylline, amphotericin B, cephalothin, chlorpromazine, dopamine, hydroxyzine, metaraminol, metoclopramide, pentobarbital, prochlorperazine, promazine, sodium bicarbonate, tetracycline, thiopental.

  • Store dry powder (for parenteral use) at room temperature. After reconstitution (initial dilution), store solutions for 1 wk under refrigeration. Intravenous infusion solutions containing penicillin G are stable at room temperature for at least 24 h.

Adverse Effects (≥1%)

Body as a Whole: Coughing, sneezing, feeling of uneasiness; systemic anaphylaxis, fever, widespread increase in capillary permeability and vasodilation with resulting edema (mouth, tongue, pharynx, larynx), laryngospasm, malaise, serum sickness (fever, malaise, pruritus, urticaria, lymphadenopathy, arthralgia, angioedema of face and extremities, neuritis prostration, eosinophilia), SLE-like syndrome, Injection site reactions (pain, inflammation, abscess, phlebitis), superinfections (especially with Candida and gram-negative bacteria), neuromuscular irritability (twitching, lethargy, confusion, stupor, hyperreflexia, multifocal myoclonus, localized or generalized seizures, coma). CV: Hypotension, circulatory collapse, cardiac arrhythmias, cardiac arrest. GI: Vomiting, diarrhea, severe abdominal cramps, nausea, epigastric distress, diarrhea, flatulence, dark discoloration of tongue, sore mouth or tongue. Urogenital: Interstitial nephritis, Loeffler's syndrome, vasculitis. Hematologic: Hemolytic anemia, thrombocytopenia. Metabolic: Hyperkalemia (penicillin G potassium); hypokalemia, alkalosis, hypernatremia, CHF (penicillin G sodium). Respiratory: Bronchospasm, asthma. Skin: Itchy palms or axilla, pruritus, urticaria, flushed skin, delayed skin rashes ranging from urticaria to exfoliative dermatitis, Stevens-Johnson syndrome, fixed-drug eruptions, contact dermatitis.

Diagnostic Test Interference

Blood grouping and compatibility tests: possible interference associated with penicillin doses greater than 20 million units daily. Urine glucose: massive doses of penicillin may cause false-positive test results with Benedict's solution and possibly Clinitest but not with glucose oxidase methods (e.g., Clinistix, Diastix, TesTape). Urine protein: massive doses of penicillin can produce false-positive results when turbidity measures are used (e.g., acetic acid and heat, sulfo-salicylic acid); Ames reagent reportedly not affected. Urinary PSP excretion tests: false decrease in urinary excretion of PSP. Urinary steroids: large IV doses of penicillin may interfere with accurate measurement of urinary 17-OHCS (Glenn-Nelson technique not affected).


Drug: Probenecid decreases renal elimination; penicillin G may decrease efficacy of oral contraceptives; colestipol decreases penicillin absorption; potassium-sparing diuretics may cause hyperkalemia with penicillin G potassium. Food: Food increases breakdown in stomach.


Peak: 15–30 min IM. Distribution: Widely distributed; good CSF concentrations with inflamed meninges; crosses placenta; distributed in breast milk. Metabolism: 16–30% metabolized. Elimination: 60% in urine within 6 h. Half-Life: 0.4–0.9 h.

Nursing Implications

Assessment & Drug Effects

  • Obtain an exact history of patient's previous exposure and sensitivity to penicillins and cephalosporins and other allergic reactions of any kind prior to treatment with penicillin.
  • Hypersensitivity reactions are more likely to occur with parenteral penicillin but may also occur with the oral drug. Skin rash is the most common type allergic reaction and should be reported promptly to physician.
  • Lab tests: Perform C&S tests prior to initiation of therapy; treatment may be started before results are known. Evaluate renal, hepatic, and hematologic systems at regular intervals in patients on high-dose therapy. Additionally, check electrolyte balance periodically in patients receiving high parenteral doses.
  • Observe all patients closely for at least 30 min following administration of parenteral penicillin. The rapid appearance of a red flare or wheal at the IM or IV injection site is a possible sign of sensitivity. Also suspect an allergic reaction if patient becomes irritable, has nausea and vomiting, breathing difficulty, or sudden fever. Report any of the foregoing to physician immediately.
  • Be aware that reactions to penicillin may be rapid in onset or may not appear for days or weeks. Symptoms usually disappear fairly quickly once drug is stopped, but in some patients may persist for 5 d or more and require hospitalization for treatment.
  • Allergy to penicillin is unpredictable. It has occurred in patients with a negative history of penicillin allergy and also in patients with no known prior contact with penicillin (sensitization may have occurred from penicillin used commercially in foods and beverages).
  • Be alert for neuromuscular irritability in patients receiving parenteral penicillin in excess of 20 million U/d who have renal insufficiency, hyponatremia, or underlying CNS disease, notably myasthenia gravis or epilepsy. Seizure precautions are indicated. Symptoms usually begin with twitching, especially of face and extremities.
  • Monitor I&O, particularly in patients receiving high parenteral doses. Report oliguria, hematuria, and changes in I&O ratio. Consult physician regarding optimum fluid intake. Dehydration increases the concentration of drug in kidneys and can cause renal irritation and damage.
  • Observe closely for signs of toxicity: Neonates, young infants, the older adult, and patients with impaired kidney function receiving high-dose penicillin therapy. Urinary excretion of penicillin is significantly delayed in these patients.
  • Observe patients on high-dose therapy closely for evidence of bleeding, and bleeding time should be monitored. (In high doses, penicillin interferes with platelet aggregation.)

Patient & Family Education

  • Understand that hypersensitivity reaction may be delayed. Report skin rashes, itching, fever, malaise, and other signs of a delayed reaction to physician immediately (see ADVERSE EFFECTS).
  • Notify physician if following symptoms appear when taking penicillin for treatment of syphilis (i.e., Jarisch-Herxheimer reaction occurs 8–24 h after treatment): Headache, chills, fever, myalgia, arthralgia, malaise, and worsening of syphilitic skin lesions. Reaction is usually self-limiting. Check with physician if symptoms do not improve within a few days or get worse.
  • Report S&S of superinfection (see Appendix F).
  • Understand importance of medical follow-up; present evidence suggests that glomerulonephritis, a possible complication of streptococcal infection, may not be prevented by penicillin.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

© 2006-2023 Last Updated On: 01/27/2023 (0)
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