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Pronunciation

(pen i SIL in jee, pa REN ter al, AYE kwee us)

Generic Available (U.S.)

Yes

Index Terms

• Benzylpenicillin Potassium
• Benzylpenicillin Sodium
• Crystalline Penicillin
• Penicillin G Potassium
• Penicillin G Sodium

U.S. Brand Names

• Pfizerpen®

Canadian Brand Names

• Crystapen®

Pharmacologic Category

• Antibiotic, Penicillin

Pharmacologic Category Synonyms

• Penicillin Derivative Antibiotic

Use: Labeled Indications

Treatment of infections (including sepsis, pneumonia, pericarditis, endocarditis, meningitis, anthrax) caused by susceptible organisms; active against some gram-positive organisms, generally not Staphylococcus aureus; some gram-negative organisms such as Neisseria gonorrhoeae, and some anaerobes and spirochetes

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal studies; therefore, penicillin G is classified as pregnancy category B. Penicillin crosses the placenta and distributes into amniotic fluid. There is no evidence of adverse fetal effects after penicillin use during pregnancy in humans. Penicillin G is the drug of choice for treatment of syphilis during pregnancy and penicillin G (parenteral/aqueous) is the drug of choice for the prevention of early-onset Group B Streptococcal (GBS) disease in newborns.

Lactation

Enters breast milk/compatible

Breast-Feeding Considerations

Very small amounts of penicillin G transfer into breast milk. Peak milk concentrations occur at approximately 1 hour after an IM dose and are higher if multiple doses are given. The manufacturer recommends that caution be exercised when administering penicillin to nursing women. Nondose-related effects could include modification of bowel flora and allergic sensitization.

Contraindications

Hypersensitivity to penicillin or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients.

• Neurovascular damage: Avoid intra-arterial administration or injection into or near major peripheral nerves or blood vessels since such injections may cause severe and/or permanent neurovascular damage.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended. In the presence of concomitant hepatic impairment, further dosage adjustment may be needed.

• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.

Special populations:

• Pediatrics: Neonates may have decreased renal clearance of penicillin and require frequent dosage adjustments depending on age.

Other warnings/precautions:

• Electrolyte imbalance: Product contains sodium and potassium; high doses of I.V. therapy may alter serum levels.

• Prolonged use: Extended duration of therapy or use associated with high serum concentrations (eg, in renal insufficiency) may be associated with an increased risk for some adverse reactions (neutropenia, hemolytic anemia, serum sickness).

Adverse Reactions

Frequency not defined.

Central nervous system: Coma (high doses), hyper-reflexia (high doses), seizures (high doses)

Dermatologic: Contact dermatitis, rash

Endocrine & metabolic: Electrolyte imbalance (high doses)

Gastrointestinal: Pseudomembranous colitis

Hematologic: Neutropenia, positive Coombs' hemolytic anemia (rare, high doses)

Local: Injection site reaction, phlebitis, thrombophlebitis

Neuromuscular & skeletal: Myoclonus (high doses)

Renal: Acute interstitial nephritis (high doses), renal tubular damage (high doses)

Miscellaneous: Anaphylaxis, hypersensitivity reactions (immediate and delayed), Jarisch-Herxheimer reaction, serum sickness

Drug Interactions

BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination

Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification

Storage

Penicillin G potassium powder for injection should be stored below 86°F (30°C). Following reconstitution, solution may be stored for up to 7 days under refrigeration. Premixed bags for infusion should be stored in the freezer (-20°C to -4°F); frozen bags may be thawed at room temperature or in refrigerator. Once thawed, solution is stable for 14 days if stored in refrigerator or for 24 hours when stored at room temperature. Do not refreeze once thawed.

Penicillin G sodium powder for injection should be stored at controlled room temperature. Reconstituted solution may be stored under refrigeration for up to 3 days.

Reconstitution

Intermittent I.V.: 5 million unit vial: Add 8.2 mL for a final concentration of 500,000 units/mL; add 3.2 mL for a final concentration of 1,000,000 units/mL. Dilute further to 50,000-145,000 units/mL prior to infusion.

Continuous I.V. infusion: 20 million unit vial: Add 11.5 mL for a final concentration of 1,000,000 units/mL. Dilute further in 1-2 L of infusion solution and administer over a 24-hour period.

Compatibility

Inactivated in acidic or alkaline solutions.

Penicillin G potassium:

Stable in dextran 6% in dextrose, dextran 6% in NS, D₅LR, D₅1/4NS, D₅1/2NS, D₅NS, D₅W, D₁₀W, LR, 1/2NS, NS, hetastarch 6%; incompatible with dextran 70 6% in dextrose, dextran 40 10% in dextrose; variable stability (consult detailed reference) in fat emulsion 10%, peritoneal dialysis solutions.

Y-site administration: Compatible: Acyclovir, amiodarone, cyclophosphamide, diltiazem, enalaprilat, esmolol, fluconazole, foscarnet, heparin, heparin with hydrocortisone sodium succinate, hydromorphone, labetalol, magnesium sulfate, meperidine, morphine, nicardipine, perphenazine, potassium chloride, tacrolimus, theophylline, verapamil, vitamin B complex with C.

Compatibility in syringe: Compatible: Caffeine citrate, heparin. Incompatible: Metoclopramide.

Compatibility when admixed: Compatible: Ascorbic acid injection, calcium chloride, calcium gluconate, chloramphenicol, cimetidine, clindamycin, colistimethate, corticotropin, dimenhydrinate, diphenhydramine, ephedrine, erythromycin lactobionate, furosemide, hydrocortisone sodium succinate, kanamycin, lidocaine, magnesium sulfate, methylprednisolone sodium succinate, metronidazole, metronidazole with sodium bicarbonate, polymyxin B sulfate, potassium chloride, potassium chloride with vitamin B complex with C, procaine, prochlorperazine edisylate, ranitidine, verapamil. Incompatible: Aminophylline, amphotericin B, chlorpromazine, dopamine, floxacillin, hydroxyzine, metaraminol, pentobarbital, phenytoin, prochlorperazine mesylate, promazine, thiopental, vancomycin, vitamin B complex with C with oxytetracycline. Variable (consult detailed reference): Amikacin, heparin, lincomycin, promethazine, sodium bicarbonate, vitamin B complex with C.

Penicillin G sodium:

Stable in dextran 40 10%; incompatible with fat emulsion 10%; variable stability (consult detailed reference) in D₅W, NS, peritoneal dialysis solution.

Y-site administration: Compatible: Clarithromycin, levofloxacin.

Compatibility in syringe: Compatible: Caffeine citrate, chloramphenicol, cimetidine, colistimethate, dimenhydramine, gentamicin, heparin, kanamycin, lincomycin, pantoprazole, polymyxin B sulfate, streptomycin.

Compatibility when admixed: Compatible: Calcium chloride, calcium gluconate, chloramphenicol, clindamycin, colistimethate, diphenhydramine, erythromycin lactobionate, furosemide, gentamicin, hydrocortisone sodium succinate, kanamycin, polymyxin B sulfate, procaine, ranitidine, verapamil, vitamin B complex with C. Incompatible: Amphotericin B, bleomycin, chlorpromazine, cytarabine, floxacillin, hydroxyzine, methylprednisolone sodium succinate, prochlorperazine mesylate, promethazine, vancomycin. Variable (consult detailed reference): Heparin, lincomycin, potassium chloride.

Mechanism of Action

Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria

Pharmacodynamics/Kinetics

Distribution: Poor penetration across blood-brain barrier, despite inflamed meninges

Relative diffusion from blood into CSF: Poor unless meninges inflamed (exceeds usual MICs)

CSF:blood level ratio: Normal meninges: <1%; Inflamed meninges: 2% to 6%

Protein binding: 65%

Metabolism: Hepatic (30%) to penicilloic acid

Half-life elimination:

Neonates: <6 days old: 3.2-3.4 hours; 7-13 days old: 1.2-2.2 hours; >14 days old: 0.9-1.9 hours

Children and Adults: Normal renal function: 30-50 minutes

End-stage renal disease: 3.3-5.1 hours

Time to peak, serum: I.M.: ~30 minutes; I.V.: ~1 hour

Excretion: Urine (58% to 85% as unchanged drug)

Dosage

Usual dosage range:

Infants ≥1 month and Children: I.M., I.V.: 100,000-400,000 units/kg/day in divided doses every 4-6 hours (maximum dose: 24 million units/day)

Adults: I.M., I.V.: 2-30 million units/day in divided doses every 4-6 hours depending on sensitivity of the organism and severity of the infection

Indication-specific dosing:

Infants ≥1 month and Children:

Meningitis (gonococcal): I.V.: 250,000 units/kg/day in 4 divided doses

Moderate infections: I.M., I.V.: 100,000-250,000 units/kg/day in 4 divided doses

Neurosyphilis: I.V.: 200,000-300,000 units/kg/day divided every 4-6 hours for 10-14 days (maximum dose: 24 million units/day)

Severe infections: I.M., I.V.: 250,000-400,000 units/kg/day in divided doses every 4-6 hours (maximum dose: 24 million units/day)

Syphilis (congenital): I.V.:

Infants: 50,000 units/kg every 12 hours for first 7 days of life, then every 8 hours for a total of 10 days (CDC, 2010)

Children: 50,000 units/kg every 4-6 hours for 10 days (CDC, 2010)

Adults:

Actinomyces species: I.V.: 10-20 million units/day in divided doses every 4-6 hours for 4-6 weeks

Clostridium perfringens: I.V.: 24 million units/day in divided doses every 4-6 hours with clindamycin

Corynebacterium diphtheriae: I.V.: 2-3 million units/day in divided doses every 4-6 hours for 10-12 days

Erysipelas: I.V.: 1-2 million units every 4-6 hours

Erysipelothrix: I.V.: 2-4 million units every 4 hours

Fascial space infections: I.V.: 2-4 million units every 4-6 hours with metronidazole

Leptospirosis: I.V.: 1.5 million units every 6 hours for 7 days

Listeria: I.V.: 15-20 million units/day in divided doses every 4-6 hours for 2 weeks (meningitis) or 4 weeks (endocarditis)

Lyme disease (meningitis): I.V.: 20 million units/day in divided doses

Neurosyphilis: I.V.: 18-24 million units/day in divided doses every 4 hours (or by continuous infusion) for 10-14 days (CDC, 2006; CDC, 2009; CDC, 2010)

Streptococcus:

Brain abscess: I.V.: 18-24 million units/day in divided doses every 4 hours with metronidazole

Endocarditis or osteomyelitis: I.V.: 3-4 million units every 4 hours for at least 4 weeks

Pregnancy (prophylaxis GBS): I.V.: 5 million units x 1 dose, then 2.5 million units every 4 hours until delivery (AGOG, 2002; CDC, 2002)

Skin and soft tissue: I.V.: 3-4 million units every 4 hours for 10 days

Toxic shock: I.V.: 24 million units/day in divided doses with clindamycin

Streptococcal pneumonia: I.V.: 2-3 million units every 4 hours

Whipple's disease: I.V.: 2 million units every 4 hours for 2 weeks, followed by oral trimethoprim/sulfamethoxazole or doxycycline for 1 year

Relapse or CNS involvement: 4 million units every 4 hours for 4 weeks

Dosing adjustment in renal impairment:

Uremic patients with Cl_cr >10 mL/minute/1.73 m²: Administer full loading dose followed by 1/2 of the loading dose given every 4-5 hours

Cl_cr <10 mL/minute/1.73 m²: Administer full loading dose followed by 1/2 of the loading dose given every 8-10 hours

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Administer normal loading dose followed by either 25% to 50% of normal dose every 4-6 hours or 50% to 100% of normal dose every 8-12 hours. For mild-to-moderate infections, administer 0.5-1 million units every 4-6 hours or 1-2 million units every 8-12 hours. For neurosyphilis, endocarditis, or serious infections, administer up to 2 million units every 4-6 hours; administer after dialysis on dialysis days or supplement with 500,000 units after dialysis (Heintz, 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.

Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: Loading dose of 4 million units, followed by 2 million units every 4-6 hours

CVVHD: Loading dose of 4 million units, followed by 2-3 million units every 4-6 hours

CVVHDF: Loading dose of 4 million units, followed by 2-4 million units every 4-6 hours

Administration: I.M.

Administer I.M. by deep injection in the upper outer quadrant of the buttock. Administer injection around-the-clock to promote less variation in peak and trough levels. Note: The 20 million unit dosage form may be administered by continuous I.V. infusion only.

Administration: I.V.

Usually administered by intermittent infusion. In some centers, large doses may be administered by continuous I.V. infusion. Note: The 20 million unit dosage form may by administered be continuous I.V. infusion only.

Intermittent I.V.: May be dissolved in small amounts of SWFI, NS, D₅W and administered peripherally as a 50,000-100,000 unit/mL solution. In fluid-restricted patients, 146,000 units/mL in SW results in a maximum recommended osmolality for peripheral infusion. Infuse over 15-30 minutes.

Continuous I.V. infusion: Determine the volume of fluid and rate of its administration required by the patient in a 24-hour period. Add the appropriate daily dosage of penicillin to this fluid. For example, if the daily dose is 10 million units and 2 L of fluid/day is required, add 5 million units to 1 L and adjust the rate of flow so the liter will be infused over 12 hours (83 mL/hour). Repeat steps (5 million units/L at 83 mL/hour) for the remaining 12 hours.

Administration: I.V. Detail

pH: 6-7.5

Monitoring Parameters

Periodic electrolyte, hepatic, renal, cardiac and hematologic function tests during prolonged/high-dose therapy; observe for signs and symptoms of anaphylaxis during first dose

Test Interactions

False-positive or negative urinary glucose determination using Clinitest®; positive Coombs' [direct]; false-positive urinary and/or serum proteins

Dietary Considerations

Some products may contain potassium and/or sodium.

Patient Education

This drug can only be given by injection or infusion. Report immediately any redness, swelling, burning, or pain at infusion site or any signs of allergic reaction (eg, respiratory or swallowing difficulty, chest tightness, rash, hives, swelling of lips or mouth). Maintain adequate hydration unless instructed to restrict fluid intake. If being treated for sexually-transmitted disease, partner will also need to be treated. May cause confusion or drowsiness. Report signs of opportunistic infection (eg, fever, chills, diarrhea, unhealed sores, white plaques in mouth or vagina, purulent vaginal discharge).

Geriatric Considerations

Despite a reported prolonged half-life, it is usually not necessary to adjust the dose of penicillin G or VK in elderly to account for renal function changes with age, however, it is advised to calculate an estimated creatinine clearance and adjust dose accordingly.

Additional Information

1 million units is approximately equal to 625 mg.

Anesthesia and Critical Care Concerns/Other Considerations

Clinical Pearls/Comments: One million units is approximately equal to 625 mg.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May rarely cause drowsiness or confusion

Mental Health: Effects on Psychiatric Treatment

None reported

Nursing: Physical Assessment/Monitoring

Assess results of culture and sensitivity tests and patient's allergy history prior to starting therapy. Use with caution and monitor closely in presence of renal impairment or seizure disorder. Avoid intravascular or intra-arterial administration or injection into or near major peripheral nerves or blood vessels; may cause severe and/or permanent neurovascular damage. Monitor for hypersensitivity reactions, opportunistic infection (fever, chills, unhealed sores, white plaques in mouth or vagina, purulent vaginal discharge, fatigue), CNS changes, and thrombophlebitis.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Infusion, premixed iso-osmotic dextrose solution, as potassium: 1 million units (50 mL); 2 million units (50 mL); 3 million units (50 mL)

Injection, powder for reconstitution, as potassium: 5 million units, 20 million units

Pfizerpen®: 5 million units, 20 million units [contains potassium 65.6 mg (1.68 mEq) per 1 million units, sodium 6.8 mg (0.3 mEq) per 1 million units]

Injection, powder for reconstitution, as sodium: 5 million units

References

American College of Obstetricians and Gynecologists,“ACOG Committee Opinion: Number 279, December 2002. Prevention of Early-Onset Group B Streptococcal Disease in Newborns,” Obstet Gynecol, 2002, 100(6):1405-12.

American Academy of Pediatrics Committee on Infectious Diseases, “Treatment of Bacterial Meningitis,” Pediatrics, 1988, 81(6):904-7.

Baddour LM, Wilson WR, Bayer AS, et al, “Infective Endocarditis. Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association - Executive Summary: Endorsed by the Infectious Diseases Society of America,” Circulation, 2005, 111(23):3167-184.

Centers for Disease Control and Prevention, “Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://aidsinfo.nih.gov/contentfiles/Pediatric_OI.pdf

Centers for Disease Control and Prevention, “Sexually Transmitted Diseases Treatment Guidelines - 2006,”MMWR Recomm Rep, 2006, 56(RR-11):1-94. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5511a1.htm

Centers for Disease Control and Prevention (CDC), "Sexually Transmitted Diseases Treatment Guidelines, 2010," MMWR Recomm Rep, 2010, 59(RR-12):1-110.

Donowitz GR and Mandell GL, “Beta-Lactam Antibiotics,” N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Gilbert DN, Moellering RC, Eliopoulos GM, et al, eds, The Sanford Guide To Antimicrobial Therapy, 2006, 36th ed, Hyde Park, VT: Antimicrobial Therapy, Inc, 2006, 6-7.

Hansen JM, Kampmann J, and Laursen H, “Renal Excretion of Drugs in the Elderly,” Lancet, 1970, 1(657):1170.

Leikola E and Vartia KO, “On Penicillin Levels in Young and Geriatric Subjects,” J Gerontol, 1957, 12:48-52.

Prober CG, Stevenson DK, and Benitz WE, “The Use of Antibiotics in Neonates Weighing Less Than 1200 Grams,” Pediatr Infect Dis J, 1990, 9(2):111-21.

Quagliarello VJ and Scheld WM, “Treatment of Bacterial Meningitis,” N Engl J Med, 1997, 336(10):708-16.

Schrag S, Gorwitz R, Fultz-Butts K, et al, “Prevention of Perinatal Group B Streptococcal Disease. Revised Guidelines from CDC,” MMWR, Recomm Rep, 51(RR11):1-22.

Tunkel AR, Hartman BJ, Kaplan SL, et al, “Practice Guidelines for the Management of Bacterial Meningitis,” Clin Infect Dis, 2004, 39(9):1267-84.

Wickerts CJ, Asaba H, Gunnarsson B, et al, “Combined Carbon Haemoperfusion and Haemodialysis in the Treatment of Penicillin Intoxication,” Br Med J, 1980, 280(6226):1254-5.

Wright AJ, “The Penicillins,” Mayo Clin Proc, 1999, 74(3):290-307.

Yoshikawa TT, “Antimicrobial Therapy for the Elderly Patient,” J Am Geriatr Soc, 1990, 38(12):1353-72.

International Brand Names

• Benpen (AU)
• Broncobiot (PE)
• Lascacilin (PY)
• Pencarv (PH)
• Pengesod (MX)
• Penicilina Northia (AR)
• Penicillin G (BG)
• Penicillin G- Natrium (AT)
• Pisacilina (CO)
• Sodipen (MX)
• Unicil 1 Mega (CO)

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Last full review/revision May 2011

Content last modified May 2011