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Medication Safety Issues
Sound-alike/look-alike issues:
Penicillin may be confused with penicillamine
Pronunciation
(pen i SIL in jee, pa REN ter al, AYE kwee us)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
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), hyperreflexia (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
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
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. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
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.
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
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): Infants: I.V.: 50,000 units/kg every 4-6 hours for 10 days
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
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 interval in renal impairment:
Uremic patients with Clcr >10 mL/minute/1.73 m2: Administer full loading dose followed by 1/2 of the loading dose given every 4-5 hours
Clcr <10 mL/minute/1.73 m2: Administer full loading dose followed by 1/2 of the loading dose given every 8-10 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.
Administration: I.V.
Usually administered by intermittent infusion. In some centers, large doses may be administered by continuous I.V. infusion.
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
Injection powder for reconstitution as potassium contains sodium 6.8 mg (0.3 mEq) and potassium 65.6 mg (1.68 mEq) per 1 million units
Injection solution (premixed) as a potassium contains sodium 23.5 mg (1.02 mEq) and potassium 66.5 mg (1.7 mEq) per 1 million units
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. If you have diabetes, drug may cause false test results with Clinitest®, consult prescriber for alternative method of glucose monitoring. May cause confusion or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report persistent adverse effects or signs of opportunistic infection (eg, fever, chills, diarrhea, unhealed sores, white plaques in mouth or vagina, purulent vaginal discharge, fatigue).
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. Assess potential for interactions with other pharmacological agents (eg, decreased or increased levels/effects of penicillin G). 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. Advise patients with diabetes about use of Clinitest®; may cause false positive or negative. Assess effectiveness (resolution of infections) and adverse reactions (eg, hypersensitivity reactions, opportunistic infection [fever, chills, unhealed sores, white plaques in mouth or vagina, purulent vaginal discharge, fatigue], CNS changes, thrombophlebitis). Teach patient possible side effects/appropriate interventions and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Infusion, as potassium [premixed iso-osmotic dextrose solution, frozen]: 1 million units (50 mL), 2 million units (50 mL), 3 million units (50 mL) [contains sodium 1.02 mEq and potassium 1.7 mEq per 1 million units]
Injection, powder for reconstitution, as potassium (Pfizerpen®): 5 million units, 20 million units [contains sodium 6.8 mg (0.3 mEq) and potassium 65.6 mg (1.68 mEq) per 1 million units]
Injection, powder for reconstitution, as sodium: 5 million units [contains sodium 1.68 mEq per 1 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,” Circulation, 2005, 111(23):e394-434.
Centers for Disease Control and Prevention, "Sexually Transmitted Diseases Treatment Guidelines - 2002," MMWR Recomm Rep, 2002, 51(RR-6):1-78. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5106a1.htm.
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
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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