Cardiovascular: Myocardial depression, vasodilation, conduction disturbances

Central nervous system: Confusion, drowsiness, myoclonus, CNS stimulation, seizure

Hematologic: Positive Coombs' reaction, hemolytic anemia, neutropenia

Local: Pain at injection site, thrombophlebitis, sterile abscess at injection site

Renal: Interstitial nephritis

Miscellaneous: Pseudoanaphylactic reactions, hypersensitivity reactions, Jarisch-Herxheimer reaction, serum sickness

Aminoglycosides: May be synergistic against selected organisms

Methotrexate: Penicillins may increase the exposure to methotrexate during concurrent therapy; monitor.

Oral contraceptives: Anecdotal reports suggesting decreased contraceptive efficacy with penicillins have been refuted by more rigorous scientific and clinical data.

Probenecid, disulfiram: May increase penicillin levels

Tetracyclines: May decrease penicillin effectiveness

Warfarin: Effects of warfarin may be increased

Duration: Therapeutic: 15-24 hours

Absorption: I.M.: Slow

Distribution: Penetration across the blood-brain barrier is poor, despite inflamed meninges; enters breast milk

Protein binding: 65%

Metabolism: ~30% hepatically inactivated

Time to peak, serum: 1-4 hours

Excretion: Urine (60% to 90% as unchanged drug)

Clearance: Renal: Delayed in neonates, young infants, and with impaired renal function

Children: 25,000-50,000 units/kg/day in divided doses 1-2 times/day; not to exceed 4.8 million units/24 hours

Anthrax, inhalational (postexposure prophylaxis): 25,000 units/kg every 12 hours (maximum: 1,200,000 units every 12 hours); see "Note" in Adults dosing

Congenital syphilis: 50,000 units/kg/day for 10-14 days

Adults: 0.6-4.8 million units/day in divided doses every 12-24 hours

Anthrax:

Inhalational (postexposure prophylaxis): 1,200,000 units every 12 hours

Note: Overall treatment duration should be 60 days. Available safety data suggest continued administration of penicillin G procaine for longer than 2 weeks may incur additional risk for adverse reactions. Clinicians may consider switching to effective alternative treatment for completion of therapy beyond 2 weeks.

Cutaneous (treatment): 600,000-1,200,000 units/day; alternative therapy is recommended in severe cutaneous or other forms of anthrax infection

Endocarditis caused by susceptible viridans Streptococcus (when used in conjunction with an aminoglycoside): 1.2 million units every 6 hours for 2-4 weeks

Neurosyphilis: I.M.: 2-4 million units/day with 500 mg probenecid by mouth 4 times/day for 10-14 days; penicillin G aqueous I.V. is the preferred agent

Hemodialysis: Moderately dialyzable (20% to 50%)

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

Paryani SG, Vaughn AJ, Crosby M, et al, "Treatment of Asymptomatic Congenital Syphilis: Benzathine Versus Procaine Penicillin G Therapy,"J Pediatr, 1994, 125(3):471-5.

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.