PENICILLIN G
For general information on the penicillins, including adverse effects, contraindications, overdosage, drug interactions and monitoring parameters, refer to the monograph: Penicillins, General Information.
Chemistry - Penicillin G is a natural penicillin and is obtained from cultures Penicillium chrysogenum and is available in several different salt forms. Penicillin G potassium (also known asbenzylpenicillin potassium, aqueous or crystalline penicillin) occurs as colorless or white crystals, or white crystalline powder. It is very soluble in water and sparingly soluble in alcohol. Potency ofpenicillin G potassium is usually expressed in terms of Units. One mg of penicillin G potassium isequivalent to 1440-1680 USP Units (1355-1595 USP Units for the powder for injection). Afterreconstitution, penicillin G potassium powder for injection has a pH of 6-8.5, and contains 1.7 mEqof potassium per 1 million Units.
Penicillin G sodium (also known as benzylpenicillin sodium, aqueous or crystalline penicillin)occurs as colorless or white crystals, or white to slightly yellow, crystalline powder. Approximately25 mg is soluble in 1 ml of water. Potency of penicillin G sodium is usually expressed in terms of
Units. One mg of penicillin G sodium is equivalent to 1500-1750 USP Units (1420-1667 USP
Units for the powder for injection). After reconstitution, penicillin G sodium powder for injectionhas a pH of 6-7.5, and contains 2 mEq of sodium per 1 million Units.
Penicillin G procaine (also known as APPG, Aqueous Procaine Penicillin G, Benzylpenicillin
Procaine, Procaine Penicillin G, Procaine Benzylpenicillin) is the procaine monohydrate salt ofpenicillin G. In vivo it is hydrolyzed to penicillin G and acts as a depot, or repository form ofpenicillin G. It occurs as white crystals or very fine, white crystalline powder. Approximately 4-4.5mg are soluble in 1 ml of water and 3.3 mg are soluble in 1 ml of alcohol. Potency of penicillin Gprocaine is usually expressed in terms of Units. One mg of penicillin G procaine is equivalent to900-1050 USP Units. The commercially available suspension for injection is buffered with sodiumcitrate and has a pH of 5-7.5. It is preserved with methylparaben and propylparaben.
Penicillin G Benzathine (also known as Benzathine Benzylpenicillin, Benzathine Penicillin G,
Benzylpenicillin Benzathine, Dibenzylethylenediamine Benzylpenicillin) is the benzathinetetrahydrate salt of penicillin G. It is hydrolyzed in vivo to penicillin G and acts as a long-actingform of penicillin G. It occurs as an odorless, white, crystalline powder. Solubilities are 0.2-0.3mg/ml of water and 15 mg/ml of alcohol. One mg of penicillin G benzathine is equivalent to 1090-1272 USP Units. The commercially available suspension for injection is buffered with sodiumcitrate and has a pH of 5-7.5. It is preserved with methylparaben and propylparaben.
Penicillin G sodium and potassium powder for injection can be stored at room temperature (15-30°C). After reconstituting, the injectable solution is stable for 7 days when kept refrigerated (2-8°C) and for 24 hours at room temperature.
Penicillin G procaine should be stored at 2-8°C; avoid freezing. Benzathine penicillin G should bestored at 2-8°C.
All commonly used IV fluids (some Dextran products are incompatible) and the following drugsare reportedly compatible with penicillin G potassium: ascorbic acid injection, calciumchloride/gluconate, cephapirin sodium, chloramphenicol sodium succinate, cimetidine HCl, clin-damycin phosphate, colistimethate sodium, corticotropin, dimenhydrinate, diphenhydramine HCl, ephedrine sulfate, erythromycin gluceptate/lactobionate, hydrocortisone sodium succinate, kanamycin sulfate, lidocaine HCl, methicillin sodium, methylprednisolone sodium succinate, metronidazole with sodium bicarbonate, nitrofurantoin sodium, polymyxin B sulfate, potassiumchloride, prednisolone sodium phosphate, procaine HCl, prochlorperazine edisylate, sodium iodide, sulfisoxazole diolamine and verapamil HCl.
The following drugs/solutions are either incompatible or data conflicts regarding compatibilitywith penicillin G potassium injection: amikacin sulfate, aminophylline, cephalothin sodium, chlorpromazine HCl, dopamine HCl, heparin sodium, hydroxyzine HCl, lincomycin HCl, metoclopramide HCl, oxytetracycline HCl, pentobarbital sodium, prochlorperazine mesylate, promazine
HCl, promethazine HCl, sodium bicarbonate, tetracycline HCl and vitamin B-complex with C.
The following drugs/solutions are reportedly compatible with penicillin G sodium injection:
Dextran 40 10%, dextrose 5% (some degradation may occur if stored for 24 hours), sodiumchloride 0.9% (some degradation may occur if stored for 24 hours), calcium chloride/gluconate, chloramphenicol sodium succinate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, diphenhydramine HCl, erythromycin lactobionate, gentamicin sulfate, hydrocortisone sodiumsuccinate, kanamycin sulfate, methicillin sodium, nitrofurantoin sodium, polymyxin B sulfate, prednisolone sodium phosphate, procaine HCl, verapamil HCl and vitamin B-complex with C.
The following drugs/solutions are either incompatible or data conflicts regarding compatibilitywith penicillin G sodium injection: amphotericin B, bleomycin sulfate, cephalothin sodium, chlorpromazine HCl, heparin sodium, hydroxyzine HCl, lincomycin HCl, methylprednisolonesodium succinate, oxytetracycline HCl, potassium chloride, prochlorperazine mesylate, promethazine HCl and tetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for morespecific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacokinetics (specific) - Penicillin G potassium is poorly absorbed orally as a result ofrapid acid-catalyzed hydrolysis. When administered on an empty (fasted) stomach, oral bioavailability is only about 15-30%. If given with food, absorption rate and extent will be decreased.
Penicillin G potassium and sodium salts are rapidly absorbed after IM injections and yield highpeak levels usually within 20 minutes of administration. In horses, equivalent doses given either IVor IM demonstrated that IM dosing will provide serum levels above 0.5 micrograms/ml for abouttwice as long as IV administration [approx. 3-4 hours (IV) vs. 6-7 hours (IM)].
Procaine penicillin G is slowly hydrolyzed to penicillin G after IM injection. Peak levels are muchlower than with parenterally administered aqueous penicillin G sodium or potassium, but serumlevels are more prolonged.
Benzathine penicillin G is also very slowly absorbed after IM injections after being hydrolyzed tothe parent compound. Serum levels can be very prolonged, but levels attained generally only exceed
MIC's for the most susceptible Streptococci, and the use of benzathine penicillin G should belimited to these infections when other penicillin therapy is impractical.
After absorption, penicillin G is widely distributed throughout the body with the exception of the
CSF, joints and milk. CSF levels are generally only 10% or less of those found in the serum whenmeninges are not inflamed. Levels in the CSF may be greater in patients with inflamed meninges orif probenecid is given concurrently. Binding to plasma proteins is approximately 50% in mostspecies.
Penicillin G is principally excreted unchanged into the urine through renal mechanisms via bothglomerular filtration and tubular secretion. Elimination half-lives are very rapid and are usually onehour or less in most species (if normal renal function exists).
Chemistry - Penicillin G is a natural penicillin and is obtained from cultures Penicillium chrysogenum and is available in several different salt forms. Penicillin G potassium (also known asbenzylpenicillin potassium, aqueous or crystalline penicillin) occurs as colorless or white crystals, or white crystalline powder. It is very soluble in water and sparingly soluble in alcohol. Potency ofpenicillin G potassium is usually expressed in terms of Units. One mg of penicillin G potassium isequivalent to 1440-1680 USP Units (1355-1595 USP Units for the powder for injection). Afterreconstitution, penicillin G potassium powder for injection has a pH of 6-8.5, and contains 1.7 mEqof potassium per 1 million Units.
Penicillin G sodium (also known as benzylpenicillin sodium, aqueous or crystalline penicillin)occurs as colorless or white crystals, or white to slightly yellow, crystalline powder. Approximately25 mg is soluble in 1 ml of water. Potency of penicillin G sodium is usually expressed in terms of
Units. One mg of penicillin G sodium is equivalent to 1500-1750 USP Units (1420-1667 USP
Units for the powder for injection). After reconstitution, penicillin G sodium powder for injectionhas a pH of 6-7.5, and contains 2 mEq of sodium per 1 million Units.
Penicillin G procaine (also known as APPG, Aqueous Procaine Penicillin G, Benzylpenicillin
Procaine, Procaine Penicillin G, Procaine Benzylpenicillin) is the procaine monohydrate salt ofpenicillin G. In vivo it is hydrolyzed to penicillin G and acts as a depot, or repository form ofpenicillin G. It occurs as white crystals or very fine, white crystalline powder. Approximately 4-4.5mg are soluble in 1 ml of water and 3.3 mg are soluble in 1 ml of alcohol. Potency of penicillin Gprocaine is usually expressed in terms of Units. One mg of penicillin G procaine is equivalent to900-1050 USP Units. The commercially available suspension for injection is buffered with sodiumcitrate and has a pH of 5-7.5. It is preserved with methylparaben and propylparaben.
Penicillin G Benzathine (also known as Benzathine Benzylpenicillin, Benzathine Penicillin G,
Benzylpenicillin Benzathine, Dibenzylethylenediamine Benzylpenicillin) is the benzathinetetrahydrate salt of penicillin G. It is hydrolyzed in vivo to penicillin G and acts as a long-actingform of penicillin G. It occurs as an odorless, white, crystalline powder. Solubilities are 0.2-0.3mg/ml of water and 15 mg/ml of alcohol. One mg of penicillin G benzathine is equivalent to 1090-1272 USP Units. The commercially available suspension for injection is buffered with sodiumcitrate and has a pH of 5-7.5. It is preserved with methylparaben and propylparaben.
Storage, Stability, Compatibility
Penicillin G sodium and potassium should be protected frommoisture to prevent hydrolysis of the compounds. Penicillin G potassium tablets and powder fororal solution should be stored at room temperature in tight containers; avoid exposure to excessiveheat. After reconstituting, the oral powder for solution should be stored from 2-8°C (refrigerated)and discarded after 14 days.Penicillin G sodium and potassium powder for injection can be stored at room temperature (15-30°C). After reconstituting, the injectable solution is stable for 7 days when kept refrigerated (2-8°C) and for 24 hours at room temperature.
Penicillin G procaine should be stored at 2-8°C; avoid freezing. Benzathine penicillin G should bestored at 2-8°C.
All commonly used IV fluids (some Dextran products are incompatible) and the following drugsare reportedly compatible with penicillin G potassium: ascorbic acid injection, calciumchloride/gluconate, cephapirin sodium, chloramphenicol sodium succinate, cimetidine HCl, clin-damycin phosphate, colistimethate sodium, corticotropin, dimenhydrinate, diphenhydramine HCl, ephedrine sulfate, erythromycin gluceptate/lactobionate, hydrocortisone sodium succinate, kanamycin sulfate, lidocaine HCl, methicillin sodium, methylprednisolone sodium succinate, metronidazole with sodium bicarbonate, nitrofurantoin sodium, polymyxin B sulfate, potassiumchloride, prednisolone sodium phosphate, procaine HCl, prochlorperazine edisylate, sodium iodide, sulfisoxazole diolamine and verapamil HCl.
The following drugs/solutions are either incompatible or data conflicts regarding compatibilitywith penicillin G potassium injection: amikacin sulfate, aminophylline, cephalothin sodium, chlorpromazine HCl, dopamine HCl, heparin sodium, hydroxyzine HCl, lincomycin HCl, metoclopramide HCl, oxytetracycline HCl, pentobarbital sodium, prochlorperazine mesylate, promazine
HCl, promethazine HCl, sodium bicarbonate, tetracycline HCl and vitamin B-complex with C.
The following drugs/solutions are reportedly compatible with penicillin G sodium injection:
Dextran 40 10%, dextrose 5% (some degradation may occur if stored for 24 hours), sodiumchloride 0.9% (some degradation may occur if stored for 24 hours), calcium chloride/gluconate, chloramphenicol sodium succinate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, diphenhydramine HCl, erythromycin lactobionate, gentamicin sulfate, hydrocortisone sodiumsuccinate, kanamycin sulfate, methicillin sodium, nitrofurantoin sodium, polymyxin B sulfate, prednisolone sodium phosphate, procaine HCl, verapamil HCl and vitamin B-complex with C.
The following drugs/solutions are either incompatible or data conflicts regarding compatibilitywith penicillin G sodium injection: amphotericin B, bleomycin sulfate, cephalothin sodium, chlorpromazine HCl, heparin sodium, hydroxyzine HCl, lincomycin HCl, methylprednisolonesodium succinate, oxytetracycline HCl, potassium chloride, prochlorperazine mesylate, promethazine HCl and tetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for morespecific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Uses, Indications
Natural penicillins remain the drugs of choice for a variety of bacteria, including group A beta-hemolytic streptococci, many gram positive anaerobes, spirochetes, gramnegative aerobic cocci, and some gram negative aerobic bacilli. Generally, if a bacteria is susceptibleto a natural penicillin, either penicillin G or V is preferred for treating that infection as long asadequate penetration of the drug to the site of the infection occurs and the patient is nothypersensitive to penicillins.Pharmacokinetics (specific) - Penicillin G potassium is poorly absorbed orally as a result ofrapid acid-catalyzed hydrolysis. When administered on an empty (fasted) stomach, oral bioavailability is only about 15-30%. If given with food, absorption rate and extent will be decreased.
Penicillin G potassium and sodium salts are rapidly absorbed after IM injections and yield highpeak levels usually within 20 minutes of administration. In horses, equivalent doses given either IVor IM demonstrated that IM dosing will provide serum levels above 0.5 micrograms/ml for abouttwice as long as IV administration [approx. 3-4 hours (IV) vs. 6-7 hours (IM)].
Procaine penicillin G is slowly hydrolyzed to penicillin G after IM injection. Peak levels are muchlower than with parenterally administered aqueous penicillin G sodium or potassium, but serumlevels are more prolonged.
Benzathine penicillin G is also very slowly absorbed after IM injections after being hydrolyzed tothe parent compound. Serum levels can be very prolonged, but levels attained generally only exceed
MIC's for the most susceptible Streptococci, and the use of benzathine penicillin G should belimited to these infections when other penicillin therapy is impractical.
After absorption, penicillin G is widely distributed throughout the body with the exception of the
CSF, joints and milk. CSF levels are generally only 10% or less of those found in the serum whenmeninges are not inflamed. Levels in the CSF may be greater in patients with inflamed meninges orif probenecid is given concurrently. Binding to plasma proteins is approximately 50% in mostspecies.
Penicillin G is principally excreted unchanged into the urine through renal mechanisms via bothglomerular filtration and tubular secretion. Elimination half-lives are very rapid and are usually onehour or less in most species (if normal renal function exists).