© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International
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Elephant specific information, if available, is in blue.
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 as benzylpenicillin 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 of penicillin G potassium is usually expressed in terms of Units. One mg of penicillin G potassium is equivalent to 1440-1680 USP Units (1355-1595 USP Units for the powder for injection). After reconstitution, penicillin G potassium powder for injection has a pH of 6-8.5, and contains 1.7 mEq of 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. Approximately 25 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 injection has 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 of penicillin G. In vivo it is hydrolyzed to penicillin G and acts as a depot, or repository form of penicillin G. It occurs as white crystals or very fine, white crystalline powder. Approximately 4-4.5 mg are soluble in 1 ml of water and 3.3 mg are soluble in 1 ml of alcohol. Potency of penicillin G procaine is usually expressed in terms of Units. One mg of penicillin G procaine is equivalent to 900-1050 USP Units. The commercially available suspension for injection is buffered with sodium citrate 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 benzathine tetrahydrate salt of penicillin G. It is hydrolyzed in vivo to penicillin G and acts as a long-acting form of penicillin G. It occurs as an odorless, white, crystalline powder. Solubilities are 0.2-0.3 mg/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 sodium citrate 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 from moisture to prevent hydrolysis of the compounds. Penicillin G potassium tablets and powder for oral solution should be stored at room temperature in tight containers; avoid exposure to excessive heat. 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 be stored at 2-8°C.
All commonly used IV fluids (some Dextran products are incompatible) and the following drugs are reportedly compatible with penicillin G potassium: ascorbic acid injection, calcium chloride/gluconate, cephapirin sodium, chloramphenicol sodium succinate, cimetidine HCl, clindamycin 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, potassium chloride, 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 compatibility with 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), sodium chloride 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 sodium succinate, 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 compatibility with penicillin G sodium injection: amphotericin B, bleomycin sulfate, cephalothin sodium, chlorpromazine HCl, heparin sodium, hydroxyzine HCl, lincomycin HCl, methylprednisolone sodium 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 more specific 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, gram negative aerobic cocci, and some gram negative aerobic bacilli. Generally, if a bacteria is susceptible to a natural penicillin, either penicillin G or V is preferred for treating that infection as long as adequate penetration of the drug to the site of the infection occurs and the patient is not hypersensitive to penicillins.
Pharmacokinetics (specific) – Penicillin G potassium is poorly absorbed orally as a result of rapid 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 high peak levels usually within 20 minutes of administration. In horses, equivalent doses given either IV or IM demonstrated that IM dosing will provide serum levels above 0.5 micrograms/ml for about twice 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 much lower than with parenterally administered aqueous penicillin G sodium or potassium, but serum levels are more prolonged.
Benzathine penicillin G is also very slowly absorbed after IM injections after being hydrolyzed to the 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 be limited 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 when meninges are not inflamed. Levels in the CSF may be greater in patients with inflamed meninges or if probenecid is given concurrently. Binding to plasma proteins is approximately 50% in most species.
Penicillin G is principally excreted unchanged into the urine through renal mechanisms via both glomerular filtration and tubular secretion. Elimination half-lives are very rapid and are usually one hour or less in most species (if normal renal function exists).
For susceptible infections:
a) Penicillin G potassium: 5000 – 50,000 Units/kg IV qid
Penicillin G sodium: 5000 – 50,000 Units/kg IV qid
Penicillin G procaine: 5000 – 50,000 Units/kg IM bid (Robinson 1987)
b) Penicillin G sodium: 25,000 – 50,000 Units/kg IV, IM q6h
Penicillin G procaine: 20,000 – 100,000 Units/kg IM q12h
Penicillin G benzathine: 50,000 Units/kg IM q2 days (Upson 1988)
c) Initially give Penicillin G (aqueous, sodium salt used in experiment) 10,000 IU/kg IM with procaine penicillin G at 15,000 IU/kg IM q12h. If infection is severe, penicillin G sodium at 10,000 IU/kg at the same time as the procaine penicillin G. (Love et al. 1983)
d) For treatment of botulism: Penicillin G sodium or potassium 22,000 – 44,000 IU/kg IV qid (do not use oral penicillin therapy). (Johnston and Whitlock 1987)
e) For preoperative antibiotic prophylaxis for colic: Penicillin G potassium 40,000 IU IV qid with gentamicin 2.2 mg/kg IV tid. (Stover 1987)
f) For respiratory infections (Streptococci): Initially, 20,000 – 40,000 U/kg of aqueous penicillin G (sodium/potassium) IM with 20,000 u/kg IM of procaine penicillin G which is then continued bid. (Beech 1987a)
g) For foals: Penicillin G Na or K: 25,000 – 50,000 U/kg IV q6-8h;
Procaine penicillin G 25,000 – 50,000 U/kg IM q12h. Use the longer dose interval or smaller dose in premature foals or those less than 7 days old. (Caprile and Short 1987)
h) Procaine penicillin G 25,000 Units/kg IM q12-24h
Penicillin G sodium: 15,000 – 20,000 U/kg IV or IM q6h (Baggot and Prescott 1987)
i) Penicillin G potassium: 12,500 – 100,000 Units/kg IV q4h
Penicillin G sodium: 12,500 – 100,000 Units/kg IV q4h
Penicillin G procaine: 20,000 – 50,000 Units/kg IM q12h (Brumbaugh 1987)
a) Procaine penicillin G (150,000 IU/ml) in combination with benzathine penicillin (150,000 IU / ml): 4,545 IU/kg q 96 hours for Bacillus anthracis, Corynebacterium diphtherae, Streptococci spp, Staphylococci (non- penicillinase producing).
Procaine penicillin G (150,000 IU/ml) in combination with benzathine penicillin (150,000 IU / ml): 2,273/kg q 48 h for Bacillus anthracis, Corynebacterium diphtherae, Streptococci spp, Staphylococci (non-penicillinase producing).
Procaine penicillin G (150,000 IU/ml) in combination with benzathine penicillin (150,000 IU / ml): 4,545 IU/kg q 36 h for Clostridia
Procaine penicillin G (150,000 IU/ml) in combination with benzathine penicillin (150,000 IU / ml): 4,545 IU/kg q 24 h for Pasteurella multocida (Schmidt, 1978).
a) Schmidt,M.J. 1978. Penicillin and amoxicillin in elephants: A study comparing dose regimens administered with serum levels achieved in healthy elephants. Journal of Zoo Animal Medicine 9:(4):127-136 Abstract: Several dose regimens of an aqueous suspension of benzathine penicillin G combined with procaine penicillin G, and an aqueous suspension of amoxicillin were administered to five healthy adult female Asian elephants. Blood samples were drawn and serum levels of the drugs were measured after each dose was administered. Based upon serum levels, suggestions are made for therapeutic dose regimens for clinical use of both penicillin and amoxicillin in elephants, based on comparable data available for other large domestic animals.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Penicillin G Procaine Injection 300,000 Units/ml in 100 ml and 250 ml bottles
Crystacillin® 300 A.S. Veterinary (Solvay); (OTC) Approved for use in cattle, sheep, horses, and swine. Do not exceed 7 days of treatment in non-lactating dairy cattle, beef cattle, swine or sheep, and 5 days in lactating dairy cattle. Milk withdrawal = 48 hours. Slaughter withdrawal: Calves (non-ruminating) 7 days; cattle 4 days; sheep 8 days; swine 6 days.
Note: These withdrawal times are for the labeled dosage of 6,600 U/kg once daily which is rarely used clinically today. Actual withdrawal times may be longer. There are other generically labeled products available that may have different withdrawal times; refer to label for more information.
Note: There are several penicillin G procaine combination products available for the veterinary market. These products may contain dihydrostreptomycin, streptomycin or novobiocin, and be available in either intramammary or injectable dosage forms.
Penicillin G Benzathine 150,000 U/ml with Penicillin G Procaine Injection 150,000 Units/ml for Injection in 100 ml and 250 ml vials
Flo-Cillin® (Fort Dodge), Pen BP-48® (Pfizer), Crystiben® (Solvay), Dual-Pen® (TechAmerica), generic; (OTC) Approved (most products) in dogs, horses and beef cattle. Slaughter withdrawal: cattle=30 days. Actual species approvals and withdrawal times may vary with the actual product; refer to the label of the product you are using.
Penicillin G (aqueous) Potassium Powder for Injection 1,000,000 units in vials, 5,000,000 units in vials, 10,000,000 units in vials, 20,000,000 units/vial (Rx) Penicillin G Potassium® (Apothecon); Pfizerpen® (Roerig) (Rx)
Penicillin G (aqueous) Potassium Premixed Frozen Injection: 1,000,000 units, 2,000,000 units & 3,000,000 units in 50 mls Penicillin G Potassium® (Baxter) (Rx)
Penicillin G (aqueous) Sodium Powder for Injection 5 million Units/vial; Penicillin G Sodium® (Apothecon) (Rx)
Penicillin G Potassium Oral Tablets 200,000 Units, 250,000 Units, 400,000 Units, 500,000 Units, 800,000 Units; Penicillin G Potassium® (Rugby) (Rx); Pentids ‘400’® (Apothecon) (Rx); Pentids ‘800’® (Apothecon) (Rx); generic, (Rx)
Penicillin G Potassium Oral Powder for Suspension 400,000 Units/5 ml in 100 ml and 200 ml; Pentids ‘400’ for Syrup® (Apothecon) (Rx)
Penicillin G (aqueous) Procaine for Injection 300,000 Units/ml in 10 ml vials, 500,000 Units/ml (600,00 units/1.2 ml) in 12 ml vials, 600,000 Units/unit dose in 1 ml Tubex, 1.2 million Units/unit dose in 2 ml Tubex &, 2.4 million Units/unit dose in 4 ml syringes; Crysticillin 300 A.S.® (Apothecon); Pfizerpen-AS® (Roerig); Crysticillin 600 A.S.® (Apothecon); Wycillin® (Wyeth-Ayerst); (Rx)
Penicillin G Benzathine for Injection 300,000 Units/ml in 10 ml vials; 600,000 unit/dose in 1 ml Tubex; 1,200,000 units/dose in 2 ml Tubex; 2,400,000 units/dose in 4 ml syringes; Bicillin L-A® (Wyeth-Ayerst);Permapen® (Roerig) (Rx)
Penicillin G Benzathine & Procaine Combined for Injection 300,000 units/ml (150,000 units each penicillin G benzathine & penicillin G procaine) in 10 ml vials; 600,000 units/dose (300,000 units each penicillin G benzathine & penicillin G procaine) in 1 ml Tubex; 1,200,000 units/dose in 2 ml Tubex; 2,400,000 units/dose in 4 ml syringe; 900,000 units penicillin G benzathine and 300,000 units penicillin G procaine per dose in 2 ml Tubex; Bicillin C-R® (Wyeth-Ayerst); Bicillin C-R 900/300® (Wyeth-Ayerst) (Rx)