Bicillin (Penicillin G Benzathine)

BICILLIN® L-A

Wyeth-Ayerst

Penicillin G Benzathine

Antibiotic

Action And Clinical Pharmacology: Actions: Penicillin G exerts a bactericidal action against penicillin-sensitive microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall mucopeptide. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. Penicillin G exerts high in vitro activity against staphylococci (except penicillinase-producing strains), streptococci (Groups A,C,G,H,L and M) and pneumococci. Other organisms sensitive to penicillin G are: N. gonorrhoeae, C. diphtheriae, B. anthracis, Clostridia, A. bovis, S. moniliformis, L. monocytogenes, and Leptospira. T. pallidum is extremely sensitive to the bactericidal action of penicillin G.

Pharmacokinetics: I.M. penicillin G benzathine is absorbed very slowly into the bloodstream from the i.m. site and converted by hydrolysis to penicillin G. This combination of hydrolysis and slow absorption results in blood serum levels much lower but much more prolonged than other parenteral penicillins.

Approximately 60% of penicillin G is bound to serum protein. The drug is distributed throughout the body tissues in widely varying amounts. Highest levels are found in the kidneys with lesser amounts in the liver, skin, and intestines. Penicillin G penetrates into all other tissues to a lesser degree with a very small level found in the cerebrospinal fluid. With normal kidney function the drug is excreted rapidly by tubular excretion. In neonates and young infants and in individuals with impaired kidney function, excretion is considerably delayed.

Sensitivity Plate Testing: If the Kirby-Bauer method of disc sensitivity is used, a 10-unit penicillin disc should give a zone greater than 28 mm when tested against a penicillin-sensitive bacterial strain.

Indications And Clinical Uses: In the treatment of infections due to penicillin-G-sensitive microorganisms that are susceptible to the low and very prolonged serum levels common to this particular dosage form. Therapy should be guided by bacteriological studies (including sensitivity tests) and by clinical response.

The following infections will usually respond to adequate dosage of i.m. penicillin G benzathine.

Streptococcal infections (Group A without bacteremia): mild-to-moderate infections of the upper respiratory tract (e.g., pharyngitis).

Venereal infections: syphilis, yaws, bejel, and pinta.

Medical conditions in which penicillin G benzathine therapy is indicated as prophylaxis: Rheumatic fever and/or chorea: Prophylaxis with penicillin G benzathine has proven effective in preventing recurrence of these conditions. It has also been used as follow-up prophylactic therapy for rheumatic heart disease and acute glomerulonephritis.

Contra-Indications: A history of a previous hypersensitivity reaction to any of the penicillins is a contraindication.

Do not inject into or near an artery or nerve.

Manufacturers’ Warnings In Clinical States: Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history of sensitivity to multiple allergens.

There have been well-documented reports of individuals with a history of penicillin hypersensitivity reactions who have experienced severe hypersensitivity reactions when treated with a cephalosporin. Before therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins and other allergens. If an allergic reaction occurs, the drug should be discontinued and the patient treated with the usual agents, e.g., pressor amines, antihistamines, and corticosteroids.

Inadvertent intravascular administration, including inadvertent direct intra-arterial injection or injection immediately adjacent to arteries, of penicillin G benzathine and other penicillin preparations has resulted in severe neurovascular damage, including transverse myelitis with permanent paralysis, gangrene requiring amputation of digits and more proximal portions of extremities, and necrosis and sloughing at and surrounding the injection site. Such severe effects have been reported following injections into the buttock, thigh, and deltoid areas.

Other serious complications of suspected intravascular administration which have been reported include immediate pallor, mottling or cyanosis of the extremity both distal and proximal to the injection site followed by bleb formation; severe edema requiring anterior and/or posterior compartment fasciotomy in the lower extremity. The above-described severe effects and complications have most often occurred in infants and small children. Prompt consultation with an appropriate specialist is indicated if any evidence of compromise of the blood supply occurs at, proximal to, or distal to the site of injection. See Contraindications, Precautions and Dosage.

Quadriceps femoris fibrosis and atrophy have been reported following repeated i.m. injections of penicillin preparations into the anterolateral thigh.

Injection into or near a nerve may result in permanent neurological damage.

Precautions: Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma.

Care should be taken to avoid i.v. or intra-arterial administration, or injection into or near major peripheral nerves or blood vessels, since such injection may produce neurovascular damage. See Contraindications, Warnings and Dosage.

The use of antibiotics may result in overgrowth of nonsusceptible organisms. Constant observation of the patient is essential. If new infections due to bacteria or fungi appear during therapy, the drug should be discontinued and appropriate measures taken.

Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy.

In streptococcal infections, therapy must be sufficient to eliminate the organism; otherwise, the sequelae of streptococcal disease may occur. Cultures should be taken following completion of treatment to determine whether streptococci have been eradicated.

Pregnancy: Penicillins readily cross the placenta. The effect, if any, on the fetus is not known. Although generally considered to be safe, penicillin G benzathine should be used during pregnancy only if clearly needed.

Lactation: Soluble penicillin G is excreted in breast milk. The effect on the infant, if any, is not known. Caution should be used when penicillin G benzathine is administered to a nursing woman.

Drug Interactions: Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin, and concurrent use of these drugs should be avoided. The rate of excretion of the penicillins is decreased by concomitant administration of probenecid; probenecid prolongs, as well as increases, blood levels of the penicillins.

Laboratory Tests: In prolonged therapy with penicillin and particularly with high-dosage schedules, periodic evaluation of the renal and hematopoietic systems is recommended.

Laboratory Test Interactions : Penicillins can interfere with the copper sulfate reagent method of testing for glycosuria, resulting in falsely elevated or falsely decreased readings. Such interference does not occur with the glucose oxidase method.

Adverse Reactions: Penicillin is a substance of low toxicity but does possess a significant index of sensitization. The following hypersensitivity reactions associated with use of penicillin have been reported: skin rashes, ranging from maculopapular eruptions to exfoliative dermatitis; urticaria; laryngeal edema; serum-sickness like reactions, including chills, fever, edema, arthralgia, and prostration. Fever and eosinophilia may frequently be the only reaction observed. Severe and often fatal anaphylaxis has been reported (see Warnings).

Hemolytic anemia, leukopenia, thrombocytopenia, neuropathy and nephropathy are infrequent reactions and usually associated with high doses of parenteral penicillin.

As with other treatments for syphilis, the Jarisch-Herxheimer reaction has been reported.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: There have been no reported overdosages. Usually, the penicillins have minimal direct toxicity to man. However, the viscous nature of penicillin G benzathine suspension may cause any of the local neurovascular effects described under Warnings. Since there is no antidote, treatment should be symptomatic and supportive.

Anaphylactic Shock: In adults, initially epinephrine HCl 0.5 mg (0.5 mL of a 1:1 000 solution) may be given by the s.c. or i.m. route followed by 0.025 to 0.05 mg (0.25 to 0.5 mL of a 1:10 000 solution) given i.v. in repeated doses every 5 to 15 minutes until relief of bronchospasm and hypotension has occurred, or excessive tachycardia induced.

In pediatrics, initially epinephrine HCl 0.01 mg/kg (0.01 mL/kg of a 1:1 000 solution) or 0.3 mg/m(0.3 mL/mof a 1:1 000 solution) may be given by the s.c. route. Single pediatric doses should not exceed 0.5 mg. Doses may be repeated every 20 minutes to 4 hours, depending on the severity of the condition and the response of the patient.

Aminophylline, oxygen and i.v. corticosteroids may also be required. Mild hypersensitivity reactions may respond to antihistamines, pressor amines or corticosteroids.

Dosage And Administration: The following dosages are recommended: Streptococcal Group A – upper respiratory infections (e.g., pharyngitis): Adults: a single dose of 1.2 million IU. Older children: a single dose of 900 000 IU. Children and infants under 27 kg: a single dose of 300 000 to 600 000 IU.

Venereal Infections: Syphilis – Primary, secondary, and latent: 2.4 million IU (1 dose).

Late (tertiary and neurosyphilis): 2.4 million IU at 7-day intervals for 3 doses.

Congenital: under 2 years of age: 50 000 IU/kg; ages 2 to 12 years: adjust dosage based on adult dosage schedule.

Yaws, Bejel, and Pinta: a single dose of 1.2 million IU.

Prophylaxis: for rheumatic fever and glomerulonephritis: Following an acute attack, penicillin G benzathine (parenteral) may be given in doses of 1 200 000 IU once a month or 600 000 IU every 2 weeks.

Directions for Use (see package insert for illustrations): Administer by deep, i.m. injection in the upper, outer quadrant of the buttock. In infants and small children, the midlateral aspect of the thigh may be preferable. When doses are repeated, vary the injection site. Care should be taken to avoid i.v. or intra-arterial administration, or injection into or near major peripheral nerves or blood vessels, since such injection may produce neurovascular damage. Discontinue delivery of the dose if the subject complains of severe immediate pain at the injection site or if, especially in infants and young children, symptoms or signs occur suggesting onset of severe pain.

The Wyeth-Ayerst Tubex cartridge for this product incorporates several features that are designed to facilitate the visualization of blood on aspiration if a blood vessel is inadvertently entered.

The design of this cartridge is such that blood which enters its needle will be quickly visualized as a red or dark-colored “spot”. This “spot” will appear on the barrel of the glass cartridge immediately proximal to the blue hub. The Tubex is designed with 2 orientation marks, in order to determine where this “spot” can be seen. First insert and secure the cartridge in the Tubex injector in the usual fashion. Locate the yellow rectangle at the base of the blue hub. This yellow rectangle is aligned with the blood visualization “spot”. An imaginary straight line, drawn from this yellow rectangle to the shoulder of the glass cartridge, will point to the area on the cartridge where the “spot” can be visualized. When the needle cover is removed, a second yellow rectangle will be visible. The second yellow rectangle is also aligned with the blood visualization “spot” to assist the operator in locating this “spot”. The glass cartridge should be rotated by turning the plunger of the syringe clockwise until the yellow rectangle is visualized.

Thus, before the needle is inserted into the selected muscle, it is important for the operator to orient the yellow rectangles so that any blood which may enter after needle insertion and during aspiration can be visualized in the area on the cartridge where it will appear and not be obscured by any obstructions.

After selection of the proper site and insertion of the needle into the selected muscle, aspirate by pulling back on the plunger. While maintaining negative pressure for 2 to 3 seconds, carefully observe the barrel of the cartridge in the area previously identified (see above) for the appearance of a red or dark-colored “spot”.

Blood or “typical blood color” may not be seen if a blood-vessel has been entered – only a mixture of blood and penicillin G benzathine. The appearance of any discoloration is reason to withdraw the needle and discard the glass Tubex cartridge. If it is elected to inject at another site, a new cartridge should be used. If no blood or discoloration appears, inject the contents of the cartridge slowly.

Some Tubex cartridges may contain a small air bubble which may be disregarded, since it does not affect administration of the product.

Because of the high concentration of suspended material in this product, the needle may be blocked if the injection is not made at a slow, steady rate.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Tubex Injector: Note: The Tubex Injector is reusable: do not discard.

Directions for Use: Before proceeding, see important information above.

To load a Tubex Sterile Cartridge-Needle Unit into the Tubex Injector: 1) Turn the ribbed collar to the “Open” position until it stops. 2) Hold the Injector with the open end up and fully insert the Tubex Sterile Cartridge-Needle Unit. Firmly tighten the ribbed collar in the direction of the “Close” arrow. 3) Thread the plunger rod into the plunger of the Tubex Sterile Cartridge-Needle Unit until slight resistance is felt. The Injector is now ready for use in the usual manner.

To administer: Method of administration is the same as with conventional syringe. Remove needle cover by grasping it securely: twist and pull. Introduce needle into patient, aspirate by pulling back slightly on the plunger, and inject.

To remove empty Tubex Cartridge-Needle Unit and dispose into a vertical needle disposal container: 1) Do not recap the needle. Disengage the plunger rod. 2) Hold the Injector, needle down, over a vertical needle disposal container and loosen the ribbed collar. Tubex Cartridge-Needle Unit will drop into the container. 3) Discard the needle cover.

To remove empty Tubex Cartridge-Needle Unit and dispose into a horizontal (mailbox) needle disposal container: 1) Do not recap the needle. Disengage the plunger rod. 2) Open the horizontal (mailbox) needle disposal container. Insert Tubex Cartridge-Needle Unit, needle pointing down, halfway into container. Close the container lid on cartridge. Loosen ribbed collar; Tubex Cartridge Unit will drop into the container. 3) Discard the needle cover.

The Tubex Injector is reusable and should not be discarded. Used Tubex Cartridge-Needle Units should not be employed for successive injections or as multiple dose containers. They are intended to be used only once and discarded.

Note: Any graduated markings on Tubex Sterile Cartridge-Needle Units are to be used only as a guide in mixing, withdrawing, or administering measured doses.

Wyeth-Ayerst does not recommend and will not accept responsibility for the use of any cartridge-needle units other than Tubex Cartridge-Needle Units in the Tubex Injector.

Availability And Storage: Each 2 mL of aqueous suspension contains: penicillin G benzathine 1 200 000 IU. Nonmedicinal ingredients: methylparaben, povidone, propylparaben, sodium carboxymethylcellulose, sodium citrate and water for injection. Boxes of 10 single use disposable Tubex Sterile Cartridge-Needle Units (20 gauge´1 1/4 inch needle) of 2 mL with a reusable Tubex Injector and one insert. Store under refrigeration (2 to 8°C). May be removed from refrigerator and stored for 7 days at a temperature not exceeding 30°C.

BICILLIN® L-A Wyeth-Ayerst Penicillin G Benzathine Antibiotic

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