Bicillin L - A- Penicillin G Benzathine injection, Suspension prescribing information
WARNING
NOT FOR INTRAVENOUS USE. DO NOT INJECT INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS. THERE HAVE BEEN REPORTS OF INADVERTENT INTRAVENOUS ADMINISTRATION OF PENICILLIN G BENZATHINE WHICH HAS BEEN ASSOCIATED WITH CARDIORESPIRATORY ARREST AND DEATH. Prior to administration of this drug, carefully read the WARNINGS , ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections of the labeling.
INDICATIONS AND USAGE
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bicillin L-A and other antibacterial drugs, Bicillin L-A should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Intramuscular penicillin G benzathine is indicated 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 intramuscular penicillin G benzathine:
Mild-to-moderate infections of the upper-respiratory tract due to susceptible streptococci.
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.
DOSAGE AND ADMINISTRATION
Streptococcal (Group A) Upper Respiratory Infections (for example, pharyngitis)
Adults—a single injection of 1,200,000 units; older pediatric patients—a single injection of 900,000 units; infants and pediatric patients under 60 lbs.—300,000 to 600,000 units.
Syphilis
Primary, secondary, and latent—2,400,000 units (1 dose). Late (tertiary and neurosyphilis)—2,400,000 units at 7-day intervals for three doses.
Congenital—under 2 years of age: 50,000 units/kg/body weight; ages 2 to 12 years: adjust dosage based on adult dosage schedule.
Yaws, Bejel, and Pinta —1,200,000 units (1 injection).
Prophylaxis —for rheumatic fever and glomerulonephritis.
Following an acute attack, penicillin G benzathine (parenteral) may be given in doses of 1,200,000 units once a month or 600,000 units every 2 weeks.
METHOD OF ADMINISTRATION
BICILLIN L-A IS INTENDED FOR INTRAMUSCULAR INJECTION ONLY. DO NOT INJECT INTO OR NEAR AN ARTERY OR NERVE, OR INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS. (SEE WARNINGS SECTION.)
Administer by DEEP INTRAMUSCULAR INJECTION in the upper, outer quadrant of the buttock (dorsogluteal) or the ventrogluteal site. In neonates, infants and small children, the midlateral aspect of the thigh may be preferable. Administration in the anterolateral thigh is not recommended due to the adverse effects observed (see WARNINGS section), and vascularity of this region. When doses are repeated, vary the injection site.
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.
CONTRAINDICATIONS
A history of a previous hypersensitivity reaction to any of the penicillins is a contraindication.
ADVERSE REACTIONS
As with other penicillins, untoward reactions of the sensitivity phenomena are likely to occur, particularly in individuals who have previously demonstrated hypersensitivity to penicillins or in those with a history of allergy, asthma, hay fever, or urticaria.
As with other treatments for syphilis, the Jarisch-Herxheimer reaction has been reported.
The following adverse reactions have been reported with Bicillin L-A during post-marketing experience:
Skin and Appendages: Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS). (See WARNINGS .)
Immune System Disorders: Acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction (Kounis syndrome).
The following have been reported with parenteral penicillin G (the active moiety in Bicillin L-A):
General: Hypersensitivity reactions including the following: skin eruptions (maculopapular to exfoliative dermatitis), urticaria, laryngeal edema, fever, eosinophilia; other serum sickness-like reactions (including chills, fever, edema, arthralgia, and prostration); and anaphylaxis including shock and death: severe cutaneous adverse reactions (SCAR), such as toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). (See WARNINGS .) Note: Urticaria, other skin rashes, and serum sickness-like reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, penicillin G should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to therapy with penicillin G. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be administered as indicated.
Gastrointestinal: Pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. (See WARNINGS section.)
Hematologic: Hemolytic anemia, leukopenia, thrombocytopenia.
Neurologic: Neuropathy.
Urogenital: Nephropathy.
The following adverse events have been temporally associated with parenteral administration of penicillin G benzathine (a component of Bicillin L-A):
Body as a Whole: Hypersensitivity reactions including allergic vasculitis, pruritus, fatigue, asthenia, and pain; aggravation of existing disorder; headache, Nicolau syndrome.
Cardiovascular: Cardiac arrest; hypotension; tachycardia; palpitations; pulmonary hypertension; pulmonary embolism; vasodilation; vasovagal reaction; cerebrovascular accident; syncope.
Gastrointestinal: Nausea, vomiting; blood in stool; intestinal necrosis.
Hemic and Lymphatic: Lymphadenopathy.
Injection Site: Injection site reactions including pain, inflammation, lump, abscess, necrosis, edema, hemorrhage, cellulitis, hypersensitivity, atrophy, ecchymosis, and skin ulcer. Neurovascular reactions including warmth, vasospasm, pallor, mottling, gangrene, numbness of the extremities, cyanosis of the extremities, and neurovascular damage.
Metabolic: Elevated BUN, creatinine, and SGOT.
Musculoskeletal: Joint disorder; periostitis; exacerbation of arthritis; myoglobinuria; rhabdomyolysis.
Nervous System: Nervousness; tremors; dizziness; somnolence; confusion; anxiety; euphoria; transverse myelitis; seizures; coma. A syndrome manifested by a variety of CNS symptoms such as severe agitation with confusion, visual and auditory hallucinations, and a fear of impending death (Hoigne's syndrome), has been reported after administration of penicillin G procaine and, less commonly, after injection of the combination of penicillin G benzathine and penicillin G procaine. Other symptoms associated with this syndrome, such as psychosis, seizures, dizziness, tinnitus, cyanosis, palpitations, tachycardia, and/or abnormal perception in taste, also may occur.
Respiratory: Hypoxia; apnea; dyspnea.
Skin: Diaphoresis.
Special Senses: Blurred vision; blindness.
Urogenital: Neurogenic bladder; hematuria; proteinuria; renal failure; impotence; priapism.
Drug Interactions
Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin, and concurrent use of these drugs should be avoided.
Concurrent administration of penicillin and probenecid increases and prolongs serum penicillin levels by decreasing the apparent volume of distribution and slowing the rate of excretion by competitively inhibiting renal tubular secretion of penicillin.
Description
Bicillin L-A (penicillin G benzathine injectable suspension) is available for deep intramuscular injection. Penicillin G benzathine is prepared by the reaction of dibenzylethylene diamine with two molecules of penicillin G. It is chemically designated as (2 S , 5 R , 6 R )-3,3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid compound with N,N' - dibenzylethylenediamine (2:1), tetrahydrate. It occurs as a white, crystalline powder and is very slightly soluble in water and sparingly soluble in alcohol. Its chemical structure is as follows:
Bicillin L-A contains penicillin G benzathine in aqueous suspension with sodium citrate buffer and, as w/v, approximately 0.65% sodium citrate, 0.59% povidone, 0.54% carboxymethylcellulose sodium, 0.53% lecithin, 0.12% methylparaben, and 0.013% propylparaben.
Bicillin L-A contains approximately 0.11 mEq of sodium per 600,000 units of penicillin G (approximately 2.59 mg of sodium per 600,000 units of penicillin G).
Bicillin L-A suspension in the disposable-syringe formulation is viscous and opaque. It is available in a 1 mL, 2 mL, and 4 mL sizes containing the equivalent of 600,000 (actual volume of 1.17 mL contains 620,100), 1,200,000 (actual volume of 2.34 mL contains 1,240,200), and 2,400,000 (actual volume of 4.67 mL contains 2,475,100) units respectively of penicillin G as the benzathine salt. Read CONTRAINDICATIONS , WARNINGS , PRECAUTIONS , and DOSAGE AND ADMINISTRATION sections prior to use.
CLINICAL PHARMACOLOGY
General
Penicillin G benzathine has an extremely low solubility and, thus, the drug is slowly released from intramuscular injection sites. The drug is hydrolyzed 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.
Intramuscular administration of 300,000 units of penicillin G benzathine in adults results in blood levels of 0.03 to 0.05 units per mL, which are maintained for 4 to 5 days. Similar blood levels may persist for 10 days following administration of 600,000 units and for 14 days following administration of 1,200,000 units. Blood concentrations of 0.003 units per mL may still be detectable 4 weeks following administration of 1,200,000 units.
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 and the spinal fluid to a lesser degree. 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.
Microbiology
Mechanism of Action
Penicillin G exerts a bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall peptidoglycan, rendering the cell wall osmotically unstable.
Resistance
Penicillin is not active against penicillinase-producing bacteria or against organisms resistant to beta-lactams because of alterations in the penicillin-binding proteins. Resistance to penicillin G has not been reported in Streptococcus pyogenes .
Antimicrobial Activity
Penicillin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Gram-positive bacteria
Beta-hemolytic streptococci (groups A, B, C, G, H, L and M).
Other microorganisms Treponema pallidum Treponema carateum
Susceptibility Testing
For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC .
HOW SUPPLIED
Bicillin L-A (penicillin G benzathine injectable suspension) is supplied in packages of 10 disposable syringes as follows:
1 mL size, containing 600,000 units per syringe, (21 gauge, thin-wall 1-inch needle for pediatric use), with 0.11 mEq of sodium per 600,000 units of penicillin G (2.59 mg of sodium per 600,000 units of penicillin G), NDC 60793-700-10.
2 mL size, containing 1,200,000 units per syringe, (21 gauge, thin-wall 1-1/2-inch needle), with 0.22 mEq of sodium per 1,200,000 units of penicillin G (5.17 mg of sodium per 1,200,000 units of penicillin G), NDC 60793-701-10.
4 mL size, containing 2,400,000 units per syringe (18 gauge, × 1–1/2-inch needle), with 0.45 mEq of sodium per 2,400,000 units of penicillin G (10.32 mg of sodium per 2,400,000 units of penicillin G), NDC 60793-702-10.
Store in a refrigerator, 2° to 8°C (36° to 46°F).
Keep from freezing.
Mechanism of Action
Penicillin G exerts a bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall peptidoglycan, rendering the cell wall osmotically unstable.
