Gentamicin

INDICATIONS AND USAGE: To reduce the development of drug-resistant bacteria and maintain the effectiveness of Gentamicin Injection, USP and other antibacterial drugs, Gentamicin Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible 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. Gentamicin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species and Staphylococcus species (coagulase-positive and coagulase-negative). Clinical studies have shown gentamicin injection to be effective in bacterial neonatal sepsis; bacterial septicemia and serious bacterial infections of the central nervous system (meningitis), urinary tract, respiratory tract, gastrointestinal tract (including peritonitis), skin, bone and soft tissue (including burns). Aminoglycosides, including gentamicin, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are susceptible to these antibiotics and are not susceptible to antibiotics having less potential for toxicity. Specimens for bacterial culture should be obtained to isolate and identify causative organisms and to determine their susceptibility to gentamicin. Gentamicin injection may be considered as initial therapy in suspected or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing. The decision to continue therapy with this drug should be based on the results of susceptibility tests, the severity of the infection and the important additional concepts contained in the BOXED WARNINGS . If the causative organisms are resistant to gentamicin, other appropriate therapy should be instituted. In serious infections when the causative organisms are unknown, gentamicin injection may be administered as initial therapy in conjunction with a penicillin-type or cephalosporin-type drug before obtaining results of susceptibility testing. If anaerobic organisms are suspected as etiologic agents, consideration should be given to using other suitable antimicrobial therapy in conjunction with gentamicin. Following identification of the organism and its susceptibility, appropriate antibiotic therapy should then be continued. Gentamicin injection has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa. It has also been found effective when used in conjunction with a penicillin-type drug for treatment of endocarditis caused by group D streptococci. Gentamicin injection has also been shown to be effective in the treatment of serious staphylococcal infections. While not the antibiotic of first choice, gentamicin injection may be considered when penicillins or other less potentially toxic drugs are contraindicated and bacterial susceptibility tests and clinical judgment indicate its use. It may also be considered in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms. In the neonate with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug is also usually indicated as concomitant therapy with gentamicin.

DOSAGE AND ADMINISTRATION: Gentamicin injection may be given intramuscularly or intravenously. The patient’s pretreatment body weight should be obtained for calculation of correct dosage. The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass. It is desirable to limit the duration of treatment with aminoglycosides to short term. Patients with Normal Renal Function Adults The recommended dosage of gentamicin injection for patients with serious infections and normal renal function is 3 mg/kg/day, administered in three equal doses every eight hours (Table 3) . For patients with life-threatening infections, dosages up to 5 mg/kg/day may be administered in three or four equal doses. This dosage should be reduced to 3 mg/kg/day as soon as clinically indicated (Table 3) . It is desirable to measure both peak and trough serum concentrations of gentamicin to determine the adequacy and safety of the dosage. When such measurements are feasible, they should be carried out periodically during therapy to assure adequate but not excessive drug levels. For example, the peak concentration (at 30 to 60 minutes after intramuscular injection) is expected to be in the range of 4 to 6 mcg/mL. When monitoring peak concentrations after intramuscular or intravenous administration, dosage should be adjusted so that prolonged levels above 12 mcg/mL are avoided. When monitoring trough concentrations (just prior to the next dose), dosage should be adjusted so that levels above 2 mcg/mL are avoided. Determination of the adequacy of a serum level for a particular patient must take into consideration the susceptibility of the causative organism, the severity of the infection and the status of the patient’s host-defense mechanisms. In patients with extensive burns, altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides. In such patients treated with gentamicin, measurement of serum concentrations is recommended as a basis for dosage adjustment. Table 3 Dosage Schedule Guide for Adults with Normal Renal Function (Dosage at Eight-Hour Intervals) 40 mg per mL Patient’s Weight* kg (lb) Usual Dose for Serious Infections 1 mg/kg q8h (3 mg/kg/day) Dose for Life-Threatening Infections (Reduce As Soon As Clinically Indicated) 1.7 mg/kg q8h** (5 mg/kg/day) mg/dose mL/dose mg/dose mL/dose q8h q8h 40 (88) 40 1 66 1.6 45 (99) 45 1.1 75 1.9 50 (110) 50 1.25 83 2.1 55 (121) 55 1.4 91 2.25 60 (132) 60 1.5 100 2.5 65 (143) 65 1.6 108 2.7 70 (154) 70 1.75 116 2.9 75 (165) 75 1.9 125 3.1 80 (176) 80 2 133 3.3 85 (187) 85 2.1 141 3.5 90 (198) 90 2.25 150 3.75 95 (209) 95 2.4 158 4 100 (220) 100 2.5 166 4.2 * The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass. ** for q6h schedules, dosage should be recalculated. Children 6 to 7.5 mg/kg/day (2 to 2.5 mg/kg administered every eight hours). Infants and Neonates 7.5 mg/kg/day (2.5 mg/kg administered every eight hours). Premature or Full-Term Neonates One Week of Age or Less 5 mg/kg/day (2.5 mg/kg administered every 12 hours). For further information concerning the use of gentamicin in infants and children, see gentamicin injection (pediatric) product information. The usual duration of treatment for all patients is 7 to 10 days. In difficult and complicated infections, a longer course of therapy may be necessary. In such cases monitoring of renal, auditory and vestibular functions is recommended, since toxicity is more apt to occur with treatment extended for more than 10 days. Dosage should be reduced if clinically indicated. For Intravenous Administration The intravenous administration of gentamicin may be particularly useful for treating patients with bacterial septicemia or those in shock. It may also be the preferred route of administration for some patients with congestive heart failure, hematologic disorders, severe burns or those with reduced muscle mass. For intermittent intravenous administration in …

CONTRAINDICATIONS: Hypersensitivity to gentamicin is a contraindication to its use. A history of hypersensitivity or serious toxic reactions to other aminoglycosides may contraindicate use of gentamicin because of the known cross-sensitivity of patients to drugs in this class.

ADVERSE REACTIONS: To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Nephrotoxicity Adverse renal effects, as demonstrated by the presence of casts, cells or protein in the urine or by rising BUN, NPN, serum creatinine or oliguria, have been reported. They occur more frequently in patients with a history of renal impairment (especially if dialysis is required) and in patients treated for longer periods or with larger doses than recommended. Neurotoxicity Serious adverse effects on both vestibular and auditory branches of the eighth nerve have been reported, primarily in patients with renal impairment (especially if hemodialysis is required) and in patients on high doses and/or prolonged therapy. Symptoms include dizziness, vertigo, tinnitus, roaring in the ears and also hearing loss, which, as with the other aminoglycosides, may be irreversible. Hearing loss is usually manifested initially by diminution of high-tone acuity. Other factors which may increase the risk of toxicity include excessive dosage, dehydration and previous exposure to other ototoxic drugs. Peripheral neuropathy or encephalopathy, including numbness, skin tingling, muscle twitching, convulsions and a myasthenia gravis-like syndrome have been reported. NOTE: The risk of toxic reactions is low in patients with normal renal function who did not receive gentamicin sulfate at higher doses or for longer periods of time than recommended. Other reported adverse reactions possibly related to gentamicin include: respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight loss and hypotension and hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever and headache; nausea, vomiting, increased salivation and stomatitis; purpura, pseudotumor cerebri, acute organic brain syndrome, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly and splenomegaly. Laboratory abnormalities possibly related to gentamicin include: increased levels of serum transaminase (SGOT, SGPT), serum LDH and bilirubin; decreased serum calcium, magnesium, sodium and potassium; anemia, leukopenia, granulocytopenia, transient agranulocytosis, eosinophilia, increased and decreased reticulocyte counts and thrombocytopenia. While clinical laboratory test abnormalities may be isolated findings, they may also be associated with clinically related signs and symptoms. For example, tetany and muscle weakness may be associated with hypomagnesemia, hypocalcemia and hypokalemia. While the local tolerance of gentamicin sulfate is generally excellent, there has been an occasional report of pain at the injection site. Subcutaneous atrophy or fat necrosis suggesting local irritation has been reported rarely.

Nephrotoxicity Adverse renal effects, as demonstrated by the presence of casts, cells or protein in the urine or by rising BUN, NPN, serum creatinine or oliguria, have been reported. They occur more frequently in patients with a history of renal impairment (especially if dialysis is required) and in patients treated for longer periods or with larger doses than recommended.

Neurotoxicity Serious adverse effects on both vestibular and auditory branches of the eighth nerve have been reported, primarily in patients with renal impairment (especially if hemodialysis is required) and in patients on high doses and/or prolonged therapy. Symptoms include dizziness, vertigo, tinnitus, roaring in the ears and also hearing loss, which, as with the other aminoglycosides, may be irreversible. Hearing loss is usually manifested initially by diminution of high-tone acuity. Other factors which may increase the risk of toxicity include excessive dosage, dehydration and previous exposure to other ototoxic drugs. Peripheral neuropathy or encephalopathy, including numbness, skin tingling, muscle twitching, convulsions and a myasthenia gr …

Mechanism of Action Gentamicin, an aminoglycoside, binds to the prokaryotic ribosome, inhibiting protein synthesis in susceptible bacteria. It is bactericidal in vitro against Gram-positive and Gram-negative bacteria.

DESCRIPTION Gentamicin sulfate, a water-soluble antibiotic of the aminoglycoside group, is derived by the growth of Micromonospora purpurea , an actinomycete. It has the following structural formula. Structural Formula Gentamicin Injection, USP is a sterile, nonpyrogenic aqueous solution for parenteral administration. Each mL contains: Gentamicin sulfate equivalent to 40 mg gentamicin, methylparaben 1.8 mg and propylparaben 0.2 mg as preservatives, sodium metabisulfite 3.2 mg and edetate disodium 0.1 mg, Water for Injection q.s. Sodium hydroxide and/or sulfuric acid may have been added for pH adjustment. Structural Formula

OVERDOSAGE: In the event of overdose or toxic reactions, hemodialysis may aid in the removal of gentamicin from the blood, and is especially important if renal function is, or becomes, compromised. The rate of removal of gentamicin is considerably less by peritoneal dialysis than it is by hemodialysis. In the newborn infant, exchange transfusions may also be considered.

HOW SUPPLIED: Gentamicin Injection, USP, containing gentamicin 40 mg per mL is supplied as follows: Product Code Unit of Sale Strength Each PRX1002 NDC 63323-010-94 Unit of 25 80 mg per 2 mL (40 mg per mL) NDC 63323-010-41 2 mL Multiple Dose Vial PRX1020 NDC 63323-010-95 Unit of 25 800 mg per 20 mL (40 mg per mL) NDC 63323-010-42 20 mL Multiple Dose Vial Also available, Gentamicin Injection (Pediatric), 20 mg per 2 mL (10 mg per mL), supplied in 2 mL (20 mg) vials in packages of 25. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. The container closure is not made with natural rubber latex. PREMIERProRx ® is a registered trademark of Premier Healthcare Alliance, L.P., used under license. Manufactured by: Fresenius Kabi Lake Zurich, IL 60047 www.fresenius-kabi.com/us 451333C Revised: October 2023 PremierProRx Logo