GARAMYCIN INJECTION I.M/I.V. Schering-Plough

Transcription

1 GARAMYCIN INJECTION I.M/I.V. Schering-Plough Composition Each ml contains gentamicin sulfate equivalent to 40 mg gentamicin base. Properties Contains the aminoglycoside antibiotic gentamicin sulfate with broad spectrum bactericidal properties; for intramuscular (IM), intravenous (IV.), subconjunctival or subtenon injection, nebulization or direct endotracheal instillation. Indications For the treatment of infections caused by susceptible microorganisms. Effective in the treatment of septicemia and bacteremia including neonatal sepsis; serious infections of the central nervous system (CNS) including meningitis; infections of the kidney, pelvis, genitourinary tract, respiratory tract and gastrointestinal tract; skin, bone and soft tissue infections including infected burns and wounds; intraabdominal infections including peritonitis; ocular infections. As initial therapy in suspected or confirmed Gram negative infections. In serious infections, when the causative microorganisms are unknown, may be administered as initial therapy in conjunction with suitable antimicrobial therapy. Has been used effectively in combination with carbenicillin or ticarcillin for the treatment of life threatening infections caused by Pseudomonas aeruginosa and in conjunction with a penicillin type drug for the treatment of endocarditis caused by group D streptococci. In the neonate with suspected sepsis or staphylococcal pneumonia, a penicillin type drug usually is indicated as concomitant therapy with gentamicin. Also shown to be effective in the treatment of serious staphylococcal infections. In the peri operative period, may be started pre operatively and continued postoperatively for treatment of suspected or proven infection due to susceptible microorganisms. Subconjunctival administration is recommended for treatment of endophthalmitis caused by sensitive microorganisms. May be used prophylactically in patients undergoing high risk intra ocular surgery, especially if pro operative cultures or smears contain Gram negative microorganisms. May be administered by direct endotracheal instillation or nebulization, as an adjunct to systemic therapy in the treatment of serious pulmonary infections, and intrathecally, as an adjunct to systemic therapy in the treatment of CNS infections caused by Susceptible Gram negative microorganisms. Contraindications Hypersensitivity or serious toxic reactions to gentamicin or other aminoglycosides. Side Effects Nephrotoxicity Occur more frequently in patients with a history of renal impairment and in those treated for long periods or with larger than recommended doses. Neurotoxicity Side effects on both vestibular and auditory branches of the eighth cranial nerve have been reported primarily in patients with renal impairment and in patients on high doses and/or prolonged therapy; symptoms include dizziness, vertigo, tinnitus, roaring in the ears and hearing loss. Hearing loss is usually manifested initially by diminution of high-tone acuity and may be irreversible. As with other aminoglycosides, vestibular abnormalities also may be irreversible. Other factors that may increase risk of aminoglycoside induced ototoxicity; dehydration, concomitant administration of ethacrynic acid or furosemide or previous exposure to other ototoxic drugs. Numbness, skin tingling, muscle twitching, convulsions and myasthenia gravis like syndrome also have been reported. Other adverse reactions; respiratory depression, visual disturbances, decreased appetite, weight loss, hypotension, hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever, head

2 ache; nausea, vomiting, increased salivation, stomatitis; purpura, pseudotumor cerebri, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly, splenomegaly; occasional pain at the injection site and rarely, subcutaneous atrophy or fat necrosis. Laboratory abnormalities possibly related to gentamicin include increased serum transaminase (SGOT, SGPT), increased serum LDH and bilirubin, decreased serum calcium, sodium and potassium; anemia, leukopenia, granulocytopenia, transient agranulocytosis, increased and decreased reticulocyte counts and thrombocytopenia. Storage Store between 2º and 30ºC. Precautions Patients treated with aminoglycosides should be under close clinical observation. Monitor renal and eighth cranial nerve function during therapy particularly in patients with known or suspected reduced renal function. Urinalysis results and blood urea nitrogen (BUN), serum creatinine or creatinine clearance should be determined periodically; evidence of oto or nephro toxicity requires dosage adjustment or discontinuance of therapy. To assure adequate levels and to avoid potentially toxic levels, aminoglycoside serum concentrations should be monitored; avoid prolonged peak serum levels >12 µg/mi and trough concentrations >2 µg/mi. Reduced aminoglycoside serum concentrations may occur in patients with extensive burns; measurement of serum levels is recommended as a basis for dosage adjustment in such patients. Avoid concurrent and/or sequential systemic or topical use of other potentially neuro and/or nephrotoxic drugs (such as cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin and viomycin). Avoid concurrent use with potent diuretics (such as ethacrynic acid or furosemide) as certain diuretics by themselves may cause ototoxicity. Risk of toxicity is enhanced by dehydration, advanced age and intravenous administration of diuretics. Antibiotics administered by local irrigation or application may have potentially toxic effects. Concurrent administration with some cephalosporins may increase incidence of nephrotoxicity. Neuromuscular blockade and respiratory paralysis have been reported in cats receiving high doses; consider this possibility if gentamicin is administered to patients receiving neuromuscular blocking agents, anesthetics or massive transfusions of citrate anticoagulated blood; if blockade occurs, calcium salts may reverse these phenomena. Use with caution in patients with neuromuscular disorders (such as myasthenia gravis, parkinsonism or infant botulism). In elderly patients, reduced renal function may not be evident in results of BUN or serum creatinine tests and creatinine clearance determinations may be more useful; monitoring of renal function in such patients is particularly important. A Fanconi like syndrome with aminoaciduria and metabolic acidosis has been reported in some adults and infants treated with gentamicin. Cross allergenicity among aminoglycosides has been demonstrated. Patients should be well hydrated during therapy. In vitro mixing of an aminoglycoside with beta lactam type antibiotics (penicillins or cephalosporins) may result in significant mutual inactivation. When an aminoglycoside and a penicillin type drug are administered separately by different routes, reduction in aminoglycoside serum half life or serum levels has been reported in patients with impaired renal function and in some patients with normal renal function. A reduction in gentamicin serum halt life has been reported in patients with severe renal impairment who received carbenicillin concomitantly with gentamicin. Such inactivation of the aminoglycoside is clinically significant only in patients with severely impaired renal function. Reduction in gentamicin serum half life has been reported in patients with severe renal impairment receiving carbenicillin concomitantly. Overgrowth of non susceptible microorganisms may occur; should superinfection develop, institute appropriate antimicrobial therapy. When administered by direct endotracheal instilla

3 tion in conjunction with systemic aminoglycoside therapy, consider the possibility of enhanced serum levels. This product contains sodium bisulfite, a sulfite that may cause allergic type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in susceptible people. Because of the potential for serious adverse reactions from aminoglycosides in nursing infants, discontinue nursing or therapy, taking into account the importance of drug to mother. Safety in pregnancy has not been established. In the event of overdose or toxic reactions, hemodialysis will aid in the removal of gentamicin from the blood. Dosage and Administration Recommended dosage for IM. and IV. administration is identical. Do not physically premix with other drugs. In combination with other antibiotics, dosage of Garamycin Injection must not be reduced. Measure peak and trough gentamicin serum concentrations, it possible, to assure adequate but not excessive levels. Peak concentration is expected to be in the range of 4 to 6 µg/mi; avoid trough levels >2 µg/mi. Determination of the adequacy of a serum level for a particular patient must take into consideration susceptibility of the causative microorganism, severity of infection and status of patient s host-defence mechanisms. Usual duration of treatment is seven to ten days. In complicated infections requiring longer courses of therapy, dosage should be reduced if clinically indicated and monitoring of renal, auditory and vestibular functions is recommended. IM. Administration: Adult patients with normal renal function recommended dosage for serious infections is 3 mg/kg/day in three equal doses every eight hours or two equal doses every 12 hours. A simplified dosing for adults weighing over 60 kg is 80 mg three times daily; for adults 60 kg or less, 60 mg three times daily. For life threatening infections, dosages up to 5 mg/kg/day may be administered in three or four equal doses; reduce to 3 mg/kg/day as soon as clinically indicated. For moderate sys temic or urinary tract infections (UTI), 2 mg/kg/ day may be administered in two equal doses; increase to 3 mg/kg/day in three equal doses if prompt clinical response is not apparent. For chronic or recurrent UTI, a dose of 160 mg may be administered once a day for seven to ten days; if body weight is less than 50 kg, single daily dose should be 3 mg/kg body weight. Pediatric patients with normal renal function Premature or full term neonates one week of age or less: 5 to 6 mg/kg/day (2.5 to 3 mg/kg every 12 hours). Neonates over one week of age and infants: 7.5 mg/kg/day (2.5 mg/kg every 8 hours). Children: 6 to 7.5 mg/kg/ day (2 to 2.5 mg/kg every 8 hours). A Garamycin Pediatric Injection formulation is available. Patients with impaired renal function dosage must be adjusted. Whenever possible, monitor gentamicin serum concentrations. Dosage schedules are not intended as rigid recommendations but are provided as guides to dosage adjustments when measurement of gentamicin serum concentrations is not feasible. One method of dosage adjustment is to increase the interval between administration of usual doses. Since serum creatinine concentration has a high correlation with serum half-life of gentamicin, this laboratory test may provide guidance for adjustment of the interval between doses. Interval between doses (in hours) may be approximated by multiplying the serum creatinine level (mg/100 ml) by 8. With serious systemic infections, it may be desirable to administer gentamicin more frequently but in reduced dosage in which case gentamicin serum concentrations should be measured. After the usual initial dose, however, a rough guide for determining reduced dose at eight hour intervals is to divide the normally recommended dose by the serum creatinine level. Note that the status of renal function may be changing over the course of the infectious process. In adults with renal failure undergoing hemodialysis, amount of gentamicin removed from the blood may vary depending upon several factors including the dialysis method used. A six-hour

4 hemodialysis may reduce gentamicin serum concentrations by approximately 50%. Shorter dialysis sessions will remove less drug. Recommended dosage at the end of each dialysis period is 1 to 1.7 mg/kg depending upon the severity of infection; 2 to 2.5 mg/kg may be administered to children. I.V Administration: Is useful for patients with septicemia, those in shock and some patients with congestive heart failure, hematologic disorders, severe burns or reduced muscle mass. For adults, a single dose of Garamycin Injection, may be diluted in 50 to 200 ml of sterile normal saline solution or sterile 5% dextrose in water (use less diluent in infants and children). Infuse over a period of one half to two hours. In certain circumstances, a single dose may be given directly into a vein or IV. tubing slowly over a period of 2 to 3 minutes. Subconjunctival and Subtenon Administration: Should be given only by those experienced in such administration. Usual dose ranges from 10 to 20 mg depending upon severity of infection. After instilling topical anesthetic, inject under aseptic conditions using a tuberculin syringe with a gauge needle. Repeat after 24 hours if necessary. Inhalation Therapy: Usual dose is 20 to 40 mg given by direct endotracheal instillation or nebulization every 8 to 12 hours diluted with physiologic saline to a volume of about 2 ml. Specific Dosage Regimens: Gonorrhea in males and females a single IM. dose ranging from 240 to 280 mg for treatment of gonococcal urethritis (including infections due to strains resistant to penicillin and other antibiotics) in the male and gonococcal infections involving the lower genital tract in the female. If Garamycin Injection, 40 mg/ml is used, one-half of the dose should be injected into each buttock. For convenience, Garamycin Injection, 280 mg/2 ml is available, UTI (recurrent or chronic) A single daily dose of 160 mg administered IM. for 7 to 10 days. Garamycin Injection, 160 mg/2 ml. is available. In adults weighing less than 50 kg, a single dose of 3 mg/kg body weight should be administered daily.

5 GARAMYCIN PEDIATRIC INJECTION I.M./I.V. Schering-Plough Composition Each ml contains gentamicin sulfate equivalent to 10 mg gentamicin base. Properties Contains the aminoglycoside antibiotic gentamicin sulfate with broad spectrum bactericidal properties; for intra muscular (IM.), intravenous (IV.), subconjunctival or subtenon injection, nebulization or direct endotracheal instillation. Indications For the treatment of infections caused by susceptible microorganisms: Pseudomonas aeruginosa, Proteus sp., (indolepositive and indole negative), Escherichia coli, Klebsiella Enterobacter Serratia sp., Citrobacter sp.. Providencia sp., Staphylococcus sp. (coagulase positive and coagulase negative, including penicillin and methicillin resistant strains) and Neisseria gonorrhoeae. Effective in the treatment of septicemia and bacteremia including neonatal sepsis; serious infections of the central nervous system (CNS) including meningitis; infections of the kidney, pelvis, genitourinary tract, respiratory tract and gastrointestinal tract; skin, bone and soft tissue infections including infected burns and wounds; Intraabdominal infections including peritonitis; ocular infections. As initial therapy in suspected or confirmed Gram negative infections. In serious infections, when causative microorganisms are unknown, may be administered as initial therapy in conjunction with a penicillin or cephalosporin type drug; if anaerobic microorganisms are suspected, use in conjunction with suitable antimicrobial therapy. Has been used effectively in combination with carbenicillin for the treatment of life threatening infections caused by Pseudomonas aeruginosa and in conjunction with a penicillin type drug for the treatment of endocarditis caused by group D streptococci. In the neonate with suspected sepsis or staphy lococcal pneumonia, a penicillin type drug usually is indicated as concomitant therapy with gentamicin. Also shown to be effective in the treatment of serious staphylococcal infections. Subconjunctival administration is recommended for treatment of endophthalmitis caused by sensitive microorganisms. May be used prophylactically in patients undergoing high risk intraocular surgery, especially if preoperative cultures or smears contain Gramnegative microorganisms. May be administered by direct endotracheal instillation or nebulization, as an adjunct to systemic therapy in the treatment of serious pulmonary infections and intrathecally, as an adjunct to systemic therapy in the treatment of serious CNS infections caused by susceptible Gramnegative micro organisms. Contraindications Hypersensitivity or serious toxic reactions to gentamicin or other aminoglycosides. Side Effects Renal Side effects occur more frequently in patients with a history of renal impairment and in those treated for longer periods or with larger than recommended doses. Side effects on both vestibular and auditory branches of the eighth cranial nerve have been reported primarily in patients with renal impairment and in patients on high doses and/or prolonged therapy; symptoms include dizziness, vertigo, tinnitus, roaring in the ears and hearing loss. Hearing loss is usually manifested initially by diminution of high tone acuity; may be irreversible. As with other aminoglycosides, vestibular abnormalities may also be irreversible. Other factors that may increase risk of ototoxicity: dehydration, concomitant administration of ethacrynic acid or furosemide or previous exposure to other ototoxic drugs. Numbness, skin tingling, muscle twitching and convulsions also have been reported. Other Side effects include respiratory depression, lethargy, confusion, depression,

6 visual disturbances, decreased appetite, weight loss, hypotension, hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever, headache; nausea, vomiting, increased salivation, stomatitis; purpura, pseudotumor cerebri, pulmonary fibrosis, alopecia, mint pain, transient hepatomegaly, splenomegaly; occasional pain at injection site and rarely, subcutaneous atrophy or fat necrosis. Laboratory abnormalities possibly related to gentamicin include increased serum transaminase (SCOT, SGPT), increased serum lactic dehydrogenase (LDH) and bilirubin; decreased serum calcium, sodium and potassium; anemia, leukopenia, granulocytopenia, transient agranulocytosis, increased and decreased reticulocyte counts and thrombocytopenia. Precautions Clinically observe patients treated with aminoglycosides closely. Monitor renal and eighth cranial nerve function during therapy, particularly in patients with known or suspected reduced renal function. Urinalysis BUN, serum creatinine or creatinine clearance should be determined periodically; evidence of oto or nephrotoxicity requires dosage adjustment or discontinuance of therapy. To assure adequate levels and avoid potentially toxic levels, aminoglycoside serum concentrations should be monitored; avoid prolonged peak serum levels above 12 µg/mi and trough concentrations above 2 µg/mi. Reduced aminoglycoside serum concentrations may occur in patients with extensive burns; measurement of serum levels is recommended as a basis for dosage adjustment in such patients. Avoid concurrent and/or sequential systemic or topical use of other potentially neuro and/or nephrotoxic drugs (such as cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin and viomycin). Avoid concurrent use with potent diuretics (such as ethacrynic acid or furosemide) as certain diuretics by themselves may cause ototoxicity. Risk of toxicity is enhanced by dehydration, advanced age and intravenous administration of diuretics. Antibiotics administered by local irrigation or application may have potentially toxic effects. Concurrent administration with some cephalosporins may increase incidence of nephrotoxicity. Neuromuscular blockade and respiratory paralysis have been reported in cats receiving high doses; consider this possibility if gentamicin is administered to patients receiving neuromuscular blocking agents, anesthetics or massive transfusions of citrate anticoagulated blood, if blockade occurs, calcium salts may reverse these phenomena. Use with caution in patients with neuromuscular disorders (such as myasthenia gravis or parkinsonism). Use aminoglycosides with caution in patients with neuromuscular disorders since these drugs theoretically may aggravate muscle weakness because of their potential curare like effects on the neuromuscular function. A Fanconi like syndrome with amino aciduria and metabolic acidosis has been reported in some adults and infants treated with gentamicin. Cross allergenicity among aminoglycosides has been demonstrated. Patients should be well hydrated during therapy. In vitro mixing of an aminoglycoside with beta lactam type antibiotics (penicillins or cephalosporins) may result in significant mutual inactivation. When an aminoglycoside and a penicillin type drug are administered separately by different routes, reduction in aminoglycoside serum half life or serum levels has been reported in patients with impaired renal function and in some patients with normal renal function. Reduction in gentamicin serum half life has been reported in patients with severe renal impairment who received carbenicillin concomitantly with gentamicin. Such inactivation of the aminoglycoside is clinically significant only in patients with severely impaired renal function. Overgrowth of nonsusceptible microorganisms may occur; should superinfection develop, institute appropriate antimicrobial therapy. When administered by direct endotracheal instillation in conjunction with systemic aminoglycoside therapy, consider possi

7 bility of enhanced serum levels. This drug contains sodium bisulfite, a sulfite that may cause allergic type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in susceptible people. In the event of overdose or toxic reactions, hemodialysis will aid in the removal of gentamicin from the blood. Storage Store between 2º and 30ºC. Dosage and Administration Recommended dosage for IM, and IV. administration is identical. Obtain pre treatment body weight for calculation of correct dosage. Do not physically premix with other drugs. In combination with other antibiotics, dosage of Garamycin Pediatric Injection must not be reduced. Measure peak and trough gentamicin serum concentrations, if possible, to assure adequate, but not excessive levels. Peak concentration is expected to be in the range of 4 to 6 µg/ml; trough levels above 2 µg/ml should be avoided. Determination of the adequacy of a serum level for a particular patient must take into consideration susceptibility of the causative microorganism, severity of infection and status of patient s host-defence mechanisms. Usual duration of treatment is seven to ten days. In complicated infections requiring longer course of therapy, dosage should be reduced if clinically indicated and monitoring of renal, auditory and vestibular functions is recommended. I.M. Administration: Patients with normal renal function Premature or full term neonates one week of age or less: 5 to 6 mg/kg/day (2.5 to 3 mg/kg every 12 hours). Neonates over one week of age and infants: 7.5 mg/kg/day (2.5 mg/kg every 8 hours), Children: 6 to 7.5 mg/kg/ day (2 to 2.5 mg/kg every 8 hours). Patients with impaired renal function dosage must be adjusted. Whenever possible, monitor gentamicin serum concentrations. Dosage schedules are not intended as rigid recommendations but are provided as guides to dosage adjustments when mea surement of gentamicin serum concentrations is not feasible. One method of dosage adjustment is to increase the interval between administration of usual doses. Since serum creatinine concentration has a high correlation with gentamicin serum half life, this laboratory test may provide guidance for adjustment of the interval between doses. In infants and children with serious renal impairment, interval between doses (in hours) may be approximated by multiplying serum creatinine level (mg/100 ml) by 8. With serious systemic infections and renal impairment, it may be desirable to administer gentamicin more frequently but in reduced dosage in which case gentamicin serum concentrations should be measured. After usual initial dose, a rough guide for determining reduced dose at eight hour intervals is to divide the normally recommended dose by the serum creatinine level. Status of renal function may change over the course of the infectious process. In patients with renal failure undergoing hemodialysis, amount of gentamicin removed from the blood may vary depending upon several factors including dialysis method used. A six hour hemodialysis may reduce gentamicin serum concentrations by approximately 50%. Shorter dialysis sessions will remove less drug. Recommended dosage at the end of each dialysis period is 2 to 2.5 mg/kg. I.V Administration: Is useful for patients with septicemia, those in shock and some patients with congestive heart failure, hematologic disorders, severe burns or reduced muscle mass. A single dose of Garamycin Pediatric Injection may be diluted in sterile normal saline solution or sterile 5º dextrose in water. Infuse solution over a period of one halt to two hours. In certain circumstances, a single dose may be given directly into a vein or IV. tubing slowly over a period of 2 to 3 minutes. Subconjunctival and Sub Tenon Administration: Should be given only by those experienced in such administration. Usual dose ranges from 10 to 20 mg depending upon

8 severity of infection. Garamycin Injection, 40 mg/ml, should be used because of the volume required to administer these doses. After instilling topical anesthetic, inject under aseptic conditions using a tuberculin syringe with a gauge needle. Repeat after 24 hours if necessary. Inhalation Therapy: Usual dose is mg given by direct endotracheal instillation or nebulization every 8 to 12 hours diluted with physiologic saline to a volume of 2 ml.