Great resource for drug information, reviews and discussions
Amikin (Amikacin Sulfate)
How do you rate this drug's effectiveness?
Pharmacology
Amikacin is a semi-synthetic aminoglycoside antibiotic which exhibits activity primarily against gram-negative organisms, including Pseudomonas. It is a bactericidal antibiotic affecting bacterial growth by specific inhibition of protein synthesis in susceptible bacteria.
Pharmacokinetics: Amikacin is readily available and rapidly absorbed via the i.v. and i.m. routes of administration. The mean serum half-life is 2.2hours with a mean renal clearance rate of 1.24mL/kg/min. No accumulation is associated with dosing at 12hour intervals in individuals with a normal renal function.
In 36 neonates, after i.m. or i.v. administration of 7.5mg/kg every 12hours, the mean serum half-life is 5.4±2.0hours and the mean peak serum level is 17.7±5.4µg/mL. No accumulation has been observed for a dosing period of 10to 14days. After an i.m. dose of 7.5mg/kg to 8neonates, the mean peak serum level was reached at 32minutes.
Amikacin is not metabolized, small amounts (1 to 2% of the dose) are excreted in the bile, while the remainder 98to 99% is excreted in the urine via glomerular filtration. The mean human serum protein binding is 11% over a concentration range of 5to 50µg/mL of serum. The volume of distribution of amikacin is 25to 30% of body weight. Amikacin pharmacokinetics remain linear over the entire dosage range studied (0.5µg/kg to 9mg/kg).
Tolerance studies in normal volunteers revealed amikacin to be well tolerated locally following repeated i.m. dosing. When givenmaximally recommended doses, no ototoxicity or nephrotoxicity was reported. There is no evidence of drug accumulation with repeated dosing for 10days when administered according to recommended doses.
A dose of 7.5mg/kg was administered to healthy women prior to therapeutic abortion and sterilization by hysterectomy. Amikacin reached a peak concentration of 8µg/g in the fetal lung and 16.8µg/g in the fetal kidney. No antibiotic activity was found in the fetal liver.
Amikacin is a semi-synthetic aminoglycoside antibiotic which exhibits activity primarily against gram-negative organisms, including Pseudomonas. It is a bactericidal antibiotic affecting bacterial growth by specific inhibition of protein synthesis in susceptible bacteria.
Pharmacokinetics: Amikacin is readily available and rapidly absorbed via the i.v. and i.m. routes of administration. The mean serum half-life is 2.2hours with a mean renal clearance rate of 1.24mL/kg/min. No accumulation is associated with dosing at 12hour intervals in individuals with a normal renal function.
In 36 neonates, after i.m. or i.v. administration of 7.5mg/kg every 12hours, the mean serum half-life is 5.4±2.0hours and the mean peak serum level is 17.7±5.4µg/mL. No accumulation has been observed for a dosing period of 10to 14days. After an i.m. dose of 7.5mg/kg to 8neonates, the mean peak serum level was reached at 32minutes.
Amikacin is not metabolized, small amounts (1 to 2% of the dose) are excreted in the bile, while the remainder 98to 99% is excreted in the urine via glomerular filtration. The mean human serum protein binding is 11% over a concentration range of 5to 50µg/mL of serum. The volume of distribution of amikacin is 25to 30% of body weight. Amikacin pharmacokinetics remain linear over the entire dosage range studied (0.5µg/kg to 9mg/kg).
Tolerance studies in normal volunteers revealed amikacin to be well tolerated locally following repeated i.m. dosing. When givenmaximally recommended doses, no ototoxicity or nephrotoxicity was reported. There is no evidence of drug accumulation with repeated dosing for 10days when administered according to recommended doses.
A dose of 7.5mg/kg was administered to healthy women prior to therapeutic abortion and sterilization by hysterectomy. Amikacin reached a peak concentration of 8µg/g in the fetal lung and 16.8µg/g in the fetal kidney. No antibiotic activity was found in the fetal liver.
Indications
Amikacin Is A Semi-synthetic Aminoglycoside Antibiotic Which Exhibits Activity Primarily Against Gram-negative Organisms, Including Pseudomonas. It Is A Bactericidal Antibiotic Affecting Bacterial Growth By Specific Inhibition Of Protein Synthesis In Susceptible Bacteria.
Pharmacokinetics: Amikacin Is Readily Available And Rapidly Absorbed Via The I.v. And I.m. Routes Of Administration. The Mean Serum Half-life Is 2.2hours With A Mean Renal Clearance Rate Of 1.24mL/kg/min. No Accumulation Is Associated With Dosing At 12hour Intervals In Individuals With A Normal Renal Function.
In 36 Neonates, After I.m. Or I.v. Administration Of 7.5mg/kg Every 12hours, The Mean Serum Half-life Is 5.4±2.0hours And The Mean Peak Serum Level Is 17.7±5.4µg/mL. No Accumulation Has Been Observed For A Dosing Period Of 10to 14days. After An I.m. Dose Of 7.5mg/kg To 8neonates, The Mean Peak Serum Level Was Reached At 32minutes.
Amikacin Is Not Metabolized, Small Amounts (1 To 2% Of The Dose) Are Excreted In The Bile, While The Remainder 98to 99% Is Excreted In The Urine Via Glomerular Filtration. The Mean Human Serum Protein Binding Is 11% Over A Concentration Range Of 5to 50µg/mL Of Serum. The Volume Of Distribution Of Amikacin Is 25to 30% Of Body Weight. Amikacin Pharmacokinetics Remain Linear Over The Entire Dosage Range Studied (0.5µg/kg To 9mg/kg).
Tolerance Studies In Normal Volunteers Revealed Amikacin To Be Well Tolerated Locally Following Repeated I.m. Dosing. When Givenmaximally Recommended Doses, No Ototoxicity Or Nephrotoxicity Was Reported. There Is No Evidence Of Drug Accumulation With Repeated Dosing For 10days When Administered According To Recommended Doses.
A Dose Of 7.5mg/kg Was Administered To Healthy Women Prior To Therapeutic Abortion And Sterilization By Hysterectomy. Amikacin Reached A Peak Concentration Of 8µg/g In The Fetal Lung And 16.8µg/g In The Fetal Kidney. No Antibiotic Activity Was Found In The Fetal Liver.
Amikacin Is A Semi-synthetic Aminoglycoside Antibiotic Which Exhibits Activity Primarily Against Gram-negative Organisms, Including Pseudomonas. It Is A Bactericidal Antibiotic Affecting Bacterial Growth By Specific Inhibition Of Protein Synthesis In Susceptible Bacteria.
Pharmacokinetics: Amikacin Is Readily Available And Rapidly Absorbed Via The I.v. And I.m. Routes Of Administration. The Mean Serum Half-life Is 2.2hours With A Mean Renal Clearance Rate Of 1.24mL/kg/min. No Accumulation Is Associated With Dosing At 12hour Intervals In Individuals With A Normal Renal Function.
In 36 Neonates, After I.m. Or I.v. Administration Of 7.5mg/kg Every 12hours, The Mean Serum Half-life Is 5.4±2.0hours And The Mean Peak Serum Level Is 17.7±5.4µg/mL. No Accumulation Has Been Observed For A Dosing Period Of 10to 14days. After An I.m. Dose Of 7.5mg/kg To 8neonates, The Mean Peak Serum Level Was Reached At 32minutes.
Amikacin Is Not Metabolized, Small Amounts (1 To 2% Of The Dose) Are Excreted In The Bile, While The Remainder 98to 99% Is Excreted In The Urine Via Glomerular Filtration. The Mean Human Serum Protein Binding Is 11% Over A Concentration Range Of 5to 50µg/mL Of Serum. The Volume Of Distribution Of Amikacin Is 25to 30% Of Body Weight. Amikacin Pharmacokinetics Remain Linear Over The Entire Dosage Range Studied (0.5µg/kg To 9mg/kg).
Tolerance Studies In Normal Volunteers Revealed Amikacin To Be Well Tolerated Locally Following Repeated I.m. Dosing. When Givenmaximally Recommended Doses, No Ototoxicity Or Nephrotoxicity Was Reported. There Is No Evidence Of Drug Accumulation With Repeated Dosing For 10days When Administered According To Recommended Doses.
A Dose Of 7.5mg/kg Was Administered To Healthy Women Prior To Therapeutic Abortion And Sterilization By Hysterectomy. Amikacin Reached A Peak Concentration Of 8µg/g In The Fetal Lung And 16.8µg/g In The Fetal Kidney. No Antibiotic Activity Was Found In The Fetal Liver.
Contraindications
In patients with known allergy to amikacin or any component of the formulation. A history of hypersensitivity or serious toxic reactions to aminoglycosides may contraindicate the use of any aminoglycoside because of the known cross-sensitivities of patients to drugs in this class.
In patients with known allergy to amikacin or any component of the formulation. A history of hypersensitivity or serious toxic reactions to aminoglycosides may contraindicate the use of any aminoglycoside because of the known cross-sensitivities of patients to drugs in this class.
Safety Information / Warning
Patients receiving amikin should be under close observation and evaluation because of the potential ototoxicity and nephrotoxicity associated with its use. Safety for treatment periods which are longer than 14days has not been established.
Neurotoxicity, manifested as vestibular and/or bilateral auditory ototoxicity, can occur in patients treated with aminoglycosides. The risk of aminoglycoside-induced ototoxicity is greater in patients with impaired renal function, and in those who receive high doses, or in those whose therapy is prolonged. High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo may occur and may be evidence of vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions. The risk of ototoxicity due to aminoglycosides increases with the degree of exposure to either persistently high peak or high trough serum concentrations. Patients developing cochlear or vestibular damage may not have symptoms during therapy to warn them of developing eighth nerve toxicity, and total or partial irreversible bilateral deafness or disabling vertigo may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.
Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function, and in those who receive high doses, or in those whose therapy is prolonged.
Renal and eighth-cranial nerve function should be closely monitored especially in patients with known or suspected renal impairment at the onset of therapy, and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. Urine should be examined for decreased specific gravity, increased excretion of proteins, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained where feasible in patients old enough to be tested, particularly high risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.
Concurrent and/or sequential systemic, oral, or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericinB, cephaloridine, paromomycin, viomycin, polymyxinB, colistin, vancomycin, or other aminoglycosides should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration.
The concurrent use of amikacin with potent diuretics (ethacrynic acid, or furosemide) should be avoided since diuretics by themselves may cause ototoxicity. In addition, when administered i.v., diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.
Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and following oral use of aminoglycosides. The possibility of respiratory paralysis should be considered if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular blocking agents such as tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood. If neuromuscular blockade occurs, calcium salts may reverse respiratory paralysis, but mechanical respiratory assistance may be necessary.
Amikacin contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is uncommon and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic subjects.
If amikacin is used concurrently with other antibacterial agents to treat mixed or superinfections, it should not be physically mixed. Each agent should be administered separately in accordance with its recommended route of administration and dosage schedule.
Patients receiving amikin should be under close observation and evaluation because of the potential ototoxicity and nephrotoxicity associated with its use. Safety for treatment periods which are longer than 14days has not been established.
Neurotoxicity, manifested as vestibular and/or bilateral auditory ototoxicity, can occur in patients treated with aminoglycosides. The risk of aminoglycoside-induced ototoxicity is greater in patients with impaired renal function, and in those who receive high doses, or in those whose therapy is prolonged. High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo may occur and may be evidence of vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions. The risk of ototoxicity due to aminoglycosides increases with the degree of exposure to either persistently high peak or high trough serum concentrations. Patients developing cochlear or vestibular damage may not have symptoms during therapy to warn them of developing eighth nerve toxicity, and total or partial irreversible bilateral deafness or disabling vertigo may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.
Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function, and in those who receive high doses, or in those whose therapy is prolonged.
Renal and eighth-cranial nerve function should be closely monitored especially in patients with known or suspected renal impairment at the onset of therapy, and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. Urine should be examined for decreased specific gravity, increased excretion of proteins, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained where feasible in patients old enough to be tested, particularly high risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.
Concurrent and/or sequential systemic, oral, or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericinB, cephaloridine, paromomycin, viomycin, polymyxinB, colistin, vancomycin, or other aminoglycosides should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration.
The concurrent use of amikacin with potent diuretics (ethacrynic acid, or furosemide) should be avoided since diuretics by themselves may cause ototoxicity. In addition, when administered i.v., diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.
Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and following oral use of aminoglycosides. The possibility of respiratory paralysis should be considered if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular blocking agents such as tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood. If neuromuscular blockade occurs, calcium salts may reverse respiratory paralysis, but mechanical respiratory assistance may be necessary.
Amikacin contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is uncommon and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic subjects.
If amikacin is used concurrently with other antibacterial agents to treat mixed or superinfections, it should not be physically mixed. Each agent should be administered separately in accordance with its recommended route of administration and dosage schedule.
Precautions
Aminoglycosides are quickly and almost totally absorbed when they are applied topically, except to the urinary bladder, in association with surgical procedures. Irreversible deafness, renal failure and death due to neuromuscular blockade have been reported following irrigation of both small and large surgical fields with an aminoglycoside preparation.
The concurrent or serial use of other ototoxic or nephrotoxic agents should be avoided either systemically or topically because of the potential for additive effects. Increased nephrotoxicity has been reported following concomitant parenteral administration of aminoglycoside antibiotics and cephalosporins. Concomitant cephalosporin use may spuriously elevate creatinine serum level determinations.
Ototoxicity: A pre-treatment audiogram should be performed in patients with renal and pre-existing eighth nerve impairment and an audiogram should be repeated during therapy. When tinnitus or subjective hearing loss occurs in patients, the attending physician should strongly consider discontinuing treatment with amikacin (see Warnings).
Nephrotoxicity: Patients should be well hydrated during treatment and renal function should be assessed by the usual methods prior to starting therapy and daily during the course of treatment. A reduction of dosage (see Dosage) is required if evidence of renal dysfunction occurs such as presence of urinary casts, white or red cells, albuminuria, decreased creatinine clearance, decreased urine specific gravity, increased BUN, serum creatinine, or oliguria. If azotemia increases, or if a progressive decrease in urinary output occurs, treatment should be stopped.
Elderly patients may have reduced renal function which may not be evident in routine screening tests such as BUN or serum creatinine. A creatinine clearance determination may be more useful. Monitoring of renal function in elderly patients during treatment with aminoglycosides is particularly important.
Neurotoxicity: Neuromuscular blockade and muscular paralysis have been demonstrated in laboratory animals given high doses of amikacin. The possibility of neuromuscular blockade and respiratory paralysis should be considered when amikacin is administered concomitantly with anesthetic or neuromuscular blocking drugs. If blockade occurs, calcium salts may reverse this phenomenon.
Aminoglycosides should be used with caution in patients with muscular disorders such as myasthenia gravis or parkinsonism since these drugs may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.
Pregnancy: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta and there have been several reports of total irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. Although serious side effects to the fetus or newborns have not been reported in the treatment of pregnant women with other aminoglycosides, the potential for harm exists. Reproduction studies of amikacin have been performed in rats and mice and revealed no evidence of impaired fertility or harm to the fetus due to amikacin. There are no well controlled studies in pregnant women, but investigational experience does not include any positive evidence of adverse effects to the fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Lactation: It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while a patient is receiving any drug, since many drugs are excreted in human milk.
Children: Aminoglycosides should be used with caution in premature and neonatal infants because of the renal immaturity of these patients and the resulting prolongation of serum half-life of these drugs.
Other: As with other antibiotics, the use of amikacin may result in overgrowth of nonsusceptible organisms. If this occurs, appropriate therapy should be instituted.
In vitro admixture of aminoglycosides with beta-lactam antibiotics (penicillins or cephalosporins) may result in significant mutual inactivation. A reduction in serum activity may also occur when an aminoglycoside or penicillin-type drug is administered in vivo by separate routes. Inactivation of the aminoglycoside is clinically significant only in patients with severely impaired renal function. Inactivation may continue in specimens of body fluids collected for assay, resulting in inaccurate aminoglycoside readings. Such specimens should be properly handled (assayed promptly, frozen, or treated with beta-lactamase).
Aminoglycosides are quickly and almost totally absorbed when they are applied topically, except to the urinary bladder, in association with surgical procedures. Irreversible deafness, renal failure and death due to neuromuscular blockade have been reported following irrigation of both small and large surgical fields with an aminoglycoside preparation.
The concurrent or serial use of other ototoxic or nephrotoxic agents should be avoided either systemically or topically because of the potential for additive effects. Increased nephrotoxicity has been reported following concomitant parenteral administration of aminoglycoside antibiotics and cephalosporins. Concomitant cephalosporin use may spuriously elevate creatinine serum level determinations.
Ototoxicity: A pre-treatment audiogram should be performed in patients with renal and pre-existing eighth nerve impairment and an audiogram should be repeated during therapy. When tinnitus or subjective hearing loss occurs in patients, the attending physician should strongly consider discontinuing treatment with amikacin (see Warnings).
Nephrotoxicity: Patients should be well hydrated during treatment and renal function should be assessed by the usual methods prior to starting therapy and daily during the course of treatment. A reduction of dosage (see Dosage) is required if evidence of renal dysfunction occurs such as presence of urinary casts, white or red cells, albuminuria, decreased creatinine clearance, decreased urine specific gravity, increased BUN, serum creatinine, or oliguria. If azotemia increases, or if a progressive decrease in urinary output occurs, treatment should be stopped.
Elderly patients may have reduced renal function which may not be evident in routine screening tests such as BUN or serum creatinine. A creatinine clearance determination may be more useful. Monitoring of renal function in elderly patients during treatment with aminoglycosides is particularly important.
Neurotoxicity: Neuromuscular blockade and muscular paralysis have been demonstrated in laboratory animals given high doses of amikacin. The possibility of neuromuscular blockade and respiratory paralysis should be considered when amikacin is administered concomitantly with anesthetic or neuromuscular blocking drugs. If blockade occurs, calcium salts may reverse this phenomenon.
Aminoglycosides should be used with caution in patients with muscular disorders such as myasthenia gravis or parkinsonism since these drugs may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.
Pregnancy: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta and there have been several reports of total irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. Although serious side effects to the fetus or newborns have not been reported in the treatment of pregnant women with other aminoglycosides, the potential for harm exists. Reproduction studies of amikacin have been performed in rats and mice and revealed no evidence of impaired fertility or harm to the fetus due to amikacin. There are no well controlled studies in pregnant women, but investigational experience does not include any positive evidence of adverse effects to the fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Lactation: It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while a patient is receiving any drug, since many drugs are excreted in human milk.
Children: Aminoglycosides should be used with caution in premature and neonatal infants because of the renal immaturity of these patients and the resulting prolongation of serum half-life of these drugs.
Other: As with other antibiotics, the use of amikacin may result in overgrowth of nonsusceptible organisms. If this occurs, appropriate therapy should be instituted.
In vitro admixture of aminoglycosides with beta-lactam antibiotics (penicillins or cephalosporins) may result in significant mutual inactivation. A reduction in serum activity may also occur when an aminoglycoside or penicillin-type drug is administered in vivo by separate routes. Inactivation of the aminoglycoside is clinically significant only in patients with severely impaired renal function. Inactivation may continue in specimens of body fluids collected for assay, resulting in inaccurate aminoglycoside readings. Such specimens should be properly handled (assayed promptly, frozen, or treated with beta-lactamase).
Side Effects / Adverse Effects
All aminoglycosides have the potential to induce ototoxicity, renal toxicity and neuromuscular blockade (see Warnings and Precautions). These toxicities occur more frequently in patients with renal impairment, in patients treated with other ototoxic or nephrotoxic drugs, and in patients treated for longer periods and/or with higher doses than recommended.
Nephrotoxicity: renal failure, abnormal urinalysis, including albuminuria, presence of red and white cells and granular casts; azotemia, hemoglobinuria, oliguria, elevated BUN or serum creatinine levels or a decrease in creatinine clearance. In most cases, these changes have been reversible when the drug has been discontinued.
As would be expected with any aminoglycoside, reports of toxic nephropathy and acute renal failure have been received during postmarketing surveillance.
Neurotoxicity/Ototoxicity: Toxic effects on the eighth cranial nerve can result in hearing loss, loss of balance, or both. Amikacin primarily affects auditory function. Cochlear damage includes high frequency deafness and usually occurs before clinical hearing loss can be detected by audiometric testing. Tinnitus, vertigo, dizziness, nystagmus, fullness in ear, staggering, and partial (reversible to irreversible) deafness have been reported, usually associated with higher than recommended dosage. Rapid development of hearing loss may occur in patients with poor kidney function treated concurrently with amikacin and one of the rapidly acting diuretic agents given i.v. These have included ethacrynic acid, furosemide and mannitol.
Neurotoxicity/Neuromuscular Blockage: Acute muscular paralysis and apnea can occur following treatment with aminoglycoside drugs.
Other: The following adverse reactions of the drug have also been observed: skin rash, drug fever, nausea and vomiting, headache, paresthesia, arthralgia, hypomagnesemia, tremor, eosinophilia, anemia, and hypotension. When administered i.m., mild to severe pain at injection sites, as well as localized burning and erythema. Induration and sterile ulcers have been noted on rare occasions. Macular infarction sometimes leading to permanent loss of vision has been reported following intravitreous administration (injection into the eye) of amikacin. The following adverse effects have been observed although it is felt they are not drug-related: hematological changes including decrease in hematocrit and hemoglobin, thrombocytopenia, granulocytopenia/lymphocytosis; hepatic changes, including increased serum bilirubin, serum transaminases (AST, ALT), hepatic enzymes, and alkaline phosphatase; pruritus, upper gastrointestinal bleeding, diarrhea, fatigue, weakness, focal premature nodal and ventricular contractions, vasoconstriction, seizures, Bell's palsy, phlebitis and thrombophlebitis.
All aminoglycosides have the potential to induce ototoxicity, renal toxicity and neuromuscular blockade (see Warnings and Precautions). These toxicities occur more frequently in patients with renal impairment, in patients treated with other ototoxic or nephrotoxic drugs, and in patients treated for longer periods and/or with higher doses than recommended.
Nephrotoxicity: renal failure, abnormal urinalysis, including albuminuria, presence of red and white cells and granular casts; azotemia, hemoglobinuria, oliguria, elevated BUN or serum creatinine levels or a decrease in creatinine clearance. In most cases, these changes have been reversible when the drug has been discontinued.
As would be expected with any aminoglycoside, reports of toxic nephropathy and acute renal failure have been received during postmarketing surveillance.
Neurotoxicity/Ototoxicity: Toxic effects on the eighth cranial nerve can result in hearing loss, loss of balance, or both. Amikacin primarily affects auditory function. Cochlear damage includes high frequency deafness and usually occurs before clinical hearing loss can be detected by audiometric testing. Tinnitus, vertigo, dizziness, nystagmus, fullness in ear, staggering, and partial (reversible to irreversible) deafness have been reported, usually associated with higher than recommended dosage. Rapid development of hearing loss may occur in patients with poor kidney function treated concurrently with amikacin and one of the rapidly acting diuretic agents given i.v. These have included ethacrynic acid, furosemide and mannitol.
Neurotoxicity/Neuromuscular Blockage: Acute muscular paralysis and apnea can occur following treatment with aminoglycoside drugs.
Other: The following adverse reactions of the drug have also been observed: skin rash, drug fever, nausea and vomiting, headache, paresthesia, arthralgia, hypomagnesemia, tremor, eosinophilia, anemia, and hypotension. When administered i.m., mild to severe pain at injection sites, as well as localized burning and erythema. Induration and sterile ulcers have been noted on rare occasions. Macular infarction sometimes leading to permanent loss of vision has been reported following intravitreous administration (injection into the eye) of amikacin. The following adverse effects have been observed although it is felt they are not drug-related: hematological changes including decrease in hematocrit and hemoglobin, thrombocytopenia, granulocytopenia/lymphocytosis; hepatic changes, including increased serum bilirubin, serum transaminases (AST, ALT), hepatic enzymes, and alkaline phosphatase; pruritus, upper gastrointestinal bleeding, diarrhea, fatigue, weakness, focal premature nodal and ventricular contractions, vasoconstriction, seizures, Bell's palsy, phlebitis and thrombophlebitis.
Overdose
Symptoms and Treatment: In the event of overdosage or toxic reactions, peritoneal dialysis or hemodialysis will aid in the removal of amikacin from the blood. Amikacin levels are also reduced during continuous arteriovenous hemofiltration. In the newborn infant, exchange transfusion may also be considered. These procedures are of particular importance in patients with impaired renal function.
Symptoms and Treatment: In the event of overdosage or toxic reactions, peritoneal dialysis or hemodialysis will aid in the removal of amikacin from the blood. Amikacin levels are also reduced during continuous arteriovenous hemofiltration. In the newborn infant, exchange transfusion may also be considered. These procedures are of particular importance in patients with impaired renal function.
Recommended Dosage
A maximum total adult dose of 15g during a course of treatment by all recommended routes of administration should not be exceeded. Treatment should not exceed 1.5g/day and should not be administered for longer than 10days. In the unusual circumstance, where treatment beyond 10days or a dose larger than 1.5g daily or 15g total is considered, the use of amikacin should be reevaluated. If administration of amikacin is prolonged, renal and auditory functions, and serum amikacin levels should be monitored daily.
Whenever possible, amikacin concentrations in serum should be measured to assure adequate, but not excessive levels. It is desirable to measure both peak and trough serum concentrations intermittently during therapy. Peak concentrations (30to 90minutes after injection) above 35µg/mL and trough concentrations (just prior to the next dose) above 10µg/mL should be avoided. Dosage should be adjusted as indicated.
At the recommended dosage level, uncomplicated infections due to amikacin-sensitive organisms should respond in 24 to 48 hours. If definite clinical response does not occur within 3 to 5 days, therapy should be stopped and the antibiotic susceptibility pattern of the invading organism should be rechecked. Failure of the infection to respond may be due to resistance of the organism or to the presence of septic foci requiring surgical drainage.
Administration in Patients with Impaired Renal Function: In patients with impaired renal function, it is necessary to prolong the interval between doses.
One suggested method for estimating dosage in patients with known or suspected diminished renal function is to multiply the serum creatinine concentration level (mg/100 mL) by 9and to use the resulting figure as the interval (in hours) between doses (see below); e.g.: if the creatinine concentration is 2.0mg/100mL, the recommended dose (7.5mg/kg) should be administered every 18hours. It should be emphasized that since renal function may alter appreciably during therapy, the serum creatinine should be checked frequently. Changes in the concentration would, of course, necessitate changes in the dosage frequency.
The dosage interval may be calculated by the following formula: serum creatinine (mg/100mL)´9=dosage interval (in hours).
If there is evidence of progressive renal dysfunction during therapy, discontinuation of the drug should be considered.
These dosage schedules must be used in conjunction with careful clinical and laboratory observations of the patient and should be modified as necessary, including modification when dialysis is being performed.
Infants and Neonates: In order to insure adequate therapeutic concentrations, which may be critical, while at the same time avoiding potentially toxic concentrations, serum concentrations should be monitored.
Dosage in Adults, Children and Neonates: The patient's pretreatment body weight should be obtained for calculation of correct dosage.
I.M. Route: The recommended daily dose is 15mg/kg to be administered at 7.5mg/kg every 12hours (500mg twice a day).
I.V. Administration: The recommended daily dose is 15mg/kg to be administered at 7.5mg/kg every 12hours (500mg twice a day). The solution for i.v. use is prepared by adding the contents of 500mg/2mL vial to 250mL of sterile diluent and is administered over a 30to 60minute period. Solutions for i.v. administration should be used within 12 hours after preparation.
Stability and Compatibility: Amikin is supplied as a colorless solution which requires no refrigeration. At times the solution becomes a pale yellow; however, this does not indicate a loss of potency. Dark colored solutions should be discarded.
If amikacin is used concurrently with other antibacterial agents to treat mixed or superinfections, it should not be physically mixed. Each agent should be administered separately in accordance with its recommended route of administration and dosage schedule.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit.
Because of the potential toxicity of aminoglycosides, “fixed dosage” recommendations which are not based upon body weight are not advised. Rather, it is essential to calculate the dosage to fit the needs of each patient.
A maximum total adult dose of 15g during a course of treatment by all recommended routes of administration should not be exceeded. Treatment should not exceed 1.5g/day and should not be administered for longer than 10days. In the unusual circumstance, where treatment beyond 10days or a dose larger than 1.5g daily or 15g total is considered, the use of amikacin should be reevaluated. If administration of amikacin is prolonged, renal and auditory functions, and serum amikacin levels should be monitored daily.
Whenever possible, amikacin concentrations in serum should be measured to assure adequate, but not excessive levels. It is desirable to measure both peak and trough serum concentrations intermittently during therapy. Peak concentrations (30to 90minutes after injection) above 35µg/mL and trough concentrations (just prior to the next dose) above 10µg/mL should be avoided. Dosage should be adjusted as indicated.
At the recommended dosage level, uncomplicated infections due to amikacin-sensitive organisms should respond in 24 to 48 hours. If definite clinical response does not occur within 3 to 5 days, therapy should be stopped and the antibiotic susceptibility pattern of the invading organism should be rechecked. Failure of the infection to respond may be due to resistance of the organism or to the presence of septic foci requiring surgical drainage.
Administration in Patients with Impaired Renal Function: In patients with impaired renal function, it is necessary to prolong the interval between doses.
One suggested method for estimating dosage in patients with known or suspected diminished renal function is to multiply the serum creatinine concentration level (mg/100 mL) by 9and to use the resulting figure as the interval (in hours) between doses (see below); e.g.: if the creatinine concentration is 2.0mg/100mL, the recommended dose (7.5mg/kg) should be administered every 18hours. It should be emphasized that since renal function may alter appreciably during therapy, the serum creatinine should be checked frequently. Changes in the concentration would, of course, necessitate changes in the dosage frequency.
The dosage interval may be calculated by the following formula: serum creatinine (mg/100mL)´9=dosage interval (in hours).
If there is evidence of progressive renal dysfunction during therapy, discontinuation of the drug should be considered.
These dosage schedules must be used in conjunction with careful clinical and laboratory observations of the patient and should be modified as necessary, including modification when dialysis is being performed.
Infants and Neonates: In order to insure adequate therapeutic concentrations, which may be critical, while at the same time avoiding potentially toxic concentrations, serum concentrations should be monitored.
Dosage in Adults, Children and Neonates: The patient's pretreatment body weight should be obtained for calculation of correct dosage.
I.M. Route: The recommended daily dose is 15mg/kg to be administered at 7.5mg/kg every 12hours (500mg twice a day).
I.V. Administration: The recommended daily dose is 15mg/kg to be administered at 7.5mg/kg every 12hours (500mg twice a day). The solution for i.v. use is prepared by adding the contents of 500mg/2mL vial to 250mL of sterile diluent and is administered over a 30to 60minute period. Solutions for i.v. administration should be used within 12 hours after preparation.
Stability and Compatibility: Amikin is supplied as a colorless solution which requires no refrigeration. At times the solution becomes a pale yellow; however, this does not indicate a loss of potency. Dark colored solutions should be discarded.
If amikacin is used concurrently with other antibacterial agents to treat mixed or superinfections, it should not be physically mixed. Each agent should be administered separately in accordance with its recommended route of administration and dosage schedule.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit.
Because of the potential toxicity of aminoglycosides, “fixed dosage” recommendations which are not based upon body weight are not advised. Rather, it is essential to calculate the dosage to fit the needs of each patient.
Supplied / Packaging
EachmL of aqueous solution contains: amikacin sulfate 250mg, sodium bisulfite 0.66%, and sodium citrate 2.5% with pH adjusted to 4.5 with sulfuric acid. Nonmedicinal ingredients: sodium bisulfite 0.66% w/v (preservative), sodium citrate 2.5% w/v (buffer), sulfuric acid 7.7% w/v, water for injection. Sodium: <1mmol (8.0mg)/vial. 2mL single dose vials of 500mg.
EachmL of aqueous solution contains: amikacin sulfate 250mg, sodium bisulfite 0.66%, and sodium citrate 2.5% with pH adjusted to 4.5 with sulfuric acid. Nonmedicinal ingredients: sodium bisulfite 0.66% w/v (preservative), sodium citrate 2.5% w/v (buffer), sulfuric acid 7.7% w/v, water for injection. Sodium: <1mmol (8.0mg)/vial. 2mL single dose vials of 500mg.
