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  • CLASSES

    Aminoglycoside Antibiotics
    Ophthalmological Anti-infectives
    Topical Aminoglycosides, Plain or in Combination

    BOXED WARNING

    Dehydration, nephrotoxicity, renal disease, renal failure, renal impairment

    Patients receiving systemic aminoglycosides, such as gentamicin, should be closely monitored for nephrotoxicity. Aminoglycosides are associated with major toxic effects on the renal tubules. The risks of severe nephrotoxic adverse reactions are increased in patients with pre-existing renal disease, renal impairment, renal failure, or in those with normal renal function who receive high doses or prolonged therapy. Nephrotoxicity can manifest as decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine). When monitoring gentamicin serum concentrations during the use of conventional dose regimens, the manufacturer states that prolonged peak concentrations above 12 mcg/mL should be avoided and trough concentrations above 2 mcg/mL should be avoided. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Renal function should be closely monitored. Evidence of nephrotoxicity requires dosage adjustment or discontinuance of therapy. Hemodialysis may aid in gentamicin removal in the event of overdose or toxic reactions, especially if renal is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Avoid concurrent and/or sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic and/or neurotoxic because toxicity may be additive. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity.

    Hearing impairment, neurotoxicity, ototoxicity, tinnitus

    Patients receiving systemic aminoglycosides, such as gentamicin, should be closely monitored for neurotoxicity, including ototoxicity and hearing impairment. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Neurotoxicity is manifested by bilateral auditory toxicity which often is permanent and, sometimes, by vestibular ototoxicity. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Vertigo may occur and may indicate vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of hearing loss increases with the degree of exposure and continues to progress after stopping the drug. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. In patients with pre-existing renal impairment or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe ototoxic adverse reactions are sharply increased. When monitoring gentamicin serum concentrations in patients receiving conventional dosing regimens, the manufacturer states that prolonged peak concentrations above 12 mcg/mL should be avoided and trough concentrations above 2 mcg/mL should be avoided. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Eighth cranial nerve function should be closely monitored. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, or hearing loss) requires dosage adjustment or discontinuance of therapy. Aminoglycoside-induced ototoxicity is usually irreversible. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Aminoglycosides should not be given concomitantly with potent diuretics since certain diuretics by themselves may cause ototoxicity. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity. Audiology tests are recommended by the manufacturer.

    Pregnancy

    Systemic exposure to gentamicin may cause fetal harm during human pregnancy; the drug should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. There have been reports of total irreversible bilateral congenital deafness (eighth cranial nerve toxicity) in children whose mothers received a related aminoglycoside, streptomycin, during pregnancy. Serious side effects to mother, fetus or newborn have not been reported in the treatment of pregnant women with other aminoglycosides. Animal reproduction studies conducted on rats and rabbits did not reveal evidence of impaired fertility or harm to the fetus due to gentamicin sulfate.However, it is not known whether gentamicin sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Gentamicin rapidly crosses the placenta into fetal circulation and amniotic fluid, with peak cord serum levels averaging 34% to 44% of maternal serum concentrations after administration to women in labor. One reported case of potential congenital defects occurred after a 10-day maternal antibiotic course including gentamicin around gestational week 7. At birth, the infant had impaired renal function and small kidneys, and at 4.5 years of age, he was diagnosed with renal cystic dysplasia. It is unknown if fetal gentamicin exposure contributed to the renal problems. In a study of pregnant patients treated for pyelonephritis, the clinical and pregnancy outcomes of 62 patients who received ampicillin plus gentamicin did not differ from patients who received either cefazolin or ceftriaxone monotherapy. A case-control surveillance study that took place from 1980 to 1996 included a small number of women who received gentamicin (n = 19 in case and control groups) and showed no risk for teratogenicity with gentamicin. The ophthalmic and topical preparations of gentamicin do not appear likely to result in fetal harm when used as directed for limited exposure/treatment durations; however, gentamicin has been shown to depress body weights, kidney weights, and median glomerular counts in newborn rats when administered systemically to pregnant rats in daily doses approximately 500 times the maximum recommended ophthalmic human dose.

    DEA CLASS

    Rx

    DESCRIPTION

    Aminoglycoside antibiotic
    Used for a variety of gram-negative bacterial infections as well as synergistically for gram-positive bacterial infections, such as endocarditis
    Major toxicities include nephrotoxicity, ototoxicity, neurotoxicity; careful patient monitoring is suggested. Available in a variety of dosage forms to be used topically, via ophthalmic route, and as systemic parenteral therapy.

    COMMON BRAND NAMES

    Garamycin, Genoptic, Genoptic SOP, Gentacidin, Gentafair, Gentak, Gentasol, Ocu-Mycin

    HOW SUPPLIED

    Garamycin/Genoptic SOP/Gentak/Gentamicin/Gentamicin Sulfate/Ocu-Mycin Ophthalmic Ointment: 0.3%, 1g, 3mg
    Garamycin/Genoptic/Gentacidin/Gentafair/Gentak/Gentamicin/Gentamicin Sulfate/Gentasol/Ocu-Mycin Ophthalmic Sol: 0.3%
    Garamycin/Gentamicin/Gentamicin Sulfate Intramuscular Inj Sol: 1mL, 10mg, 40mg
    Garamycin/Gentamicin/Gentamicin Sulfate/Gentamicin Sulfate, Sodium Chloride/Gentamicin, Sodium Chloride Intravenous Inj Sol: 1mL, 10mg, 40mg, 100-0.9%, 120-0.9%, 60-0.9%, 70-0.9%, 80-0.9%, 90-0.9%
    Gentamicin/Gentamicin Sulfate Topical Cream: 0.1%
    Gentamicin/Gentamicin Sulfate Topical Ointment: 0.1%

    DOSAGE & INDICATIONS

    For the treatment of lower respiratory tract infections, including community-acquired pneumonia (CAP) and nosocomial pneumonia.
    NOTE: Serum gentamicin concentrations should be used to guide dosage adjustments. Dosage of aminoglycosides should be based on an estimate of lean body mass.
    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    3 mg/kg/day IV or IM given in 3 divided doses, while doses up to 5 mg/kg/day IV or IM in 3 to 4 divided doses may be required in life-threatening infections. Peak concentrations for these doses are expected to be approximately 4 to 6 mcg/mL. Adjust dosage based on serum concentration monitoring. Avoid peak concentrations more than 12 mcg/mL and trough concentrations more than 2 mcg/mL; use patient-specific information to guide the determination of adequate serum concentrations. For CAP, clinical practice guidelines recommend an aminoglycoside in combination with an antipseudomonal beta-lactam and a respiratory fluoroquinolone (i.e., levofloxacin, moxifloxacin) or azithromycin for patients with risk factors for Pseudomonas infection. Clinical practice guidelines recommend treatment for a minimum of 5 days and the patient should be afebrile for 48 to 72 hours with no more than 1 sign of clinical instability before discontinuation. For patients with nosocomial pneumonia and risk factors for gram-negative resistance or with a high mortality risk, add as a second antipseudomonal agent. Clinical practice guidelines recommend treatment for 7 days. In patients with risk factors for MRSA, add vancomycin or linezolid.

    Children and Adolescents

    2 to 2.5 mg/kg/dose IV or IM every 8 hours.

    Infants

    2.5 mg/kg/dose IV or IM every 8 hours.

    Premature infants 30 days and older weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for all infants older than 7 days ; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 8 to 29 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 8 hours.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 8 to 12 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for all neonates older than 7 days.

    Neonates 8 to 29 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for neonates 0 to 7 days old and 2.5 mg/kg/dose every 8 hours for neonates older than 7 days ; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 0 to 7 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 12 hours.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 12 to 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for all neonates 0 to 7 days.

    Neonates 0 to 7 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for neonates 0 to 7 days old ; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Intravenous dosage (extended-interval dosing)†
    Adults

    5 to 7 mg/kg IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary. For CAP, clinical practice guidelines recommend an aminoglycoside in combination with an antipseudomonal beta-lactam and a respiratory fluoroquinolone (i.e., levofloxacin, moxifloxacin) or azithromycin for patients with risk factors for Pseudomonas infection. Clinical practice guidelines recommend treatment for a minimum of 5 days and the patient should be afebrile for 48 to 72 hours with no more than 1 sign of clinical instability before discontinuation. For patients with nosocomial pneumonia and risk factors for gram-negative resistance or with a high mortality risk, add as a second antipseudomonal agent. Clinical practice guidelines recommend treatment for 7 days. In patients with risk factors for MRSA, add vancomycin or linezolid.

    Infants, Children, and Adolescents

    5 to 7.5 mg/kg/dose IV every 24 hours. One study in children 3 months to 18 years (n = 114) suggested daily (i.e., every 24 hours) age-specific doses of 9.5 mg/kg/dose (3 months to younger than 2 years), 8.5 mg/kg/dose (2 to 7 years), and 7 mg/kg/dose (8 to 18 years) may be more appropriate to achieve goal gentamicin concentrations.

    Premature infants 30 days and older weighing less than 1.2 kg

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2 kg

    4 to 5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    5 mg/kg/dose IV every 24 to 36 hours.

    Neonates 8 to 29 days weighing less than 1.2 kg

    5 mg/kg/dose IV every 36 hours.

    Neonates 0 to 7 days weighing more than 2 kg

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one protocol, the usual dosage of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if the neonate was also receiving indomethacin.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    5 mg/kg/dose IV every 36 to 48 hours.

    Neonates 0 to 7 days weighing less than 1.2 kg

    4 to 5 mg/kg/dose IV every 48 hours.

    Neonates on Extracorporeal Membrane Oxygenation (ECMO)

    2.5 to 3 mg/kg/dose IV every 18 to 24 hours. Subsequent dosing should be individualized by monitoring serum drug concentrations. When ECMO is discontinued, dosage adjustment may be required.

    For the treatment of meningitis, bone and joint infections, and intraabdominal infections (peritonitis).
    NOTE: Serum concentrations should be used to guide dosage adjustments. In most patients, dosage of aminoglycosides should be based on an estimate of lean body mass.
    For intrathecal or intraventricular administration in patients with meningitis due to susceptible organisms.
    Intrathecal† or Intraventricular† dosage (preservative free intrathecal injection only)
    Adults

    4 to 8 mg intrathecally or intraventricularly once daily in combination with parenteral therapy. Gentamicin was previously available as an injectable product specifically formulated for intrathecal administration.

    Infants, Children, and Adolescents

    1 to 2 mg intrathecally or intraventricularly once daily in combination with parenteral therapy.

    For peritoneal dialysis-associated peritonitis† in patients with end-stage renal disease.
    Intraperitoneal† dosage
    Adults

    Intraperitoneal (IP) gentamicin can administered continuously in each dialysate exchange bag with a loading dose of 8 mg/L initially and then a maintenance dose of 4 mg/L. Alternatively, for intermittent dosing, administer 0.6 mg/kg/dose IP for anuric patients and 0.75 mg/kg/dose IP for non-anuric patients once daily during the long-dwell periods. Treat for 2 to 3 weeks depending on infecting organism and the patient's clinical status.

    Infants, Children, and Adolescents

    Intraperitoneal (IP) gentamicin can administered continuously in each dialysate exchange bag with a loading dose of 8 mg/L initially and then a maintenance dose of 4 mg/L. Alternatively, for intermittent dosing, administer 0.6 mg/kg/dose IP for anuric patients and 0.75 mg/kg/dose IP for non-anuric patients once daily during the long-dwell periods. Treat for 2 to 3 weeks depending on infecting organism and the patient's clinical status.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    3 mg/kg/day IV or IM given in 3 divided doses, while doses up to 5 mg/kg/day IV or IM in 3 to 4 divided doses may be required in life-threatening infections. Peak concentrations for these doses are expected to be approximately 4 to 6 mcg/mL. Adjust dosage based on serum concentration monitoring. Avoid peak concentrations more than 12 mcg/mL and trough concentrations more than 2 mcg/mL; use patient-specific information to guide the determination of adequate serum concentrations.

    Children and Adolescents

    2 to 2.5 mg/kg/dose IV or IM every 8 hours.

    Infants

    2.5 mg/kg/dose IV or IM every 8 hours.

    Premature infants 30 days and older weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for all neonates and infants older than 7 days; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 8 to 29 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 8 hours.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 8 to 12 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for all neonates older than 7 days.

    Neonates 8 to 29 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for neonates 0 to 7 days old and 2.5 mg/kg/dose every 8 hours for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 0 to 7 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 12 hours.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 12 to 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for all neonates 0 to 7 days old.

    Neonates 0 to 7 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for neonates 0 to 7 days old; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Intravenous dosage (extended-interval dosing)†
    Adults

    5 to 7 mg/kg IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary.

    Infants, Children, and Adolescents

    5 to 7.5 mg/kg/dose IV every 24 hours. One study in children 3 months to 18 years (n = 114) suggested daily (i.e., every 24 hours) age-specific doses of 9.5 mg/kg/dose (3 months to younger than 2 years), 8.5 mg/kg/dose (2 to 7 years), and 7 mg/kg/dose (8 to 18 years) may be more appropriate to achieve goal gentamicin concentrations.

    Premature infants 30 days and older weighing less than 1.2 kg

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2 kg

    4 to 5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    5 mg/kg/dose IV every 24 to 36 hours.

    Neonates 8 to 29 days weighing less than 1.2 kg

    5 mg/kg/dose IV every 36 hours.

    Neonates 0 to 7 days weighing more than 2 kg

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one protocol, the usual dosage of 4 mg/kg/dose every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if the neonate was also receiving indomethacin.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    5 mg/kg/dose IV every 36 to 48 hours.

    Neonates 0 to 7 days weighing less than 1.2 kg

    4 to 5 mg/kg/dose IV every 48 hours.

    Neonates on Extracorporeal Membrane Oxygenation (ECMO)

    2.5 to 3 mg/kg/dose IV every 18 to 24 hours. Subsequent dosing should be individualized by monitoring serum drug concentrations. When ECMO is discontinued, dosage adjustment may be required.

    For the treatment of infective endocarditis.
    NOTE: Serum gentamicin concentrations should be used to guide dosage adjustments. Dosage of aminoglycosides should usually be based on an estimate of lean body mass.
    Intravenous or Intramuscular dosage
    Adults

    3 mg/kg/day IV or IM in 1 dose, or alternately, divided every 8 hours, is recommended by clinical practice guidelines. The FDA-approved dosage is 3 mg/kg/day IV or IM divided every 8 hours for severe infections and 5 mg/kg/day IV or IM divided every 8 hours for life-threatening infections. Clinical practice guidelines recommend gentamicin in combination with ceftriaxone for 2 weeks for native valve endocarditis (NVE) due to highly penicillin-susceptible Viridans group streptococci (VGS) and S. gallolyticus (bovis) infections. For relatively penicillin-resistant VGS NVE, gentamicin for 2 weeks plus penicillin G (or ampicillin) for 4 weeks is recommended. Gentamicin plus penicillin G (or ampicillin) or ceftriaxone for 6 weeks is recommended for prosthetic valve endocarditis (PVE) due to penicillin-resistant VGS; for penicillin-sensitive VGS PVE, may add gentamicin for first 2 weeks to penicillin G (or ampicillin) or ceftriaxone for 6 weeks. Add gentamicin for 2 weeks of at least 6-week course of rifampin and oxacillin or nafcillin for methicillin-sensitive staphylococci or rifampin and vancomycin for methicillin-resistant staphylococci PVE infections. Gentamicin with ampicillin or penicillin G for 4 to 6 weeks is preferred therapy for susceptible enterococcal NVE or PVE; in penicillin-resistant infection or patients unable to tolerate a beta-lactam, use gentamicin with vancomycin for 6 weeks for enterococcal NVE and PVE. An aminoglycoside in combination with a beta-lactam for 6 weeks is also recommended for endocarditis due to non-HACEK gram-negative microorganisms. For patients with early (less than 1 year after surgery) culture-negative PVE, gentamicin plus cefepime, vancomycin, and rifampin could be reasonable empiric therapy; treat culture-negative endocarditis for 4 to 6 weeks.

    Children and Adolescents

    1 to 2 mg/kg/dose IV every 8 hours is recommended by clinical practice guidelines. The FDA-approved dosage is 2 to 2.5 mg/kg/dose IV or IM every 8 hours. Clinical practice guidelines recommend gentamicin plus ampicillin; sulbactam with or without vancomycin for culture-negative, community-acquired native valve endocarditis (NVE) or late (more than 1 year after surgery) prosthetic valve endocarditis (PVE); alternately, gentamicin plus vancomycin may be used. Treat for 4 to 6 weeks for NVE and for 6 weeks with rifampin for PVE. Gentamicin plus vancomycin, cefepime, and rifampin (if prosthetic material is present) is recommended for culture-negative nosocomial endocarditis associated with vascular cannulae or early (less than 1 year after surgery) PVE; treat for 4 to 6 weeks, with a longer course for PVE. Use gentamicin plus penicillin G or ampicillin for endocarditis due to relatively penicillin-resistant streptococci, including enterococci; alternately, may use ceftriaxone plus gentamicin for streptococci or vancomycin plus gentamicin for enterococci. Treat for 4 weeks for NVE and for 6 weeks for PVE; duration of gentamicin depends on valve type and/or organism and varies from 2 weeks to full course. For methicillin-resistant staphylococcal NVE, gentamicin for 3 to 5 days may be added to nafcillin or oxacillin for 6 weeks; if PVE, add rifampin and use gentamicin for first 2 weeks of at least 6-week course. Additionally, gentamicin is a preferred therapy in combination with a third or fourth generation cephalosporin, or alternately, a broad-spectrum penicillin, for at least 6 weeks for non-HACEK gram-negative microorganisms. An aminoglycoside plus ampicillin for 4 weeks is recommended as an alternate therapy for endocarditis due to HACEK microorganisms.

    Infants

    2.5 mg/kg/dose IV or IM every 8 hours.

    Premature infants 30 days and older weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for all neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 8 to 29 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 8 hours.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 8 to 12 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for all neonates older than 7 days.

    Neonates 8 to 29 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 0 to 7 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 12 hours.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 12 to 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for all neonates 0 to 7 days old.

    Neonates 0 to 7 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for neonates 0 to 7 days old; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    For the treatment of skin and skin structure infections (e.g., cellulitis, burn wound infection).
    NOTE: Serum gentamicin concentrations should be used to guide dosage adjustments. Dosage of aminoglycosides should usually be based on an estimate of lean body mass.
    For the treatment of minor bacterial skin infection including, folliculitis, furunculosis, impetigo, eczema, pyoderma gangrenosum, sycosis barbae, infectious eczematoid dermatitis, pustular acne, pustular psoriasis, infected seborrheic dermatitis, infected contact dermatitis, and infected excoriations.
    Topical dosage
    Adults, Adolescents, and Children

    Apply to the affected skin area 3—4 times daily.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    The manufacturer recommends 3 mg/kg/day IV or IM given in 3 divided doses, while doses up to 5 mg/kg/day IV or IM in 3—4 divided dose may be required in life-threatening infections. Peak concentrations for these doses are expected to be approximately 4—6 mcg/mL. The manufacturer recommends dosage adjustments based on serum concentration monitoring. Additionally, the manufacturer states to avoid peak concentrations > 12 mcg/mL and trough concentrations > 2 mcg/mL; however, it is suggested that patient-specific information should be used to guide the determination of adequate serum concentration.

    Children and Adolescents

    The manufacturer recommends 2—2.5 mg/kg IV or IM every 8 hours.

    Infants

    The manufacturer recommends 2.5 mg/kg IV or IM every 8 hours.

    Neonates > 7 days

    The manufacturer recommends 2.5 mg/kg IV or IM every 8 hours; however, this dosing does not account for gestational age or birthweight and could be excessive in some patients.

    Neonates <= 7 days

    The manufacturer recommends 2.5 mg/kg IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight and could be excessive in some patients.

    Intravenous dosage (extended-interval dosing)†
    Adults

    Studies of once daily or 'pulse' dosing have typically used doses of 5—7 mg/kg IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random level drawn 8—12 hours after the first dose; dosing intervals of 24, 36, and in some cases, 48—72 hours, may be necessary.

    For the treatment of blepharitis, blepharoconjunctivitis, bacterial conjunctivitis, corneal ulcer, dacryocystitis, keratitis, keratoconjunctivitis, and acute meibomianitis.
    Ophthalmic dosage (ointment)
    Adults, Adolescent, Children, and Infants

    Apply a small amount (approximately 1/2 inch ribbon) of ointment to the affected eye(s) 2—3 times daily.

    Neonates

    Safety and efficacy have not been established.

    Ophthalmic dosage (solution)
    Adults, Adolescents, Children, and Infants

    Instill 1—2 drops into the infected eye every 4 hours. For severe infections, instill up to 2 drops every 1 hour.

    Neonates

    Safety and efficacy have not been established.

    For the treatment of bacteremia and sepsis.
    NOTE: Serum concentrations should be used to guide dosage adjustments. In most patients, dosage of aminoglycosides should be based on an estimate of lean body mass.
    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    3 mg/kg/day IV or IM given in 3 divided doses, while doses up to 5 mg/kg/day IV or IM in 3 to 4 divided doses may be required in life-threatening infections. Peak concentrations for these doses are expected to be approximately 4 to 6 mcg/mL. Adjust dosage based on serum concentration monitoring. Avoid peak concentrations more than 12 mcg/mL and trough concentrations more than 2 mcg/mL; use patient-specific information to guide the determination of adequate serum concentrations. For the treatment of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and vancomycin failure, clinical practice guidelines recommend 1 mg/kg/dose IV every 8 hours in combination with high dose daptomycin for 2 weeks. Routine use of gentamicin for MRSA bacteremia is not recommended. Sepsis clinical practice guidelines suggest extended-interval dosing when possible. Start within 1 hour of sepsis recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Children and Adolescents

    2 to 2.5 mg/kg/dose IV or IM every 8 hours.

    Infants

    2.5 mg/kg/dose IV or IM every 8 hours.

    Premature infants 30 days and older weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for all neonates and older than 7 days; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 8 to 29 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 8 hours. Extend the interval to 18 to 24 hours for neonates on ECMO. Individualize subsequent dosing by monitoring serum drug concentrations. When ECMO is discontinued, dosage adjustment may be required.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 8 to 12 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for all neonates older than 7 days.

    Neonates 8 to 29 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose every 8 hours for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 0 to 7 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 12 hours. Extend the interval to 18 to 24 hours for neonates on ECMO. Individualize subsequent dosing by monitoring serum drug concentrations. When ECMO is discontinued, dosage adjustment may be required.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 12 to 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for all neonates 0 to 7 days old.

    Neonates 0 to 7 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for neonates 0 to 7 days old; however, this dosing does not account for gestational age or birthweight. NOTE: In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Intravenous dosage (extended-interval dosing)†
    Adults

    5 to 7 mg/kg IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Infants, Children, and Adolescents

    5 to 7.5 mg/kg/dose IV every 24 hours. One study in children 3 months to 18 years (n = 114) suggested daily (i.e., every 24 hours) age-specific doses of 9.5 mg/kg/dose (3 months to younger than 2 years), 8.5 mg/kg/dose (2 to 7 years), and 7 mg/kg/dose (8 to 18 years) may be more appropriate to achieve goal gentamicin concentrations.

    Premature infants 30 days and older weighing less than 1.2 kg

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2 kg

    4 to 5 mg/kg/dose IV every 24 hours. In neonates with hypoxic ischemic encephalopathy (HIE) receiving hypothermia, a gentamicin dosing interval of 36 hours has been recommended due to a lower gentamicin clearance in these patients.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    5 mg/kg/dose IV every 24 to 36 hours.

    Neonates 8 to 29 days weighing less than 1.2 kg

    5 mg/kg/dose IV every 36 hours.

    Neonates 0 to 7 days weighing more than 2 kg

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one protocol, the usual dosage of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if the neonate was also receiving indomethacin. In neonates with hypoxic ischemic encephalopathy (HIE) receiving hypothermia, a gentamicin dosing interval of 36 hours has been recommended due to a lower gentamicin clearance in these patients.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    5 mg/kg/dose IV every 36 to 48 hours.

    Neonates 0 to 7 days weighing less than 1.2 kg

    4 to 5 mg/kg/dose IV every 48 hours.

    For the treatment of urinary tract infection (UTI).
    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    The manufacturer recommends 3 mg/kg/day IV or IM given in 3 divided doses, while doses up to 5 mg/kg/day IV or IM in 3 to 4 divided dose may be required in life-threatening infections. Peak concentrations for these doses are expected to be approximately 4 to 6 mcg/mL. The manufacturer recommends dosage adjustments based on serum concentration monitoring. Additionally, the manufacturer states to avoid peak concentrations more than 12 mcg/mL and trough concentrations more than 2 mcg/mL; however, it is suggested that patient-specific information should be used to guide the determination of adequate serum concentration.

    Children and Adolescents

    2 to 2.5 mg/kg/dose IV or IM every 8 hours.

    Infants

    2.5 mg/kg/dose IV or IM every 8 hours.

    Premature Infants 30 days and older weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for neonates older than 7 days ; however, this dosing does not account for gestational age or birthweight. In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 8 to 29 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 8 hours.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 8 to 12 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 8 hours for neonates older than 7 days.

    Neonates 8 to 29 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose every 8 hours for neonates older than 7 days ; however, this dosing does not account for gestational age or birthweight. In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Neonates 0 to 7 days weighing more than 2 kg

    2.5 mg/kg/dose IV or IM every 12 hours.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    2.5 mg/kg/dose IV or IM every 12 to 18 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for neonates 0 to 7 days old.

    Neonates 0 to 7 days weighing less than 1.2 kg

    2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2.5 mg/kg/dose IV or IM every 12 hours for neonates 0 to 7 days old ; however, this dosing does not account for gestational age or birthweight. In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.

    Intravenous dosage (extended-interval dosing)†
    Adults

    Studies of once daily or 'pulse' dosing have typically used doses of 5 to 7 mg/kg IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random level drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and in some cases, 48 to 72 hours, may be necessary. For pyelonephritis, the Infectious Diseases Society of America (IDSA) recommends that aminoglycosides may be given alone or in combination with ampicillin or with an extended-spectrum cephalosporin or penicillin. A one-time extended interval dose of an aminoglycoside may also be used prior to oral therapy for patients who do not require hospitalization.

    Infants, Children, and Adolescents

    5 to 7.5 mg/kg/dose IV every 24 hours. One study in children 3 months to 18 years (n = 114) suggested daily (i.e., every 24 hours) age-specific doses of 9.5 mg/kg/dose (3 months to younger than 2 years), 8.5 mg/kg/dose (2 to 7 years), and 7 mg/kg/dose (8 to 18 years) may be more appropriate to achieve goal gentamicin concentrations.

    Premature Infants 30 days and older weighing less than 1.2 kg

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2 kg

    4 to 5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing 1.2 to 2 kg

    5 mg/kg/dose IV every 24 to 36 hours.

    Neonates 8 to 29 days weighing less than 1.2 kg

    5 mg/kg/dose IV every 36 hours.

    Neonates 0 to 7 days weighing more than 2 kg

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one protocol, the usual dosage of 4 mg/kg/dose every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    5 mg/kg/dose IV every 36 to 48 hours.

    Neonates 0 to 7 days weighing less than 1.2 kg

    4 to 5 mg/kg/dose IV every 48 hours.

    Neonates on Extracorporeal Membrane Oxygenation (ECMO)

    2.5 to 3 mg/kg/dose IV every 18 to 24 hours. Subsequent dosing should be individualized by monitoring serum drug concentrations. When ECMO is discontinued, dosage adjustment may be required.

    For the treatment of pelvic inflammatory disease (PID)† with or without complications of tubo-ovarian abscess† .
    Intravenous or Intramuscular dosage
    Adults

    The CDC recommends gentamicin 2 mg/kg IV or IM loading dose, then an appropriate maintenance dose (1.5 mg/kg IV every 8 hours) plus clindamycin IV. Single daily dosing 3—5 mg/kg IV every 24 hours may be used as an alternative to traditional gentamicin dosing. Parenteral therapy may be discontinued 24 hours after a patient improves clinically; therapy should be continued with oral doxycycline or oral clindamycin to complete a total of 14 days of therapy. When tubo-ovarian abscess is present, oral clindamycin plus doxycycline should be used to complete 14 days of therapy.

    For the treatment of plague† infection due to exposure to Yersinia pestis in an individual patient or in a contained casualty setting.
    NOTE: Streptomycin is the drug of choice to treat plague in most patients, however, because gentamicin is more widely available it is an acceptable alternative. Gentamicin is the preferred agent in pregnant women.
    Intravenous or Intramuscular dosage
    Adults and Adolescents

    5 mg/kg IM or IV once daily for 10 days. Alternatively, 2 mg/kg IM or IV loading dose, followed by 1.7 mg/kg IM or IV 3 times daily for 10 days could be used. The risk of serious infection following plague exposure supports the use of gentamicin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin. Intravenous doxycycline, ciprofloxacin, or chloramphenicol could be used as third-line alternatives. Women who are breast-feeding should be treated with the same antibiotic as the infant.

    Children

    2.5 mg/kg IM or IV 3 times daily for 10 days. Alternatively 5 mg/kg IM or IV once daily for 10 days could be used. The risk of serious infection following plague exposure supports the use of gentamicin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin. Intravenous doxycycline, ciprofloxacin, or chloramphenicol could be used as third-line alternatives.

    For the initial treatment of tularemia† infection due to exposure to Francisella tularensis.
    For tularemia† in an individual patient or in a contained casualty setting.
    NOTE: Streptomycin is the drug of choice to treat tularemia in most patients, however, because gentamicin is more widely available it is an acceptable alternative. Gentamicin is the preferred agent in pregnant women; if gentamicin is contraindicated streptomycin should be used.
    Intravenous or Intramuscular dosage
    Adults and Adolescents

    5 mg/kg IM or IV once daily for 10 days. Alternatively, 2 mg/kg IM or IV loading dose, followed by 1.7 mg/kg IM or IV every 8 hours for 10 days could be used. The risk of serious infection following tularemia exposure supports the use of gentamicin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin. IV doxycycline, chloramphenicol, or ciprofloxacin could be used as third-line alternatives. Women who are breast-feeding should be treated with the same antibiotic as the infant.

    Children

    2.5 mg/kg IM or IV every 8 hours for 10 days. Alternatively 5 mg/kg IM or IV once daily for 10 days could be used. The risk of serious infection following tularemia exposure supports the use of gentamicin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin. IV doxycycline, chloramphenicol, or ciprofloxacin could be used as third-line alternatives.

    For tularemia† in a mass casualty setting or for tularemia prophylaxis†.
    NOTE: Doxycycline and ciprofloxacin are preferred agents in this setting.
    Intravenous or Intramuscular dosage
    Adults and Adolescents

    5 mg/kg IM or IV once daily. Alternatively, 2 mg/kg IM or IV loading dose, followed by 1.7 mg/kg IM or IV every 8 hours could be used. If treatment is begun in the incubation period of tularemia and continued daily for 14 days, exposed individuals might be protected against symptomatic infection. The risk of serious infection following tularemia exposure supports the use of gentamicin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of doxycycline or ciprofloxacin.

    Children

    2.5 mg/kg IM or IV every 8 hours. Alternatively 5 mg/kg IM or IV once daily could be used. If treatment is begun in the incubation period of tularemia and continued daily for 14 days, exposed individuals might be protected against symptomatic infection. The risk of serious infection following tularemia exposure supports the use of gentamicin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of doxycycline or ciprofloxacin.

    For surgical infection prophylaxis†.
    Intravenous or Intramuscular dosage
    Adults

    5 mg/kg IV or IM as a single dose within 60 minutes prior to the surgical incision; or alternately, 1.5 mg/kg IV as a single dose for gynecology procedures. No intraoperative redosing and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. Clinical practice guidelines recommend gentamicin in combination with another appropriate antimicrobial (i.e., vancomycin, clindamycin, or metronidazole depending on procedure) as an alternate therapy for patients with beta-lactam allergy undergoing gastrointestinal, biliary tract, uncomplicated appendectomy, colorectal, urogynecology, or transplant procedures.

    Infants, Children, and Adolescents

    2.5 mg/kg IV or IM as a single dose within 60 minutes prior to the surgical incision. No intraoperative redosing and a duration of prophylaxis less than 24 hours are recommended by clinical practice guidelines. Clinical practice guidelines recommend gentamicin, in combination with another appropriate antimicrobial (i.e., vancomycin, clindamycin, or metronidazole depending on procedure), as an alternate therapy for patients with beta-lactam allergy undergoing gastrointestinal, biliary tract, uncomplicated appendectomy, colorectal, urologic, or transplant procedures.

    For the treatment of chronic Bartonella quintana† bacteremia (bartonellosis†) in combination with doxycycline.
    Intravenous dosage
    Adults

    In a randomized open trial, gentamicin 3 mg/kg/day IV for 14 days was used with doxycycline (200 mg/day PO for 28 days) to treat homeless patients with positive blood cultures for Bartonella quintana. Data from 20 patients (9 received treatment and 11 placebo) were evaluated. Bartonella quintana was eradicated in 7 of 9 patients in the treatment group and 2 of 11 placebo patients; no patient developed endocarditis. Based on the results of the study, the combination of gentamicin and doxycycline is recommended for chronic B. quintana bacteremia. Prior to this study, the authors retrospectively reviewed data of homeless patients with B. quintana bacteremia. These data showed that patients treated with the combination of doxycycline and gentamicin were cured whereas those treated with beta-lactams or doxycycline alone were not.

    For the treatment of granuloma inguinale† (Donovanosis) due to Klebsiella granulomatis.
    Intravenous dosage
    Adults

    1 mg/kg IV every 8 hours is suggested by the CDC as an addition to oral therapy in patients that show no improvement within the first few days of therapy or in patients with HIV. The treatment duration is at least 3 weeks and until all of the lesions have completely healed.

    Adolescents

    1 mg/kg IV every 8 hours is suggested by the CDC as an addition to oral therapy in patients that show no improvement within the first few days of therapy or in patients with HIV. The treatment duration is at least 3 weeks and until all of the lesions have completely healed.

    For the treatment of cephalosporin-resistant gonorrhea†.
    Intramuscular dosage
    Adults

    240 mg IM as a single dose plus azithromycin 2 g PO as a single dose is recommended by the CDC as an option for patients with severe cephalosporin allergy or those with treatment failure after retreatment with preferred regimen. In patients with cephalosporin-resistant N. gonorrhoeae who have failed high dose ceftriaxone, the World Health Organization (WHO) also suggests this combination or just gentamicin alone. Appropriate treatment of sexual partners is necessary.

    Adolescents

    240 mg IM as a single dose plus azithromycin 2 g PO as a single dose is recommended by the CDC as an option for patients with severe cephalosporin allergy or those with treatment failure after retreatment with preferred regimen. In patients with cephalosporin-resistant N. gonorrhoeae who have failed high dose ceftriaxone, the World Health Organization (WHO) also suggests this combination or just gentamicin alone. Appropriate treatment of sexual partners is necessary.

    For the empiric treatment of febrile neutropenia†.
    NOTE: Serum concentrations should be used to guide dosage adjustments. In most patients, dosage of aminoglycosides should be based on an estimate of lean body mass.
    For the treatment of febrile neutropenia in adults.
    Intravenous dosage (extended-interval dosing)
    Adults

    Studies of once daily or 'pulse' dosing have typically used doses of 5 to 7 mg/kg IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random level drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and in some cases, 48 to 72 hours, may be necessary. Aminoglycosides are recommended as an option in for febrile neutropenia in combination with an antipseudomonal beta-lactam in patients with complications or those with suspected or documented resistance.

    Intravenous dosage (conventional dosing)
    Adults

    The manufacturer recommends up to 5 mg/kg/day IV or IM in 3 to 4 divided dose for life-threatening infections. Studies in patients with febrile neutropenia have used initial doses of either 80 mg IV or 1.5 mg/kg IV every 8 hours with dose adjustments to maintain peak concentrations of 4 to 8 mcg/ml. Aminoglycosides are recommended as an option in combination with an antipseudomonal beta-lactam in patients with complications or those with suspected or documented resistance.

    For the treatment of febrile neutropenia in pediatric patients.
    Intravenous dosage (extended-interval dosing)
    Infants, Children, and Adolescents

    7 to 8 mg/kg/dose IV every 24 hours. In a pharmacokinetic analysis of data from a retrospective study in pediatric patients with febrile neutropenia, age-specific initial doses of 10.5 mg/kg/dose IV (1 year to less than 6 years), 9.5 mg/kg/dose IV (girls 6 years and older), and 7.5 mg/kg/dose IV (boys 6 years and older) given every 24 hours were recommended to achieve target serum gentamicin peak concentrations. The efficacy of once daily gentamicin for febrile neutropenia has been established in several studies in pediatric patients. Gentamicin, in combination with an antipseudomonal penicillin or cephalosporin, has been successfully used for the empiric treatment of febrile neutropenia in children. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.

    Intravenous dosage (conventional dosing)
    Infants, Children, and Adolescents

    2 to 2.5 mg/kg/dose IV every 8 hours. Gentamicin, in combination with an antipseudomonal penicillin or cephalosporin, has been successfully used for the empiric treatment of febrile neutropenia in children. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Aminoglycoside dosing is highly variable and dependent on several factors. The FDA lists the maximum recommended therapeutic dose as 5 mg/kg/day IV/IM; however, doses of 7 mg/kg/day IV have been used in extended-interval dosing regimens. There is no maximum dose stated for ophthalmic or topical administration.

    Geriatric

    Aminoglycoside dosing is highly variable and dependent on several factors. The FDA lists the maximum recommended therapeutic dose as 5 mg/kg/day IV/IM; however, parenteral doses of 7 mg/kg/day IV have been used in extended-interval dosing regimens. There is no maximum dose stated for ophthalmic or topical administration.

    Adolescents

    Aminoglycoside dosing is highly variable and dependent on several factors. The FDA lists the maximum recommended therapeutic dose for children as 7.5 mg/kg/day. There is no maximum dose stated for ophthalmic or topical administration.

    Children

    Aminoglycoside dosing is highly variable and dependent on several factors. The FDA lists the maximum recommended therapeutic dose as 7.5 mg/kg/day IV/IM. There is no maximum dose stated for ophthalmic or topical administration.

    Infants

    Aminoglycoside dosing is highly variable and dependent on several factors. The FDA lists the maximum recommended therapeutic dose as 7.5 mg/kg/day IV/IM. There is no maximum dose stated for ophthalmic or topical administration.

    Neonates

    > 7 days: Aminoglycoside dosing is highly variable and dependent on several factors. The FDA lists the maximum recommended therapeutic dose as 7.5 mg/kg/day IV/IM; however, this dosing does not account for gestational age or birthweight and could be excessive in some patients.
    <= 7 days: Aminoglycoside dosing is highly variable and dependent on several factors. The FDA lists the maximum recommended therapeutic dose as 5 mg/kg/day IV/IM; however, this dosing does not account for gestational age or birthweight and could be excessive in some patients.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Gentamicin does not undergo hepatic metabolism. Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Conventional dosing:
    The manufacturer recommends either maintaining the standard dose and increasing the interval between doses or decreasing the dose while maintaining an every 8 hour dosing interval. To increase the dosing interval, the manufacturer recommends multiplying the patient's serum creatinine (mg/100 mL) by 8 to determine the dosing interval (i.e. serum creatinine of 2 mg/100 mL would yield a dosing interval of 16 hours). To decrease the dose, the manufacturer recommends dividing the patient's standard dose by the serum creatinine (mg/100 mL) to determine the lower recommended dose. For example, if a patient was receiving a standard dose of 60 mg IV every 8 hours and had a serum creatinine of 2 mg/100 mL, the dose would be adjusted to 30 mg IV every 8 hours. The manufacturer does suggest measuring gentamicin serum concentrations and adjusting the dose accordingly. Additionally, renal function status may change throughout the course of therapy. Several dosing regimens and nomograms designed to maintain traditional gentamicin serum concentrations have been published in the literature for dosing gentamicin in patients with renal impairment. However, these predictive dosage regimens and nomograms may result in gentamicin serum concentrations outside the targeted range; therefore, doses should be adjusted based on patient-specific serum concentrations. Factors such as site of infection and organism susceptibility may alter the goals of therapy; thereby altering dosing in patients with renal impairment. The initial dosing interval should be individualized based on specific patient and disease-state characteristics, serum concentrations goals, site of infection, organism susceptibility, weight, age, and degree and stability of renal impairment (acute vs. chronic). Further dosing should be guided by serum gentamicin concentrations.
     
    Interval adjustment of extended-interval dosing of 5 or 7 mg/kg† :
    CrCl 60 mL/minute or more: No dosage adjustment is needed. Adjust doses based on serum concentrations and organism MIC.
    CrCl 40 to 59 mL/minute: 5 or 7 mg/kg IV every 36 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl 20 to 39 mL/minute: 5 or 7 mg/kg IV every 48 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl less than 20 mL/minute: 5 or 7 mg/kg IV once, then follow serial concentrations to determine time of next dose (serum concentration less than 1 mcg/mL). Adjust doses based on serum concentrations and organism MIC.
     
    Dose adjustment of extended-interval dosing of 5 mg/kg† :
    CrCl more than 80 mL/minute: No dosage adjustment is needed. Adjust doses based on serum concentrations and organism MIC.
    CrCl 60 to 79 mL/minute: 4 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl 50 mL/minute: 3.5 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl 40 mL/minute: 2.5 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl less than 30 mL/minute: Use traditional dosing. Adjust doses based on serum concentrations and organism MIC.
     
    Intermittent hemodialysis
    Adults: The manufacturer recommends 1 to 1.7 mg/kg IV or IM after the initial hemodialysis session. Doses should be guided by serum gentamicin concentrations. Factors such as patient size, site of infection, and organism susceptibility should also be considered. Pre-dialysis dosing has been studied in patients receiving hemodialysis and generally requires larger gentamicin doses. Pre-dialysis dosing may also produce higher target peak serum concentrations with minimal accumulation. Other recommendations suggest giving half of a full dose after dialysis.
    Infants, Children, and Adolescents: The manufacturer recommends 2 mg/kg IV or IM after the initial hemodialysis session. Subsequent doses should be guided by serum gentamicin concentrations. Factors such as patient size, site of infection, and organism susceptibility should also be considered.
     
    Continuous ambulatory peritoneal dialysis (CAPD)
    The International Society for Peritoneal Dialysis (ISPD) states that intraperitoneal (IP) gentamicin can administered continuously in each dialysate exchange bag with a loading dose of 8 mg/L and a maintenance dose of 4 mg/L. Alternatively, an IP dose of 0.6 mg/kg can be administered in 1 exchange bag per day.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Vials for injection: Dilute prior to IV infusion. The calculated dose is added to 50—200 mL of 5% Dextrose injection or 0.9% Sodium Chloride injection. For infants and children, the volume of diluent should be less.
    Premixed IV bags: Administer as a secondary medication unit. After removing overwrap, check for leaks by squeezing inner bag firmly. Do not use plastic containers in series connections due to the risk of air embolism. Attach to administration set. Do not introduce additives to the solution.
    Infuse IV over 30 minutes to 2 hours. Do not physically premix with other drugs.

    Intramuscular Administration

    Inject deeply into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel.

    Other Injectable Administration

    Intrathecal or Intraventricular Administration
    The appropriate dose of the preservative-free gentamicin injection should be drawn into a 5—10 ml syringe.
    After puncture is complete and CSF culture specimens obtained, insert the syringe containing gentamicin into the hub of the spinal needle.
    Allow CSF (about 10% of estimated CSF total volume) to flow into the syringe and mix with the drug.
    Inject intrathecally over 3—5 minutes with the bevel of the needle directed upward.
    If CSF is grossly purulent or if it is unobtainable, may mix gentamicin with sterile normal saline (preservative-free) before injection.
    May also be administered directly into the subdural space or directly into the ventricles, including administration by use of an implanted device.

    Topical Administration
    Cream/Ointment/Lotion Formulations

    Rub cream or ointment gently into cleansed affected area. Care should be taken to avoid further contamination of the infected skin.
    Treated area may be covered with sterile gauze if desired.
    Crusts from impetigo should be removed before application to permit maximum contact between the antibiotic and the infection.
    Use of topical gentamicin under gelatin packing may be used for infected stasis ulcers.

    Ophthalmic Administration

    Apply topically to the eye. Solution is not for injection; for topical ophthalmic use only.
    Instruct patient on proper instillation of eye ointment or solution (see Patient Information).
    Do not to touch the tip of the tube or dropper to the eye, fingertips, or other surface.

    STORAGE

    Generic:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Garamycin:
    - Avoid excessive heat (above 104 degrees F)
    - Store at or below 77 degrees F
    Genoptic:
    - Avoid excessive heat (above 104 degrees F)
    - Store at or below 77 degrees F
    Genoptic SOP:
    - Store between 36 to 86 degrees F
    Gentacidin:
    - Avoid excessive heat (above 104 degrees F)
    - Store at or below 77 degrees F
    Gentafair:
    - Avoid excessive heat (above 104 degrees F)
    - Store at or below 77 degrees F
    Gentak :
    - Avoid excessive heat (above 104 degrees F)
    - Store at or below 77 degrees F
    Gentasol:
    - Avoid excessive heat (above 104 degrees F)
    - Store at or below 77 degrees F
    Ocu-Mycin:
    - Avoid excessive heat (above 104 degrees F)
    - Store at or below 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Dehydration, nephrotoxicity, renal disease, renal failure, renal impairment

    Patients receiving systemic aminoglycosides, such as gentamicin, should be closely monitored for nephrotoxicity. Aminoglycosides are associated with major toxic effects on the renal tubules. The risks of severe nephrotoxic adverse reactions are increased in patients with pre-existing renal disease, renal impairment, renal failure, or in those with normal renal function who receive high doses or prolonged therapy. Nephrotoxicity can manifest as decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine). When monitoring gentamicin serum concentrations during the use of conventional dose regimens, the manufacturer states that prolonged peak concentrations above 12 mcg/mL should be avoided and trough concentrations above 2 mcg/mL should be avoided. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Renal function should be closely monitored. Evidence of nephrotoxicity requires dosage adjustment or discontinuance of therapy. Hemodialysis may aid in gentamicin removal in the event of overdose or toxic reactions, especially if renal is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Avoid concurrent and/or sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic and/or neurotoxic because toxicity may be additive. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity.

    Hearing impairment, neurotoxicity, ototoxicity, tinnitus

    Patients receiving systemic aminoglycosides, such as gentamicin, should be closely monitored for neurotoxicity, including ototoxicity and hearing impairment. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Neurotoxicity is manifested by bilateral auditory toxicity which often is permanent and, sometimes, by vestibular ototoxicity. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Vertigo may occur and may indicate vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of hearing loss increases with the degree of exposure and continues to progress after stopping the drug. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. In patients with pre-existing renal impairment or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe ototoxic adverse reactions are sharply increased. When monitoring gentamicin serum concentrations in patients receiving conventional dosing regimens, the manufacturer states that prolonged peak concentrations above 12 mcg/mL should be avoided and trough concentrations above 2 mcg/mL should be avoided. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Eighth cranial nerve function should be closely monitored. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, or hearing loss) requires dosage adjustment or discontinuance of therapy. Aminoglycoside-induced ototoxicity is usually irreversible. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Aminoglycosides should not be given concomitantly with potent diuretics since certain diuretics by themselves may cause ototoxicity. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity. Audiology tests are recommended by the manufacturer.

    Aminoglycoside hypersensitivity, sulfite hypersensitivity

    Gentamicin is contraindicated in patients with aminoglycoside hypersensitivity. Allergenic reactions to aminoglycosides are generally uncommon, but hypersensitivity with one agent may demonstrate cross sensitivity with another aminoglycoside. Some formulations of intravenous gentamicin contain sodium metabisulfite; therefore, patients with sulfite hypersensitivity should use parenteral gentamicin with caution. Sulfite sensitivity is seen more frequently in asthmatic patients.

    Botulism, electrolyte imbalance, myasthenia gravis, neuromuscular disease, parkinsonism, respiratory depression, respiratory insufficiency

    Systemic aminoglycosides, such as gentamicin, are associated with neuromuscular blockade and may cause severe neuromuscular weakness lasting hours to days. Respiratory paralysis, respiratory insufficiency, or respiratory depression may occur when aminoglycosides are instilled after local irrigation and after topical application during surgical procedures. Neuromuscular blockade has also been reported with both oral and parenteral use of aminoglycosides. Clinicians should be aware of the possibility of neuromuscular blockade and respiratory paralysis if aminoglycosides are administered by any route with systemic absorption, especially in patients receiving anesthetics, neuromuscular-blocking agents (e.g., tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood). Corrective therapy is required for any electrolyte imbalance, which may aggravate risk for neuromuscular/neurological symptoms. During or after aminoglycoside therapy, paresthesias, tetany, positive Chvostek and Trousseau signs, and mental confusion have been described in patients with hypomagnesemia, hypocalcemia, and hypokalemia. In infants, tetany and muscle weakness have been described. Aminoglycosides may aggravate muscle weakness in patients with neuromuscular disease such as myasthenia gravis, botulism, or parkinsonism.

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents, like systemic gentamicin, have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Antimicrobial resistance, corneal abrasion, fungal infection, viral infection

    Prescribing gentamicin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria, contributing to antimicrobial resistance. Treatment with gentamicin may result in overgrowth of nonsusceptible organisms, including fungal infection or viral infection. If this occurs, appropriate therapy is indicated. ] Use of ophthalmic ointments may delay healing of corneal abrasion or lesions.

    Pregnancy

    Systemic exposure to gentamicin may cause fetal harm during human pregnancy; the drug should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. There have been reports of total irreversible bilateral congenital deafness (eighth cranial nerve toxicity) in children whose mothers received a related aminoglycoside, streptomycin, during pregnancy. Serious side effects to mother, fetus or newborn have not been reported in the treatment of pregnant women with other aminoglycosides. Animal reproduction studies conducted on rats and rabbits did not reveal evidence of impaired fertility or harm to the fetus due to gentamicin sulfate.However, it is not known whether gentamicin sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Gentamicin rapidly crosses the placenta into fetal circulation and amniotic fluid, with peak cord serum levels averaging 34% to 44% of maternal serum concentrations after administration to women in labor. One reported case of potential congenital defects occurred after a 10-day maternal antibiotic course including gentamicin around gestational week 7. At birth, the infant had impaired renal function and small kidneys, and at 4.5 years of age, he was diagnosed with renal cystic dysplasia. It is unknown if fetal gentamicin exposure contributed to the renal problems. In a study of pregnant patients treated for pyelonephritis, the clinical and pregnancy outcomes of 62 patients who received ampicillin plus gentamicin did not differ from patients who received either cefazolin or ceftriaxone monotherapy. A case-control surveillance study that took place from 1980 to 1996 included a small number of women who received gentamicin (n = 19 in case and control groups) and showed no risk for teratogenicity with gentamicin. The ophthalmic and topical preparations of gentamicin do not appear likely to result in fetal harm when used as directed for limited exposure/treatment durations; however, gentamicin has been shown to depress body weights, kidney weights, and median glomerular counts in newborn rats when administered systemically to pregnant rats in daily doses approximately 500 times the maximum recommended ophthalmic human dose.

    Breast-feeding

    Although the manufacturer does not give recommendations for gentamicin use during breast feeding, gentamicin use appears compatible with breast-feeding. Small amounts of gentamicin are excreted into breast milk. In a study of 10 women who received systemic gentamicin prophylaxis (80 mg IM every 8 hours) for 5 days, mean maternal gentamicin serum concentrations on day four obtained 1 and 7 hours after a dose were 3.95 mcg/mL and 1.02 mcg/mL, respectively. Corresponding mean milk concentrations at 1, 3, 5, and 7 hours after the dose were 0.42 mcg/mL, 0.48 mcg/mL, 0.49 mcg/mL, and 0.41 mcg/mL, respectively. Gentamicin also has extremely poor oral bioavailability, and therefore, significant absorption of ingested drug by the breast-fed infant is not expected. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    Sexually transmitted disease

    Gentamicin may be used to treat certain sexually transmitted diseases (STD). All patients with a diagnosed or suspected STD should be tested for other STDs, which may include HIV, syphilis, chlamydia, and gonorrhea, at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.

    Neonates, premature neonates

    Use systemic gentamicin with caution in neonates and premature neonates due to renal immaturity and the prolongation of serum half-life of the drug, which increases the risk of aminoglycoside-induced toxicity. When gentamicin is used in the neonatal population, careful monitoring is warranted for signs and symptoms of toxicity including auditory, vestibular, and renal toxicity and neuromuscular blockade.

    Geriatric

    Geriatric patients may be at increased risk of gentamicin neurotoxicity and nephrotoxicity. Elderly patients may have decreased renal function; therefore, care should be taken in dose selection and gentamicin monitoring when using systemic gentamicin therapy. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of parenteral gentamycin must be accompanied by monitoring of renal function tests, including a baseline value, and serum gentamycin concentrations, with the exception of single dose prophylactic administration. Serious consequences may occur insidiously if adequate monitoring does not occur; the drug may cause or worsen hearing loss and renal failure. Use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    ADVERSE REACTIONS

    Severe

    azotemia / Delayed / Incidence not known
    proteinuria / Delayed / Incidence not known
    renal tubular acidosis (RTA) / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    hearing loss / Delayed / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    pulmonary fibrosis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    agranulocytosis / Delayed / Incidence not known

    Moderate

    pyuria / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    tetany / Early / Incidence not known
    encephalopathy / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    confusion / Early / Incidence not known
    hallucinations / Early / Incidence not known
    pseudotumor cerebri / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    conjunctival hyperemia / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    erythema / Early / Incidence not known
    stomatitis / Delayed / Incidence not known
    respiratory depression / Rapid / Incidence not known
    hepatomegaly / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    splenomegaly / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known

    Mild

    ocular irritation / Rapid / 1.0-10.0
    cylindruria / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    dizziness / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    weakness / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known
    headache / Early / Incidence not known
    lethargy / Early / Incidence not known
    skin irritation / Early / Incidence not known
    rash (unspecified) / Early / Incidence not known
    purpura / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    alopecia / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    hypersalivation / Early / Incidence not known
    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    fever / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acyclovir: (Major) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
    Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity, even in patients who have normal renal function.
    Agalsidase Beta: (Moderate) Theoretically, there is a possible drug interaction between agalsidase beta and gentamicin due to a risk of decreased intracellular alpha galactosidase A activity induced by gentamicin.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
    Aminosalicylate sodium, Aminosalicylic acid: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B lipid complex (ABLC): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B liposomal (LAmB): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as the aminoglycosides, as the risk of renal impairment may be increased.
    Aspirin, ASA: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Carisoprodol: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Dipyridamole: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Omeprazole: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Oxycodone: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Pravastatin: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Atracurium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Minor) Antiemetics, like scopolamine, should be used carefully with amikacin because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Azelastine; Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Urinary concentrations of gentamicin could interfere with the therapeutic effectiveness of BCG. Postpone instillation of BCG if the patient is receiving antibiotics.
    Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as aminoglycosides (particularly kanamycin, streptomycin, and neomycin).Use of topically administrated preparations containing bacitracin, especially when applied to large surface areas, with aminoglycosides may have additive nephrotoxic potential.
    Beclomethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Betamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bismuth Subsalicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bleomycin: (Moderate) Previous treatment with nephrotoxic agents, like aminoglycosides, may result in decreased clearance of bleomycin if renal function has been impaired.
    Botulinum Toxins: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
    Budesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Budesonide; Formoterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bumetanide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Capreomycin: (Major) The concomitant use of capreomycin and aminoglycosides may increase the risk of nephrotoxicity and neurotoxicity. Since capreomycin is eliminated by the kidney, coadministration of capreomycin with other potentially nephrotoxic drugs, including aminoglycosides may increase serum concentrations of either capreomycin or aminoglycosides. Theoretically, coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with capreomycin resulting from administration of large doses or rapid intravenous infusion. Aminoglycosides have also been reported to interfere with nerve transmission at the neuromuscular junction. Concomitant administration of capreomycin with aminoglycosides should be avoided if possible; however, if they must be coadministered, use extreme caution.
    Carbetapentane; Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carboplatin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely.
    Cefepime: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotetan: (Minor) Cefotetan's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefoxitin: (Minor) Cefoxitin's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefprozil: (Minor) Cefprozil's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime; Avibactam: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftizoxime: (Minor) Ceftizoxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefuroxime: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Codeine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpromazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Choline Salicylate; Magnesium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Ciclesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cidofovir: (Severe) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
    Cisatracurium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Cisplatin: (Major) Aminoglycosides should be used cautiously in patients receiving cisplatin. Aminoglycosides can aggravate the nephrotoxicity and electrolyte loss seen with cisplatin if given concurrently or shortly after cisplatin therapy. Concurrent use of cisplatin and other nephrotoxic agents also known to be ototoxic (i.e., aminoglycosides) may increase the risk of cisplatin-induced ototoxicity.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Codeine; Phenylephrine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Codeine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Corticosteroids: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Corticotropin, ACTH: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cyclizine: (Minor) Cyclizine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Cyclosporine: (Major) Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as aminoglycosides.
    Cytarabine, ARA-C: (Minor) Cytarabine may reduce the efficacy of gentamicin in certain infections. The lack of a prompt therapeutic response may indicate the need for reevaluation of antibacterial therapy.
    Deferasirox: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
    Deflazacort: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Dexamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Dextromethorphan; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Digoxin: (Major) The coadministration of gentamicin and digoxin resulted in a 129-212% increase in the serum concentration of digoxin. Measure serum digoxin concentrations before initiating gentamicin. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring.
    Dimenhydrinate: (Minor) Dimenhydrinate and other antiemetics should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity, including nausea secondary to vertigo.
    Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Ibuprofen: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Naproxen: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Doxacurium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Enflurane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Entecavir: (Moderate) Because entecavir is primarily eliminated by the kidneys and aminoglycosides can affect renal function, concurrent administration with aminoglycosides may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Ethacrynic Acid: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Etomidate: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Fludrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Flunisolide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluphenazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by aminoglycosides.
    Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Salmeterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Formoterol; Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as aminoglycosides.
    Furosemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Gallium Ga 68 Dotatate: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including intravenous mannitol. In addition, intravenous mannitol may alter the serum and tissue concentrations of tobramycin, thereby, increasing the risk for aminoglycoside toxicities. If possible, avoid concurrent use. If these drugs must be used together, it would be prudent to monitor renal function, serum electrolytes, and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates). Studies to evaluate a potential interaction between inhaled formulations of mannitol and tobramycin have not been conducted.
    Gallium: (Severe) Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, such as aminoglycosides, may increase the risk for developing severe renal insufficiency. If use of an aminoglycoside is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of the aminoglycoside is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl.
    Galsulfase: (Minor) There is a possible drug interaction between galsulfase and medications which may impact lysosomal efficacy. Gentamicin slightly increases the intralysosomal pH of proximal tubular cells and decreases the activity of the lysosomal proteinases, cathepsin B and L, which are proteolytic activators of other lysosomal enzymes. Because similar interactions have occurred between gentamicin and other therapies used for a similar disease, the effectiveness of galsulfase therapy should be monitored during coadministration.
    Ganciclovir: (Major) Concurrent use of nephrotoxic agents, such as the aminoglycosides, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Ginger, Zingiber officinale: (Minor) Ginger may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Gold: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
    Halothane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
    Hydrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Ibandronate: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Ibuprofen lysine: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
    Ifosfamide: (Moderate) Nephrotoxic agents, such as the aminoglycosides, can increase the nephrotoxicity of ifosfamide. Damaged kidney tubules may be less likely to convert mesna to its active kidney protecting form, which may contribute to the potential for increased ifosfamide toxicity. Clinicians should be alert for an increased risk of ifosfamide toxicity, including neurotoxicity, renal toxicity, and bone marrow suppression.
    Immune Globulin IV, IVIG, IGIV: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
    Iohexol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iopamidol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iopromide: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Ioversol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Isoflurane: (Moderate) Halogenated anesthetics may be associated with enhanced neuromuscular blocking effects. Aminoglycosides may potentiate this effect, however, it appears this is only seen when aminoglycosides are used to irrigate the abdominal cavity during surgery, a practice which has been discouraged. It is believed that this problem is less likely to occur with parenteral aminoglycoside therapy since patients are exposed to smaller amounts of drug.
    Isosulfan Blue: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Ketamine: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
    Magnesium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Mannitol: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including intravenous mannitol. In addition, intravenous mannitol may alter the serum and tissue concentrations of tobramycin, thereby, increasing the risk for aminoglycoside toxicities. If possible, avoid concurrent use. If these drugs must be used together, it would be prudent to monitor renal function, serum electrolytes, and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates). Studies to evaluate a potential interaction between inhaled formulations of mannitol and tobramycin have not been conducted.
    Meclizine: (Minor) Meclizine and other antiemetics should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo).
    Meperidine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Mesoridazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Methohexital: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Methylprednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Mivacurium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Neuromuscular blockers: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Non-Ionic Contrast Media: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Nonsteroidal antiinflammatory drugs: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as gentamicin.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Pamidronate: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
    Pancuronium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Pentamidine: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Perphenazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Perphenazine; Amitriptyline: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Phenylephrine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Polymyxin B: (Major) The concomitant use of systemic Polymyxin B with systemic aminoglycosides increases the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
    Polymyxins: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
    Prednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Prednisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Propofol: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Pyridostigmine: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
    Rapacuronium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Rocuronium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Salicylates: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Salsalate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Scopolamine: (Minor) Antiemetics, like scopolamine, should be used carefully with amikacin because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Sevoflurane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    Streptozocin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
    Succinylcholine: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Sulfacetamide: (Moderate) Based on the possibility of in vitro antagonism, avoid using sulfacetamide sodium concomitantly with gentamicin sulfate.
    Sulfacetamide; Sulfur: (Moderate) Based on the possibility of in vitro antagonism, avoid using sulfacetamide sodium concomitantly with gentamicin sulfate.
    Surfactants: (Major) Aminoglycosides are commonly given via nebulization to the airway for the prevention and treatment of pneumonia and are known to be at risk for inactivation of their antibiotic activity, mainly due to their susceptibility for changes in pH. A reduced activity of gentamicin may occur in the presence of surfactant.
    Tacrolimus: (Moderate) Additive nephrotoxicity is possible if aminoglycosides are used with tacrolimus. Care should be taken in using tacrolimus with other nephrotoxic drugs. Assessment of renal function in patients who have received tacrolimus is recommended, as the tacrolimus dosage may need to be reduced
    Telavancin: (Major) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs (e.g., systemic aminoglycosides) may lead to additive nephrotoxicity. Televancin is closely related to vancomycin. In one clinical study, vancomycin coadministration, high aminoglycoside trough levels, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Closely monitor renal function and adjust telavancin doses based on creatinine clearance/renal function, and aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
    Tenofovir Alafenamide: (Moderate) Tenofovir-containing products, should be avoided with concurrent or recent use of a nephrotoxic agent, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir, and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
    Tenofovir, PMPA: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Thiopental: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Thioridazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis).
    Torsemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Tretinoin, ATRA: (Moderate) The concomitant use of systemic tretinoin, ATRA and systemic gentamicin should be done cautiously due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.
    Triamcinolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Trifluoperazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Trimethobenzamide: (Minor) Because of trimethobenzamide's antiemetic pharmacology, the drug may effectively mask dizziness, tinnitus, or vertigo that are associated with ototoxicity induced by various medications, including the aminoglycosides. Clinicians should be aware of this potential interaction and take it into consideration when monitoring for aminoglycoside-induced side effects.
    Tubocurarine: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Urea: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including urea. In addition, urea may alter the serum and tissue concentrations of tobramycin, thereby, increasing the risk for aminoglycoside toxicities. If possible, avoid concurrent use. If these drugs must be used together, it would be prudent to monitor renal function, serum electrolytes, and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Valganciclovir: (Major) Concurrent use of nephrotoxic agents, such as aminoglycosides, with valganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Vancomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Vecuronium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aminoglycosides, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
    Zalcitabine, ddC: (Moderate) Drugs such as parenteral aminoglycosides may increase the risk of developing peripheral neuropathy or other zalcitabine-associated adverse events by interfering with the renal clearance of zalcitabine and thereby raising systemic drug exposure. Coadministration of these drugs with zalcitabine requires frequent clinical and laboratory monitoring, with dosage adjustment for any significant change in renal function.
    Zoledronic Acid: (Moderate) Since zoledronic acid is eliminated by the kidney, coadministration of zoledronic acid with other potentially nephrotoxic drugs may increase serum concentrations of either zoledronic acid and/or these coadministered drugs. Theoretically, the chronic coadministration of zoledronic acid with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity.

    PREGNANCY AND LACTATION

    Pregnancy

    Systemic exposure to gentamicin may cause fetal harm during human pregnancy; the drug should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. There have been reports of total irreversible bilateral congenital deafness (eighth cranial nerve toxicity) in children whose mothers received a related aminoglycoside, streptomycin, during pregnancy. Serious side effects to mother, fetus or newborn have not been reported in the treatment of pregnant women with other aminoglycosides. Animal reproduction studies conducted on rats and rabbits did not reveal evidence of impaired fertility or harm to the fetus due to gentamicin sulfate.However, it is not known whether gentamicin sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Gentamicin rapidly crosses the placenta into fetal circulation and amniotic fluid, with peak cord serum levels averaging 34% to 44% of maternal serum concentrations after administration to women in labor. One reported case of potential congenital defects occurred after a 10-day maternal antibiotic course including gentamicin around gestational week 7. At birth, the infant had impaired renal function and small kidneys, and at 4.5 years of age, he was diagnosed with renal cystic dysplasia. It is unknown if fetal gentamicin exposure contributed to the renal problems. In a study of pregnant patients treated for pyelonephritis, the clinical and pregnancy outcomes of 62 patients who received ampicillin plus gentamicin did not differ from patients who received either cefazolin or ceftriaxone monotherapy. A case-control surveillance study that took place from 1980 to 1996 included a small number of women who received gentamicin (n = 19 in case and control groups) and showed no risk for teratogenicity with gentamicin. The ophthalmic and topical preparations of gentamicin do not appear likely to result in fetal harm when used as directed for limited exposure/treatment durations; however, gentamicin has been shown to depress body weights, kidney weights, and median glomerular counts in newborn rats when administered systemically to pregnant rats in daily doses approximately 500 times the maximum recommended ophthalmic human dose.

    Although the manufacturer does not give recommendations for gentamicin use during breast feeding, gentamicin use appears compatible with breast-feeding. Small amounts of gentamicin are excreted into breast milk. In a study of 10 women who received systemic gentamicin prophylaxis (80 mg IM every 8 hours) for 5 days, mean maternal gentamicin serum concentrations on day four obtained 1 and 7 hours after a dose were 3.95 mcg/mL and 1.02 mcg/mL, respectively. Corresponding mean milk concentrations at 1, 3, 5, and 7 hours after the dose were 0.42 mcg/mL, 0.48 mcg/mL, 0.49 mcg/mL, and 0.41 mcg/mL, respectively. Gentamicin also has extremely poor oral bioavailability, and therefore, significant absorption of ingested drug by the breast-fed infant is not expected. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Gentamicin is bactericidal in action. Similar to other aminoglycosides, it works by inhibiting bacterial protein synthesis through irreversible binding to the 30 S ribosomal subunit of susceptible bacteria. Gentamicin is actively transported into the bacterial cell where it binds to receptors present on the 30 S ribosomal subunit. This binding interferes with messenger RNA (mRNA). As a result, abnormal, nonfunctional proteins are formed due to misreading of the bacterial DNA. Eventually, susceptible bacteria die because of the lack of functional proteins. One aspect essential to aminoglycoside lethality is the need to achieve intracellular concentrations in excess of extracellular. Anaerobic bacteria are not susceptible to aminoglycosides due, at least in part, to a lack of an active transport mechanism for aminoglycoside uptake. The uptake of aminoglycosides may be facilitated by the presence of inhibitors of the bacterial cell wall (i.e., beta-lactams, vancomycin).
     
    Against gram-negative aerobic rods, aminoglycosides exhibit 'concentration-dependent killing' and a 'post-antibiotic effect' (PAE). 'Concentration-dependent killing' describes the principle that bactericidal effects increase as the concentration increases. PAE is where suppression of bacterial growth continues after the antibiotic concentration falls below the bacterial MIC. The post-antibiotic effect can be bacteria specific, as well as drug specific. The PAE of aminoglycosides is short for most gram-positive organisms (< 2 hours) and longer for gram-negative organisms (2—8 hours), such as E. coli, K. pneumoniae, and P. aeruginosa. Both of these phenomena are being exploited in designing dosage regimens that employ higher doses administered at longer intervals. The major pharmacodynamic parameters that determine efficacy of aminoglycosides are the serum peak concentration to MIC ratio (peak:MIC) and the AUC to MIC ration (AUC:MIC). Both time-kill studies as well as studies in humans have shown that a peak:MIC of > 8—12:1 is associated with successful regimens. An AUC:MIC ratio of > 125 has also been associated with a successful regimen.
     
    The mechanism of renal toxicity with aminoglycosides is associated with accumulation of aminoglycosides in the renal tubule, which is a saturable process. Elevated serum trough concentrations are associated with an increased risk of toxicity.
     
    The mechanism of ototoxicity relates to the aminoglycoside-induced destruction of sensory hair cells of the inner ear. The cochlear sensory cells that are most vulnerable are in the basal end, thereby leading to high-frequency hearing loss first. As ototoxicity ascends toward the apex of the cochlea, the lower frequencies are affect. Sensory cells that deal with vestibular function may also be affected. Aminoglycosides may cause free-radical damage to sensory cells and neurons. Biochemically, aminoglycosides may bind to polyphospoinositides, which are part of the transmembrane signaling system mediating physiological effects of hormones, neurotransmitters, and neuromodulators which may interfere with essential mechanisms of cell physiology.  Neural destruction without any cochlear hair cell damage has also been described. There may also be a genetic mitochondrial RNA mutation that may predispose some patients to aminoglycoside ototoxicity. Aminoglycosides enter the inner ear rapidly, but it is suggested that aminoglycoside concentrations do not correlate with the development of ototoxicity. Likely, the aminoglycoside concentrations in the inner ear dissipate slowly, which is consistent with the possibility of developing ototoxicity days to weeks after drug discontinuation.
     
    For gram-negative organisms and Staphylococcus aureus the Clinical and Laboratory Standards Institute (CLSI) defines MICs of <= 4 mcg/mL as susceptible, 8 mcg/mL as intermediate, and >= 16 mcg/mL as resistant for gentamicin. However, based on the pharmacodynamic properties of aminoglycosides, an MIC of >= 2 mcg/mL would likely lead to unacceptably low probabilities of good clinical outcome when using reasonable dosage regimens.
     
    Aminoglycoside resistance is well documented. There are a variety of resistance mechanisms employed by different pathogens. Enzymatic inhibition by gram-negative pathogens and Enterococcus sp. via aminoglycoside-modifying enzymes is achieved by modification of the aminoglycoside as it is transported across the cytoplasmic membrane. Alterations in the inner membrane porin channels by Pseudomonas aeruginosa decrease antimicrobial penetration to the site of activity within the bacterial cell. Some gram-negative organisms and Enterococcus sp. can alter the ribosomal target sites of the aminoglycosides to decrease binding, thereby decreasing antimicrobial activity. Aminoglycosides can also be actively transported out of the bacterial cells via efflux pumps.

    PHARMACOKINETICS

    Gentamicin is administered intravenously, intramuscularly, topically, and via the ophthalmic route. Gentamicin distributes into extracellular fluid. Volume of distribution approximates extracellular space; therefore, peak serum concentrations may be lower in patients with a large volume of extracellular fluid. Protein binding of gentamicin is low (0% to 30%). Gentamicin can be detected in the serum, lymph, tissues, sputum, synovial fluid, and peritoneal fluid. Concentrations in the renal cortex may be 8 times higher than in the serum. Gentamicin crosses the peritoneal wall and the placental membranes. There is poor diffusion into the subarachnoid space with systemic administration; therefore, concentrations in the cerebrospinal fluid are often low and dependent upon dose, rate of penetration, and degree of meningeal inflammation. There is minimal penetration into ocular tissues after systemic administration.
     
    Gentamicin is not metabolized. Approximately >= 70% of the gentamicin dose is recovered in the urine after 24 hours. Elimination is almost exclusively via glomerular filtration. Reabsorption of a small amount of the drug by the proximal tubule results in accumulation in the renal cortex, which may be responsible for nephrotoxicity. Renal clearance of gentamicin is similar to endogenous creatinine. The endogenous creatinine clearance rate and serum creatinine concentration have a high correlation with the half-life of gentamicin. Minimal amounts are excreted into bile. Thus, elimination half-life varies according to renal function. Febrile states may be associated with decreased serum concentrations and a shorter half-life. In severely burned patients, the half-life may also be decreased. In patients with normal renal function, the serum half-life is approximately 2 hours; however, there is considerable interpatient variation.

    Oral Route

    Gentamicin is not absorbed when administered orally.

    Intravenous Route

    When administered by IV infusion over a 2-hour period, gentamicin serum concentrations are similar to those obtained by intramuscular administration.

    Intramuscular Route

    After intramuscular administration, gentamicin peak serum concentrations usually occur between 30 to 60 minutes and are similar to those obtained from intravenous infusion. In patients with normal renal function, peak serum concentrations are usually up to 4 times the single intramuscular dose (i.e., 1 mg/kg dose yields approximately a 4 mcg/mL peak serum concentration) with some interpatient variability. Gentamicin, administered at doses of 1 mg/kg every 8 hours for 7 to 10 days, is unlikely to accumulate in the serum in patients with normal renal function. Higher doses and/or prolonged periods of treatment may cause gentamicin accumulation. Doses of 4 mg/kg/day or higher may result in a slight, progressive rise in both peak and trough concentrations.

    Topical Route

    Gentamicin may be used as a topical cream or ointment. Systemic absorption from application to intact skin is negligible. However, topical gentamicin may be absorbed systemically from areas of denuded, burned or granulating areas, or via topical sinus irrigation. However, unless applied to very large areas and for long durations of time, detectable serum levels are usually well below levels associated with systemic therapy.

    Other Route(s)

    Ophthalmic Route
    Gentamicin is administered topically to the eye as a solution or as an ointment. Systemic absorption by these routes is expected to be negligible.