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Gentamicin (Systemic)

Pronunciation

Pronunciation

(jen ta MYE sin)

Index Terms

  • Gentamicin Sulfate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Generic: 10 mg/mL (2 mL); 40 mg/mL (2 mL, 20 mL)

Solution, Injection [preservative free]:

Generic: 10 mg/mL (2 mL)

Solution, Intravenous:

Generic: 60 mg (50 mL); 70 mg (50 mL); 80 mg (50 mL, 100 mL); 90 mg (100 mL); 100 mg (50 mL, 100 mL); 120 mg (100 mL); 10 mg/mL (6 mL, 8 mL [DSC], 10 mL)

Pharmacologic Category

  • Antibiotic, Aminoglycoside

Pharmacology

Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits resulting in a defective bacterial cell membrane

Absorption

Intramuscular: Rapid and complete; Oral: Poorly absorbed (<1%) (MacDougall 2011)

Distribution

Primarily into extracellular fluid (highly hydrophilic); high concentration in the renal cortex; minimal penetration to CSF and ocular tissues via IV route

Vd: Higher in neonates than older pediatric patients; increased by edema, ascites, fluid overload; decreased with dehydration

Neonates: 0.45 ± 0.1 L/kg

Infants: 0.4 ± 0.1 L/kg

Children:0.35 ± 0.15 L/kg

Adolescents: 0.3 ± 0.1 L/kg

Adults: 0.2 to 0.3 L/kg (Leggett 2015)

CSF:blood level ratio: Normal meninges: <10%; Inflamed meninges: ≤25% (MacDougall 2011)

Excretion

Urine (>70% as unchanged drug)

Clearance: Directly related to renal function

Neonates: 0.045 ± 0.01 L/hour/kg

Infants: 0.1 ± 0.05 L/hour/kg

Children: 0.1 ± 0.03 L/hour/kg

Adolescents: 0.09 ± 0.03 L/hour/kg

Time to Peak

Serum: IM: 30 to 90 minutes; IV: 30 minutes after 30-minute infusion (MacDougall 2011); Note: Distribution may be prolonged after larger doses. One study reported a 1.7-hour distribution period after a 60-minute, high-dose aminoglycoside infusion (Demczar 1997).

Half-Life Elimination

Neonates: <1 week: 3 to 11.5 hours; 1 week to 1 month: 3 to 6 hours

Infants: 4 ± 1 hour

Children: 2 ± 1 hour

Adolescents: 1.5 ± 1 hour

Adults: ~2 hours (Regamey 1973); Renal failure: mean: 41 ± 24 hours; Range: 6 to 127 hours (Dager 2006)

Protein Binding

<30%

Special Populations: Renal Function Impairment

Clearance is decreased in renal impairment.

Use: Labeled Indications

Serious infections: Treatment of serious infections (eg, sepsis, meningitis, urinary tract infections, respiratory tract infections, peritonitis, bone infections, skin and soft tissue infections) caused by susceptible strains of the following microorganisms: P. aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella species, Enterobacter species, Serratia species, Citrobacter species, and Staphylococcus species (coagulase-positive and coagulase-negative); treatment of infective endocarditis caused by enterococci, in combination with other antibiotics.

Use: Unlabeled

Surgical (preoperative) prophylaxis

Contraindications

Hypersensitivity to gentamicin, other aminoglycosides, or any component of the formulation

Dosing: Adult

In underweight and nonobese patients, use of total body weight (TBW) instead of ideal body weight for determining the initial mg/kg/dose is widely accepted (Nicolau 1995). Ideal body weight (IBW) also may be used to determine doses for patients who are neither underweight nor obese (Gilbert 2009).

Initial and periodic plasma drug levels (eg, peak and trough with conventional dosing, post dose level at a prespecified time with extended-interval dosing) should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery).

Usual dosage ranges:

Conventional: IM, IV: 3 to 5 mg/kg/day in divided doses every 8 hours

Once daily (extended-interval dosing [EID]): IV: 5 to 7 mg/kg/day once daily; not recommended in patients with ascites, burns covering >20% of the total body surface area, cystic fibrosis, end-stage renal disease (eg, requiring hemodialysis), endocarditis, infants, mycobacterial infections, or pregnancy (Bailey 1997; Nicolau 1995)

Indication-specific dosing: IM, IV:

Brucellosis (off-label use): 5 mg/kg once daily for 7 days (range: 5 to 14 days); administered in combination with 6 weeks of doxycycline (Ariza 2007). Additional data may be necessary to further define the role of gentamicin in this condition.

Cerebrospinal fluid (CSF) shunt infection (off-label route): Intraventricular: 4 to 8 mg/day (IDSA [Tunkel 2004])

Gonococcal infection, uncomplicated (patients with severe cephalosporin allergy) (off-label use): IM: 240 mg as a single dose in combination with oral azithromycin (CDC [Workowski 2015])

Granuloma inguinale (donovanosis) (off-label use): 1 mg/kg/dose every 8 hours; gentamicin must be used in addition to the recommended antibiotic agent and only if improvement is not evident within the first days of therapy (CDC [Workowski 2015])

Infective endocarditis, treatment (AHA [Baddour 2015]):

Enterococcus (native or prosthetic valve) (off-label dose): IV, IM: 3 mg/kg/day in 2 or 3 divided doses in combination with a beta-lactam or vancomycin (choice of concomitant antibiotic and treatment duration are dependent on organism sensitivity testing and source of infection)

S. aureus (prosthetic valve; methicillin-susceptible or methicillin-resistant) (off-label dose): IV, IM: 3 mg/kg/day in 2 or 3 divided doses for 2 weeks; use in combination with other antibiotics (choice of concomitant antibiotic dependent on organism sensitivity testing)

Viridans group streptococcus (VGS) and S. bovis (native or prosthetic valve) (off-label use): IV, IM: 3 mg/kg/day once daily (preferred) or in 3 divided doses (alternative) in combination with other antibiotics (choice of concomitant antibiotic and treatment duration are dependent on organism sensitivity testing and source of infection)

Meningitis due to Enterococcus spp (off-label use) or Pseudomonas aeruginosa: IV: 5 mg/kg/day in divided doses every 8 hours (administered with other antimicrobials [varies by causative organism and susceptibility]) (IDSA [Tunkel 2004])

Pelvic inflammatory disease (off-label): Loading dose: 2 mg/kg IV or IM, then 1.5 mg/kg IV every 8 hours or 3 to 5 mg/kg IV once daily in combination with clindamycin IV. Transition from parenteral to oral therapy can usually be initiated within 24 to 48 hours of clinical improvement for a total treatment duration of 14 days (CDC [Workowski 2015])

Plague (Yersinia pestis), treatment (off-label use): 5 mg/kg/dose once daily or 2 mg/kg loading dose, then 1.7 mg/kg/dose every 8 hours; duration of therapy is 10 to 14 days, or until 2 days after patient is afebrile (CDC 2015)

Pneumonia, hospital-acquired or ventilator-associated (off-label): IV: 5 to 7 mg/kg/day once daily for 7 days; may consider shorter or longer duration depending on rate of clinical improvement. When used as empiric therapy, use in combination with an agent active against S. aureus and an additional antipseudomonal agent. Note: Aminoglycosides are not recommended as monotherapy in patients with hospital-acquired or ventilator-associated pneumonia due to P. aeruginosa. (Kalil 2016)

Surgical (preoperative) prophylaxis (off-label use): IV: 5 mg/kg within 60 minutes prior to surgical incision with or without other antibiotics (procedure dependent). Note: Dose is based on actual body weight unless >20% above ideal body weight, then dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW) (Bratzler 2013)

Tularemia (off-label use): 5 mg/kg/dose once daily for 10 days (Dennis 2001) or 5 mg/kg/day in 2 divided doses for ≥10 days (WHO 2007)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Individualization is critical because of the low therapeutic index.

Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW).

Initial and periodic plasma drug levels (eg, peak and trough with conventional dosing) should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery).

Usual dosage ranges: IM, IV:

Infants: IM, IV: 2.5 mg/kg/dose every 8 hours

Children and Adolescents: IM, IV: 2 to 2.5 mg/kg/dose every 8 hours

Surgical (preoperative) prophylaxis (off-label use): Children: IV: 2.5 mg/kg within 60 minutes prior to surgical incision with or without other antibiotics (procedure dependent). Note: Dose is based on actual body weight unless >20% above ideal body weight, then dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW) (Bratzler 2013).

Dosing: Renal Impairment

Adults:

Conventional dosing:

Manufacturer’s labeling: Administer usual dosage for initial dose, then estimate reduced dose by dividing initial dose by patient’s serum creatinine level (in mg/dL) and administer every 8 hours (eg, a 60 kg patient with serum creatinine of 2 mg/dL at a dose of 1 mg/kg would receive an initial dose of 60 mg, followed by 30 mg every 8 hours)

Alternate dosing (Aronoff 2007): Note: Renally adjusted dose recommendations are based on doses of 1.7 mg/kg/dose every 8 hours or 5 to 7 mg/kg/dose once daily.

GFR >50 mL/minute: No dosage adjustment necessary.

GFR 10 to 50 mL/minute: Administer every 12 to 48 hours

GFR <10 mL/minute: Administer every 48 to 72 hours

Once daily (extended-interval dosing (EID)) (Nicolau 1995; Bailey 1997): Note: Base initial dosing interval on the following; adjust interval based on serum levels using institution-specific policies.

CrCl ≥60 mL/minute: Administer every 24 hours

CrCl 40 to 59 mL/minute: Administer every 36 hours

CrCl 20 to 39 mL/minute: Administer every 48 hours

CrCl <20 mL/minute: Monitor serum levels and redose when gentamicin level is less than 1 mcg/mL or use conventional dosing.

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days) (Heintz 2009): Dialyzable (~50%; variable; dependent on filter, duration, and type of IHD):

Loading dose of 2 to 3 mg/kg loading dose followed by:

Mild UTI or synergy: 1 mg/kg/dose every 48 to 72 hours; consider redosing for pre-HD or post-HD concentrations <1 mg/L

Moderate-to-severe UTI: 1 to 1.5 mg/kg/dose every 48 to 72 hours; consider redosing for pre-HD concentrations <1.5 to 2 mg/L or post-HD concentrations <1 mg/L

Systemic gram-negative rod infection: 1.5 to 2 mg/kg/dose every 48 to 72 hours; consider redosing for pre-HD concentrations <3 to 5 mg/L or post-HD concentrations <2 mg/L

Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.

Peritoneal dialysis (PD) (Li 2010):

Intermittent dosing: 0.6 mg/kg per exchange once daily; allow to dwell ≥6 hours

Continuous dosing (all exchanges): Loading dose: 8 mg/L; maintenance dose: 4 mg/L

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as target drug concentrations (if appropriate). Note: The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH/CVVHD/CVVHDF:

Mild UTI or synergy: Loading dose of 2 to 3 mg/kg/dose followed by 1 mg/kg every 24 to 36 hours (redose when concentration <1 mg/L [Heintz 2009])

Moderate to severe UTI: Loading dose of 2 to 3 mg/kg/dose followed by 1 to 1.5 mg/kg every 24 to 36 hours (redose when concentration <1.5 to 2 mg/L [Heintz 2009])

Systemic gram-negative infection: Loading dose of 2 to 3 mg/kg/dose followed by 1.5 to 2.5 mg/kg every 24 to 48 hours (generally accepted to redose when concentration <2 mg/L; one reference suggests redosing when <3 mg/L [Heintz 2009])

Infants, Children, and Adolescents:

The following adjustments have been recommended (Aronoff 2007): Note: Renally adjusted dose recommendations are based on doses of 2.5 mg/kg/dose every 8 hours:

GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary.

GFR 30 to 50 mL/minute/1.73 m2: Administer every 12 to 18 hours

GFR 10 to 29 mL/minute/1.73 m2: Administer every 18 to 24 hours

GFR <10 mL/minute/1.73 m2: Administer every 48 to 72 hours

Intermittent hemodialysis (IHD): 2 mg/kg/dose; redose as indicated by serum concentration

Peritoneal dialysis (PD): 2 mg/kg/dose; redose as indicated by serum concentration

Continuous renal replacement therapy (CRRT): 2 to 2.5 mg/kg/dose every 12 to 24 hours, monitor serum concentrations.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; however dosage adjustment is not likely to be necessary (does not undergo hepatic metabolism).

Dosing: Obesity

In moderate obesity (TBW/IBW ≥1.25) or greater (eg, morbid obesity [TBW/IBW >2]), initial dosage requirement may be estimated using a dosing weight of IBW + 0.4 (TBW - IBW) (Traynor 1995).

Administration

IM: Administer by deep IM route if possible.

IV: Infuse over 30 to 120 minutes.

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.

Compatibility

Stable in dextran 40, D5W, D10W, mannitol 20%, LR, NS; incompatible with fat emulsion 10%.

Y-site administration: Incompatible with allopurinol, amphotericin B cholesteryl sulfate complex, azithromycin, furosemide, hetastarch in NS, idarubicin, indomethacin, iodipamide meglumine, pemetrexed, propofol, warfarin.

Storage

Store intact vials and premixed bags at 20°C to 25°C (68°F to 77°F). Protect from freezing. IV infusion solutions mixed in NS or D5W are stable for 48 hours at room temperature and refrigeration (Goodwin 1991).

Drug Interactions

AbobotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of AbobotulinumtoxinA. Monitor therapy

Agalsidase Alfa: Gentamicin (Systemic) may diminish the therapeutic effect of Agalsidase Alfa. Avoid combination

Agalsidase Beta: Gentamicin (Systemic) may diminish the therapeutic effect of Agalsidase Beta. Avoid combination

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin may enhance the ototoxic effect of Aminoglycosides. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Monitor therapy

CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Monitor therapy

Cardiac Glycosides: Aminoglycosides may decrease the serum concentration of Cardiac Glycosides. This effect has only been demonstrated with oral aminoglycoside administration. Monitor therapy

Cefazedone: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (2nd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (3rd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (4th Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalothin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephradine: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Consider therapy modification

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy

OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Monitor therapy

Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Monitor therapy

Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Consider therapy modification

RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Test Interactions

Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro, leading to a potential underestimation of aminoglycoside serum concentration.

Adverse Reactions

Frequency not defined.

Cardiovascular: Edema, hypertension, hypotension, phlebitis, thrombophlebitis

Central nervous system: Abnormal gait, ataxia, brain disease, confusion, depression, dizziness, drowsiness, headache, lethargy, myasthenia, numbness, paresthesia, peripheral neuropathy, pseudomotor cerebri, seizure, vertigo

Dermatologic: Alopecia, erythema, pruritus, skin rash, urticaria

Endocrine & metabolic: Hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, weight loss

Gastrointestinal: Anorexia, Clostridium difficile-associated diarrhea, decreased appetite, enterocolitis, nausea, sialorrhea, stomatitis, vomiting

Genitourinary: Casts in urine (hyaline, granular), changes in distal tubules (dysfunction), Fanconi-like syndrome (infants and adults; high dose, prolonged course), oliguria, proteinuria

Hematologic & oncologic: Agranulocytosis, anemia, eosinophilia, granulocytopenia, leukopenia, purpura, reticulocytopenia, reticulocytosis, splenomegaly, thrombocytopenia

Hepatic: Hepatomegaly, increased liver enzymes

Hypersensitivity: Anaphylaxis, anaphylactoid reaction, hypersensitivity reaction

Local: Injection site reaction, pain at injection site

Neuromuscular & skeletal: Arthralgia, muscle cramps, muscle fatigue (myasthenia gravis-like syndrome), muscle twitching, tremor, weakness

Ophthalmic: Visual disturbance

Otic: Auditory impairment, hearing loss (associated with persistently increased serum concentrations; early toxicity usually affects high-pitched sound), tinnitus

Renal: Decreased creatinine clearance, decreased urine specific gravity, increased blood urea nitrogen, increased serum creatinine, polyuria, renal failure (high trough serum concentrations), renal tubular necrosis

Respiratory: Dyspnea, laryngeal edema, pulmonary fibrosis, respiratory depression

Miscellaneous: Fever

ALERT: U.S. Boxed Warning

Toxicity:

Ensure that patients treated with aminoglycosides are under close clinical observation because of the potential toxicity associated with their use.

As with other aminoglycosides, gentamicin is potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosages or prolonged therapy.

Neurotoxicity, manifested by ototoxicity, both vestibular and auditory, can occur in patients treated with gentamicin, primarily in those with preexisting renal damage and in patients with healthy renal function treated with higher doses and/or for longer periods than recommended. Aminoglycoside-induced ototoxicity is usually irreversible. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions.

Closely monitor renal and eighth cranial nerve functions, especially in patients with known or suspected reduced renal function at onset of therapy, and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Examine urine for decreased specific gravity, increased excretion of protein, and the presence of cells or casts. Periodically determine serum urea nitrogen (BUN), serum creatinine, or creatinine clearance (CrCl). When feasible, it is recommended that serial audiograms be obtained in patients old enough to be tested, particularly high-risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, or hearing loss) or nephrotoxicity requires dosage adjustment or discontinuance of the drug. As with the other aminoglycosides, on rare occasions, changes in renal and eighth cranial nerve function may not manifest until soon after completion of therapy.

Monitor serum concentrations of aminoglycosides when feasible to ensure adequate levels and to avoid potentially toxic levels. When monitoring gentamicin peak concentrations, adjust dosage so that prolonged levels above 12 mcg/mL are avoided. When monitoring gentamicin trough concentrations, adjust dosage so that levels above 2 mcg/mL are avoided. Excessive peak or trough serum concentrations of aminoglycosides may increase the risk of renal and eighth cranial nerve toxicity. In the event of overdose or toxic reactions, hemodialysis may aid in the removal of gentamicin from the blood, especially if renal function is, or becomes, compromised. The rate of removal of gentamicin is considerably less by peritoneal dialysis than by hemodialysis.

Avoid concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as cisplatin, cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, and viomycin. Other factors that may increase patient risk of toxicity are advanced age and dehydration.

Avoid the concurrent use of gentamicin with potent diuretics, such as ethacrynic acid or furosemide, since certain diuretics by themselves may cause ototoxicity. In addition, when administered intravenously (IV), diuretics may enhance aminoglycoside toxicity by altering the antibiotic concentration in serum and tissue.

Pregnancy:

Aminoglycosides can cause fetal harm when administered to a pregnant woman.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Cross-sensitivity to other aminoglycosides may occur.

• Nephrotoxicity: [US Boxed Warning]: May cause nephrotoxicity; usual risk factors include preexisting renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible.

• Neuromuscular blockade and respiratory paralysis: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or neuromuscular blockers.

• Neurotoxicity: [US Boxed Warning]: May cause neurotoxicity; usual risk factors include preexisting renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Electrolyte abnormalities: Use with caution in patients with hypocalcemia, hypokalemia, or hypomagnesemia.

• Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss.

• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis.

• Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.

Special populations:

• Pregnancy: [US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Neurotoxic and/or nephrotoxic drugs: [US Boxed Warning]: Avoid concomitant or sequential use of other neurotoxic and/or nephrotoxic drugs (eg, cisplatin, polymyxin B, colistin, vancomycin, other aminoglycosides).

• Potent diuretics: [US Boxed Warning]: Avoid concomitant use with potent diuretics (eg, ethacrynic acid, furosemide) since diuretics themselves may cause ototoxicity and may enhance aminoglycoside toxicity.

Other warnings/precautions:

• Long-term use: Risk of toxicity is increased with extended duration of administration; additional monitoring may be required with long-term use.

• Surgical irrigation: May be almost completely systemically absorbed after local irrigation and/or topical application (except to the urinary bladder) during surgical procedures. Consider potential for nephrotoxicity, neuromuscular blockade, ototoxicity, and respiratory paralysis when administering aminoglycosides in this manner.

Monitoring Parameters

Urinalysis, urine output, BUN, serum creatinine, plasma gentamicin levels (as appropriate to dosing method). Levels are typically obtained after the third dose in conventional dosing. Hearing should be tested before, during, and after treatment; particularly in those at risk for ototoxicity or who will be receiving prolonged therapy (>2 weeks)

Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.

Pregnancy Risk Factor

D

Pregnancy Considerations

[US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman. Gentamicin crosses the placenta. There are several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists.

Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of gentamicin may be altered (Popović 2007). Gentamicin use has been evaluated for various infections in pregnant women including the treatment of acute pyelonephritis (Jolley 2010) and as an alternative antibiotic for prophylactic use prior to cesarean delivery (Bratzler 2013).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), change in balance, severe dizziness, passing out, hearing loss, tinnitus, muscle weakness, burning or numbness feeling, twitching, seizures, shortness of breath, illogical thinking, depression, vision changes, or severe headache (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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