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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Gentamicin (systemic): Drug information

Gentamicin (systemic): Drug information
(For additional information see "Gentamicin (systemic): Patient drug information" and see "Gentamicin (systemic): Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
ALERT: US 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.

Pharmacologic Category
  • Antibiotic, Aminoglycoside
Dosing: Adult

Note: Aminoglycoside dosing weight: For underweight patients (ie, total body weight [TBW] < ideal body weight [IBW]), calculate the dose based on TBW. For nonobese patients (ie, TBW 1 to 1.25 × IBW), calculate the dose based on TBW or IBW. TBW may be preferred in nonobese patients who may have increased Vd (eg, critically ill). For obese patients (ie, TBW >1.25 x IBW), use 40% adjusted body weight ([0.4 x {TBW-IBW}] + IBW) for initial weight-based dosing and for estimating kidney function with Cockcroft-Gault (CrCl) (Bailey 1997; Blackburn 2015; Nicolau 1995; Pai 2014; Rea 2008; Traynor 1995). Therapeutic drug monitoring: Monitoring of serum concentrations is recommended to ensure efficacy and avoid toxicity, particularly in critically ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, major surgery). Timing and frequency of concentration monitoring is individualized based on dosing and monitoring strategy (Buijk 2002; Drew 2020; Nezic 2014).

Usual dosage range:

Gram-negative infections:

Conventional/traditional dosing: IV, IM: 3 to 5 mg/kg/day in divided doses every 8 hours (Zaske 1982; manufacturer's labeling). Some experts favor an initial loading dose of 2.5 to 3 mg/kg (Drew 2020). Target peak concentration depends on indication and site of infection; in general, adjust dose to achieve peak of 4 to 6 mcg/mL for urinary tract infections and 7 to 10 mcg/mL for serious infections (including life-threatening infections). Target trough concentrations should be <2 mcg/mL; ideal target <1 mcg/mL (Bertino 1994; Drew 2020; Matzke 1983).

High-dose extended-interval dosing (once-daily dosing): IV: 5 to 7 mg/kg once daily; use with caution in patients with CrCl <40 mL/minute (Bailey 1997; Buijk 2002; Drew 2020; Hodiamont 2017; Nicolau 1995). Adjust gentamicin dose and interval to achieve an extrapolated peak concentration of ~15 to 20 mcg/mL and trough concentration ≤1 mcg/mL; ideal target <0.5 mcg/mL (Buijk 2002; Drew 2020; Leggett 2015; Nicolau 1995; Pagkalis 2011). Note: Published nomograms for dosage adjustment may not apply to patients with altered pharmacokinetics (eg, patients with ascites, burns covering >20% total BSA, end-stage renal disease requiring hemodialysis, pregnancy) (Bailey 1997; Nicolau 1995); some experts do not use this method in such populations (Drew 2020).

Synergy dosing for non-CNS gram-positive infections:

IV, IM: 3 mg/kg/day in 1 to 3 divided doses in combination with a gram-positive active agent (AHA [Baddour 2015]; Leggett 2015; Olaison 2002). When divided doses are used, adjust gentamicin dose to achieve peak concentration of 3 to 4 mcg/mL and trough concentration <1 mcg/mL (AHA [Baddour 2015]).

Indication-specific dosing:

Bartonella spp. infections (off-label use):

Bacteremia with or without endocarditis: IV: 3 mg/kg/day in 1 or 3 divided doses in combination with doxycycline for 2 weeks, followed by doxycycline monotherapy (Foucault 2003; Rolain 2004; Spach 2019b; Spach 2019c; Spach 2019d). Some experts do not suggest gentamicin as part of the regimen for patients with HIV and bacteremia without endocarditis (HHS [OI adult 2020]).

Cat scratch disease, disseminated (eg, hepatosplenic, prolonged systemic febrile illness) (alternative agent): IV: 2 mg/kg as a single loading dose, followed by 1.5 mg/kg every 8 hours in combination with rifampin for 10 to 14 days (Spach 2019a).

Note: In contrast to other gram-negative infections, target a gentamicin peak concentration of 3 to 4 mcg/mL and trough concentration of <1 mcg/mL when divided doses are used (Spach 2019b; Spach 2019d).

Bloodstream infection:

Adjunctive empiric therapy for patients with sepsis/septic shock and concern for resistant gram-negative bacteria (eg, immunosuppression, prevalent local resistance, recent antibiotic exposure): IV: 5 to 7 mg/kg once daily in combination with a second gram-negative active agent; once culture and susceptibility results are available, can generally discontinue and use a single agent with documented activity. Gentamicin should not be used as monotherapy (Gilbert 1998; Machuca 2017; Moehring 2019; Nicolau 1995; SCCM [Rhodes 2017]; Shields 2016).

Antibiotic lock technique (catheter-salvage strategy) (off-label use): Note: For infections caused by susceptible organisms when the catheter cannot be removed; use in addition to systemic antibiotics (Girand 2019; IDSA [Mermel 2009]).

Intracatheter: Prepare lock solution to final concentration of gentamicin 1 to 5 mg/mL (may be combined with heparin) (Battistella 2010; Fortún 2006; IDSA [Mermel 2009]; Vercaigne 2002). The gentamicin concentration may vary by institution, catheter type, and whether heparin is utilized; solutions with heparin are preferred. Prepare solution immediately before instillation with a sufficient volume to fill the catheter (2 to 5 mL). Instill into each lumen of the catheter access port with a dwell time of up to 72 hours, depending on frequency of catheter use. Withdraw lock solution prior to catheter use; replace with fresh gentamicin lock solution after catheter use. Antibiotic lock therapy is given for the same duration as systemic antibiotics (Girand 2019; IDSA [Mermel 2009]; Krishnasami 2002).

Brucellosis (alternative agent) (off-label use):

IV, IM: 5 mg/kg once daily in combination with doxycycline. Note: Duration depends on extent of disease; gentamicin is usually given for the first 5 to 14 days of therapy, followed by doxycycline monotherapy (Ariza 2007; Hasanjani Roushan 2006; Skalsky 2008). Additional agents or other regimens are preferred for neurobrucellosis, endocarditis, and infection in pregnant women (Bosilkovski 2019).

CNS infection, health care-associated (eg, cerebrospinal fluid [CSF] shunt infection) (adjunct to systemic therapy):

Note: Reserved for infections due to multidrug-resistant organisms, infections refractory to appropriate parenteral therapy, or when infected shunts cannot be removed (Baddour 2019; Friedman 2019).

Intraventricular (use a preservative-free preparation): Initial: 4 to 8 mg/day; some experts recommend adjusting dosage and administration interval based on CSF gentamicin concentrations (goal: 10 to 20 times MIC of causative organism), ventricle size, and daily output from ventricular drain (IDSA [Tunkel 2017]). When intraventricular gentamicin is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF). Duration is individualized according to clinical and microbiologic response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Endocarditis, treatment:

Enterococcus spp. (native or prosthetic valve, without high-level gentamicin resistance): IV, IM: 1 mg/kg every 8 hours as part of an appropriate combination regimen. Duration is 4 to 6 weeks depending on duration of symptoms prior to presentation, source of infection, and the specific combination regimen (AHA [Baddour 2015]). Note: For native-valve endocarditis due to ampicillin-susceptible Enterococcus faecalis, some experts prefer a combination regimen that does not contain gentamicin (Sexton 2020a).

Staphylococcus spp. (prosthetic valve) (off-label use): IV, IM: 1 mg/kg every 8 hours for the first 2 weeks of an appropriate combination regimen; the other components should be continued for a total of ≥6 weeks (AHA [Baddour 2015]).

Viridans group streptococci and Streptococcus bovis (off-label use):

Native valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): IV, IM: 3 mg/kg/day once daily (preferred) or in 3 divided doses (alternative) in combination with a beta-lactam for 2 weeks. Note: This regimen is reserved for patients with uncomplicated infection, prompt response to therapy, and no preexisting renal failure (AHA [Baddour 2015]).

Native valve: Relatively penicillin-resistant (MIC >0.12 and <0.5 mcg/mL): IV, IM: 3 mg/kg/day once daily (preferred) or in 3 divided doses (alternative) in combination with a beta-lactam. Gentamicin duration is for the first 2 weeks of the total 4-week regimen (AHA [Baddour 2015]).

Native valve: Penicillin-resistant (MIC ≥0.5 mcg/mL): IV, IM: 3 mg/kg/day in 2 to 3 divided doses in combination with a beta-lactam. The duration of this regimen is not well established; infectious diseases consultation recommended (AHA [Baddour 2015]).

Prosthetic valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): IV, IM: 3 mg/kg/day once daily (preferred) or in 3 divided doses (alternative) in combination with a beta-lactam. Gentamicin duration is for the first 2 weeks of the total 6-week regimen (AHA [Baddour 2015]).

Prosthetic valve: Relatively penicillin-resistant (MIC >0.12 and <0.5 mcg/mL) or fully penicillin-resistant (MIC ≥0.5 mcg/mL): IV, IM: 3 mg/kg/day once daily or in 3 divided doses in combination with a beta-lactam for 6 weeks (AHA [Baddour 2015]); some experts prefer 3 divided doses for these isolates and also prefer shorter courses of the gentamicin component (≥2 weeks) for relatively penicillin-resistant strains (Karchmer 2020).

Meningitis, bacterial:

Enterococcus spp.: IV: 5 mg/kg/day in 1 or 3 divided doses (IDSA [Tunkel 2004]; Murray 2020); give as part of an appropriate combination regimen and individualize duration based on clinical response (IDSA [Tunkel 2004]; Murray 2020; Pintado 2003).

Listeria monocytogenes: IV: 5 mg/kg/day in 3 divided doses in combination with ampicillin or penicillin. Gentamicin is given until clinical improvement (typically ≥7 days) or in poor responders for up to 21 days, as long as there are no signs of nephrotoxicity or ototoxicity; total duration of antibiotic therapy is ≥21 days (Gelfand 2020; IDSA [Tunkel 2017]; Tunkel 2019).

Osteomyelitis, prevention, following open fractures (type III [severe contamination or comminution]) (off-label use): IV: 5 mg/kg every 24 hours as part of an appropriate combination regimen; ideally administer within 6 hours of injury. Duration is 72 hours after injury or up to 24 hours after wound closure (EAST [Hoff 2011]; Russell 2001; Schmitt 2020).

Pelvic infections (off-label use):

Note: Dose is based on actual body weight. For patients >1.2 × IBW, use 40% adjusted body weight (IBW + [0.4 × (TBW-IBW)]) (ACOG 2018).

Intra-amniotic infection (chorioamnionitis): IV: 5 mg/kg once daily (preferred) or 2 mg/kg loading dose followed by 1.5 mg/kg every 8 hours (alternative); give in combination with ampicillin. In women undergoing cesarean delivery, an anti-anaerobic agent should also be added. Continue regimen until vaginal delivery or for 1 dose after cesarean delivery (ACOG 2017; Locksmith 2005; Martingano 2019). Note: Some experts recommend 1 additional dose after vaginal delivery and extension of antibiotics after cesarean delivery until patient is afebrile and asymptomatic ≥48 hours (Tita 2019).

Postpartum endometritis: IV: 5 mg/kg once daily (preferred) or 1.5 mg/kg every 8 hours (alternative). Give in combination with clindamycin. Treat until the patient is clinically improved (no fundal tenderness) and afebrile for 24 to 48 hours (Chen 2021; Del Priore 1996; Livingston 2003; Mackeen 2015). Note: For women known to be colonized with group B Streptococcus, additional agents or other regimens are preferred (Chen 2021).

Peritonitis, treatment (peritoneal dialysis patients) (off-label use): As a component of empiric therapy or for pathogen-directed therapy.

Note: Intraperitoneal administration is preferred to IV administration. Once culture results are available, switch to another active antibiotic class, if possible, to decrease the risk of toxicity; otherwise, duration of therapy is ≥3 weeks for patients with adequate clinical response (Burkart 2019; ISPD [Li 2016]). Consider a 25% dose increase in patients with significant residual renal function (urine output >100 mL/day) (ISPD [Li 2010]; ISPD [Li 2016]; Mancini 2018; Szeto 2018).

Intermittent (strongly preferred): Intraperitoneal: 0.6 mg/kg added to one exchange of dialysis solution once daily (allow to dwell ≥6 hours) (ISPD [Li 2016]).

Continuous (with every exchange) (dose is per liter of dialysate): Intraperitoneal: Loading dose: 8 mg/L of dialysate with first exchange of dialysate; maintenance dose: 4 mg/L of dialysate with each subsequent exchange of dialysate (ISPD [Li 2016]).

Plague ( Yersinia pestis ), treatment (off-label use):

IV, IM: 5 mg/kg once daily or 2 mg/kg loading dose, then 1.7 mg/kg every 8 hours; duration of therapy is 7 to 14 days and at least until 2 days after patient has defervesced (CDC 2015; Inglesby 2000; Stout 2021).

Sepsis or septic shock, adjunctive empiric gram-negative coverage (eg, in the setting of intra-abdominal infection, pneumonia, gram-negative bacteremia, or severe burn):

Note: Some experts reserve for patients with immunocompromising conditions or risk for resistant gram-negative pathogens, in particular Pseudomonas aeruginosa (Moehring 2019; Schmidt 2019).

IV: 5 to 7 mg/kg once daily in combination with a second gram-negative agent (SCCM [Rhodes 2017]; Schmidt 2019); once culture and susceptibility tests are available, can generally discontinue and use a single agent with documented activity. Gentamicin should not be used as monotherapy for severe infections outside of the urinary tract (Gilbert 1998; Kanj 2020; Machuca 2017; Nicolau 1995; SCCM [Rhodes 2017]; Schmidt 2019; Shields 2016).

Sexually transmitted infections:

Gonococcal infection, uncomplicated (infection of the cervix, urethra, or rectum) (alternative agent in severe cephalosporin allergy) (off-label use): IM: 240 mg (administer as two 3 mL injections) in combination with oral azithromycin, each as a single dose (CDC [St. Cyr 2020]; CDC [Workowski 2015]; Kirkcaldy 2014; Ross 2019). Note: For treatment failure, consult an infectious diseases specialist and report to the CDC through state and local health departments within 24 hours of diagnosis (CDC [St. Cyr 2020]; CDC [Workowski 2015]).

Pelvic inflammatory disease (including tubo-ovarian abscess) (off-label use): IV, IM: 3 to 5 mg/kg once daily or 2 mg/kg as a loading dose followed by 1.5 mg/kg every 8 hours; give as part of an appropriate combination regimen; after 24 to 48 hours of sustained clinical improvement, transition to oral therapy to complete at least 14 days of treatment (CDC [Workowski 2015]).

Surgical prophylaxis (alternative agent for select GI tract, GU tract, or gynecologic/obstetric procedures) (off-label use):

IV: 5 mg/kg as a single dose within 60 minutes prior to surgical incision; give in combination with other antibiotics (procedure dependent) (ASHP/IDSA/SIS/SHEA [Bratzler 2013]). Note: In cases where extension of prophylaxis is warranted postoperatively, total duration should be ≤24 hours (Anderson 2019). Postoperative prophylaxis is not recommended in clean and clean-contaminated surgeries (CDC [Berríos-Torres 2017]).

Tularemia (off-label use):

IV, IM: 5 mg/kg/day in 1 to 3 divided doses (Dennis 2001; IDSA [Stevens 2014]; Penn 2020; WHO 2007); duration is generally 7 to 10 days but should be extended for severe cases or for patients with a delayed response to treatment (IDSA [Stevens 2014]; Penn 2020).

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms) (alternative agent): Note: Some experts reserve for use when other long-acting parenteral antimicrobials (eg, ceftriaxone) or fluoroquinolones cannot be used due to allergy, intolerance, unmodifiable drug interactions, or resistance (Hooton 2021).

Inpatients: IV, IM: 5 mg/kg once daily. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Hooton 2021; IDSA/ESCMID [Gupta 2011]; Ryanto 2019; Wie 2014).

Outpatients: IV, IM: 5 mg/kg once, followed by 5 to 14 days of appropriate oral therapy (Hooton 2021; IDSA/ESCMID [Gupta 2011]). Note: For patients who are systemically ill or at risk for more severe illness, some experts continue daily parenteral therapy pending culture and susceptibility testing results (Hooton 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Adult

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]) (Bailey 1997; Nicolau 1995): 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.

Note: In patients with sepsis/septic shock and severe renal impairment, the SSC guidelines do not recommend use of once-daily dosing. Patients with mild renal impairment should still receive once-daily dosing with an extended interval (ie, up to 3 days) (SSC [Rhodes 2017]).

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.

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])

Dosing: Hepatic Impairment: Adult

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: Pediatric

(For additional information see "Gentamicin (systemic): Pediatric drug information")

Note: Initial dosing recommendations presented. Monitoring of serum concentrations is recommended to ensure efficacy and avoid toxicity, particularly in critically ill patients with serious infection or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, major surgery). Timing and frequency of concentration monitoring is individualized based on dosing and monitoring strategy (Begg 1999; Jenh 2011; Knoderer 2003; Zobell 2016; manufacturer's labeling). Routes of administration may vary (including IM, IV, intraperitoneal, intrathecal, and intraventricular); use caution. Some dosing is based on tobramycin studies.

Dosing consideration for obesity: In obese pediatric patients, use adjusted body weight (IBW + 0.4 [TBW – IBW]) to calculate initial dosage (Koshida 1989; manufacturer's labeling). Alternatively, adjusted body weight for obese pediatric patients may be calculated using the equation 0.7 x TBW (Bradley 2021), or fat-free mass can be used to calculate the initial dose in pediatric patients ≥2 years regardless of body habitus (Moffett 2018). Dosage should then be individualized based upon serum concentration monitoring.

General dosing, susceptible infection: Note: Optimal dose and frequency not established in patients receiving extracorporeal membrane oxygenation (ECMO); patient-specific considerations (eg, reason for ECMO) and variability with ECMO procedure itself make extrapolation of pharmacokinetic data and dosing to all patients receiving ECMO difficult; closely monitor serum concentrations and determine individual dosing needs in these patients.

Conventional dosing: Infants, Children, and Adolescents: IM, IV: 2 to 2.5 mg/kg/dose every 8 hours (Red Book [AAP 2021]).

Extended-interval dosing: Limited data available:

Weight-directed: Infants, Children, and Adolescents: IV: 5 to 7.5 mg/kg/dose every 24 hours in patients with normal renal function (Bradley 2021; Contopoulos-Ioannidis 2004; Red Book [AAP 2021]).

Age-directed: Based on data from 114 patients, the following has been suggested (McDade 2010):

Infants and Children ≥3 months to <2 years: IV: 9.5 mg/kg/dose every 24 hours.

Children 2 to <8 years: IV: 8.5 mg/kg/dose every 24 hours.

Children ≥8 years and Adolescents: IV: 7 mg/kg/dose every 24 hours.

Brucellosis: Limited data available: Infants, Children, and Adolescents: IV, IM: 5 mg/kg/dose once daily as part of an appropriate combination regimen (WHO 2006). Note: Duration depends on extent of disease; gentamicin is usually given for the first 7 to 14 days of therapy (Red Book [AAP 2021]; WHO 2006).

CNS infection:

Meningitis, including health care-associated meningitis: Infants, Children, and Adolescents: IV: 7.5 mg/kg/day divided every 8 hours in combination with other antibiotics; duration should be individualized based on patient characteristics, infecting organism, and response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Ventriculitis, including health care–associated ventriculitis and cerebrospinal fluid (CSF) shunt infections: Limited data available; optimal dose not established (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]; Mangi 1977; McCracken 1976). Dosage and administration interval can be adjusted based on CSF gentamicin concentrations, ventricle size, and daily output from ventricular drain. Duration is individualized according to clinical and microbiological response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Intraventricular/intrathecal (use a preservative-free preparation):

Infants and Children: 1 to 2 mg/day.

Adolescents: Dosing recommendations not reported; however, in adults: 4 to 8 mg/day has been suggested.

Cystic fibrosis, pulmonary infection: Infants, Children, and Adolescents:

Conventional dosing: IM, IV: 3.3 mg/kg/dose every 8 hours (Flume 2009).

Extended-interval dosing: IV: 10 to 12 mg/kg/dose every 24 hours (Flume 2009; Van Meter 2009; Zobell 2016); maximum reported dose from a survey of 28 Cystic Fibrosis (CF) Foundation-accredited centers ranged from 12 to 20 mg/kg/dose (Zobell 2016). Note: The CF Foundation recommends extended-interval dosing as preferred over conventional dosing.

Endocarditis, treatment:

Synergy dosing (eg, gram-positive bacteria): Children and Adolescents: IV: 3 to 6 mg/kg/day divided every 8 hours; use in combination with other antibiotics dependent on pathogen and source of infection (ie, valve type) (AHA [Baltimore 2015]).

Treatment dosing (eg, gram-negative bacteria): Children and Adolescents: IV: 7.5 mg/kg/day divided every 8 hours; use in combination with other antibiotics (AHA [Baltimore 2015]).

Gonococcal infection, uncomplicated infection of the cervix, urethra, or rectum (alternative agent for severe cephalosporin allergy): Limited data available:

Children ≥45 kg and Adolescents: IM: 240 mg once (administer as two 3 mL injections) in combination with single dose of oral azithromycin (CDC [St. Cyr 2020]; Kirkcaldy 2014). Note: For treatment failure, consult an infectious diseases specialist and report to the CDC through state and local health departments within 24 hours of diagnosis (CDC [St. Cyr 2020]; CDC [Workowski 2015]).

Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 3 to 7.5 mg/kg/day divided every 8 to 24 hours; use in combination with other antibiotics (IDSA [Solomkin 2010]; Surgical Infection Society [Mazuski 2017]).

Peritonitis (peritoneal dialysis) (ISPD [Warady 2012]): Limited data available: Infants, Children, and Adolescents:

Intermittent: Intraperitoneal:

Anuric: 0.6 mg/kg/dose every 24 hours in the long dwell.

Nonanuric: 0.75 mg/kg/dose every 24 hours in the long dwell.

Continuous: Intraperitoneal: Loading dose: 8 mg per liter of dialysate; maintenance dose: 4 mg per liter.

Surgical prophylaxis: Infants, Children, and Adolescents: IV: 2.5 mg/kg as a single dose; administer within 60 minutes prior to surgical incision with or without other antibiotics (procedure dependent) (ASHP/IDSA [Bratzler 2013]; Red Book [AAP 2021]).

Tularemia: Infants, Children, and Adolescents: IM, IV: 5 to 6 mg/kg/day in 2 to 3 divided doses (WHO 2007); usual duration is 7 to 10 days; a shorter course (ie, 5 to 7 days) may be considered for mild disease; longer duration and concomitant antibiotics are required for severe illness (eg, meningitis) (IDSA [Stevens 2014]; Red Book [AAP 2021]).

Urinary tract infection (UTI):

Conventional dosing: Infants, Children, and Adolescents: IV: 7.5 mg/kg/day divided every 8 hours until clinical improvement and able to tolerate oral intake; complete course with oral antibiotics; duration should be individualized based upon age, severity, and degree of urinary tract involvement (eg, patients <24 months or with pyelonephritis: 7 to 14 days; older patients with uncomplicated cystitis: 3 to 7 days) (AAP 2011; Balighian 2018).

Extended-interval dosing: Limited data available: Based on data from 90 patients (ages: 1 month to 12 years), the following age-directed dosing has been suggested (Carapetis 2001): Note: Patients were transitioned to oral therapy once afebrile for 24 hours.

Infants and Children <5 years: IV: 7.5 mg/kg/dose every 24 hours.

Children 5 to 10 years: IV: 6 mg/kg/dose every 24 hours.

Children 11 to 12 years: IV: 4.5 mg/kg/dose every 24 hours.

Single-dose regimen: Limited data available: Note: Recommended for treatment of uncomplicated cystitis caused by antimicrobial resistant gram-negative pathogens (IDSA [Tamma 2020]):

Infants, Children, and Adolescents: IM: 5 mg/kg as a single dose; dosing based on 2 prospective studies evaluating single-dose IM gentamicin in patients 1 month to 15 years and a systematic review evaluating studies of various single-dose aminoglycosides in pediatric and adult patients (Goodlet 2018; Khan 1987; Varese 1980); one study limited doses to 300 mg (Khan 1987). An overall pooled cure rate for single dose IM aminoglycoside for treatment of children and adults with mainly uncomplicated cystitis was reported as 94.5% ± 4.3% (Goodlet 2018). Note: Guidelines do not address pediatric dosing; recommended aminoglycoside doses in adults include IV single doses (IDSA [Tamma 2020]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

Parenteral: Note: Gentamicin serum concentrations should be monitored in patients with kidney impairment; following the initial dose, subsequent doses may be determined based on therapeutic monitoring.

Infants, Children, and Adolescents: IM, IV:

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: 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: Pediatric

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Obesity: Adult

The recommendations for dosing in obese patients are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):

IV: Use adjusted body weight for initial weight-based dosing when targeting Cmax/minimum inhibitory concentration (MIC) goals with either loading dose equation (based on target aminoglycoside concentration and estimated Vd) or mg/kg approach and when estimating kidney function with Cockcroft-Gault (CrCl) (Bland 2018; Pai 2014; Traynor 1995). Alternatively, use adjusted body weight to estimate CrCl and aminoglycoside dosing with the Bayesian approach when targeting AUC/MIC goals (Bland 2018; Pai 2014). Note: If aminoglycoside therapy is continued, use Cmax/MIC or AUC/MIC goals to optimize therapy, especially in the critically ill where weight and kidney function may be poor surrogates of Vd and clearance (Hassan 1987; Rughoo 2014).

Rationale for recommendations: Aminoglycosides are hydrophilic medications with a low Vd and clearance that is proportional to GFR. Pharmacokinetic studies have observed adjusted body weight, using a correction factor of 0.4, is the most appropriate weight metric to correct Vd in the setting of obesity. However, there is wide variation in the correction factors reported that could lead to under- or overdosing in clinical practice (MacDougall 2011; Pai 2007). Early use of therapeutic drug monitoring is recommended (Pai 2014).

Dosage Forms: US

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

Solution, Injection:

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

Solution, Injection [preservative free]:

Generic: 10 mg/mL (2 mL)

Solution, Intravenous [preservative free]:

Generic: 60 mg (50 mL); 80 mg (50 mL, 100 mL); 100 mg (50 mL, 100 mL); 120 mg (100 mL)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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, Intravenous:

Generic: 70 mg ([DSC]); 80 mg (50 mL); 100 mg (100 mL)

Administration: Adult

IM: Administer undiluted. Gentamicin in NS is not intended for IM administration.

IV: Infuse over 30 to 120 minutes.

Some penicillins (eg, carbenicillin, ticarcillin, 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.

Intraventricular (off-label route): Use preservative-free preparations only. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow gentamicin solution to equilibrate in the cerebrospinal fluid (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Administration: Pediatric

Parenteral:

IM: May be administered undiluted.

IV: Administer as diluted solution by slow intermittent infusion over 30 to 120 minutes; usual infusion time is 30 to 60 minutes; consider longer infusion time (60 to 120 minutes) with high doses. Shorter infusion times (≤5 minutes) have been reported in pediatric patients, including preterm and term neonates, receiving ≤4 mg/kg/dose (Bergenwall 2019; König 2015; Robinson 2001). Avoid infusing concomitantly with penicillins or cephalosporins if feasible; consult drug interactions database for more information.

Intrathecal/intraventricular: Use preservative-free preparations only; must be diluted prior to administration. No specific administration information available; it has been suggested that instillation of small volumes (<3 mL) over 1 to 2 minutes is safe (Cook 2009). When administered through a ventricular drain, clamp drain for 15 to 60 minutes to allow gentamicin solution to equilibrate in the cerebrospinal fluid (CSF) (IDSA [Tunkel 2017]).

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: Pseudomonas 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: Off-Label: Adult

Bartonella spp. infections; Brucellosis; Endocarditis, treatment (viridans group streptococci and Streptococcus bovis [native or prosthetic valve]) (adults); Gonococcal infection, uncomplicated (patients with severe cephalosporin allergy); Intra-amniotic infection; Osteomyelitis, prevention, following open fractures (type III [severe contamination or comminution]); Pelvic inflammatory disease; Peritonitis, treatment (peritoneal dialysis patients); Plague (Yersinia pestis), treatment; Postpartum endometritis; Surgical prophylaxis (alternative agent for select GI tract, GU tract, or gynecologic/obstetric procedures); Tularemia

Medication Safety Issues
Sound-alike/look-alike issues:

Gentamicin may be confused with gentian violet, kanamycin, vancomycin

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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, Clostridioides difficile-associated diarrhea, decreased appetite, enterocolitis, nausea, sialorrhea, stomatitis, vomiting

Genitourinary: Casts in urine (hyaline, granular), 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

Contraindications

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

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 Clostridioides 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 preexisting 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 preexisting 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:

• 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.

Warnings: Additional Pediatric Considerations

Use with caution in pediatric patients on extracorporeal membrane oxygenation (ECMO); pharmacokinetics of aminoglycosides may be altered; dosage adjustment and close monitoring necessary. Oral use for the prevention of NEC in premature neonates may potentially increase the risk for development of resistant bacteria; routine use for this is not recommended (Bury 2001; Reber 2004).

Metabolism/Transport Effects

None known.

Drug Interactions

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

Agalsidase Beta: Gentamicin (Systemic) may diminish the therapeutic effect of Agalsidase Beta. Management: Avoid concomitant use of gentamicin with agalsidase beta when possible as gentamicin could antagonize intracellular alpha-galactosidase activity. Risk D: Consider therapy modification

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

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

Ataluren: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, an increased risk of nephrotoxicity may occur with the concomitant use of ataluren and aminoglycosides. Risk X: Avoid combination

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

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

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

Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Risk C: Monitor therapy

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

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

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

Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

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

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Management: Avoid coadministration of colistimethate and aminoglycosides whenever possible due to the risk of nephrotoxicity and neuromuscular blockade. If coadministration cannot be avoided, monitor renal and neuromuscular function. Risk D: Consider therapy modification

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

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

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

Kanamycin: Aminoglycosides may enhance the adverse/toxic effect of Kanamycin. Management: Coadministration of kanamycin and other potentially ototoxic or nephrotoxic agents, such as aminoglycosides, is not recommended. If this combination must be used, monitor carefully neurotoxic, ototoxic, or nephrotoxic effects. Risk D: Consider therapy modification

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

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

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

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

Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy

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

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

Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: 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. Risk D: Consider therapy modification

Tacrolimus (Systemic): Aminoglycosides may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

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

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

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

Pregnancy Considerations

Gentamicin crosses the placenta.

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

Breast-Feeding Considerations

Gentamicin is present in breast milk (Celiloglu 1994).

The relative infant dose (RID) of gentamicin is 1.56% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 7.5 mg/kg/day.

In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

The RID of gentamicin was calculated using a milk concentration of 0.78 mcg/mL, providing an estimated daily infant dose via breast milk of 0.117 mg/kg/day. This milk concentration was obtained following maternal administration gentamicin 80 mg IM three times daily for 5 days postpartum (Celiloglu 1994).

In general, modification of bowel flora may occur with any antibiotic exposure (Chung 2002).

The World Health Organization (WHO) considers gentamicin to be compatible with breastfeeding. Infants should be monitored for thrush and diarrhea (WHO 2002).

Monitoring Parameters

Urinalysis, urine output, BUN, serum creatinine, plasma gentamicin levels (as appropriate to dosing method). Levels are typically obtained before and 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.

Reference Range

Conventional dosing:

Timing of serum samples: Draw peak 30 minutes after 30-minute infusion has been completed or 1 hour after IM injection; draw trough immediately before next dose is due.

Therapeutic levels:

Peak:

Sepsis, pneumonia, other serious infections (including life-threatening infections): 7 to 10 mcg/mL (Drew 2020; Matzke 1983; Zaske 1986).

Urinary tract infections, including pyelonephritis: 4 to 6 mcg/mL (Matzke 1983).

Synergy against gram-positive organisms: 3 to 4 mcg/mL (AHA [Baddour 2015]).

Trough:

Gram-negative infections: <2 mcg/mL (ideal target <1 mcg/mL) (Bertino 1994; Drew 2020; Matzke 1983).

Synergy against gram-positive organisms: <1 mcg/mL (AHA [Baddour 2015]).

Obtain drug levels after the third dose unless renal dysfunction/toxicity suspected.

High-dose extended interval dosing (once-daily dosing): Obtain a random gentamicin level between 6 and 14 hours after the start of the gentamicin infusion. Refer to institution-specific nomogram/policies to determine appropriate dosing interval. Alternatively, obtain 2 random gentamicin levels and adjust dose and interval to achieve an extrapolated peak concentration of ~15 to 20 mcg/mL and trough concentration ≤1 mcg/mL; ideal target <0.5 mcg/mL (Buijk 2002; Drew 2020; Leggett 2015; Nicolau 1995; Pagkalis 2011). When therapy is continued for 5 days or more, monitor the gentamicin levels once or twice weekly (Bailey 1997; Nicolau 1995).

Intraventricular therapeutic drug monitoring: Limited data available (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]): Prior to administration of the next intraventricular dose, withdraw a sample of CSF. This trough CSF concentration divided by the gentamicin MIC of the isolated bacterial pathogen (inhibitory quotient) should exceed 10 to 20.

Mechanism of Action

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

Pharmacodynamics and Pharmacokinetics

Absorption: IM: 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: Varies with age; 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; Xuan 2004).

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

Lung:

Bronchial secretion Cmax (peak): serum Cmax (peak) ratio: ~50%, varies with time and route (IM vs IV) (Pennington 1975).

Epithelial lining fluid Cmax (peak): serum Cmax (peak) ratio: ~32%, varies with time (Heffernan 2019; Panidis 2005; Rodvold 2011).

Protein binding: <30%.

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).

Time to peak, serum: IM: 30 to 90 minutes; IV: 30 minutes after 30-minute infusion (MacDougall 2011); Note: Distribution is prolonged after larger doses (≥90 minutes after 30- to 60-minute infusion of 7 mg/kg) (Demczar 1997; McNamara 2001; Wallace 2002).

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.

Adults: 0.06 L/hour/kg (Xuan 2004).

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Renal function impairment: Clearance is decreased in renal impairment.

Anti-infective considerations:

Parameters associated with efficacy: Gram-negative bacilli:Concentration-dependent; associated with Cmax (peak)/minimum inhibitory concentration (MIC), goal: ≥8 to 10 (Kashuba 1999; Moore 1987; Zelenitsky 2003) or AUC24/MIC, goal: 30 to 50 (mild/moderate infection, immunocompetent patient) or 80 to 100 (severe infection) (Bland 2018; Craig 2011; Drusano 2007; Nielsen 2011).

Expected drug exposure in patients with normal renal function:

Cmax (peak), postdistributional:

Infants, children, and adolescents (varies with age; values are generalized):

Neutropenic fever: 7 mg/kg: ~17 mg/L (Shankar 1999).

Critically ill: 7 to 8 mg/kg: 15 to 22 mg/L (Lopez 2010).

1.5 to 2.5 mg/kg: ~5 to 6 mg/L (Alsultan 2019; Knoderer 2003).

Adults:

7 mg/kg: ~22 mg/L (Finnell 1998; Xuan 2004).

2 mg/kg: ~6 mg/L (Demczar 1997).

AUC24:

Children and adolescents:

Neutropenic fever: 7 to 8 mg/kg: ~45 to 80 mg•hour/L (Bialkowski 2016).

Adults:

7 mg/kg: ~70 to 110 mg•hour/L (Barclay 1995; Craig 2011; Finnell 1998).

Parameters associated with toxicity: Nephrotoxicity is associated with more frequent administration and elevated Cmin (trough) concentrations leading to renal accumulation (Bertino 1993; Rybak 1999; Verpooten 1989); AUC has also been found to be predictive (Rybak 1999).

Postantibiotic effect: Bacterial killing continues after gentamicin concentration drops below the MIC of targeted pathogen; generally ~0.5 to 12 hours, though the actual time of postantibiotic effect varies significantly based on multiple factors including organism, gentamicin Cmax (peak), and concomitant antimicrobial therapy (Craig 2011; Gudmundsson 1993; Lacy 1998; Urban 1997).

Pricing: US

Solution (Gentamicin Sulfate Injection)

10 mg/mL (per mL): $1.03 - $2.57

40 mg/mL (per mL): $0.50 - $1.94

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Agentam (PH);
  • Alcomicin (AE, BF, BH, BJ, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW);
  • Apigent (AE, BH, CY, IQ, IR, JO, LB, LY, OM, QA, SA, SY, YE);
  • Azupel (PY);
  • Bacticid (LK);
  • Balticin (ID);
  • Biogaracin (IN);
  • Cidomycin (AE, BH, CY, EG, GB, IE, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE, ZA);
  • Diakarmon (AE, BF, BH, BJ, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW);
  • Duracoll (Implant) (BE);
  • Epigent (AE, BH, CY, EG, ET, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Ethigent (ID);
  • Evozar (BR);
  • Gamicin (TW);
  • Gantalyn (CL);
  • Garalone (PT);
  • Garamicin (TH);
  • Garamicina (BR, CO);
  • Garamycin (AE, BH, CH, CY, CZ, EG, HK, HR, ID, IN, IQ, IR, JO, KW, LB, LY, NL, OM, PL, QA, RU, SA, SE, SG, SY, TH, TR, TW, YE);
  • Garasent (MY, SG);
  • Garasone (CZ);
  • Gem (LK);
  • Gemycin (JO);
  • Genacin (PK);
  • Genbexil (EC);
  • Genmisil (VN);
  • Genoptic (AU, BH, CY);
  • Gensumycin (FI, NO, SE);
  • Genta-590 (PE);
  • Gentabiotic (PE);
  • Gentabrand (EC);
  • Gentac (TW);
  • Gentacare (PH);
  • Gentaderm (AR);
  • Gentagram (BR, PE);
  • Gental (PY, TH);
  • Gentalline (FR);
  • Gentalyn (IT, PE, VE);
  • Gentam (KW, QA, SA);
  • Gentamax (EC);
  • Gentamed (CY, JO);
  • Gentamen (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Gentamil (CR, DO, GT, HN, NI, PA, SV);
  • Gentamina (AR, PY);
  • Gentamytrex (NL);
  • Gentapro (KR, SG);
  • Gentarad (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Gentasil (PE);
  • Gentasporin (IN);
  • Gentatrim (IL);
  • Gentawin (TH);
  • Genticin (AE, BF, BH, BJ, CI, CY, ET, GB, GH, GM, GN, IE, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MT, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TR, TZ, UG, YE, ZM, ZW);
  • Genticyn (IN);
  • Gentocil (PT);
  • Hexamycin (DK);
  • Intagenta (ET);
  • Jie Li Tai (CN);
  • Lacromycin (IL);
  • Lyramycin (IN);
  • Maxigen (PH);
  • Miragenta (CO);
  • Miramycin (HK, SG, TH);
  • Mycin (LK, PH);
  • Nelgen (PH);
  • Obogen (PH);
  • Ophtagram (BE);
  • Optimycin (BF, BJ, CI);
  • Provisual (AR);
  • Qutacin (TW);
  • Refobacin (AT, DE);
  • Rigaminol (PE);
  • Rocy Gen (PH);
  • Rovixida (AR);
  • Rupegen (AR);
  • Servigenta (MY);
  • Sulmycin (DE);
  • Tondex (CR, DO, GT, HN, NI, PA, SV);
  • Versigen (TH)


For country abbreviations used in Lexicomp (show table)

REFERENCES

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