No

Antibiotic, Aminoglycoside

Short-term treatment of serious or life-threatening infections including septicemia, peritonitis, intra-abdominal abscess, lower respiratory tract infections, urinary tract infections; skin, bone, and joint infections caused by susceptible organisms; active against Pseudomonas aeruginosa, E. coli, Proteus, Klebsiella, Serratia, Enterobacter, Citrobacter, and other gram-negative bacilli

D

Known hypersensitivity to netilmicin (aminoglycosides, bisulfites)

Use with caution in patients with pre-existing renal insufficiency, vestibular or cochlear impairment, myasthenia gravis, hypocalcemia, conditions which depress neuromuscular transmission. Parenteral aminoglycosides are associated with nephrotoxicity or ototoxicity; the ototoxicity may be proportional to the amount of drug given and the duration of treatment; tinnitus or vertigo are indications of vestibular injury and impending hearing loss; renal damage is usually reversible.

>10%:

Central nervous system: Neurotoxicity

Otic: Ototoxicity (auditory), ototoxicity (vestibular)

Renal: Nephrotoxicity, decreased creatinine clearance

1% to 10%: Dermatologic: Skin itching, redness, rash, swelling

<1%: Difficulty in breathing, drowsiness, weakness, headache, tremors, muscle cramps, pseudomotor cerebri, anorexia, nausea, vomiting, weight loss, increased salivation, enterocolitis, granulocytopenia, agranulocytosis, thrombocytopenia, photosensitivity, erythema, burning, stinging

Serum levels monitoring is recommended. Signs and symptoms of overdose include ototoxicity, nephrotoxicity, and neuromuscular toxicity.

Treatment of choice following a single acute overdose appears to be the maintenance of good urine output of at least 3 mL/kg/hour. Dialysis is of questionable value in the enhancement of aminoglycoside elimination. If required, hemodialysis is preferred over peritoneal dialysis in patients with normal renal function. Careful hydration may be all that is required to promote diuresis and therefore the enhancement of the drug's elimination. Chelation with penicillins is experimental.

Increased/prolonged effect of depolarizing and nondepolarizing neuromuscular blocking agents

Increased toxicity: Concurrent use of amphotericin, vancomycin, ethacrynic acid, furosemide and other nephrotoxic agents may increase nephrotoxicity

Interferes with protein synthesis in bacterial cell by binding to 30S ribosomal subunits

Absorption: I.M.: Well absorbed

Distribution: To extracellular fluid including serum, abscesses, ascitic, pericardial, pleural, synovial, lymphatic, and peritoneal fluids; high concentrations in urine; crosses placenta

Half-life: 2-3 hours (age and renal function dependent)

Time to peak serum concentration: I.M.: Within 30-60 minutes

Elimination: Excreted by glomerular filtration

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). In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW). Peak and trough plasma drug levels 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).

Neonates <6 weeks: 2-3.25 mg/kg/dose every 12 hours

Children 6 weeks to 12 years: 1-2.5 mg/kg/dose every 8 hours

Children >12 years and Adults: 1.5-2 mg/kg/dose every 8-12 hours

Some clinicians suggest a daily dose of 4-7 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.

Dosing adjustment in renal impairment: Initial dose:

All patients should receive a loading dose of at least 2 mg/kg (subsequent dosing should be base on serum concentrations)

Cl_cr greater than or equal to 60 mL/minute: Administer every 8 hours

Cl_cr 40-60 mL/minute: Administer every 12 hours

Cl_cr 20-40 mL/minute: Administer every 24 hours

Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Dose as for Cl_cr 10-40 mL/minute and follow levels

Infuse over approximately 30 minutes

Therapeutic: Peak: 4-10 mg/mL (SI: 8-21 mmol/L); Trough: <2 mg/mL (SI: 4 mmol/L); Toxic: Peak: >10 mg/mL (SI: >21 mmol/L); Trough: >2 mg/mL (SI: >4.2 mmol/L)

Penicillins may decrease aminoglycoside serum concentrations in vitro

May cause drowsiness or dizziness

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Report any dizziness or sensations of ringing or fullness in ears

Peak levels are drawn 30 minutes after the end of a 30-minute infusion; trough levels are drawn within 30 minutes before the next dose; give other antibiotic drugs at least 1 hour before or after gentamicin, if possible.

Injection, as sulfate: 100 mg/mL (1.5 mL)

Begg EJ and Barclay ML, "Aminoglycosides - 50 Years On," Br J Clin Pharmacol, 1995, 39(6):597-603.

Blaser J, König C, Simmen HP, et al, "Monitoring Serum Concentrations for Once-Daily Netilmicin Dosing Regimens," J Antimicrob Chemother, 1994, 33(2):341-8.

Cunha BA, "Aminoglycosides: Current Role in Antimicrobial Therapy," Pharmacotherapy, 1988, 8(6):334-50.

Edson RS and Terrell CL, "The Aminoglycosides," Mayo Clin Proc, 1999, 74(5):519-28.

Lortholary O, Tod M, Cohen Y, et al, "Aminoglycosides," Med Clin North Am, 1995, 79(4):761-87.

McCormack JP and Jewesson PJ, "A Critical Reevaluation of the "Therapeutic Range" of Aminoglycosides," Clin Infect Dis, 1992, 14(1):320-39.

Rozdzinski E, Kern WV, Reichle A, et al, "Once-Daily Versus Trice-Daily Dosing of Netilmicin in Combination With b-lactam Antibiotics as Empirical Therapy for Febrile Neutropenic Patients," J Antimicrob Chemother, 1993, 31(4):585-98.